Posted on: June 28, 2022 Posted by: AKDSEO Comments: 0
Thursday, February 10, 2022
#178  Evaluation of quality of life data reporting in metastatic kidney cancer trials

FG Bell*

JC Henegan

University of Mississippi, University of Mississippi, University Park, MS, US, Jackson, MS

Purpose of Study

Health related quality of life (HRQoL) results provide information as to the general impact on a patient’s life that a therapy may have. Both statistical and clinical significance should be reported for HRQoL but not all studies present both pieces of information.

We sought to identify if there is a difference in the frequency of the presentation of statistical significance of HRQoL versus clinical significance of HRQoL in phase III studies of investigational agents in metastatic renal cell carcinoma reporting longitudinal results of overall HRQoL.

Methods Used

A Medline search using the MESH term ‘Kidney Neoplasms’ and filtering for Phase III clinical trials was conducted. The articles were reviewed and those studies which included longitudinal results of overall HRQoL in phase III studies of investigational agents in metastatic renal cell carcinoma were included in the analysis. The binomial test was used to calculate a z-score, with the frequency of the reporting of statistical significance used as the expected probability of reporting of clinical significance.

Summary of Results

31 phase III trials were able to be included in the analysis. Of these, 26 (83%) reported if a result was statistically significant and 21 (68%) reported if a result was clinically significant. Due to the small sample size the data did not meet the requirements for a z-test.

Conclusions

There is a nominal increase in the frequency of the presentation of statistical significance of HRQoL versus clinical significance of HRQoL in phase III studies of investigational agents in metastatic renal cell carcinoma reporting longitudinal results of overall HRQoL. However, the small sample size prevented the planned statistical analysis from being able to be reliably performed.

#179  Cardiomyopathy after doxorubicin

C Bergeron*

A Garcia

LSU Health New Orleans, New Orleans, LA

Purpose of Study

To highlight the importance of a thorough work-up for new onset heart failure in patients treated with doxorubicin

Methods Used

Review of Electronic Health Records and literature review

Summary of Results

A 59-year-old female with PMH of hypertension was diagnosed with left breast cancer. She underwent a modified radical mastectomy and pathology showed a stage III breast cancer. Transthoracic echocardiogram (ECHO) showed left ventricular (LV) hypertrophy with normal cardiac function (left ventricular ejection fraction, LVEF > 55%). Electrocardiogram (ECG) showed LV hypertrophy and no additional abnormalities. She started adjuvant chemotherapy with dose-dense doxorubicin (D), cyclophosphamide, and paclitaxel. Cumulative dose of D was 240 mg/m2. Two months after completing D, she presented with tachycardia. She reported 5 months of progressive dyspnea since beginning chemotherapy, followed by an acute worsening of dyspnea 2 weeks prior to presentation.

At presentation, brain natriuretic peptide was elevated. CXR showed signs of volume overload. ECG showed anteroseptal infarct of undetermined age. ECHO showed a LVEF of 25–30%. The patient was diagnosed with new onset heart failure (HF) with reduced ejection fraction (HFrEF) secondary to doxorubicin cardiomyopathy (DCMP). Following stabilization, she was discharged on goal-directed medical therapy for HFrEF and referred for follow-up with cardiology. At follow-up, nuclear stress testing revealed a large mid-distal defect in the anteroseptal wall corresponding to left anterior descending artery (LAD) territory infarction. Left heart catheterization and coronary angiography showed 100% occlusion of the LAD and 80% of the left circumflex artery, suggesting ischemic cardiomyopathy as the true cause of this patient’s new onset HFrEF.*

DCMP is a well-described cause of dilated cardiomyopathy. Dilated cardiomyopathy is defined by ventricular dilatation with systolic dysfunction, in the absence of coronary artery disease, hypertension, valvular disease, or congenital heart disease. The absence of these conditions is required for the diagnosis of dilated cardiomyopathy and subsequently DCMP. Risk factors for DCMP include age (> 65 years), female gender, preexisting cardiovascular disorders, hypertension, smoking, obesity, diabetes and high cumulative dose. It is usually classified as acute (occurs during treatment), subacute (detected within 1 year) and chronic (detected years after exposure). The prognosis of DCMP is poor and therefore it is essential to rule out treatable causes of HFrEF.

Conclusions

Cardiomyopathy is a well described, but uncommon side effect of D. Symptomatic HF is seen in approximately 1% of patients. Our patient had several risk factors for DCMP. This case highlights the importance of thorough evaluation for the cause of newly diagnosed HF even when the etiology seems straightforward. While D is a well described caused of dilated cardiomyopathy, ruling out more common causes of LV dysfunction are necessary to make the diagnosis.

#180  Leukemia cutis: an uncommon presentation of acute myeloid leukemia

D Beyer*

M Lieux

B Van Court

C Pham

C Van Dreumel

DA Van

SM Ford

R Foret

LS Engel

S Sanne

LSU Health New Orleans, New Orleans, LA

Case Report

Introduction

Leukemia Cutis is a rare condition characterized by infiltration of neoplastic cells into the epidermis and dermis with a characteristic dermatologic appearance. Leukemia cutis generally portends a poor prognosis in the setting of newly diagnosed blood cancers.

Case

A 31-year-old man without past medical history presented after 1 month of progressive dyspnea on exertion, worsening fevers, thirty pound unintentional weight loss and diffuse rash on all extremities and trunk. Physical exam was significant for fever, tachycardia and scattered petechia and erythematous papules and macules on his bilateral upper and lower extremities. Initial laboratory findings were significant for leukocytosis (222,000) with 94% immature mononuclear cells and thrombocytopenia (8,000). Punch biopsy was performed and pathology returned leukemia cutis with myeloid features. Bone marrow biopsy was significant for acute myeloid leukemia with 86% large blastoid cells. Patient was started on induction chemotherapy with cytarabine and idarubicin resulting in slow resolution of rash.

Discussion

Leukemia cutis is a challenging diagnosis and rare presentation of leukemia. When coupled with a new diagnosis of acute myeloid leukemia, as in this patient, portends a worse prognosis. This patient presented in blast crisis with cutaneous involvement and new diagnosis of acute myeloid leukemia was made promptly based on bone marrow biopsy results. Prompt dermatologic consultation resulted in diagnosis of leukemia cutis based on punch biopsy. After initiation of induction chemotherapy (cytarabine and idarubicin), his cutaneous lesions subsided significantly.

#181  Cobalamin deficiency masquerading as possible thrombotic microangiopathy

L Bradley*

E LeJeune

The University of Mississippi Medical Center, Jackson, MS

Case Report

Prompt recognition of Thrombotic Thrombocytopenic Purpura (TTP) is of utmost importance for clinicians considering the near 100% mortality rate associated with delayed treatment. Cobalamin (B12) deficiency is a rare cause of hemolytic anemia and can sometimes mimic the presentation of TTP. Though an infrequent diagnosis, pseudo-thrombotic microangiopathy (TMA) can in some cases result in inappropriate treatment with plasmapheresis if not distinguished from true TTP early. Here we present a case of severe B12 deficiency causing a TMA like syndrome.

58 year old African American male presented to the emergency department complaining of shortness of breath. His laboratory values were discovered to be white blood cell count 9.89 TH/cmm with normal differential, hemoglobin 5.7 g/dL, hematocrit 18.1%, platelet count 75,000 TH/cmm. He was admitted to the internal medicine service for further evaluation. Further workup revealed MCV of 127 fl, LDH >3500 U/L, Haptoglobin <10, and Total bilirubin of 2.22 mg/dL with indirect bilirubin 1.80 mg/dL. Reticulocyte count 1.2%. Direct antibody coombs test was negative. Serum B12 level was 150 with Methylmalonic acid of 5.52umol/mmol. On peripheral blood smear 1–3 schistocytes per high power field, rare tear drop cells, and numerous hypersegmented neutrophils were observed. ADAMTS-13 activity level was 78%.

Plasmapheresis was held and B12 1000 mcg IM was given daily for 7 days, then weekly for 4 weeks, followed by monthly indefinitely. On hospital follow up 6 weeks later patient had complete resolution of his anemia and thrombocytopenia. Serum B12 level was >500. He was referred to gastroenterology for further evaluation of suspected B12 malabsorption etiology.

Though rare, B12 deficiency causing hemolytic anemia is a known disease process and should be considered in the differential for hemolytic anemia. The pathogenesis of low B12 causing hemolytic anemia is uncertain but it has been demonstrated in vitro that elevated levels of homocysteine can lead to endothelial damage likely resulting in hemolysis. Early recognition of this patient’s pseudo-TMA likely shortened his hospital stay and prevented unnecessary initiation of plasmapheresis.

#182  Correlation between intubation and palliative care: what is the trend?

OH Brunson*

The University of Mississippi Medical Center, Jackson, MS

Purpose of Study

Over the last twenty years there has been an increase in the number of endotracheal intubations.1 In that same time period, palliative care has emerged with a focus on quality of life and alleviating suffering in patients with chronic, severe illness. More recently societal guidelines, including the American Society of Clinical Oncology, have recommended early integration of palliative care. 2,3 Hypothetically, earlier goals of care discussions could lead to less invasive interventions, such as intubation. With this focus on earlier intervention, we aim to study the correlation between inpatient palliative care consultation and intubations at our institution.

Methods Used

Utilizing a function of EPIC electronic medical record SlicerDicer, we were able to identify patients admitted to the University of Mississippi Medical Center with a co-occurrence of intubation and palliative care consult, examine patient demographics and calculate relative risk (RR).

Summary of Results

We first looked at intubations, which increased by 136% from 2012–2016 with the rate of change from 2017–2020 varying by only 1–2% a year. Next, we looked at palliative care consults. Since inpatient palliative care became available in 2017, the number of consults increased by 39% (264 to 367). We then analyzed 99,622 admissions from 2017–2020 to look for co-occurrences of intubation and palliative care consultation during the same admission. In the general population, excluding patients with a cancer diagnosis, co-occurrences increased by 86% from 2017–2020 (23 to 43). In cancer patients, co-occurrences increased initially by 600% from 2017–2019 (2 to 14), but then decreased by 35% in 2020. Based on this data, the RR of intubation and a palliative care consult during an admission was higher in non-cancer patients than cancer patients (RR 5.8, RR 2.3 respectively). The highest RR was seen in non-cancer patients less than 30 and 50–70 years old (RR 13.6, RR 7.8 respectively).

Conclusions

Overall, there was an increase in co-occurrences of intubation and palliative care consultation. This could be attributed to a growing palliative care service, but the excess RR in younger, non-cancer patients may point to the palliative care team being increasingly utilized in the acute, critically ill patient. Notably, co-occurrences in non-cancer patients increased compared to cancer patients in 2020, likely due to Sars-Cov2. Though co-occurrences increased in cancer patients overall, the decreased RR compared to non-cancer patients is promising. This could point to more sub-specialist involvement in inpatient palliative discussions and/or earlier goals of care discussions. There is still work to be done to emphasize earlier goals of care discussions in chronic illnesses, which could ultimately lead to a decrease in the number of co-occurrences of intubation and palliative care over time. Further investigation is needed to follow this trend.

#183  Diagnostic dilemma: primary orbital squamous cell carcinoma or not?

VK Carey1*

J Steyer1

P Goel1

A Ananthula1

SK Halat2

R Walvekar1

R Chowdry1

1LSU Health New Orleans, New Orleans, LA

2Tulane University School of Medicine, New Orleans, LA

Introduction

Primary orbital squamous cell carcinoma (SCC) is extremely rare with only 9 cases reported in literature. Secondary squamous cell carcinoma of the orbit is more common, accounting for 6.8% of orbital tumors and is usually the result of local invasion from a cutaneous primary (eyelid, conjunctiva, lacrimal gland, sino-nasal tract etc.), perineural invasion or distant metastasis. Here, we present a case of SCC of the right orbit which poses a diagnostic challenge as to the origin of the tumor and optimal management strategy.

Case

The patient is a 60-year-old male with a history of right eye injury and subsequent blindness who presented with a large right orbital mass which has been growing for a few months. The patient was struck in his right eye with metal debris several decades ago. Biopsy confirmed a diagnosis of moderately differentiated squamous cell carcinoma. Within a month of presentation, the mass continued to further grow rapidly with involvement of the entirety of the right orbit with proptosis. Ulceration along the medial canthus were noted with intermittent mild bleeding. The patient was unable to move his eyelids. CT of the orbits demonstrated a large right orbital mass extending into orbital apex with intraconal & extraconal involvement extending into the supraorbital & infraorbital fissures. The globes & optic nerve were not identified. MRI of the brain was negative for intracranial involvement. CT Chest, Abdomen, Pelvis was negative for any distant metastasis. Decision was made to proceed with right orbital exenteration, parotidectomy, modified radical neck dissection, and free flap reconstruction. Histopathology showed a 6.1 cm invasive squamous cell carcinoma with tumor invasion into the globe, extraocular muscles, orbital fat and optic nerve. Lymphovascular and perineural invasion was present. All margins were negative for malignancy. He is staged as pT4aN0M0 SCC of the right orbit. He has tolerated surgery well and plan is to start adjuvant chemo-radiation with weekly cisplatin given the risk of recurrence in his case.

Discussion

The orbit does not contain squamous epithelium, which accounts for the rarity of the disease. Case reports have detailed primary orbital SCC from dermoid cysts, lacrimal gland cysts with squamous metaplasia and conjunctival cysts occurring after ocular surgery. Squamous metaplasia is a consideration in this patient secondary to chronic irritation from his eye injury. In further review of existing literature, we inferred that we might not be able to confirm where the SCC originated in such cases with de novo orbital mass. Orbital SCC is usually treated with surgery with radiotherapy or chemoradiation depending on the extent of tumor invasion and risk of recurrence.

#184  Primary pulmonary melanoma presenting as brain metastasis

KJ Clay1*

BS Ross2

F Joiner1,2

1The University of Mississippi Medical Center, Jackson, MS

2G.V. (Sonny) Montgomery VA Medical Center, Jackson, MS

Case Report

Melanoma, a malignant tumor of pigment-producing cells, is a potentially fatal neoplasm most commonly arising from a cutaneous origin. However, cases arising from mucosal, ocular, and visceral sites are described. Here, we report a case of a primary melanoma of the lung with pulmonary and brain metastases.

A 42-year-old male with diabetes mellitus and a tobacco use disorder presented to the emergency department after a five-minute episode of aphasia associated with perioral tingling. Upon arrival, he was able to speak clearly, and he had no focal neurologic deficits. The remainder of his review of symptoms and physical exam was unremarkable. The differential diagnosis included seizure or transient ischemic attack. A non-contrast head CT revealed an acute focal hemorrhage within the left parietal lobe with a small subarachnoid component. MRI imaging further demonstrated a 1.5 cm rim-enhancing mass concerning for hemorrhagic metastasis. He was admitted. An awake craniotomy with tumor resection revealed a high-grade malignant neoplasm positive for MART1 and SOX10 and negative for GFAP, TTF-1, CK7, CK20, EMA, and CD34, which favored metastatic melanoma. This lesion was BRAF V600E positive and NRAS negative. Subsequent PET scanning revealed multiple FDG-avid pulmonary nodules, with an endob ronchial mass amenable to biopsy. Bronchoscopic biopsy of this mass demonstrated malignant cells positive for MART1 and SOX10 consistent with malignant melanoma and suggested that this was the primary lesion. A specialty-conducted dermatologic evaluation failed to reveal other potential primary sites. Initial therapy consisted of gamma knife radiation to the post-resection brain tumor bed and immunotherapy with nivolumab and ipilimumab. Two months later, an MRI showed multiple new intracranial metastases, and a PET scan showed an increase in the size of the endobronchial lesion and an increase in the number and size of the metastatic lung nodules. The patient has completed four cycles of nivolumab/ipilimumab and is being evaluated for dabrafenib/trametinib combination therapy.

Primary malignant melanoma of the lung is rare, accounting for 0.01% of all lung neoplasms. Though the pathogenesis of these tumors remains obscure, it is believed that primitive melanoblasts may migrate to the viscera during embryogenesis. New therapies have emerged for metastatic cutaneous melanoma that target specific kinases and protein receptors such as PD-1, CTLA-4, BRAF, and MEK. However, there is a paucity of data on the efficacy and safety of these treatments with non-cutaneous metastatic melanoma. This case illustrates the diagnostic and therapeutic challenges associated with this rare pathological entity.

#185  Stage ii endometrial carcinoma with false positive para-aortic lymphadenopathy: the importance of pretest probability

JA Cooper*

A Garcia

LSU Health New Orleans, New Orleans, LA

Purpose

Case report to increase awareness of pretest probability in the presence of abnormal imaging findings

Methods

Review of Electronic Health Records and literature review

Results

This patient is a 61-year-old female with a history of intermittent vaginal spotting since her early 50’s. On physical exam, normal vaginal atrophy was observed, and bi-manual recto-vaginal exam showed normal-sized uterus without adnexal masses or nodularity. A Pap-smear with dilation and curettage revealed endometrial carcinoma, endometrioid type with squamous differentiation. Hysterectomy with bilateral salpingo-oophorectomy, bilateral pelvic sentinel biopsy, and bilateral pelvic lymphadenectomy was performed. Pathology showed a grade 1 endometrioid carcinoma with greater than 50% myometrial invasion. The cervical stroma contained a 2 mm focus of tumor, and all 18 pelvic lymph nodes were negative meriting a diagnosis of Stage II endometrial carcinoma. Vaginal cuff brachytherapy, a non-morbid treatment, was offered as adjuvant therapy.

Staging PET/CT scan showed a hypermetabolic left para-aortic lymph node at the renal level suspicious for active neoplastic disease. Based on this the recommendation for adjuvant treatment was changed to extended field radiation and systemic chemotherapy, a treatment associated with significantly more toxicity. However, it was discussed that this was an unusual presentation and further evaluation was required. A CT-guided biopsy of the left para-aortic lymph node was performed and showed no malignant cells. Patient received vaginal brachytherapy. PET/CT three months later showed persistent, unchanged metabolically active left para-aortic lymphadenopathy. A repeat biopsy showed no malignancy. The scan also showed persistent chronic nephrolithiasis and obstructive uropathy of the left kidney with severe parenchymal atrophy. Uterenoscopic stone extraction with holmium laser lithotripsy and stent placement was performed. Patient remains without evidence of cancer recurrence 30 months after surgery.

Conclusions

This case shows the importance of using the pre-test probability when interpreting test results. PET/CT scan is highly sensitive and specific for endometrial cancer. However, para-aortic lymph node metastasis without pelvic lymph node metastasis from endometrial carcinoma is very rare (low pre-test probability). This low pre-test probability raised the concern about the PET/CT findings. The patient was spared the toxicity of unnecessary chemotherapy and extended field radiation. It was concluded that the findings on PET scan were related to the inflammatory process in the kidney associated with the nephrolithiasis and chronic obstructive uropathy. This case shows the importance of taking into the account the pre-test probability when interpreting any test.

#186  A different take on cardio-oncology: metastatic angiosarcoma presenting as a primary cardiac tumor

C Cutrer*

JC Henegan

The University of Mississippi Medical Center, Jackson, MS

Introduction

Cardiac tumors are very rare, mostly presenting as distant metastases. Only about 0.5% present as primary cardiac tumors and of those, the majority are benign, typically atrial myxomas (1). Angiosarcomas can rarely present as primary cardiac tumors and tend to be very aggressive. We present a case of a patient who presented with new coronary artery disease complicated by recurrent pericarditis and ultimately found to have metastatic angiosarcoma originating from the right atrium.

Case Report

Our patient is a 57 year old African-American male with a past medical history of hypertension and poly substance abuse who initially presented in January 2021 with chest pain and found to have acute coronary syndrome. He was taken for cardiac catheterization and percutaneous intervention (PCI) was performed with stent placement in left anterior descending (LAD) artery. A few weeks after his PCI, patient was readmitted for pericarditis and also complained of fatigue and weight loss, so computerized tomography of the chest, abdomen and pelvis (CT CAP) was obtained to rule out malignancy and it did not show any evidence of disease. Over the next few months, our patient had recurrent chest pain and weight continued to decline as fatigue worsened. He finally represented to the emergency room in July 2021 with chest pain and CT CAP was again obtained, only this time showing a large cardiac tumor abutting the right atrium and ventricle and evidence of metastatic disease throughout his vertebra, lungs and liver. Patient was referred to Oncology and had a biopsy of a bone lesion done via interventional radiology (IR), which showed metastatic angiosarcoma. We discussed palliative chemotherapy with single agent paclitaxel and initially patient agreed but there were delays over the next few weeks. By the time patient was able to make it back to clinic for treatment in early September, he had lost considerable weight and was wheelchair or bed bound for the majority of the day due to fatigue, weakness and pain. After further discussion, he decided to pursue hospice at home with family.

Discussion

Primary cardiac tumors are rare but when present, can be very aggressive. Angiosarcomas account for about 30% of primary malignant cardiac tumors and are typically very aggressive with a median overall survival of 4–6 months when unresectable (2). Typical treatment is surgical when feasible but chemotherapy and radiation therapy are often used, as well. Chemotherapy typically consists of taxane or anthracycline-based regimens (3). A small single arm study demonstrated a 25% (4/16) response rate for angiosarcomas to the combination of nivolumab and ipilimumab after prior chemotherapy which may lead to evaluations of this immunotherapy combination in first line therapy (4). In summary, prompt diagnosis and multidisciplinary treatment planning is important when taking care of patients with primary cardiac tumors.

#187  Pseudothrombotic microangiopathy and pancytopenia as a rare presentation of vitamin b12 deficiency

M Darweesh*

F Ghanem

R Musa

D Nunley-Gorman

East Tennessee State University James H Quillen College of Medicine, Johnson City, TN

Case Report

A 62-year-old male presented to our hospital with a few days of worsening dyspnea, associated with numbness in the left lower extremity, dizziness and transient brief chest pain that was described as a sharp intermittent pain. He denied any fever, chills, nausea, vomiting, diarrhea, headache, or recent ill contacts. The patient also denied any family history of blood or bone morrow disease. He had been released from incarceration 2 days prior to the presentation.

Complete blood count revealed pancytopenia with hemoglobin of 6.8 g/dL, MCV of 112 fL, white blood cell count of 1.2 K/uL, and platelet count of 78 K/uL. The patient was transfused with packed red blood cells and then admitted to the inpatient medicine ward for further treatment and evaluation. Blood smear confirmed the pancytopenia with severe neutropenia, macrocytosis, and moderate thrombocytopenia. In addition, it showed erythrocytes with marked poikilocytosis including occasional schistocytes and teardrop cells.

His lab investigations were notable for B12 level below 150 pg/mL (Normal range 211–911), fibrinogen of 144 mg/dL , haptoglobin less than 10 mg/dL, LDH of 1013 U/L. Other lab studies including troponin, ferritin, TIBC, serum iron, vitamin B1, PT/INR, PTT, SPEP, COVID-19, EBV, CMV, HIV, Hepatitis A, B, and C were all unrevealing. Abdominal ultrasound was significant for splenomegaly. CT head and chest x-ray were unremarkable. After starting treatment with cobalamin therapy, the patient has shown improvement in terms of cell counts, resolution of hemolysis. He also reported significant improvement in tingling and dizziness. All this confirms the diagnosis.

Vitamin B12 deficiency manifestations can vary between asymptomatic, mild, and severe. In our case, the patient presented with pseudothrombotic microangiopathy and pancytopenia. Both are rare and serious manifestations of vitamin B12 deficiency. Physicians should be aware of cobalamin deficiency as one of the etiologies for pancytopenia and pseudothrombotic microangiopathy. Therefore, an early recognition and treatment is crucial.

Abstract #187 Figure 1
#188  Catastrophic antiphospholipid syndrome collides with refractory secondary evans syndrome: a therapeutic dilemma

H Daugherty*

C Hitchcock

GD Gibson

C Milner

The University of Mississippi Medical Center, Jackson, MS

Case Report

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by both venous and arterial thromboses in the setting of persistent antiphospholipid autoantibodies. APS can be associated with mild thrombocytopenia but has rarely been seen in combination with Evans syndrome (autoimmune hemolytic anemia, immune thrombocytopenia and/or neutropenia). Here we present a case of the therapeutic dilemmas faced when these two syndromes combine.

A 36-year-old female with antiphospholipid syndrome, cirrhosis due to Budd-Chiari syndrome (BCS), and recurrent pulmonary emboli on anticoagulation presented with right upper quadrant abdominal pain and shortness of breath in addition to a reported six-month history of fatigue, fevers, night sweats, and unintentional weight loss. The patient was pancytopenic and coagulopathic with elevated but stable liver enzymes of a mixed injury pattern. Imaging confirmed known hepatic venous thrombosis with progressive hepatic infarctions. The patient was not a candidate for IR intervention, and liver transplant evaluation was initiated. A mixed autoimmune hemolytic anemia (AIHA) was confirmed by blood smear demonstrating spherocytes without schistocytes in combination with both warm and cold antibodies on Coombs’ testing. A bone marrow biopsy later revealed hypercellularity with increased megakaryocytes consistent with immune-mediated thrombocytopenia (ITP). AIHA and ITP in the setting of APS are congruous with secondary Evans syndrome. The patient initially received mg/kg prednisone without response. She was then transitioned to IV Ig for six doses, romiplostim weekly for three weeks, rituximab weekly, and lastly, plasma exchange. Despite progression of therapy and frequent transfusions, platelets remained unresponsive with worsening hemolytic anemia. The clinical course was further complicated by significant bleeding involving diffuse alveolar hemorrhage resulting in acute hypoxic respiratory failure requiring mechanical ventilation and recurrent gastrointestinal bleeding. The patient developed widespread venous thromboses with our inability to anti-coagulate, resulting in multi-organ failure including cardiogenic shock and acute renal failure consistent with catastrophic antiphospholipid syndrome (CAPS). Ultimately, the patient suffered diffuse dural venous thromboses, cerebral herniation, and was subsequently palliatively extubated.

A small subset of APS patients will develop CAPS manifested by intravascular thrombosis resulting in multiorgan failure with high mortality. Treatment focuses on limiting thrombosis and suppressing the cytokine cascade. This case demonstrates the formidable processes of an immune system gone awry despite aggressive treatment with well-validated therapeutic options and the dilemma of anticoagulation with active bleeding. Lastly, we are uncertain if more expeditious plasma exchange or the addition of cyclophosphamide or eculizumab could have made an impact on this patient’s care.

#189  A case of acquired hemophilia a due to factor viii inhibitor

C Donath*

A Siddiqui

A Arnold

Florida State University, Tallahassee, FL

Introduction

Acquired Hemophilia A (AHA) is a rare and typically incidentally found by either bleeding complications after a GI procedure, postpartum or spontaneous bleeding into the skin and soft tissues.

Case Report

72y/o female with a history of coronary artery disease s/p percutaneous coronary intervention with drug eluting stent (DES) two months prior, hyperthyroidism and rheumatoid arthritis, was admitted for acute blood loss anemia. She was on aspirin and clopidogrel given the recent DES. She has a 1-week history of fatigue, bloody diarrhea and epistaxis. She was hemodynamically stable. Lab values showed WBC 10.2 k/mm3, hemoglobin 5.5 mg/dL, hematocrit 18%, platelet 113 k/mm3, MCV 100 fl, reticulocyte 14%, smear showed slight macrocytosis, B12 1021 pg/mL, folate 36.6 ng/mL, ferritin 66.4 ng/mL, transferrin saturation 17%, LDH 450 u/L, haptoglobin 225 mg/dL, PT 14 seconds, INR 1.0, PTT 85 seconds. Two units of packed red blood cells were transfused urgently. Post transfusion hemoglobin was 8.1 mL/dL. Gastroenterology was consulted for suspected upper gastrointestinal bleed. Esophagogastroduodenoscopy showed a Dieulafoy lesion in the gastric body and greater than 20 bleeding AVMs in the duodenum/jejunum. These lesions were ablated successfully. A few hours after the procedure, the patient complained of severe abdominal pain. An emergent CT abdomen w/o contrast showed a new duodenal intramural hematoma. General Surgery did not recommend surgical intervention given very poor surgical canidate. Aspirin and clopidogrel was stopped. Meanwhile, the mixing study result came back showing an abnormal mixing pattern not corrected by incubation. Factor VIII was found to be <1% and Bethesda Titer assay was >30. This study consistent with Acquired Hemophilia A secondary to Factor VIII inhibitor. Hematology/Oncology was consulted and the patient was started on high dose prednisone, recombinant FVIII and weekly rituximab infusions for immunosuppression.

Discussion

AHA is a rare entity of bleeding disorders that is often a missed diagnosis. 50% of diagnosed cases are idiopathic with spontaneous bleeding, with the rest being due to occult malignancy, autoimmune disease, infections or post-partum bleeding. Severe bleeding can occur in up to 70% of affected patients with fatality as high as 5–10%. Unlike Congenital Hemophilia, hemarthrosis is not a part of the syndrome. Rather, spontaneous bleeding into skin and soft tissues, intramural hematomas and mucus membranes is seen. Abnormal mixing studies should lead to investigation of which bleeding factor is being consumed/inhibited, commonly factor VIII or IX by investigating the factor’s activity. Bethesda Titer assay will be useful for levels of the inhibitor itself.

Conclusion

Isolated aPTT should prompt clinicians to order mixing studies to evaluate etiology of the prolonged coagulation cascade. AHA can lead to devastating bleeding sequelae, therefore prompt recognition and treatment of AHA can be lifesaving.

#190  Therapeutic challenges in treating a newly diagnosed aplastic anemia in a patient with coexistent covid-19 infection

Z Elharabi*

E Elgwairi

M Abohelwa

G Del Rio-Pertuz

K Parmar

D Pawar

A Abdalla

K Nugent

Texas Tech University Health Sciences Center, Lubbock, TX

Introduction

Aplastic anemia is a syndrome of bone marrow failure characterized bone marrow hypoplasia. Immunosuppressive therapy is one modality of its management. We report a case in which use of this modality was hindered by lack of data showing the effects of its use during the novel COVID-19 infection.

Case presentation

A 20-year-old man with a newly diagnosed pancytopenia presented with fever, cough, headaches, and exertional dyspnea. When his vital signs were obtained, he was afebrile but his blood pressure, heart rate and oxygen saturation were within normal range. Physical exam was unremarkable. Laboratory tests showed that the white blood cell count was 1.42 K/µL, hemoglobin level was 9.7 g/dl, and platelet count was 13 K/µL. He was tested for COVID-19 infection and was found to be positive. A peripheral blood smear showed pancytopenia. A bone marrow biopsy showed hypocellular marrow with trilineage hypoplasia. Flow cytometry showed no significant trilineage abnormalities. Vitamin 12 and folate levels were within normal range. Testing for antinuclear antibodies, rheumatoid factor, HIV, hepatitis C, and hepatitis B were negative. Ultrasound of the abdomen showed no enlargement of the spleen. The PNH FLAER test was done twice and was inconclusive possibly due to hemolysis or severe pancytopenia. The patient was diagnosed with aplastic anemia, but the cause was unclear. Anti-thymocyte globulin, cyclosporine, and steroids were considered for treating the aplastic anemia, but there was concern about their unknown effect on his active COVID-19 infection. Immunosuppressive therapy was decided to be held until he was cured from his COVID-19 infection, and he was discharged after his blood cell indices improved.

Discussion

Being an infection caused by a novel virus, COVID 19 can cause a therapeutic dilemma when no data are available about the effects of certain therapies on the infection. In our patient, immunosuppressive therapy was needed to treat the aplastic anemia but there was no published literature on the effect of this treatment on the course of the infection. This should become less of an issue with time as data surrounding COVID-19 infection and its effects on other diseases and treatment modalities grow.

#191  Pulmonary nodules in a patient with breast cancer; metastasis or co-existing disease?

N Eshak*

K Parmar

M Abdelnabi

K Nugent

Texas Tech University System, Lubbock, TX

Case Report

A 54 y/o patient presented to the Oncology clinic for recently identified breast cancer. She underwent an excisional biopsy of the right breast mass, which revealed invasive ductal carcinoma; this was followed by lumpectomy with sentinel lymph node biopsy that was negative for malignancy.

While doing a CT scan for her radiotherapy planning a 6 mm pulmonary pleural-based nodule was incidentally discovered. The patient completed her radiotherapy sessions and was started on anastrozole while completing work-up for pulmonary nodule.

A chest CT scan was done showed multiple pulmonary nodules, at least six, all <1 cm in size (figure 1A).

She underwent a PET scan (figure 1B) which revealed lymphadenopathy throughout the chest, including right supraclavicular and hilar lymph nodes, as well as periportal lymphadenopathy. There was no abnormal metabolic activity in pulmonary nodules, however, the sensitivity of PET scan to detect metabolic activity in nodules <8 mm is limited, overall the picture was suggestive of metastatic disease.

The decision was made to obtain a biopsy prior to initiating any further treatment.

The patient underwent VATs with resection of 2 pulmonary nodules and a right supraclavicular lymph node biopsy. Both revealed non-caseating granulomas, with negative stains for fungi and acid-fast bacilli, and were negative for malignancy.

She was referred to both infectious diseases and rheumatology, tests for TB, Histoplasma, ANA, RF, ANCA, were all negative, ACE level was mildly elevated. A diagnosis of sarcoidosis was made, and the patient was started on inhaled steroids for management of cough, no systemic therapy was initiated as the patient was otherwise asymptomatic. A follow-up CT scan showed regression of pulmonary nodules.

Abstract #191 Figure 1

Conclusion

Pulmonary nodules and lymphadenopathy in a patient with breast cancer should raise the suspicion of metastasis. Occasionally the finding of non-caseating granuloma is found in these lesions. Sarcoidosis is a systemic granulomatous disease characterized by the development of non-caseating granulomas mostly in the lungs and hilar lymph nodes but can also involve skin, eyes, and other organ systems. The relationship between sarcoidosis or sarcoid-like reaction and breast cancer has been reported mainly as case series and case reports.

#192  Arterial thrombosis as the initial presentation of breast cancer

N Eshak*

M Abdelnabi

J Benjanuwattra

K Nugent

Texas Tech University System, Lubbock, TX

Case Report

A 45-year-old female patient presented to the clinic complaining of severe bilateral worsening leg pain for several weeks that increased with movement and improved with rest. She has a history of hypothyroidism treated with levothyroxine. Physical examination was significant for bilateral weak peripheral pulsations and cold lower extremities. Initial laboratory workup was normal. Peripheral angiogram revealed complete occlusion of the left common iliac artery and the right common femoral artery.

She underwent bilateral femoral artery exploration, open mechanical thrombectomy, stenting of the left common iliac artery, and angioplasty of the left common femoral and common/external iliac arteries (figure 1). Pathological examination of the removed tissue of the arteries confirmed to be thrombi. Hematology was consulted for work-up of a hypercoagulable state. She had no personal or family history of previous clots or miscarriage. Hypercoagulable work-up came back negative, but she was started on long-term anticoagulation. On follow-up in the clinic, she complained of a breast lump, mammogram with U/S followed by biopsy revealed bilateral invasive ductal carcinoma. She refused any surgical or medical interventions.

Patients with malignancy are at higher risk for thrombosis. Venous thromboembolism is a frequent complication in these patients and usually occurs after the diagnosis of cancer is confirmed. Thrombosis as the initial presentation of malignancy is uncommon with arterial thrombosis being more so, especially in a patient without atherosclerosis or cardiovascular risk factors.

Abstract #192 Figure 1
#193  Post-obstructive acute kidney injury due to retroperitoneal fibrosis: an unusual presentation of esophageal signet ring cell carcinoma

M Gartner*

N Tidwell

Dwight David Eisenhower Army Medical Center, Fort Gordon, GA

Introduction

Signet ring cell carcinoma (SRCC) is an aggressive and rare form of mucin-producing adenocarcinoma with an estimated incidence rate of 0.04–0.11 cases per 100,000 individuals per year. SRCC most commonly arises from the gastrointestinal tract and has a higher prevalence among men and smokers. The most common sites of metastasis remain liver, lung, and distant lymph nodes. The low disease incidence and aggressive nature present a diagnostic challenge as early signs and symptoms can be subtle. This case highlights an unusual presentation of SRCC: acute kidney injury (AKI) due to retroperitoneal fibrosis (RPF).

Case Report

A 67-year-old male presented to the emergency department with complaints of abdominal pain and reduced urine output. Initial evaluation was notable for AKI with elevated blood pressure readings. The initial concern was for obstructive ureterolithiasis prompting evaluation via computed tomography (CT) urogram. The study was notable for bilateral hydronephrosis, bilateral proximal hydroureter, stricturing of the mid to distal ureters, and retroperitoneal lymphadenopathy and fibrosis. Cystoscopy with retrograde cystoureterogram confirmed ureteral stricturing. Bilateral nephrostomy tubes were placed with resolution of his AKI. Differential diagnosis at this time included both malignant and autoimmune RPF. Immunoglobulin subtyping (with IgG and IgG4) and antinuclear antibody (ANA) screening were unremarkable. Positron emission tomography/computed tomography (PET/CT) was notable for PET avidity throughout his retroperitoneum. There was also avidity in the distal esophagus favored to represent inflammatory changes. CT-guided biopsy of the avid retroperitoneal lymph nodes was notable for adenocarcinoma with signet ring cell features with positive pankeratin, CK7, CK20, and CDX-2 and negative for TTF-1, PAX-8, GATA-3 and PSA. Follow-up esophagogastroduodenoscopy (EGD) was notable for findings consistent with reflux esophagitis were noted in the distal esophagus. Biopsy of the inflamed tissue was also notable for adenocarcinoma with signet ring cell features.

Discussion

Early manifestations of esophageal SRCC, like other esophageal carcinomas, are often subtle. Symptoms such as regurgitation, dysphagia, hoarseness, weight loss, and iron deficiency from occult blood loss usually denote locally invasive disease. Later findings are most often dependent on location of metastasis, which is usually liver, lung, and lymph nodes. This patient was diagnosed with esophageal SRCC only after being found to have findings of RPF due to metastasis to retroperitoneal lymph nodes on cross sectional imaging. Early diagnosis of SRCC remains critical as prognosis of metastatic disease is grim with 5-year survival of 1.5% and median survival of 7.9 months. On review of literature, there have only been two reported cases of SRCC presenting as retroperitoneal fibrosis highlighting this case’s importance and contribution to the medical community.

#194  Primary diffuse large B-cell lymphoma of the cecum

L Gawey1*

E Ellent2

A Garcia1

1LSU Health New Orleans, New Orleans, LA

2West Jefferson Medical Center, Marrero, LA

Purpose of Study

Case report of primary diffuse large B-cell lymphoma (DLBCL) of the cecum in patient with underlying ischemic heart disease being treated with R-CHOP chemotherapy

Methods Used

Review of Electronic Health Records and literature review

Summary of Results

A 73-year-old male with underlying ischemic heart disease and history of renal cell carcinoma presented with persistent productive cough and shortness of breath. Chest CT found new noncalcified nodules in both lungs, and further PET scan imaging revealed circumferential cecal colonic wall thickening with hypermetabolic activity, in addition to the bilateral pulmonary nodules. His last colonoscopy had been 3 years prior with only finding of benign polyps. CT-guided biopsy of a pulmonary nodule showed neoplastic cells positive for CD45, CD20, PAX5, CD10 and BCL6, and negative for SOX11; the Ki-67 index was 75–80%. The patient underwent a colonoscopy which found an infiltrative, ulcerated and fungating 5 cm mass with stigmata of recent bleeding of malignant appearance in the cecum, causing a partial obstruction. Cold forceps biopsies were performed and neoplastic cells were positive for CD20, CD10, BCL6, and MYC (50%), and negative for SOX11, CD23, BCL2, and EBER; Ki-67 index was > 90%. Fluorescence in-situ hybridization (FISH) studies for BCL2, BCL6, and MYC were negative for rearrangement, which were performed to rule-out double-hit lymphoma. The patient was diagnosed with high-grade DLBCL with germinal center phenotype of colonic origin and metastasis to the lungs. The patient began treatment with R-CHOP-21 chemotherapy, and after the first two rounds of treatment, PET CT revealed significantly decreased size and metabolic activity of cecal mass with max SUV in the cecum measuring 8.7, which was previously 26.2 pre-treatment. He has tolerated the R-CHOP relatively well with only one episode of angina-type symptoms.

The GI tract is the predominant site of secondary extra-nodal non-Hodgkin lymphoma (NHL). Primary lymphomas of the GI tract are rare, accounting for only 1–4% of malignancies arising in the stomach, small intestine, or colon. Primary colorectal lymphoma is even more rare, accounting for only 0.3% of large intestinal malignancies and 3% of GI lymphomas. The cardiotoxic effects of doxorubicin must be accounted for in patients with underlying cardiac disease when administering R-CHOP. There is limited data available from small trials that can be used to guide both prevention and management of cardiotoxicity. Additionally, there are no randomized trials for chemotherapy treatment of DLBCL that includes patients of underlying cardiac disease.

Conclusions

This case highlights the treatment considerations for primary colorectal DLBCL in an older patient with underlying ischemic heart disease. Due to the rarity and severity of primary colorectal lymphoma, there is scarce literature regarding the outcome of chemotherapy treatment options, especially in patients with underlying risk factors.

#195  The importance of recognizing growing teratoma syndrome (gts): a rare complication of non-seminamatous germ cell tumors (nsgct)

W Gibson*

K Thomas

R Chowdry

LSU Health New Orleans, New Orleans, LA

Introduction

Growing teratoma syndrome (GTS) is a rare complication of non-seminomatous germ cell tumors (NSGCT) seen in testicular and ovarian cancers. According to the diagnostic criteria first described in 1982 GTS is defined by the following criteria: normalization of elevated serum alpha fetal protein (AFP) and human chorionic gonadotropin (HCG) levels, tumor growth during or after appropriate chemotherapy for NSGCT, and the exclusive presence of mature teratoma in the resected specimen. The incidence of GTS has been reported to be 1.9 – 7.6% in testicular cases and around 12% in ovarian cases (1,2).

Case

A 32-year-old man with a past medical history of schizophrenia and polysubstance abuse was evaluated for a right testicular nodule. The ensuing workup showed a complex testicular mass concerning for malignancy, numerous pulmonary nodules in bilateral lung fields concerning for metastatic disease, and lymphadenopathy in the left supraclavicular region, mediastinum, and retroperitoneum. Initial alpha fetal protein was elevated at 43 ng/ml, beta-HCG, and LDH were within normal limits. The patient underwent a right radical orchiectomy. The pathology revealed mixed germ cell tumor in 60% of the specimen and the remaining 40% was showed teratoma. The patient received an initial cancer staging of Stage IIIC (PT1aNXM1b). The patient underwent three cycles of bleomycin, etoposide, and cisplatin. Repeat imaging showed worsening pulmonary nodules as well as retroperitoneal and supraclavicular lymphadenopathy. Due to disease progression, the patient then received two cycles of cisplatin, etoposide, and ifosfamide. Repeat CT imaging revealed further worsening retroperitoneal lymphadenopathy with evidence of compression on the inferior vena cava. AFP and HCG levels remained within normal limits throughout treatment. Biopsy of the left neck mass showed benign teratoma. Upon meeting the patient and reviewing the case, GTS was highly suspected and further chemotherapy was not recommended at this time. Instead, surgical management was pursued.

Discussion

This case highlights the importance of having a high level of suspicion for GTS in any patient with NSGCT with tumor size progression and with normalization of tumor markers after systemic chemotherapy. GTS is generally resistant to standard chemotherapy regimens. Surgical resection of residual tumor burden is the primary treatment

#196  A classic case of a rare hematologic disorder

GD Gibson*

C Bigelow

The University of Mississippi Medical Center, Jackson, MS

Case Report

IgM multiple myeloma (MM) is an exceptionally rare hematological disorder comprising less than 0.5% of MM cases. Diagnosis of IgM MM can often be a challenge in differentiating from the more prevalent disorder of Waldenstrom macroglobulinemia (WM), in which both have an IgM monoclonal gammopathy. The importance of distinguishing between these two disorders is imperative since treatment and prognosis differ appreciably.

A 48 year-old female presented to the emergency department with progressive low back pain. She previously had a traumatic fall resulting in a T6 fracture four months prior while sledding that required no surgical intervention. She wore a back brace without any reported issues until 5 weeks prior to being evaluated in the emergency room. She had no previous past medical history. Physical examination was significant for thoracic-lumbar tenderness to palpation. Magnetic resonance imaging (MRI) of her spine showed multiple osseous lesions and pathologic fracture of T6 with epidural extension of neoplasm but no cord compression. No hepatosplenomegaly reported on imaging. Labs were significant for anemia, hypercalcemia, and acute kidney injury. Subsequent labs revealed a kappa/lambda free light chain ratio elevated at 518 and serum protein electrophoresis showed a monoclonal protein spike of 2.8 g with an immunofixation showing IgM kappa protein. A bone marrow (BM) biopsy showed 68% kappa restricted plasma cells. Cytogenetics revealed a t(11;14) consistent with a CCDN1/IGH gene fusion and was negative for a MYD88 L265 mutation. She was diagnosed with MM. Treatment with lenalidomide, bortezomib, and dexamethasone was initiated. Patient responded to treatment with improvement in renal function and is undergoing evaluation for an autologous stem cell transplant.

Establishing a diagnosis of IgM MM can be challenging given rarity of the disease. IgM MM presents as any other type of MM, and the diagnosis of IgM MM requires the presence of an IgM monoclonal gammopathy with 10% or more of clonal plasma cells on BM biopsy, along with at least 1 myeloma defining event. Myeloma events are defined by the acronyms CRAB (hypercalcemia, renal insufficiency, anemia, and bone disease) and SLiM (sixty% plasmacytosis on BM, light chain ratio >100 or <0.01, and 1 lesion on MRI). All CRAB and SLiM criteria were present in this case confirming the diagnosis of MM. WM is an IgM secreting lymphoblastic lymphoma that presents with signs and symptoms of anemia, lymphadenopathy, hepatosplenomegaly, neuropathy, and hyperviscosity. The presence of t(11;14) found in our patient which leads to cyclin D1 dysregulation is common in IgM MM, but absent in WM. Somatic mutation MYD88 L265 is observed in patients with WM. This case demonstrates the importance of a thorough diagnostic approach including physical exam, labs, pathology, imaging and cytogenetics in patients presenting with IgM monoclonal gammopathy to correctly identify patients with IgM MM vs WM.

#197  Analysis of the correlation of time to treatment failure with overall survival versus correlation of progression-free survival with overall survival

GD Gibson*

JC Henegan

The University of Mississippi Medical Center, Jackson, MS

Purpose of Study

In cancer drug trials, improvement in overall survival (OS) is a meaningful measure of drug efficacy to patients. Measuring OS requires large patient numbers and prolonged follow up. To address this limitation, studies have utilized endpoints such as progression free survival (PFS) and time to treatment failure (TTF) as surrogates of an OS benefit. PFS is defined as time from randomization to objective tumor progression or death and is felt to correlate more with OS as it includes death. TTF is defined as the time from randomization to treatment discontinuation for any reason and has been suggested as a practical endpoint using real-world evidence, although it is not commonly used in clinical trials. Hazard ratio (HR) is also frequently used to estimate the treatment effect for time-to-event end points such as OS, PFS, and TTF in randomized clinical trials. We conducted a study to examine the correlation between HR for TTF and HR for OS versus the correlation between the HR for PFS and the HR for OS in a publicly available database.

Methods Used

A search of studies in clinicaltrials.gov, last performed on October 7, 2021, was done to identify all trials reporting HR of OS, PFS and TTF – trials not reporting any of these measures or trials reporting values other than the HR for each of these measures were excluded. Trials with an upper bound of the 95% confidence interval of overall survival that was > 10 were excluded due to the uncertainty associated with these results. Trials reporting TTF, PFS, and OS for multiple arms were included with each unique set of comparisons considered an individual study. The correlation of OS with TTF, OS with PFS, and TTF with PFS was calculated in Microsoft Excel. The correlation between OS with TTF was compared to the correlation between OS with PFS by the test of the difference between two dependent correlations with one variable in common.

Summary of Results

A search of clinicaltrials.gov identified 147 studies that reported information on OS, TTF, and PFS. After excluding studies not meeting the above criteria, 39 sets of pairs of OS-TTF, OS-PFS, and TTF-PFS were able to be analyzed. The correlations between TTF-OS, PFS-OS, and TTF-PFS were:

TTF-OS: 0.63

PFS-OS: 0.43

TTF-PFS: 0.79

The correlation of TTF-OS is statistically significantly greater than the correlation between PFS-OS (two sided p-value: 0.02).

Conclusions

This analysis of publicly available results of clinical trials found statistically significant difference between the correlation of the HR for TTF with OS versus the correlation of the HR for PFS with OS, with the correlation for TTF with OS being the stronger correlation. Limitations of this work include the heterogeneity of the studies and the small sample size. Further work is needed to validate this finding in an independent dataset. If validated, it would suggest that monitoring TTF would serve as a stronger correlate of OS than PFS does.

#198  Acute respiratory distress syndrome after exposure to carfilzomib (kyprolis)

P Goel*

K Qureshi

A Ananthula

R Chowdry

LSU Health New Orleans, New Orleans, LA

Case Report

Introduction

Plasma cell leukemia is very rare and an aggressive form of leukemia with a poor prognosis. Interim analysis of a phase II trial (EMN12/HOVON 129) using carfilzomib, lenalidomide, and dexamethasone (KRd) in patients with PCL ≤65 years showed a very good partial response or greater response in 80% with 33% achieving at least a complete response. Carfilzomib (Kyprolis TM) is a proteosome inhibitor and is associated with ARDS and acute respiratory failure in 2% of the cases per FDA package insert. We present a case report of acute respiratory distress syndrome presumed to be potentiated 2/2 to carfilzomib infusion.

Case

A 58-year-old male with a history of hypertension, recent COVID-19 infection and new diagnosis of untreated Plasma Cell Leukemia presented to our hospital with worsening chest pain, fatigue and dyspnea. Vitals on admission were notable for BP 158/88, HR 101, Tmax 99F and sating 100% on room air. Peripheral blood exam showed WBC: 27.7 x109/L, Hb: 8 gm/dl, platelet: 121000, corrected calcium:13.3 mg/dl, creatinine: 1.16 mg/dl, total protein:11 g/dl, uric acid: 8.2 mg/dl, B-2 micro globulin: 5.8 mg/L, Mspike: 5.6 g/dl; IgA lambda type. CT Chest abdomen pelvis revealed diffuse lytic bone lesions. Due to inability to obtain bone marrow biopsy from limited resources after Hurricane Ida and aggressive nature of the cancer, treatment was initiated based off a previous flow cytometry from the peripheral blood which showed 55% plasma cells. Patient started on chemotherapy with Cyclophosphamide, Carfilzomib, and dexamethasone with plans to change to Revlimid from cycle 2. He was also started on fluid hydration and Zometa for hypercalcemia. Patient also received aggressive blood pressure control with metoprolol, amlodipine and IV labetalol as needed. After 2nd dose of Kyprolis, he developed acute hypoxic respiratory distress and was initiated on Bipap. Chest Xray was concerning for fluid overload and/or evolving pneumonia. He was supported with diuretics and broad-spectrum antibiotics; however, he eventually was intubated. He was also started on high dose steroids. Repeat CT chest was negative for thrombosis, but showed extensive bilateral pleural -parenchymal opacities. He had a bronchoalveolar lavage with no obvious infection. Over the next 2 days, patient showed improvement and eventually self-extubated. After his recovery, we continued chemotherapy with Kyprolis and he has tolerated it without issues.

Discussion

The etiology of ARDS is likely multifactorial, however Kyprolis may have played a major role in his decompensation mainly due to the timing and known side effects of the medication. Based on a study from 2018, only 5 case reports of Kyprolis-associated non-infectious progressive lung injury were found at that time. Clinicians should be mindful of Kyprolis induced lung injury and emphasize the need for tight blood pressure control and careful administration of intravenous fluids to decrease the possibility of lung injury.

#199  Holiday hemoglobinuria: paroxysmal cold hemoglobinuria in cooler months in a patient with treated syphilis

J Graham*

S Elkins

University of Mississippi Medical Center, Jackson, MS

Case Report

Our patient is a 61-year-old woman who came to our university hospital’s attention in January 2018 with an acute presentation of abdominal and back pain, nausea, and vomiting. She was discovered to have significant kidney disease and nephrotic range proteinuria. Work-up yielded a positive RPR, which was supported by a reactive Treponema pallidum particle agglutination study and by her report of having been treated for syphilis with penicillin in the distant past.

She returned to the hospital in January 2019 with hypoglycemia and acute kidney injury following cocaine consumption. Her hemoglobin was found to be 5 g/dL. The antibody screen before transfusions was positive. It was noted that ‘the agglutination pattern may reflect an additional emerging antibody or a nonspecific reaction. Antibody specificity may become clear upon further testing.’

Hemoglobin dropped from 8.3 g/dL to 5.5 in two days several days into the admission, shortly after a urine drug screen was positive for cocaine. Hemolysis labs were notable for LDH of 1168 U/L and haptoglobin of < 10 mg/dL. Hematology was consulted, and prednisone 1 mg/kg/day was started for a suspected warm autoimmune hemolytic anemia. Hemolysis had significantly lessened one week into prednisone. She was lost to hematology follow-up.

During another admission in January 2021 (for retropharyngeal abscess), a type and screen was performed, which showed another positive antibody detection screen and tube testing consistent with a cold autoantibody. She presented again in September 2021 after a fall at a nail salon. Her hemoglobin was 5 g/dL. She was transfused and discharged. Hemolysis labs were not checked, but a urinalysis showed a small amount of blood in the urine.

She presented again five days later after another fall at a nail salon. She experienced a syncopal episode in the emergency department and significant pain and nausea and vomiting afterward. Her hemoglobin had dropped mildly since her recent discharge. Urinalysis was notable for a large amount of blood. Hemolysis labs were notable for LDH of 352 U/L, haptoglobin of < 10 mg/dL, indirect bilirubin of 1.2 mg/dL, and 4.8% reticulocytes (138 x 10^9/L). Antibody detection screen was again positive, with DAT IgG 2+, DAT C3 negative. Tube testing was ‘negative at immediate spin, 37, and AHG with negative autocontrols, but panpositive at 4 C with a positive autocontrol (3+), consistent with the patient‘s history a cold autoantibody.’

Hematology was consulted and began prednisone 1 mg/kg/day for suspected paroxysmal cold hemoglobinuria secondary to Donath-Landsteiner antibody stemming from her treated syphilis. Confirmatory testing was sent.

This case illustrates the importance of following the antibody screen and direct antiglobulin test in patients with recurrent anemia, particularly those with underlying conditions associated with autoimmune hemolysis. The character of the autoantibody may become clearer with time.

#200  Disseminated fungal infection and marijuana use in a pediatric cancer patient

M Grassi1,2*

D Citla-Sridhar1,2

KK Mason1,2

JM Mack1,2

1University of Arkansas for Medical Sciences, Little Rock, AR

2Arkansas Children s Hospital, Little Rock, AR

Case Report

Several case studies have reported invasive fungal diseases in people who use marijuana and fungal contamination of cannabis. We report a case of an immunocompromised pediatric patient that was a known marijuana user, who developed disseminated fungal infection during the course of his treatment, and succumbed to death.

Patient was a 16 year old male with T cell lymphoma, while on chemotherapy phase with escalating doses of methotrexate, who developed febrile neutropenia. He presented in septic shock and was diagnosed with a pan-resistant fungal infection (Scedosporium prolificans) with multiple sites of fungal dissemination in lungs, sinuses, skin, brain and spleen. He was treated with Voriconazole, Amphotericin, Micafungin and a new drug in development – Fosmanogepix for 4 months. With worsening disseminated fungal disease, patient was discharged to hospice, and died at home. Of note, patient was a known user of marijuana (vaping) prior to diagnosis and continued to use marijuana during treatment. He also had a medical marijuana card.

Although the frequency and duration of his marijuana use is unclear, it raises suspicion if this exposure could have resulted in colonization of his lungs with fungal organisms. Immunocompromised status with fungal colonization, likely lead to disseminated fungal infection. Studies have also shown that marijuana may have a similar effect as tobacco, and cause structural and immunological lung damage confers increased susceptibility to infection. A recent study with a commercial database showed that people who use cannabis were more likely to have fungal infections, than people who did not use cannabis.

While medical marijuana is approved in several states in the United States, especially for patients receiving chemotherapy, it is important to discuss potential health implications and risk of fungal infections with patients.

#201  Cranial and sinus plasmacytoma- a rare entity

C Kamireddy*

O Mohammadi

P Vahhabaghai

K Chakraborty

S Singal

East Tennessee State University, Johnson City, TN

Case Report

Plasmacytomas are malignant proliferation of plasma cells which can be seen with different plasma cell dyscrasias. We present a rare entity of plasmacytoma presenting as cranial and sinonasal tumor. A 60 year old gentleman with diagnosis of IgG kappa multiple myeloma three years ago. Initial bone marrow evaluation showed 70% plasma cells with no high risk cytogenetic features. He received standard of care treatment with Bortezomib, Lenalidomide and dexamethasone for a total of 12 cycles. He refused to undergo hematopoietic stem cell transplant, subsequently relapsed in one and half year. Treatment was changed to Daratumumab, Pomalidomide and dexamethasone. Patient relapsed after 18 months of treatment, at which point he was initiated on third line therapy with Ixazomib, Lenalidomide and Dexamethasone. After 4 cycles into treatment he developed symptoms of headaches and diplopia. Clinical exam was consistent with left eye constricted pupil and left lateral rectal palsy. Magnetic resonance imaging of the brain revealed an infiltrative lesion at the skill base involving the bilateral cavernous sinuses and left sphenoid sinus opacification. Paraproteinemia work up showed increase in serum Immunoglobulin G from 1284 mg/dl to 6337 mg/dl, kappa free light chain from 91.47 mg/dl to 1815 mg/dl, with a kappa/lambda ratio of 637.11 increased from 19.54. Bone marrow biopsy confirmed relapsed multiple myeloma with 90% involvement by plasma cells. The skull base lesion was highly suggestive of plasmacytoma, given the systemic evidence of myeloma relapse. Biopsy of the left sphenoid sinus mass confirmed involvement by plasmacytoma with IgG kappa monotype and immunohistochemistry positive for CD138, CD56 and kappa and negative for MUMI1, CD20 and CK AE1,3. He received palliative radiation treatments to the skull base to achieve rapid tumor response. Patient also suffered recurrent epistaxis, requiring embolization of the nasal artery. Sinus endoscopic surgery with maxillary antrostomy was attempted as well. Unfortunately even with aggressive radiation and surgical efforts, patient continued to have significant epistaxis and decided to transition to comfort care.

Extra medullary plasmacytoma of head and neck is rare, comprising 3% of all plasma cell tumors. They constitute 1% of head and neck cancers 4% of all non-epithelial tumors of nasal tract. Direct compression or involvement of cranial nerves causes cranial nerve palsies, symptoms of raised intracranial pressure and epistaxis. Differential diagnosis of the base of the skull tumor includes nasopharyngeal carcinoma, meningioma, lymphoma, pituitary adenoma and metastatic carcinoma. Biopsy showing plasma cells with monoclonal staining pattern involving the heavy chain and light chain on immunohistochemical studies help differentiate plasmacytoma from the other tumors. Radiotherapy constitutes the mainstay of treatment, surgery is limited to biopsy and control of local symptoms.

#202  False positive heparin induced thrombocytopenia in patient with anti-phospholipid antibody syndrome

C Kamireddy*

J Kim

T Pham

D Jaishankar

K Chakraborty

East Tennessee State University, Johnson City, TN

Case Report

Heparin-induced thrombocytopenia (HIT) is a catastrophic complication of heparin therapy, caused by antibodies against platelet factor 4 (PF4)-heparin complex. Patients with antiphospholipid syndrome (APS) have been rarely reported with positive PF4-heparin complex antibodies.

A 20-year-old female with no medical comorbidities, presented with fever, dyspnea and confusion. She developed respiratory failure requiring mechanical ventilation. Labs were significant for platelet count of 47k/uL, hemoglobin of 6.3 g/dL, white blood cell count of 9k/uL, and serum creatinine of 1.47 mg/dl. Coagulation panel showed a prothrombin time of 16.1, International Normalized Ratio of 1.5, and partial thromboplastin time of 53. Chest imaging showed bilateral infiltrates. Bilateral cerebral infarcts and bilateral renal infarcts were also found, suggestive of thromboembolic arterial events. Echocardiogram showed severe mitral regurgitation with thickening and calcification of the mitral leaflets. Given the neurological symptoms, acute kidney injury and thrombocytopenia, thrombotic thrombocytopenic purpura (TTP) was high on the differential. Peripheral smear showed no evidence of schistocytes, ADAMTS13 level was normal. Hemolysis and nutritional deficiencies were not evident. Patient had no known prior heparin exposure, but HIT antibody was tested positive. Prophylactic heparin was discontinued. Argatroban infusion was initiated, but serotonin release assay resulted negative. Suspicion for autoimmune disease was high given the patient‘s age and acute presentation with multiorgan involvement. Her ANA and anti-double stranded DNA titers were elevated at 1:640 and 1:2560, respectively. Complement levels C3 and C4 were low. Lupus anticoagulant was detected, and anticardiolipin antibodies IgG, IgM were positive. Patient met the criteria for catastrophic antiphospholipid antibody syndrome (CAPS). High dose steroids, cyclophosphamide and plasma exchange were started. She underwent mitral valve replacement for mitral regurgitation and had improvement in her overall clinical status with appropriate management of APS.

Both HIT and APS are immune-mediated thrombotic conditions. Reports have noted patients with APS/systemic lupus erythematosus (SLE) can have positive PF4 antibodies, even without prior heparin exposure. It is believed vascular inflammation from such autoimmune conditions may trigger an autoantibody response to PF4 released from platelets, forming an antigenic complex with endogenous heparinoids, then causing false positive HIT immunoassays. This can be distinguished by testing the functional assays. Manifestations of HIT and APS may both overlap with thrombocytopenia and arterial or venous thrombosis. Therefore, cognizance of possible false positive HIT antibodies in patients with underlying APS/SLE is important. Caution should be executed in interpreting the tests as it can lead to misdiagnosis, overtreatment or undertreatment and risk of catastrophic outcomes.

#203  Diarrhea secondary to ileal neuroendocrine tumor with no liver metastasis

H Yousuf1*

M Khan1

M Amin1

J Rahesh1

R Anand1

R Hazam1

F Khan2

A Zakir3

S Pathapati1

1Texas Tech University Health Sciences Center, Amarillo, TX

2Khyber Medical University, Peshawar, Pakistan

3King Edward Medical University, Lahore, Pakistan

Introduction

Well-differentiated neuroendocrine tumors (NETs) are relatively rare tumors that most commonly originate in the gastrointestinal tract, lung, and rarely in the genitourinary tract. We present a similar case with ileal NET, presenting with chronic diarrhea as the sole symptom without liver metastasis.

Case

A 65-year-old Caucasian male with a past medical history of hypertension and alcohol abuse presented with 2 months of watery diarrhea. Initially, it was accompanied by fever, chills, and nausea. He also reported generalized weakness and recurrent falls due to syncope. He self-medicated with Ivermectin. He reported a 20 pounds weight loss over 2 months as well as worsening oliguria. However, three days prior to admission he noticed fresh blood in his stool, prompting him to seek medical attention. On admission, he denied abdominal pain, flushing, dyspnea, or chest pain. On examination, he had mild diffuse abdominal tenderness. He had never had a colonoscopy or endoscopy at this point. On admission, his labs were significant for S.Creatinine of 18 mg/dL, a BUN of 161 mg/dL, and HCO3 of 6 mmol/L. His kidney function improved with fluid resuscitation. Stool culture and Clostridioides difficile toxins were negative.

His CT abdomen with contrast was remarkable for ’misty mesentery’ suggestive of panniculitis. Colonoscopy showed a large 3 cm submucosal polypoid nodular mass at a 10 cm distance from the ileocecal junction. Biopsy reported a well-differentiated neuroendocrine tumor (carcinoid), spanning at least 2 mm involving the lamina propria and submucosa. Liver ultrasound showed only hepatic steatosis with no lesions. 24-hour urine HIAA was 12.5 mg, chromogranin-A 1048 ng/ml, and serum serotonin level of 883 ng/ml. TTE showed no valvular abnormalities. A small bowel mass was resected along with a right hemicolectomy his diarrhea improved.

Discussion

Small bowel neuroendocrine tumors are found incidentally as they are mostly asymptomatic. These tumors are usually underdiagnosed especially in patients who do not receive screening colonoscopy, like in our patient. Often these tumors metastasize to the lymph nodes and liver and are diagnosed at a late stage. 24-Hour urine excretion of 5-HIAA has high sensitivity and specificity for carcinoid syndrome. However, in our patient, these levels were normal but elevated serotonin and chromogranin markers indicated further investigation. Symptoms are mostly associated with metastasis but our patient had characteristic chronic diarrhea with no metastasis. The recommended treatment for tumors that have not metastasized is a resection of the bowel mesentery, which resolved our patient’s illness.

Conclusion

This case focuses on chronic diarrhea being the sole presenting symptom in ileal carcinoid tumors without objective evidence of metastasis.

#204  Metastatic high grade poorly differentiated large cell neuroendocrine carcinoma of the rectum, a rare entity

H Khazrik*

C Kamireddy

R Brudnik

K Chakraborthy

S Singal

East Tennessee State University, Johnson City, TN

Case Report

Rectal neuroendocrine neoplasm (R-NEN) is a rare entity which accounts for less than 1 per 100,000 population in United States of America. Gastroenteropancreatic (GEP) neuroendocrine tumor (NETs) are classified based on grade and differentiation. Well-Differentiated Neuroendocrine Tumors include grade 1 and grade 2, and Poorly Differentiated Carcinomas (PD-NEC) enclose only grade 3 neoplasms with small cell and large cell subtypes. A subtype of the high-grade NET with well differentiated histology was recognized in 2019 WHO classification of NEN of digestive system. High-grade (G3) NET characterized by a high mitotic rate and/or high Ki-67 index (more than 20).

We present a case of metastatic poorly differentiated high grade rectal large cell NEC. 59 years old gentleman presented to hospital with abdominal pain, rectal bleeding, and weight loss. Imaging demonstrated a 6 cm mass in the rectosigmoid junction with subtotal obstruction and 2.3 cm para-aortic adenopathy. Colonoscopy noted subtotal obstruction with large rectal mass 8 cm from the anal verge. CEA was within normal range. Biopsy of both rectal mass and para-aortic lymph node was consistent with large-cell neuroendocrine carcinoma positive for CD56, synaptophysin, CDX2 with a Ki-67 > 95%. Numerous mitoses noted in lymph node. He underwent palliative loop sigmoid colostomy followed by palliative cytotoxic chemotherapy with Carboplatin and Etoposide. Atezolizumab immunotherapy was added with cycle four. Positron emission tomography scan after 4 cycles of chemotherapy revealed stable disease. Both the small or large cell poorly differentiated subtypes of high-grade neuroendocrine carcinomas (NEC) are aggressive tumor with high propensity for distant metastasis and an ominous prognosis. There is a general lack of data from prospective trials to guide treatment. These tumors show similarities in morphology and biologic behavior to small cell carcinoma of lung (SCLC); thus, treatment paradigms have paralleled those established for SCLC. Platinum-based cytotoxic treatment with etoposide or irinotecan represents the backbone of treatment for advanced/metastatic/unresectable disease. Further option of chemotherapy after platinum failure, include, fluoropyrimidine, irinotecan, temozolomide and oxaliplatin-based regimens. The efficacy of second line or later lines of chemotherapy is limited, with short median survival estimated between 5–10 months.

#205  Primary cutaneous diffuse large B-cell lymphoma leg type

H Khazrik*

C Kamireddy

R Brudnik

K Chakraborthy

D Jaishankar

East Tennessee State University, Johnson City, TN

Case Report

Primary cutaneous B-cell lymphoma (PCBCL) is a non-Hodgkin lymphoma, involving the skin in the absence of extracutaneous disease at diagnosis. The three main subtypes include primary cutaneous follicular lymphoma (PCFL), primary cutaneous marginal zone lymphoma (PCMZL) and primary cutaneous diffuse large B-cell lymphoma leg-type (PCDLBCL leg-type). While the first two subtypes are more common and an indolent disease, the PCDLBCL leg-type is an aggressive disease with poor prognosis. PCDLBCL leg-type is typically seen in elderly female patients, affecting the lower legs but 10–15% of cases arise at other sites. Pathologic diagnosis is based on morphology and immunohistochemical features of skin biopsy regardless of anatomic location.

A 62-year-old female on chronic steroids for autoimmune vasculitis, developed sacral plaques and ulcers associated with bilateral cutaneous leg nodules, vision changes and weight loss. Punch biopsy of the sacral wound revealed large-sized lymphoid cells positive for CD20, BCL2, BCL6, MUM-1 and Pax-5 with high Ki-67 (90–95%) and negative for CD10 consistent with PCDLBCL leg-type. Double/triple hit lymphoma was ruled out. PET-CT scan demonstrated a 15.2 x 10.6 cm centrally necrotic sacral, soft tissue mass, FDG avid, with no distant disease, lymphadenopathy or splenomegaly. Biopsy of lower extremity nodules, vitreous body and bone marrow were negative for lymphomatous involvement. MRI brain revealed a 6 mm mass in the left frontal region. CSF cytology was negative. Brain biopsy showed reactive gliosis and rare isolated large B-cells positive for BCL2, BCL6 and Ki67 consistent with minimal involvement with lymphoma. Patient initiated dose-adjusted R-EPOCH (rituximab, Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) to be followed by short course cranial radiation treatment (XRT) between cycle 1 and 2. She had remarkable response in the sacral tumor size after cycle 1 but rapid CNS progression complicated with hospitalization, neutropenic fever, internal jugular vein thrombosis and large retroperitoneal hematoma while on anticoagulation. She received two sessions of XRT to the brain before she decided to adopt hospice due to deterioration of performance status.

PCDLBCL leg-type has a gene expression profile similar to activated B-cell subtype of diffuse large B-cell lymphoma (DLBCL). The frequency of MYC rearrangement and MYD 88 mutation is higher in PCDLBCL – leg type. The treatment approach is with rituximab plus anthracycline-based combination chemotherapy followed by involved-field XRT if needed. PCFL and PCMZL can be treated with single modality XRT or single agent Rituximab. Unlike PCFL and PCMZL, PCDLBCL leg-type has a high frequency of eventual extracutaneous relapse leading to a lower rate 5-year disease specific survival of PCDLBCL leg-type with 50% vs 95%,98% in PCFCL, PCMZL, respectively. We present here a case of PCDLBCL Leg-type in an unusual anatomical location with rapid CNS progression.

#206  Post transplant lymphoproliferative disorder complete response with single agent rituximab treatment

D Kim*

O Mohammadi

J Kim

P Vahhabaghai

S Singal

D Jaishankar

East Tennessee State University James H Quillen College of Medicine, Johnson City, TN

Case Report

Post-transplant lymphoproliferative disorders (PTLD) is a fatal lymphoproliferative disorder associated with immunosuppression that arises in 5–10% of patients after solid organ or hematopoietic stem cell transplant. We present a case of PTLD that achieved complete response with single agent rituximab.

A 60-year-old male with juvenile type I IDDM, renal failure, severe diabetic retinopathy (legal blindness), prior renal and pancreatic transplant on maintenance immunosuppressive therapy with tacrolimus and mycophenolate presented to the hospital with acute onset abdominal pain. Imaging demonstrated high-grade small bowel obstruction, and he underwent exploratory laparotomy with enterectomy and R2 resection (gross residual disease). Labs revealed mild LDH elevation with negative EBV and CMV PCR status. Surgical pathology showed tumor cells positive for CD45, CD20, PAX5, CD10, BCL6 and negative for CD3, CD117, CK, cam 5.2, synaptophysin, CD56, CD5, CD23, MUM1, BCL2, cyclin D1, SOX11, CD34 and TdT. Ki-67 staining was 80%. MYC rearrangement was negative. TP53 mutation was positive. Final pathology reported diagnosis of monomorphic post-transplant lymphoproliferative disorder with diffuse large B-cell lymphoma. Subsequently, his tacrolimus was dose-reduced, and mycophenolate was discontinued. In addition to reduction of immunosuppressives (RI), chemoimmunotherapy was recommended to the patient, but he declined chemotherapy due to his functional status and comorbidities. He was started on rituximab weekly for 4 cycles with PET-CT monitoring for treatment response. At the completion of 4 cycles of weekly rituximab, PET-CT scan was obtained, which did not reveal any significant tumor activity. Consolidation rituximab every 3 weeks for a total of 4 cycles as per guidelines was instituted. Repeat PET scans continued to show complete response without evidence of new lesions or lymphadenopathy. Deauville score was 1 at the 10-month mark since the initiation of rituximab.

PTLD covers a wide spectrum of malignancies ranging from polyclonal early lesions to monomorphic lymphoma, as presented in this case. Available treatments include immunosuppressive reduction, chemoimmunotherapy, antiviral therapy, cytotoxic T-cell therapy, surgery or radiation. Single agent rituximab therapy has shown minimal toxicity with good efficacy with approximately 60% complete or partial response (ORR). CHOP given sequentially or concurrently with the rituximab improves overall response rate (ORR) to 90%.

Despite complete response with single agent rituximab, close surveillance is required in our patient. Inability to discontinue immunosuppressive agents completely, and exclusion of chemotherapy such as CHOP treatment portends higher relapse risk. Our case highlights a patient on immunosuppressive agents for more than 20 years after solid organ transplant developing monomorphic PTLD that was successfully treated with single agent rituximab.

#207  Retroperitoneal fibrosis in a case of metastatic breast cancer – drug or disease?

J Kim*

C Kamireddy

S Oad

S Singal

K Chakraborty

East Tennessee State University, Johnson City, TN

Introduction

Retroperitoneal fibrosis (RPF) in the setting of metastatic breast cancer is a rare pathological phenomenon. Here is a case of a patient presenting with acute kidney injury (AKI), subsequently finding ureteral obstruction.

Case

A 33-year old female reported a palpable right breast lump. Mammography and ultrasound found to have a 5.8 cm mass with biopsy confirming estrogen and progesterone receptor negative, HER2 negative intraductal carcinoma of the breast. Three right axillary lymph nodes were positive for cancer. Positron emission tomography (PET) found left-sided lymphadenopathy with biopsy proving oligometastatic breast cancer. Treatment with curative intent was pursued after multidisciplinary discussion. Neoadjuvant therapy with protein-bound paclitaxel and atezolizumab was started. Stable disease was noted on imaging, and neoadjuvant treatment changed to doxorubicin and cyclophosphamide. Then, she underwent right mastectomy, axillary lymph node dissection, and adjuvant radiotherapy. Unfortunately after completion, metastasis to the bones and contralateral breast was found. Palliative sacituzumab govitecan, a recently approved antibody-drug conjugate agent, was started, completing three cycles. Surveillance labs showed creatinine of 6.4 mg/dL, hyperphosphatemia and hyperuricemia, initially concerning for tumor lysis syndrome. Moderate bilateral hydronephrosis was found, and ureteral stents were placed. Retrograde pyelogram noted proximal ureter kinking for which etiology was unclear. Post obstructive AKI recurred, and bilateral nephrostomy tubes were placed. A month later, repeat retrograde pyelogram showed left ureter narrowing, then mid ureter dilation and narrowing again proximally. Repeat PET showed no evidence of retroperitoneal disease. Exploratory laparoscopy revealed diffuse RPF. Urology recommended higher caliber ureteral stents for subsequent follow-up.

Discussion

Structures within the retroperitoneal space include the kidneys, ureters, duodenum, ascending/descending colon, parts of the pancreas, the aorta, inferior vena cava, and iliopsoas muscle. RPF can lead to compression of these structures. Causes of fibrosis can include infection, autoimmune disease, medications, trauma, abdominal surgeries, radiotherapy, and malignancy. Malignancy contributes to 8–11% of cases. Associated cancers may include lymphomas, sarcomas, metastatic breast, gastrointestinal, renal, prostate, and lung as well as carcinoid tumors. PET scan can be used for assessment, although was unrevealing in this case. There is limited data to suggest sacituzumab contributes to RPF, but immunotherapy has been reported in a few cases, also received by this patient.

Conclusion

Retroperitoneal fibrosis is a rare entity. Management entails treatment of the underlying disease, and prognosis secondary to malignancy is poor.

#208  Mixed phenotype acute leukemia: when two lineages meet

D Kim*

J Kim

A Sinha

D Jaishankar

K Chakraborty

East Tennessee State University James H Quillen College of Medicine, Johnson City, TN

Case Report

Mixed phenotype acute leukemia (MPAL) is a rare disease entity that comprises less than 1% of all acute leukemias. It has characteristics of both acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). MPAL with features of T-ALL are particularly uncommon. We present a case of T/myeloid mixed-phenotype acute leukemia not otherwise specified (MPAL NOS).

A 70-year-old male presented to the hospital with complaints of dizziness and weakness of 2 months duration. He reported significant weight loss and easy bruising on his limbs. He was pancytopenic (WBC 3.3 K/uL, Hgb 5.7 g/dL, plt 5 K/uL) at the time of the presentation. Systemic CT imaging showed diffuse lymphadenopathy. FNA of an inguinal lymph node revealed neoplastic cells with immunohistochemistry expression of CD3, CD5, TdT, suggestive of T-ALL. Subsequent bone marrow biopsy/aspiration showed 50% blasts and 30% monocytes with atypia. Morphology was consistent with AML with monocytic features. Immunophenotyping revealed predominant myeloid differentiation with expression of MPO, CD117, CD33, HLA-DR, CD15, and partial expression of CD34 and CD13. A smaller population, approximately 10–15%, expressed T-cell lineage markers – cytoplasmic CD3, CD5, and CD7, and partially expressed CD34. T-cell gene rearrangements and JAK3 mutations noted in various T-cell neoplasms were reported. BCR-ABL1 translocation t(9;22) and KMT2A rearrangement were not detected. Abnormal male karyotype with rearrangements of chromosome 8q and 20p were suggestive of a neoplastic state.

Based on 2016 revised WHO diagnostic criteria, this patient’s leukemia met criteria for T/myeloid MPAL NOS. Outcomes in MPAL is uniformly poor compared to typical AML or ALL. Factors associated with adverse outcome include age, WBC count, Philadelphia chromosome status (Ph), extramedullary involvement, and immunophenotype (worse outcome in T-myeloid). To date, there is no optimal treatment strategy based on randomized prospective clinical trial data. For Ph(-) MPAL, a general consensus is to treat with an ALL-like regimen followed by allogeneic stem cell transplant. The patient was supported with appropriate blood product transfusion and was evaluated for intensive chemotherapy and possible hematopoietic stem cell transplant. A regimen of cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and cytarabine (HyperCVAD) was proposed. He opted for best supportive care after several discussions taking his age, co-morbidities and overall prognosis of MPAL into account.

MPAL is a rare and aggressive disease entity. Treatments are generally extrapolated from typical ALL and AML treatment strategies. It is important to determine Ph(+/-) status. Preliminary data has suggested that MPAL with t(9;22) is favorably responsive to TKI. Unfortunately, older patients typically have more aggressive disease biology and suboptimal functional status limiting intensive chemotherapy or allogeneic transplant options.

#209  Composite lymphoma comprising peripheral t-cell lymphoma not otherwise specified and b-cell follicular lymphoma

S Kolagatla*

S Chaudhary

N Moka

Appalachian Regional Healthcare, Lexington, KY

Case Report

Composite lymphoma is defined as coexistence of 2 or more morphologically and phenotypically distinct lymphomas in the same anatomical site. Composite lymphoma may include combinations of Hodgkin lymphoma (HL) and B- or T- cell Non- Hodgkin lymphoma (NHL); B- cell NHL and T- cell NHL; two distinct B- cell or T- cell NHLs. The incidence of composite lymphomas varies from 1% to 5%. The exact pathogenesis of composite lymphoma is unknown. It is challenging to establish the diagnosis and chemotherapeutic protocols for composite lymphomas. The treatment is usually directed towards the higher-grade component. Most of the cases show worse outcome with the median survival of 12 months. Here we report a case of peripheral T cell not otherwise specified (PTCL-NOS) and follicular B cell composite lymphoma (FL).

A 66-year-old female, smoker initially presented with generalized lymphadenopathy, B symptoms, hypercalcemia and exudative right-sided pleural effusion. CBC positive for moderate normocytic normochromic anemia and mild thrombocytopenia. Generalized metabolically active lymphadenopathy on PET scan (figure 1A).

Left axillary lymph node showed effacement of the architecture due to an atypical follicular proliferation composed of follicles varying in size, positive for CD20, CD79, OCT2, BCL2, BCL6 and MUM1.FL Grade-3 (figure 1B) was favored.

Polymorphic population in the background was positive for CD3, CD5, CD2, CD7 (with partial loss), CD30 and CD43 (figure 1C). Epstein Barr virus (EBV) B- cells were expanded. Based on morphology and immunohistochemistry, diagnoses of PTCL-NOS with high proliferative index was favored in the atypical T- cell population.

Recurrent hypercalcemia treated with pamidronate while awaiting diagnosis. Since PTCL-NOS is aggressive of the two lymphomas she is currently receiving brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone (BV+CHP). Given paucity of evidence to use rituximab and brentuximab vedotin concurrently. We plan to use rituximab after completion of BV+CHP followed by autologous stem cell transplant evaluation.

Abstract #209 Figure 1
Abstract #209 Figure 1

A) PET scan generalized PET avid lymphadenopathy; B) Atypical follicular proliferation composed of follicles varying in size; C) Polymorphic population in the background was positive for CD3

#210  Emicizumab in patients with acquired hemophilia a (aha)

R Ksayer*

K Zakharia

C Leissinger

M Janbain

Tulane University, New Orleans, LA

Case Report

Acquired hemophilia A(AHA) is a bleeding disorder resulting from the development of neutralizing autoantibodies (inhibitors) against FVIII in individuals with previously normal hemostasis. Subsequent to the decrease in FVIII activity, life threatening bleeds may occur. The median age at diagnosis is 64–78 years old. 89% of the patients are diagnosed after bleeding events.

Management of AHA includes eradication of the inhibitor with immunosuppressive treatment(IST) and control/prevention of bleeding.

Acute bleeding is currently managed using FVIII bypassing agents: recombinant FVIIa(rFVIIa), activated prothrombin complex concentrate, recombinant porcine FVIII(rpFVIII).Their use is associated with high risk of thrombosis in patients with underlying comorbidities and they are not good as prophylactic agents to prevent bleeds.

Emicizumab, approved for use in congenital hemophilia A as a FVIII mimetic that bridges activated factor IX and factor X, can be proposed for prophylaxis in AHA. We hypothesize that Emicizumab use in AHA can reduce the number of bleeds after first diagnosis of AHA and the need for bypassing agents. It promotes outpatient treatment and improves overall outcome in AHA.

We are reporting 2 cases of AHA successfully treated with Emicizumab.

Case#1 is a 78 y/o lady with Rheumatoid Arthritis presenting with subcutaneous hematoma on left arm and hematuria. On admission hemoglobin(Hgb) was 4.4, FVIII 5%, FVIII Inhibitor 106BU. She was started on prednisone, rpFVIII, Rituximab and red blood cells(RBC)transfusions to keep Hgb >7(3 units used). Her FVIII inhibitor was 40 after a month(mo) on treatment and FVIII recovery was low despite increased doses of rpFVIII, suggesting a cross-reacting anti-porcine activity of her inhibitor. Emicizumab was started(6 mg/kg/week for 2 doses, 3 mg/kg/week for 2 doses then 1.5 mg/kg weekly until normal FVIII level and FVIII inhibitor is not detected). Bleeding stopped after starting Emicizumab, FVIII and FVIII inhibitor levels were 78%, <0.6 after 4 mo respectively.

Case#2 is a 73 y/o man with metastatic prostate cancer admitted with leg hematoma and melena. On admission Hgb was 8.5, FVIII <1% FVIII inhibitor >500BU. He was started on prednisone, rFVIIa then rpFVIII, Rituximab, and RBC transfusions to keep Hgb >8(13 units over 2 weeks).1 week after discharge,he came back with muscle bleed Hgb 7.4, FVIII 31,FVIII inhibitor 362. FVIII recovery was inappropriate with rpFVIII. Emicizumab was started. 6 weeks later, FVIII levels recovered and the inhibitor was not detected.

In conclusion,the use of Emicizumab in AHA patients achieved marked improvement in preventing bleeding and ameliorated the overall outcome. No thrombosis were reported in both cases, nor re hospitalisation for bleeding events after starting Emicizumab. Larger studies are needed to support the benefit of initiation of such therapy at earlier stages in patients presenting with AHA.

#211  Lymphoma: a great masquerader

SM Lanka*

D Manogna

NS Saba

Tulane University School of Medicine, New Orleans, LA

Case Report

We describe the case of a 64 year-old man who presented with severe rigors, fevers, chills, night sweats, and associated unintentional weight loss. Initial computed tomography (CT) scan of the chest showed multiple lung nodules and enlarged mediastinal and hilar lymph nodes. CT of the abdomen and pelvis showed splenomegaly and multiple enlarged retroperitoneal, pelvic, and bilateral inguinal lymph nodes. Subsequent left upper lobe lung biopsy, right cervical lymph node fine needle aspirate, and left inguinal lymph node excision revealed increased eosinophils with extensive non-caseating granulomas. Cytology showed atypical cells but was indefinite for neoplasia or a B/T cell lymphoproliferative disorder. Prednisone, methotrexate, and infliximab were initiated for presumed sarcoidosis, and he was discharged from the hospital.

However, three months later, he re-presented with persistent rigors, fevers, chills, and weight loss. His symptoms did not improve with sarcoidosis treatment. CT showed persistent pleural-parenchymal opacities and thoracic lymphadenopathy with increased size of bilateral axillary lymph nodes. Cervical lymph node excision and bone marrow biopsy were performed and returned diagnostic for angioimmunoblastic T-cell lymphoma (AITL). Perivascular aggregates of atypical intermediate to large sized lymphoid cells were positive for CD3, CD4, CD5, CD10 and BCL6. The CD23 stain revealed disruption of follicular dendritic cell meshwork encasing high endothelial venules of the vascular proliferation. The patient was initiated on brentuximab, cyclophosphamide, doxorubicin, prednisone (A-CHP) regimen for chemotherapy. Repeat CT chest after cycle 1 of chemotherapy showed interval improvement in diffuse lymphadenopathy, indicating response to treatment.

AITL is a subtype of mature peripheral T-cell lymphomas derived from dysregulation of CD4+ T-follicular helper cells. It generally presents with constitutional symptoms, generalized lymphadenopathy, and hepatosplenomegaly, with a median age of diagnosis of 60 to 65 years. It can be associated with autoimmune features like hemolytic anemia, rheumatoid arthritis, and thyroiditis. The overall prognosis is poor, with a 5-year overall survival of 33 percent and a 5-year failure-free survival rate of 18 percent.

Our patient presented with presumed granulomatous disease consistent with sarcoidosis, had worsening of symptoms on immunosuppressive therapy, and was subsequently diagnosed with AITL. There are many similarities in imaging and clinical manifestations between the early stages of AITL and pulmonary sarcoidosis. AITL is often found with laboratory and autoimmune findings that can mask diagnosis, potentially delaying initiation of treatment. AITL should be suspected in patients not improving on therapy for an infectious or autoimmune process, with early consideration for re-biopsy. This can aid in early diagnosis and treatment of this aggressive disease, resulting in improved survival rate.

#212  Warm hemolytic anemia and hodgkin lymphoma

S Leon Paredes*

O Sanchez

University of South Alabama, Mobile, AL

Case Report

16-year-old female presented with dyspnea, light-headedness and fatigue for 2 days. Her past medical history was significant for anemia due to menorrhagia 5 months prior to admission. On physical exam she was found pale, tachypneic, tachycardic with normal pulse oximetry, wide pulse pressure and hepatomegaly. Blood work showed hemoglobin 3.6 g/dL, hematocrit 12.6%, MCV 115 fL, MCH 33 pg, RDW 29.3 fL with reticulocytes 47%, Ferritin 416 ng/mL, iron 98 mcg/dL and TIBC 382 mcg/dL, white blood count 22,200 mcL and total bilirubin 2.5 mg/dL, direct Coombs positive and warm antibodies positive.

Patient was diagnosed with high output cardiac failure due to autoimmune hemolytic anemia (AIHA) with warm antibodies. She was started on methylprednisolone and norethindrone.

Chest X-ray showed right upper lobe and left paravertebral masses, along with widened mediastinum. CT chest demonstrated enlarged lymph nodes with bilateral lung involvement and encasement of the trachea, consistent with lymphoma. Abdomen/pelvis CT revealed hepatomegaly, multiple splenic masses and multilevel nodal involvement. Supraclavicular lymph node biopsy performed demonstrated nodules of small lymphocytes admixed with areas of fibrosis and Reed-Sternberg-like cells but no diagnostic Reed-Sternberg cells. The atypical cells were strongly positive for CD15 and CD30, and weakly positive for PAX-5. Findings that are suggestive of Nodular Sclerosis Classic Hodgkin Lymphoma.

Anemia was treated with transfusions and hemolysis with dexamethasone until chemotherapy initiation with brentuximab, vedotin, doxorubicin, dexrazoxane, vinblastine and dacarbazine. After cycle 2 repeat CT chest showed positive response to treatment, Deauville score 3.

Autoimmune cytopenias (AICP), are associated with lymphoproliferative disorders particularly chronic lymphocytic leukemia and non-Hodgkin lymphoma. The etiology of AICPs is unknown, there are different theories such as they are triggered by paraneoplastic cytokine release or production of autoantibodies by the tumor. Warm antibodies are the typical IgG variate present and leads to RBC loss by splenic removal of sensitized cells.

Hodgkin’s lymphoma (HL) is rarely associated with autoimmune cytopenia, if at all present, it is usually at the time of diagnosis or relapse. There is a prevalence of 0.5–4.2%. The first-line treatment of AIHA is generally corticosteroids although, it seems to be less effective in the setting of HL. In some cases, treating the primary disease with chemotherapy leads to resolution of AIHA.

This case highlights the importance of further work up in pediatric patients with autoimmune hemolytic anemia (AIHA) with warm antibodies, considering than in about half of the patients AIHA is secondary to another pathology.

It also displays the significance of developing a thorough differential diagnosis even on frequent pathologies like anemia avoiding early closure.

#213  Healing power of mind body hypnosis

R Mahadevan*

S Gupte

L Linquest

C Nathan

LSU Health Shreveport, Shreveport, LA

Purpose of Study

Clinical hypnosis has been defined as a mind-body therapy that involves a deeply relaxed state, individualized mental imagery, and therapeutic suggestion. Head and neck cancer patients suffer from significant pain and distress ranging from xerostomia, anxiety, depression, surgery disfigurement, and post-radiation fibrosis resulting in several burdensome sequelae including dysphagia and decreased quality of life. Hypnosis is one of the most frequently cited forms of nonpharmacologic cognitive pain control therapy now growing in use in cancer care. Our objective is to demonstrate how clinical mind-body hypnosis can improve dysphagia in head and neck cancer survivors.

Methods Used

This will be a randomly double-blind controlled study. The aim is to understand the effect of once-daily hypnosis therapy on dysphagia severity over an eight-week treatment period. Furthermore, this study seeks to understand the necessary dosage of hypnosis therapy to influence various prevalent symptoms including mood, pain, self-image, and dysphagia in head and neck cancer survivors. One group of patients will be given the dysphagia audio to listen to daily for eight weeks while the other group will rank their top four symptoms from most to least bothersome and listen to two weeks of hypnosis audios for each symptom, totaling eight weeks. In both patient groups, pre-surveys will be given before hypnosis therapy and once weekly surveys will be administered throughout the hypnosis therapy. Final post surveys will be given at week 12 at the end of the study. As an objective measure, all participants will have a FEES (fiberoptic evolution of swallowing) study before and after the intervention. The subjective surveys administered throughout the study include Pre and Post MDADI questionnaire and PROMIS questionnaires on mood, sleep, pain, and quality of life.

Summary of Results

This study is currently in process.

Conclusions

This study is currently in process.

#214  A promising alternative: neoadjuvant endocrine therapy in estrogen and progesterone receptor-positive breast cancer

H Malik*

C Pham

A Garcia

LSU Health New Orleans, New Orleans, LA

Case Report

Neoadjuvant therapy (NT) is a treatment administered to breast cancer (BC) patients prior to surgery with either locally advanced breast cancer (LABC) or to facilitate breast-conserving surgery. In the US, neoadjuvant chemotherapy (NCT) is the most commonly used type of NT. However, an alternative is neoadjuvant endocrine therapy (NET). It has a lower toxicity profile and is suggested to be as effective as NCT. We will present 5 cases to discuss this underutilized approach.

The median age was 61 years old (range 46–77), and four patients were postmenopausal. Three patients had invasive ductal carcinoma, and two had lobular carcinoma. All patients had tumors that were strongly estrogen receptor-positive (ER+) and HER2 negative. Four had low Ki67. The 21 gene recurrence score (RS) was measured in three, and all were low. The median duration of therapy was four months (range 2–10). Three patients experienced a partial tumor response, two patients had no response. Four patients are alive, and one patient who didn’t respond developed metastatic disease and expired four years after diagnosis.

NCT is the most commonly used NT in treating BC. However, most BCs are ER+, and this subtype has been reported to respond poorly to chemotherapy. There is evidence proposing that NET may be more appropriate than NCT in certain BC subtypes. A randomized trial suggested a higher response to NET than NCT in ER+ BC. Additionally, other factors may help identify patients more likely to benefit from NET. Decreased Ki67, a marker for cell proliferation, suggests NET response, and low tumor gene profiling RS may identify patients unlikely to respond to chemotherapy.

Currently, NET is used in elderly or frail patients with ER+ BC because they cannot tolerate NCT. The use of biomarkers and tumor gene profiling may allow for the expansion to additional patient populations appropriate for NET. Furthermore, they may be spared the toxicity of NCT. Ongoing trials are evaluating this.

Abstract #214 Table 1

Patient treatment summary

#215  Hemolytic anemia secondary to methemoglobinemia after bupivacaine use

O Mohammadi*

H Khazrik

M Raafey

S Singal

K Chakraborty

East Tennessee State University, Johnson City, TN

Case Report

In methemoglobinemia, ferrous ions in hemoglobin convert to ferric ions and are unable to carry the oxygen to the tissues. Common causative agents are topical anesthetics like bupivacaine or lidocaine, antibiotics, rasburicase, nitrates, and chemical substances. Hypoxia and hemolysis are two adverse outcomes of methemoglobinemia. We present a scenario of methemoglobinemia-induced hemolysis.

This patient is a forty two-year-old male with a past medical history of type 1 diabetes and end-stage renal disease who got admitted due to osteomyelitis and underwent bone excision and debridement. Shortly after surgery, the patient started having shortness of breath and fatigue. Oxygen saturation dropped to 74% and hemoglobin trended down to 5.2 g/dl. Baseline hemoglobin was around 11 g/dl. The patient had been exposed to bupivacaine during surgery. Laboratory findings showed lactate dehydrogenase (LDH) of 650 U/L and total bilirubin of 2.9 mg/dl. Coombs’ test showed positive IgG and C3. Methemoglobin level peaked at 2.4%.

Glucose-6-phosphate dehydrogenase(G6PD) deficiency, myeloma panel, hepatitis, human immunodeficiency virus, paroxysmal nocturnal hemoglobinuria flow cytometry, hemoglobin electrophoresis, and cold agglutinin were unremarkable. Peripheral blood smear showed normocytic anemia with mild red cell clumping and spherocytosis.

The patient denied any active bleeding and underwent endoscopy which showed a clean based duodenal ulcer.

Laboratory findings were consistent with hemolysis.He responded poorly to blood transfusion, intravenous immunoglobulin showed short-term improvement and then started on prednisone 1 mg/kg which stabilized his hemoglobin, methemoglobin, LDH, and bilirubin.

Bupivacaine is a known cause of methemoglobinemia. Typical presentations of methemoglobinemia are cyanosis with low oxygen saturation, but normal arterial oxygen saturation and usually seen when methemoglobin level is more than 15%. Prompt diagnosis of methemoglobinemia is important to avoid life-threatening complications. Our patient presented with shortness of breath, hypoxia and anemia shortly after exposure to bupivacaine.

Methemoglobinemia-induced hemolysis is more common in patients with G6PD deficiency which was negative in the above patient. It should be noted that hemolysis can be seen even without G6PD deficiency.

Treatment cornerstone is to stop the offending agent. Methylene blue is indicated in methemoglobinemia when the patient is symptomatic and the methemoglobin level is more than 20%. Also, methylene blue can cause further hemolysis if a patient has G6PD deficiency and should be avoided in this population. Methylene blue was not indicated in our case due to lower levels of methylene blue.

#216  Hemophagocytic lymphohistiocytosis sans triggers

O Mohammadi*

D Kim

B Youssef

S Singal

D Jaishankar

East Tennessee State University, Johnson City, TN

Case Report

Hemophagocytic Lymphohistiocytosis (HLH) is an hyperinflammatory state due to hyperactivation of macrophages and T-cells which rarely affects adults. It can be familial or sporadic. Triggers are infections, auto-immune diseases, malignancies, and immune checkpoint inhibitors. HLH diagnostic criteria are fever, splenomegaly, bicytopenia, hypertriglyceridemia, hemophagocytosis, low/absent NK-cell-activity, elevated ferritin, and high-soluble interleukin-2-receptor (IL-2R). Five out of eight criteria are required for diagnosis.

A 54-year-old female was noted to have leukopenia during a routine visit with her family physician. Follow up labs revealed worsening leukopenia, anemia and a normal platelet count. She received Amoxicillin/Clavulanic acid for a presumed upper respiratory infection and developed nausea, diarrhea and decreased appetite. She was referred to Hematology Oncology for leukopenia. During workup she developed fatigue, night sweats and high fevers. Workup revealed WBC 2400 mcL, microcytic anemia, transaminitis with lactate dehydrogenase of 1725 U/L and ferritin of >15000 ng/mL . Peripheral blood smear showed leukopenia without immature cells or blasts and mild microcytic erythrocytes. Further tests detected CXCL-9 of 125050 pg/mL, D-dimer of >5000 ng/mL and interleukin-2- receptor of 20604 pg/mL. EBV, CMV, HSV, HHV-6, parvovirus, bartonella, leishmaniasis, bacteria and COVID-19 were negative. Computed tomography of the chest, abdomen and pelvis did not reveal lymphadenopathy. Brain imaging showed no abnormalities. Cerebrospinal fluid cytology was unremarkable. Bone marrow biopsy (BMBX) showed prominent histiocytic phagocytosis of erythroid precursors and platelets. HLH-94 treatment protocol including weekly steroid and etoposide initiated. Patient’s fever, night sweats and leukopenia resolved during hospitalization, with subsequent down trending of ferritin to 103 ng/ml, CXCL-2 to 2663 pg/mL and interleukin-2-receptor to 2,265 pg/mL. Repeat BMBX revealed significant improvement.

HLH is a rare life-threatening diagnosis. This patient with nonspecific symptoms was diagnosed with HLH (fever, bicytopenia, elevated ferritin, high-soluble IL-2R and hemophagocytic lymphohistiocytosis on BMBX). Several HLH gene mutations were tested including PRF1, UNC13D, STXBP2, although none was mutated. No infectious, rheumatologic or oncologic triggers were detected. Early diagnosis and treatment are critical. Without treatment, survival is measured in months due to multiorgan failure. This syndrome rarely presents in the absence of triggers which may cause delay in diagnosis and successful treatment. 5-year overall survival with HLH 94 protocol is 54% as opposed to 0% prior to the advent of this protocol. Etoposide and steroids are the mainstay of HLH-94. Cyclosporine can be added in the maintenance phase and hematopoietic stem cell transplant is reserved for familial or relapsed HLH.

#217  Treatment of burkitt leukemia in adolescents: an unmet need

K Parmar*

A Jones

D Pawar

K Nugent

K Bharathidasan

J Rios

S Rehman

Texas Tech University Health Sciences Center, Lubbock, TX

Introduction

Non-Hodgkin’s lymphoma accounts for approximately 7% of cancers in patients under 20 years.

Case presentation

A 21-year-old male presented with diffuse abdominal pain and weight loss. Abdominal exam showed a soft, nontender abdomen with absent bowel sounds and a hard mass inferior to the umbilicus. CT scan showed a 12 cm x 7 cm lobulated soft tissue mass in the upper abdomen posterior the stomach and surrounding the mesenteric vessels. A biopsy of the abdominal mass showed markers consistent with Burkitt lymphoma. MYC gene rearrangement was detected. LDH was 1501 u/l. MRI-Brain showed extra-axial material over cerebral convexities. Due to patient being an adolescent and evidence of better outcomes with pediatric regimens, he was started on COG ANHL1131 regimen. Pre-phase with cyclophosphamide, vincristine and prednisone was begun. Patient developed tumor lysis syndrome (TLS) with phosphorus 15.5 mg/dL despite being on prophylaxis. Patient required continuous renal replacement therapy. Ommaya reservoir was placed for intrathecal chemotherapy days 2,4 and 6. He tolerated this well with tumor lysis syndrome resolving. Repeat CT of the abdomen on hospital day 25 showed resolution of the mass found at presentation. On hospital day 31 the induction phase was begun with COPADM2- rituximab, vincristine, prednisone, high dose methotrexate, folinic acid, cyclophosphamide, and doxorubicin. On hospital day 50 round 2 of induction phase was started. The patient tolerated this course well and was discharged on hospital day 57. Repeat CT Abdomen showed disappearance of the mass.

Abstract #217 Figure 1
Abstract #217 Figure 1

A-CT Abdomen with contrast showing approximately 12 cm tra nsverse x 7 cm large area of lobulated soft tissue mass in upper abdomen posterior to the stomach and surrouniirg the mesenteric vessels. This multilobulated soft tissue mass encases majority of the mesenteric vessels and completely obscures the pancreas. B-complete resolution of the mass on repeat CT scan

Discussion

Non-Hodgkin lymphomas (NHLs) occurring in children and adolescents and young adults (AYA) are characterized by various age-related differences in tumor biology and survival. For the most part, there is remarkable divide in how pediatric patients (under the age of 18 years) with lymphoma are treated vs their young adult counterparts, and molecular data are lacking, especially in pediatric and AYA series. Due to the paucity of clinical trials in this age group, the impact of these different strategies on outcomes is not well known and needs to be studied.

#218  Vancomycin induced thrombocytopenia-a possible drug reaction

K Parmar*

A Gutal

D Pawar

G Del Rio-Pertuz

K Nugent

Texas Tech University Health Sciences Center, Lubbock, TX

Introduction

Vancomycin is considered relatively safe, but hematologic side effects have been reported infrequently.


Case Report

A 77-year-old man presented with generalized weakness. His medical conditions included peripheral arterial disease, diabetes mellitus, hypertension, and hyperlipidemia. Five weeks before, patient underwent trans metatarsal amputation of left foot due to osteomyelitis and was discharged on vancomycin and ceftriaxone for six weeks. His other medications were lisinopril, januvia, aspirin, atorvastatin, clopidogrel, ceftriaxone and Tylenol. Physical examination was unremarkable. His labs were significant for a platelet count of 3K/uL and hypokalemia. The platelets were elevated on previous admission. Coagulation panel showed an elevated prothrombin time and international normalized ratio(INR). He received enoxaparin last admission. HIT antibody was negative. Peripheral blood smear showed no schistocytes. Vancomycin was held. He received 2 bags of platelets and two doses of intravenous immunoglobulin. His anti-platelet antibody and vancomycin dependent antibodies were negative. Three days later, his platelets went up to 130X103/uL, and the patient was discharged.

Discussion

Drug induced thrombocytopenia (DIT) is usually associated with bleeding however, our patient was asymptomatic. The thrombocytopenia was seen 33 days after drug initiation. Usually, DIT is known to present 5–10 days after exposure. Antibody testing was negative which could be due to prior immunoglobulin administration or a nonimmune mechanism which is rarely reported.

#219  A very unlikely transformation

R Patel*

GD Gibson

C Milner

The University of Mississippi Medical Center, Jackson, MS

Introduction

Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL) are two lymphoid neoplasms characterized by the proliferation and accumulation of mature small CD5+ B cells that may involve bone marrow, blood, lymphoid tissues, and extranodal sites.1 CLL accounts for about 25–30% of all lymphoid neoplasms; while MCL accounts for only about 6% of all B-cell lymphomas.2Richter syndrome (RS) is defined as the transformation of CLL into an aggressive lymphoma, most commonly diffuse large B-cell lymphoma. RS occurs in approximately 2%-10% of CLL patients during their disease.4 Here we report a case of a patient with a highly unusual RS with CLL transformation to MCL.

Case presentation

A 76 year old female with history of CLL presented with progressive fatigue and abdominal discomfort. Physical exam was significant for abdominal distension and splenomegaly. Computed Tomography (CT) imaging revealed massive splenomegaly and diffuse adenopathy in chest/abdomen/pelvis. Patient with a history of multiple treatments for CLL including Bruton tyrosine kinase (BTK) inhibitors but has not been able to tolerate therapy due to side effects with medications. Initial workup revealed a white blood cell count (WBC) >600,000 and lactate dehydrogenase (LDH) >2500. Peripheral flow cytometry analysis showed CD23 negative, CD200 negative, and FMC7 positive. Fluorescence in situ hybridization analysis with extra signal of CCND1 in 86% of cells. Cytogenetics showed a deletion of 13q14. Overall findings consistent with MCL. Patient treated with Obinutuzumab and dose reduced CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone). Patient did not tolerate Obinutuzumab due to facial edema, however CHOP therapy was continued. She received a dose of rasburicase and required brief dialysis due to concern for tumor lysis syndrome. Following chemotherapy, patient had overall symptomatic improvement. WBC and LDH down trended to 395k and 1649 respectively at day of discharge. At follow up, patient reported improvement in abdominal discomfort, however patient’s daily activity remained predominantly bed bound. Discussed continued therapy with another cycle of CHOP vs Acalabrutinib/Venetoclax, or hospice. After further family discussions, patient and family collectively decided to pursue hospice care.

Discussion

MCL accounts for approximately 5–10% of non-Hodgkin’s lymphoma and is less likely to occur from RS of CLL. MCL has an aggressive clinical course with poor response to conventional chemotherapy and a median overall survival of 3–4 years. Deletion of 13q14 is significantly associated with a poorer outcome. MCL in the setting of Richter syndrome is a poor prognosis and it is important to have collaborative discussions with patients to make decisions on treatment options and goals of care.

#220  A case of hlh in a patient with rcc and mds

D Pawar*

K Parmar

A Deb

S Duangkham

Z Elharabi

S Rehman

Texas Tech University Health Sciences Center, Lubbock, TX


Introduction

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome of abnormal immune activation causing cytokine storm leading to systemic inflammation and multiple organ failure. It is rare in the adult population and initial presentation can be sub-acute that can progress rapidly. Early treatment improves survival, but diagnosis is challenging and requires a high index of suspicion.

Case report

A 69-year-old male presented with 2 days of hematuria, nausea/vomiting, poor oral intake and a syncopal episode due to dehydration that was resolved with intravenous fluids. He had a one-month history of generalized malaise, fatigue, subjective fever, night sweats, and 7lb weight loss. His past medical conditions were significant for psoriatic arthritis, hypothyroidism, and diffuse large B cell lymphoma that was treated 7y ago. His family history was significant for father with psoriasis, mother with breast cancer, and lupus and breast cancer in his sister.

Initial labs showed pancytopenia with WBC 2000, platelets 45000, hemoglobin 10.3, mild transaminitis, elevated total bilirubin of 1.8, and acute kidney injury with Cr 1.8. CT abdomen revealed cholelithiasis, 19 cm splenomegaly, and a 4×3 cm right renal mass which was biopsied and found to be grade 1 clear cell renal cell carcinoma (RCC). Two days after presentation, his pancytopenia had worsened with WBC of 830 (ANC 547), platelets 39, hemoglobin 9, and patient developed neutropenic fever of 102.9F. Workup was negative for infectious etiology. Peripheral blood smear was unrevealing. Bone marrow biopsy showed hypercellular marrow with 0% blasts, consistent with low-risk myelodysplastic syndrome (MDS). His transaminitis, bilirubinemia, renal function continued to worsen with AST in 800s, ALT in 250s, mixed bilirubinemia of 8.4, BUN 110, Cr 4.8, anion gap acidosis of 20, respectively. Five days after presentation, DIC panel was significant for coagulopathy with severe hypofibrinogenemia of 80 and D-Dimer 15688. Ferritin level had increased to 14102 from 5344 at presentation. Fasting triglycerides were elevated at 284. Clinical picture was suspicious for HLH and further HLH workup revealed his HScore to be 269, indicating 99% probability of HLH. He was started on HLH-94 protocol based treatment with improvement of lab parameters, but patient elected to pursue comfort care after 2 cycles of treatment due to severe treatment related toxicity.


Discussion

HLH has been associated with predisposing genetic defects, infections, malignancies, and rheumatologic conditions. Our patient did not show signs of recurrence of lymphoma, however both MDS and RCC have been associated with HLH and our patient had history of rheumatologic disorders. Diagnosis involves fulfilling 5 out of 8 diagnostic criteria; our patient matched 6. H-Score > 250 indicates 99% probability of HLH. Untreated patients have survival of only months and treatment based on HLH-94 protocol can improve survival.

#221  A case of dvt and pe and cardiac arrest in a patient with factor v leiden mutation and covid

D Pawar*

K Parmar

G Del Rio-Pertuz

C Morataya

Z Elharabi

M Abohelwa

K Nugent

Texas Tech University Health Sciences Center, Lubbock, TX

Introduction

Heterozygous Factor V Leiden (FVL) mutation is the most common inherited thrombophilia, most common in people of Northern European descent and in some Middle Eastern population. It increases risk of developing a deep venous thrombosis (DVT) by 5- to 7-fold, and is considered a weak risk factor, and most people never develop blood clots.


Case report

19-year-old woman presented with left lower quadrant abdominal pain, left groin pain, chest tightness and shortness of breath that had started 1 week prior to presentation. Patient had tested positive for COVID-19 six months but had only minor symptoms and recovered without needing treatment. She had completed 2nd dose of Moderna Covid vaccine two weeks ago and had been using oral contraceptive pills (OCP) for two years. Family history was significant for a paternal uncle with history of blood clots. Physical exam revealed swelling and erythema in left lower extremity up to groin area. Doppler ultrasound showed an acute DVT in the left external iliac vein, common femoral vein, deep femoral vein, superficial femoral vein, and proximal popliteal vein. Spiral computed tomography imaging of chest showed pulmonary emboli (PE) in the segmental branches of the pulmonary arteries with mild dilation of the right ventricle. Cardiac echogram (TTE) showed intact right ventricular function. Patient underwent mechanical aspiration thrombectomy with extirpation of DVT, but the procedure was complicated by PEA arrest requiring CPR for about 50–60 mins. During episode, bedside TTE showed evidence of right ventricular dilation and RV strain concerning for a massive PE. She was cannulated for V-A ECMO then underwent therapeutic hypothermia, and was successfully decannulated after six days. Patient eventually recovered and was neurologically intact. She was discharged home on warfarin and aspirin. Hypercoagulable work-up was remarkable for heterozygous FVL mutation R506Q. Both her father and mother were found to have heterozygous FVL mutation and her sister was found to have homozygous FVL mutation.


Discussion

People with FVL have additional risk factors that contribute to the development of DVT, and FVL alone does not increase the risk of developing arterial thrombosis, heart attacks and strokes. DVTs in heterozygous FVL population are considered provoked DVTs requiring anti-coagulation for a definite period, like that in general population. Curiously, patients with severe COVID-19 infection requiring ventilator support were found to have factor V levels high above the normal reference range and were found to have elevated risk for blood clots. Use of OCPs, and perhaps a recent COVID infection, although mostly asymptomatic, might have contributed to hypercoagulability in our patient. FVL mutation is not considered a contraindication to having COVID vaccination and patients with hereditary clotting disorders are recommended to have the vaccine.

#222  Acute myepolathy in an acute myelogenous leukemia

A Pivovarova*

S Ahuja

C Milner

The University of Mississippi Medical Center, Jackson, MS

Case Report

A 23 year old Choctaw female with history of acute myeloid leukemia (AML) in first clinical remission presented with painful neuropathy and bilateral ascending paralysis. Two months prior, patient was diagnosed with AML and treated with induction therapy with cytarabine and daunorubicin, along with one dose of prophylactic intrathecal methotrexate due to high white blood count at presentation. About a month prior to presentation, she received Cycle 1 of consolidation with HiDAC. She tolerated consolidation therapy with HiDAC well and was discharged home. Three weeks following consolidation, she presented with acute onset of pain and progressive arm and leg weakness. ANA reflex, acetylcholine receptor antibody, Mu SK antibody and CSF paraneoplastic panel were negative. MRI of the spine, and brachial plexus unremarkable. MRI of the brain with small incidental lesion likely related to PRES in a setting of low sodium and plasma exchange, not suggestive of AML involvement. EMG revealed predominantly motor and some sensory polyneuropathy. Cerebrospinal fluid studies significant for elevated protein and cytology without malignancy. Studies for GBM, GM1/2, GDMG, GR1B were negative. Due to concern of potential chemotherapy induced neurologic event, patient underwent plasma exchange for 5 sessions and was on a prolonged prednisone taper. Unfortunately, she failed to respond to these measures. Sural nerve biopsy was obtained which favored cytarabine toxicity.Repeat MRI brain revealed findings consistent with PRES sequela vs metabolic/toxic insults and encephalitis. Patient had a prolonged hospital stay after developing demyelinating polyneuropathy which led to her becoming ventilator dependent requiring tracheostomy placement. Due to her acuity of illness and lack of neurologic improvement, she was not given further chemotherapy. She subsequent developed a rapidly progressing relapsed AML with worsening leukocytosis, anemia and thrombocytopenia. Her clinical status continued to decline. She was developed a multiorgan failure requiring maximum pressors and cardioversion, and subsequently family elected to withdraw further life sustaining care. HiDAC regularly used as induction and consolidation therapy in AML patients. Although central nervous toxicity of HiDAC has been frequently reported and is well recognized, there are only a few publishes cases of polyneuropathy following its administration (Openshaw et al 1996). Previous study by Openshaw et al. determined a 1% prevalence rate of demyelinating polyneuropathy among 194 courses of HiDAC (Openshaw et al. 1996). Although different mechanisms of HiDAC toxicity and resulting polyneuropathy have been proposed, it still remains largely unknown.

#223  From good to worst: gaining an extra chromosome in burkitt-type acute lymphoblastic leukemia

A Rojas Figueroa*

Hospital Municipio de San Juan, San Juan, Puerto Rico

Case Report

Burkitt Lymphoma and Burkitt leukemia are classified as different manifestations of the same disease. A combination of several diagnostic methods including morphological, cytogenetics, chromosomal analysis, and immunophenotyping are necessary to diagnose B-Cell Acute Lymphoblastic Leukemia (B-ALL) with certainty. Cytogenetic abnormalities frequently seen in both manifestations include the translocations t(8;22)(q24;q11), and least frequently, the translocation t(2;8)(p12;q24) involving the immunoglobulin kappa gene locus on 2p12.

We present a rare case of a 51-year-old male patient without prior medical history who arrived at the urgency room after various episodes of epistaxis of two days of evolution as well as a petechial rash on the upper left arm and axilla. Peripheral blood examination showed hemoglobin of 10.4 g/dL, hematocrit 29.90 and platelets 23 x 10^8/L, white blood cells 12.8 x 10^7, with a lymphocytic predominance, atypical lymphocytes, and immature cells. Increased LDH at 2700 IU/L, hypercalcemia of 15.2 mg/dL, and increased alkaline phosphatase at 531 IU/L, and total bilirubin 1.64 mg/dL. HIV test and Hepatitis panel were negative. Abdominal Ultrasound was remarkable for hepatosplenomegaly. No evidence of abnormal lymphadenopathy in the chest, abdomen, or pelvis. Bone marrow biopsy was compatible for B-ALL with increased TdT-positive lymphoblast as expected in ALL. Analysis of the flow cytometric data showed a population of B-lymphoblasts (CD10+/CD19+/CD20-/CD10+/CD38+/HLA-DR+). Although the majority of the B-lymphoblast were negative for surface light chain, a minority demonstrated a tendency towards lambda light chain restriction. Chromosome analysis showed an abnormal karyotype with an apparently balanced t(8:9) (q24.;p13) involving MYC at 8q24.2 and an unknown gene on 9p13, together with the gain of chromosome X, 13, 20, and CRLF2 compatible with B-ALL with MYC rearrangement (formerly Burkitt leukemia). MYC translocations are known to be associated with an unfavorable prognosis in B-ALL.

The t (8:9) is a rare yet recurrent abnormality in B-ALL. Chromosomal aberrations in addition to t(8:14) are often present in B-ALL, most commonly affecting chromosomes 1, 6, 7,13, 17, and 22. To the best of our knowledge, B-ALL with this unknown gene on 9p13, together with the gain of chromosome X, 13, and 20 have not previously been reported. Over 60% of patients diagnosed with B-ALL and additional aberrations will have a high risk for relapse or mortality. Literature review regarding treatment alternatives for patients with these cytogenetic changes in the adult population is scarce. Our patient was started on HyperCVAD chemotherapy as induction and will be evaluated by a bone marrow transplant center.

#224  An underdiagnosed hemolytic anemia in alcoholic liver disease: zieve syndrome

D Román-Colón1*

J Feliciano-Idelfonso1

O Rodriguez-Amador1

LO Gerena Montano2

L Vazquez-Zubillaga2

O Cantres-Fonseca2

1VA Caribbean Healthcare System Mental Health Services, San Juan, Puerto Rico

2VA Caribbean Healthcare System, San Juan, Puerto Rico

Case Report

Anemia in alcoholics is a common finding which presents a broad differential diagnosis. An adequate classification requires a high index of suspicion. One of the causes is Zieve syndrome (ZS), a rarely reported disease with an unclear pathogenesis that results from alcohol abuse and consists of a triad: hemolytic anemia, jaundice and transient hyperlipidemia. This condition is frequently under-recognized and under-reported possibly due to physician unawareness and lack of pathognomonic signs or symptoms. We present a case in which a detailed evaluation for hemolytic anemia led to identification of a possible commonly missed diagnosis

A 58-year-old male with medical history of chronic liver disease secondary to alcoholism presented to the ER due to a one-week onset of left arm and leg ecchymosis secondary to a fall. Vital signs were remarkable for sinus tachycardia and orthostatism. Physical examination revealed an oriented man, a benign abdomen, scleral icterus, a large ecchymosis in his left mid arm and left lower extremity. Distal peripheral pulses and sensation remained preserved. Imaging without evidence of fractures or dislocation and abdominal CT with contrast was remarkable for chronic hepatocellular disease and a left iliacus muscle hematoma without signs of active bleeding. Laboratories revealed hemoglobin at 7.8 g/dL from 12 g/dL baseline, no leukocytosis, chronic thrombocytopenia, elevated total bilirubin with indirect predominance and multiple electrolytic deficiencies in the setting of malnutrition. Peripheral smear revealed anisocytosis with macrocytosis, burr cells and some target cells with associated elevated LDH, elevated reticulocyte count, decreased haptoglobin and negative direct antiglobulin test. Lipid profile and vitamin E were normal. HIV and hepatitis non-reactive. Patient required a total of 4 units pRBCs without signs of bleeding suspicious of non-immune hemolytic anemia. Patient’s hospitalization course then became complicated with alcohol withdrawal, septic shock secondary to aspiration pneumonia and hepatic encephalopathy requiring endotracheal intubation. Given poor prognosis, family decided for comfort measures.

When considering ZS the presence of acute-onset, extrinsic, non-immune hemolytic anemia helps distinguish the conditions. It is important to be aware of atypical presentations such as a normal lipid panel and vitamin E levels, which have been reported in literature and do not rule out the condition. Hyperlipidemia may be transient and can decrease before anemia presents. In these patients, anemia typically resolve with abstinence of alcohol intake. For this reason, it is important that clinicians confronted with hemolysis in a patient with alcoholic liver disease be aware of ZS as it will allow earlier diagnosis, prevent invasive intervention, and allow anticipation of supportive therapy with blood transfusions and nutritional supplementation.

#225  Two unexpected causes of eosinophilia

J Schaub*

S Elkins

University of Mississippi Medical Center, Clinton, MS


Introduction

Eosinophilia is a common finding in general medicine. Therefore, it is crucial to be aware of the multiple etiologies which can range from allergy/asthma, connective tissue disease, chronic infection/inflammation, medications, and uncommon hematological disorders such as myeloproliferative disorders. Here we present a patient case with chronic eosinophilia who surprisingly had two causative factors.


Case

A 43-year-old African American male with chronic eosinophilia was referred to hematology clinic for our evaluation after seeing a local oncology practice for eosinophilia that was suspected to be allergy related. In addition to an extensive history and physical exam, IgE, BCR/ABL, ANA, ANCA were collected for the workup and were normal/negative. Strongyloides IgG antibody was obtained and came back positive. Referral to Infectious disease was made regarding the concern for Strongyloidiasis and he was started on empiric treatment with Ivermectin. A CBC was repeated 3 months later revealed no improvement in eosinophilia. During this time, a previously collected CHIC2 (4Q12) deletion returned abnormal. This resulted in the diagnosis of Myeloid/Lymphoid neoplasm with PDGFR-A mutation. He then started on low dose Imatinib at 100 mg once daily with subsequent normalization of his complete blood count with differential one month later.


Discussion

Strongyloidiasis, involving the helminth Strongyloides stercoralis, is endemic in rural areas of southeastern United States. Acute infection may have urticaria or irritation at the site of skin penetration, whereas the chronic stage of strongyloidiasis is frequently asymptomatic. Treatment for patients with uncomplicated strongyloidiasis is with the anti-parasitic ivermectin. PDGFRA-related neoplasms are due to mutations on the long arm of chromosome 4 (4q12) leading to the fusion of FIP1L1 and PDGFRA. The most common presenting signs and symptoms are weakness, fatigue, cardiopulmonary symptoms, myalgias, rash, and fever, and with eventual progression to endomyocardial fibrosis with restrictive cardiomyopathy. Diagnosis is made by FISH for the CHIC2 probe and treatment utilizes low dose imatinib targeting PDGFR.


Conclusion

This case highlights the importance of maintaining a broad differential when undertaking an eosinophilia evaluation in a patient, whether from the general medicine or subspecialist standpoint. There are many causes for eosinophilia, two of which were discovered in this patient case as strongyloides infection and the hematological disorder of Myeloid/Lymphoid neoplasm with PDGFR-A mutation. Although both are uncommonly found, it is crucial to consider these two etiologies in the general workup of eosinophilia.

#226  A case of warm autoimmune hemolytic anemia

N Sherwani*

B Roubique

VR Jaber

T DiMasi

LS Engel

S Walvekar

LSU Health New Orleans, New Orleans, LA

Introduction

Warm autoimmune hemolytic anemia (AIHA) is a rare clinical disease which usually arises during or after concomitant clinical pathologies. Autoantibodies are formed against the red blood cell membrane, destroying them and causing extravascular hemolysis.

Case

A 68-year-old woman with medical history of anemia requiring transfusions, CAD s/p stents in 2007 and 2021, type 2 diabetes mellitus, hypertension, and COVID-19 infection nine months ago presented with chest pain and shortness of breath on exertion for two months. She described the pain as central, non-radiating chest tightness associated with dyspnea on exertion, which resolved with a few minutes of rest. She originally attributed this chest pain to her recent cardiac stent. Three weeks prior , She was treated for anemia (hemoglobin 5.4 gm/dL) with four units of packed red blood cells. Her hemoglobin increased to 7.9 gm/dL after transfusion with temporary improvement of her symptoms until this presentation. Her admit vitals were BP 154/65, HR 99, RR 20, O2 99% on room air, T 97.9°F. Physical exam was notable for generalized jaundice and scleral icterus. Laboratory results included hemoglobin of 6.5 gm/dL, MCV 106 fL, reticulocyte count 17.3%, peripheral blood smear with polychromatophils, total bilirubin 6.5 mg/dL, lactate dehydrogenase 321 U/L, and haptoglobin <30 mg/dL. Her EKG and troponin were normal. She was found to have hepatosplenomegaly on abdominal ultrasound. Further workup showed a direct antiglobulin test was positive with anti-IgG and complement C3 antibodies. This result confirmed the diagnosis of warm autoimmune hemolytic anemia. She received one unit of packed red blood cells with a subsequent hemoglobin of 6.1 gm/dL. She was then started on rituximab and prednisone with an increase in her hemoglobin to 6.9 gm/dL prior to discharge. The patient was discharged on high dose prednisone, scheduled for further rituximab infusions and given close follow-up with hematology and PCP. Atovaquone was added for pneumocystis jirovecii pneumonia prophylaxis during rituximab and prednisone treatment.

Discussion

Warm autoimmune hemolytic anemia is the most common type of AIHA, and its prevalence is approximately 170 per million. It can present with symptoms of chest pain, shortness of breath, and dyspnea on exertion which may at first seem to be cardiac in nature. However, further investigation with laboratory workup can reveal underlying hematologic abnormalities which can present similarly with more severe cases of AIHA. Approximately 50–60 percent of warm AIHA are associated with underlying conditions including EBV, HIV, HCV, lymphoproliferative disorders, and immunodeficiency states. It is important to consider AIHA in anemic patients with immunocompromised conditions. Cases have also been reported of new onset AIHA in association with COVID-19 infection, although there is no evidence yet of AIHA occurring several months after resolving COVID-19 infection.

#227  Compartment syndrome: an unsuspected consequence of hypercoagulable state in a patient with severe COVID-19 illness

S Siddiqui1*

K Creed1

N Randhawa2

S Shahbandar1

V Test1

1Texas Tech University Health Sciences Center, Lubbock, TX

2Franciscan Saint James Health Olympia Fields Campus, Olympia Fields, IL

Introduction

Coronavirus 19 (COVID-19) is a viral illness that is caused by SARS-CoV-2. It has a surface spike protein that binds to human angiotensin-converting enzyme 2 receptors expressed in the kidneys, lung, and vascular endothelium. Here we present a case of a 73-year-old critically ill male with COVID pneumonia and acute respiratory distress syndrome (ARDS), who developed compartment syndrome and rhabdomyolysis as a consequence of extensive right lower extremity arterial thrombosis related to a COVID induced hypercoagulable state.

Case

A 73-year-old COVID positive male with past medical history of coronary artery disease status-post triple coronary artery bypass 10 years ago and type 2 diabetes mellitus presented to the emergency department with progressively worsening dyspnea for one week. His initial oxygen saturation on room air measured 85%, so he was placed on 3 liters per minute supplementation via nasal cannula. CXR showed bilateral diffuse alveolar infiltrates and he was admitted for observation. He developed worsening respiratory failure five days into hospitalization, placed on maximum supplementation via high flow nasal cannula (HFNC), and transferred to the medical ICU. Ultimately, he was intubated and mechanically ventilated for the remainder of his hospitalization due to severe ARDS. After three days in the ICU, his right lower extremity was cold, without palpable nor detectable pulses via bedside Doppler from the femoral to pedal landmarks. Formal ultrasound Doppler that morning confirmed arterial clot extending from the right external iliac to posterior tibial arteries. The patient received embolectomy, stenting, and therapeutic heparin. Within 24 hours, though his creatinine kinase was normal, he developed significantly elevated myoglobin, lactate and worsening acidosis. The patient had a fasciotomy to the right lower extremity at bedside. The next day, he was anuric, with severe acidosis, hyperkalemia, and hypotension, requiring continuous renal replacement therapy (CRRT) and vasopressor support.

Discussion

Compartment syndrome is characterized by increased pressure within fascial compartments, leading to circulatory compromise, cellular necrosis, and rhabdomyolysis. In this case, the COVID-19 viral effect on coagulation led to extensive arterial thrombosis, complicated by compartment syndrome and renal failure necessitating CRRT. While the exact pathophysiology of the hypercoagulable state in COVID-19 illness is debated, we have observed its manifestations ranging from deep venous thrombosis (DVT), pulmonary embolism (PE), to stroke.

Conclusion

COVID-19 is known to be a virulent, multifactorial, intelligent virus with myriad end-organ and vascular consequences. When attending to the most critically ill patients with COVID-19, it is wise to consider all forms of vascular thromboembolism.

#228  Transplant associated-thrombotic microangiopathy (TA-TMA) and posterior reversible encephalopathy syndrome (PRES) in a patient with sickle cell disease post bone marrow transplant

CM Sullivan*

Z LeBlanc

LSU Health New Orleans, New Orleans, LA

Case Report

A 15-year-old male with history of severe sickle cell disease, five months post 10/10 HLA matched sibling donor bone marrow transplant, complicated by graft versus host disease (GVHD) of the skin and GI tract, hypertension, and steroid induced diabetes mellitus, presented in status epilepticus. The patient had presented one month previous with a pericardial effusion, proteinuria, and Coombs positive hemolytic anemia. He was admitted (transplant day +125) with severe headache and hypertension concerning for transplant associated thrombotic microangiopathy (TA-TMA) with supratherapeutic tacrolimus levels. Initial TMA work up was negative with normal terminal complement complex activity (sC5b- 9). He was treated with Rituximab and IVIG with resolution of his pericardial effusion and Coombs+ hemolytic anemia and was discharged. Subsequent sC5b-9 activity was elevated in conjunction with hypertension requiring >1 antihypertensive agent, thrombocytopenia, microangiopathic (Coombs negative) hemolytic anemia, and schistocytes on blood smear, consistent with diagnosis of TMA. Treatment with eculizumab, a monoclonal antibody binding to terminal compliment complex C5, was initiated. Following his 3rd eculizumab treatment he presented with hypertensive emergency in status epilepticus and was confirmed to have PRES based on MRI. Multiple anti-epileptic medications (AEDs) were required to achieve cessation of seizure activity including propofol infusion for burst suppression. Patient slowly improved with continued eculizumab infusions and strict anti-hypertensive management as evidenced by compliment blockade and cessation of epileptic activity on EEG. Following a prolonged PICU stay he was transitioned first to the BMT inpatient service and subsequently required inpatient rehabilitation for several weeks. Currently, 6 months following these events, his neurologic status has returned to baseline, has no evidence of GVHD, and no longer requires eculizumab infusions for TMA.

Discussion

TA-TMA with multi-organ dysfunction is a life threatening potential complication of bone marrow transplant caused by compliment over-activation. Multiple triggers for TMA have been identified including calcineurin inhibitors, GVHD, and viral infections. Prospective studies have demonstrated importance of monitoring for compliment over activation in high-risk patients to allow early diagnosis and treatment in improving patient outcomes. Treatment of TMA requires brief but intensive courses of eculizumab.

Conclusion

This case outlines the importance of early identification and treatment of TMA in patient outcomes and the delicate balance of controlling compliment activation and maintaining effective prophylaxis and treatment of GVHD.

#229  COVID-19 pfizer-biontech vaccine induced VTE

Y Tawfeeq1*

OH Al-Jobory1

A Hallak2

M Saadaldin1

1Texas Tech University Health Sciences Center, Amarillo, TX

2Ochsner Health, New Orleans, LA

Case Report

Between December 2019 and May 2021, there were around 200 million cases of COVID-19, with more than 3.5 million deaths all over the world. In the United States alone, there were more than thirty million cases, with around six hundred thousand deaths attributed to COVID-19. Incidents of hypercoagulability after receiving different types of COVID-19 vaccine have been reported. The incidence of deep vein thrombosis (DVT) is about 1 in 1000, and about 50% of these patients with DVT develop pulmonary embolism (PE). The incidence of DVT affecting the upper extremity exceedingly rare with an approximate incidence of 1 in 10,000. While patients receiving anticoagulation are still at risk of DVT, data on apixaban reflects a 98% protection from recurrent thrombosis.

Hypercoagulability including DVT and PE is always a rising concern in patients with COVID-19 pneumonia. We are reporting a case of a hypercoagulability state in 73-year-old lady after receiving first and second dose of Pfizer vaccine; despite being on apixaban. she has a past medical history of COPD on 2 L home oxygen. She presented with acute hypoxic respiratory failure few days after receiving the first dose of COVID-19 Pfizer vaccine. Imaging revealed right interlobar pulmonary embolism and right superficial femoral vein thrombosis without any provoking factors. She improved clinically and was discharged on apixaban. Few months later she came in with right upper extremity DVT, 7 days after receiving a second dose of Pfizer vaccine. Transesophageal Echo revealed a round mass in the left atrial appendage, which was likely a thrombus, she was discharged on warfarin.

Incidence venous thromboembolism is about 1 in 1000 individuals in the United States. Several factors can increase the hypercoagulable state. SARS-COV-2 is hypothesized to increase the risk of thromboembolism by infecting cell expressing surface receptors of ACE-2 by binding the SAR-COV-2 spike protein and activating cell pyroproptosis which activates neighboring cells inflammatory response and then activate coagulation pathway. BioNTECH mRNA vaccine induces immune response by engulfing S protein mRNA into the cell to produce spike protein and induce antibody production against SARS-COV-2 spike protein. At this time, this is the Third reported Vaccine related VTE after reporting a Pfizer BioNTech vaccine induced DVT on January 2021 After ruling out other causes of VTE in this case as well as the time between receiving the vaccine and the onset of symptoms, vaccine-induced thrombosis is the most likely cause for our patient’s thrombosis, including venous thrombosis, pulmonary embolism, and left atrial appendage thrombosis. The mechanism remains unknown but may possibly be due to enhanced immune response to the vaccine.

In patients at increased risk of thrombosis, BioNTech mRNA vaccination may induce Intravascular Coagulation, venous thromboembolism, possibly due to enhanced immune response to spike protein production.

#230  An unorthodox case of may thurner syndrome: a treatment dilemma

E Thekkedath*

R Sharma

J Farah

P Reddy

University of Florida Health at Jacksonville, Jacksonville, FL

Introduction

May Thurner Syndrome, also known as iliac vein compression syndrome, is a rarely diagnosed condition that is classically described as compression of the left common iliac vein by the overlying right common iliac artery resulting in subsequent deep venous thrombosis (DVT) of the ileofemoral veins. It most commonly affects women between the ages of 25–50 years old with a reported prevalence of approximately 20%. Here we present an atypical presentation of May Thurner syndrome due to extrinsic malignant mass compression with formation of a large left lower extremity DVT.

Case presentation

A 67 year old male with a large sigmoid colon adenocarcinoma presented to the ED with complaints of syncope and left lower extremity swelling and pain of several days duration. He was admitted to the intensive care unit for hypovolemic shock in the setting of acute gastrointestinal bleeding and was stabilized after transfusion of blood products. Computed tomography (CT) scan of the chest, abdomen, and pelvis with contrast demonstrated a pulmonary embolism and a large 6 cm mass in the sigmoid colon with compression of the left common iliac vein (Image). Doppler ultrasound of the left lower extremity confirmed the presence of a large acute occlusive deep venous thrombosis extending from the left common femoral vein to the left popliteal vein. Subsequent endoscopy and colonoscopy showed mucosal infiltration of the mass with chronic bleeding. Interventional radiology was consulted for the possibility of stent placement in the left common iliac vein, but due to the patient‘s inability to tolerate anticoagulation in the setting of chronic bleeding he was not deemed a good candidate. After discussing the severity and extent of the patient‘s cancer burden and prognosis he was agreeable to hospice care and discharged.

Abstract #230 Figure 1
Abstract #230 Figure 1

Left: Coronal cut demonstrating clot; Right: Axial cut demonstrating tumor compression

Discussion

May Thurner Syndrome is an underdiagnosed vascular disorder resulting from compression of the left common iliac vein. Our case presents an atypical presentation of this pathology with a difficult treatment dilemma. The current literature suggests that systemic anticoagulation alone is insufficient for management. The propensity for clots is generated by venous stasis distal to the anatomic compression. Stent placement in the area of compression is warranted with subsequent anticoagulation for at least 6 months to minimize risk of stent thrombosis. Unfortunately in this case, the patient was at a very high bleed risk secondary to his malignancy, and could not tolerate anticoagulation for any length of time. He was also not deemed a surgical candidate due to the significant tumor burden, metastases, and infiltration of surrounding structures.

#231  Bone pain, bleeding, organomegaly – the case of the wrinkled tissue paper

C Tilly1,2*

JM Mack1,2

1University of Arkansas for Medical Sciences, Little Rock, AR

2Arkansas Children s Hospital, Little Rock, AR

Case Report

We describe a case of an 8-year-old patient with bone pain, easy bruising, fatigue, splenomegaly concerning for malignancy – leukemia, lymphoma, solid tumor with metastatic spread – but found to have Gaucher disease.

An 8-year-old female with a history of right lower extremity fracture presented with a one-year history of intermittent right and left lower extremity pain and swelling associated with antalgic gait, fever, loss of appetite, easy bruising, fatigue, and frequent nosebleeds. Physical exam was notable for periorbital hyperpigmentation, a 2/6 systolic murmur best heard at the left lower sternal border, splenomegaly about 4 cm below the costal margin, and swelling with tenderness noted at the medial aspect of the distal left thigh and knee.

A complete blood cell count was consistent with the following: WBC 6.89 K/uL, hemoglobin level 9.0 g/dL, hematocrit 28.9%, platelet 60 K/uL, MCV 75.9 fL, MCHC 31.1 g/dL, red blood cell distribution width 17.5%, reticulocyte count 1.3%. Erythrocyte sedimentation rate >105.0 MM/HR, c-reactive protein 103.0 mg/L, LDH 185 U/L, and uric acid 5.4 mg/dL. Basic metabolic panel, calcium, and phosphorus were within normal limits. Prothrombin time 11.9 seconds (9.8–13.3 seconds), partial thromboplastin time 34.8 seconds (23.0–29.7 seconds), D-Dimer 1.10 mg/L (0.17–0.59 mg/L), and fibrinogen 567.3 mg/dL (150–400 mg/dL).

MRI of the lower extremities was diffusely abnormal with heterogenous marrow replacement concerning for an infiltrative process. CT of the chest, abdomen, and pelvis revealed marked hepatosplenomegaly. Bone marrow aspirate was normocellular with increased histocytes showing abundant, pale blue-gray cytoplasm with wrinkled paper-like fibrillar pattern. Flow cytometry was negative for an abnormal population of blasts. Genetics and orthopedic surgery were consulted. Angiotensin converting enzyme was elevated at 161.9 IU/L; chitotriosidase was elevated at 23073.3 nmol/hr/ml; and tartrate resistant acid phosphatase was elevated at 57.64 IU/L. Glucosylsphinosine was elevated at 243 ng/mL, and beta-glucosidase was decreased at 0.176 nml/mL blood/hr. Laboratory results in the setting of hepatosplenomegaly, pancytopenia, and bone involvement are consistent with Gaucher disease.

The patient received Cerezyme 60 units/kg every 2 weeks for Gaucher disease. She was followed by Hematology-Oncology due to pancytopenia with the need for blood transfusions during hospitalization. Due to significant bone pain, the patient was prescribed acetaminophen, naproxen, and oxycodone with close follow-up in chronic pain clinic.

Bone pain, pancytopenia, and hepatosplenomegaly are consistently associated with malignancy; however, it is important to include genetic abnormalities, like Gaucher disease, in the differential diagnosis. There are three distinct types of this rare inherited genetic disorder. Because the most common form can occur at any age, prompt diagnosis is crucial to prevent long term effects of Gaucher disease.

#232  Questioning the use of absolute neutrophil count to diagnose spontaneous bacterial peritonitis in patients with malignant ascites

P Zito

S Mahato

A Chapple

D Tran*

W Beversdorf

E Rinker

A Garcia

LSU Health New Orleans, New Orleans, LA

Purpose of Study

Spontaneous Bacterial Peritonitis (SBP) is defined as an infection in the ascitic fluid (AF) without evidence of an intra-abdominal infection. It occurs almost exclusively in patients with cirrhosis and it is seen in up to 30% of hospitalized patients. It is reported to be rare in patients with malignant ascites (MA) occurring in less than 5% of patients. The gold standard to establish the diagnosis of SBP is a positive AF bacterial culture. However, studies in patients with ascites secondary to cirrhosis and portal hypertension demonstrated that an absolute neutrophil count (ANC) ≥250 cells/mm3 highly correlated with positive cultures and became the diagnostic test used in clinical practice. There is very limited data evaluating the ANC count in patients with MA. We hypothesized that ANC alone many not be enough to diagnose SBP in patients with MA. The purpose of this study is to describe the characteristics of AF in patients with MA, with particular emphasis on ANC and compare them with the AF in patients with other conditions (cirrhosis, SBP, liver metastasis).

Methods Used

We identified all patients with cytology proven malignant ascites treated at University Medical Center New Orleans New Orleans between an 8-year period as well as patients with ascites due to other conditions. Patients were identified through tumor registry, pathology databases, and medical and surgical oncology clinics. Fisher exact tests were used to compare categorical variables across ascites groups and Wilcoxon rank-sum tests were used to compare continuous categorical variables. Linear regression was used to adjust for potential confounders in assessing the relationship between type of ascites and the logarithm of ascites ANC.

Summary of Results

We identified 50 patients that met inclusion criteria (35 with malignant and 15 with benign ascites and no SBP). The primary outcome of interest was whether ascites ANC differed between ascites type. We found that the ascites ANC of malignant ascites was significantly higher than benign patients (average 2187.46 vs 132.11, p-value=0.001). 34% of patients with MA had ANC > 250. Multivariable linear regression model predicting log of ascites ANC value shows that the only significant predictor of ascites ANC is ascites type (Estimate = -2.17, 95% CI = -3.69,-0.65, p-value <0.001) indicating that the log of ascites ANC value decreases if a patient has benign ascites compared to malignant ascites. MA also had higher albumin, LDH and RBCs.

Conclusions

Our study confirms that malignant ascites is characterized by a high ANC compared to ascites in cirrhosis. Using ANC alone may not be enough to diagnose SBP in patients with malignant ascites. Limitations to this study include small sample size and retrospective analysis. Our patients with MA and high ANC could indeed have SBP. If so, a very large proportion of our patients with MA had SBP, which contradicts the literature. In future analysis, we will compare the characteristics of MA with that of SBP.

#233  Sinonasal melanoma – a dramatic diagnostic turn of events

J Kim

H khazrik

P Vahhabaghai*

S Singal

K Chakraborty

East Tennessee State University, Johnson City, TN

Case Report

Sinonasal melanomas are a rare entity in comparison to cutaneous melanomas. Here we share a case with this diagnosis.

An 82-year old male presented with persistent tooth pain, sinus headache, and right nasal drainage. Evaluation by otorhinolaryngology detected a right sinus mass. Biopsies were inconclusive and then sent to an outside tertiary center. He developed severe pain, apraxia/ophthalmoplegia, fixed pupillary dilation, and vision loss of the right eye. Magnetic resonance imaging of the face and sinuses showed a large mass eroding through the middle and superior turbinates, extending past midline, into the right orbit, maxillary sphenoid, and through the cribriform plate. There was dural enhancement, suggesting perineural spread without overt brain parenchyma invasion. The tumor was deemed unresectable. Positron emission tomography scan noted a station IIB left hypermetabolic cervical lymph node and a non-hypermetabolic right lower lobe lung nodule. The pathologic diagnosis was an exhaustive effort, requiring reviews of three pathologists. Ultimately, malignant melanoma with rhabdoid features was confirmed. Immunohistochemistry (IHC) revealed SOX10 focally positive, a marker seen in melanoma but negative for other melanoma markers such as MART1 and S100. BRAF mutation was negative. A tentative stage III versus Stage IV status was confirmed after multidisciplinary discussion. Palliative radiation to the right sinus and left neck was administered followed by palliative immunotherapy with pembrolizumab. The patient was able to complete one cycle before declining. Several weeks later, he succumbed to his disease.

As 90% of head and neck cancers are of squamous cell histology, this case shares a rare instance of sinonasal melanoma without classic IHC markers. Greater than 90% of melanomas are cutaneous, about 5% uveal in origin, and 1% are mucosal melanomas. Among the rare mucosal melanomas, head and neck (55%), anorectal (24%), and vulvovaginal (18%) are the commoner anatomic sites of origin than the urinary tract, small bowel, and gallbladder. For melanomas arising in the head and neck, 70% develop in the sinuses and nasal cavities. Forty percent of mucosal melanomas are amelanotic, whereas amelanosis is noted in less than 10% of cutaneous melanoma. Etiology, risk factors, and pathogenesis are largely unclear. These tumors can be difficult to diagnose and often IHC is vital. Unlike cutaneous melanoma, data on treatment specifically for sinonasal/mucosal melanoma is limited. Surgery and radiotherapy are used when feasible. Systemic therapy may include immunotherapy and targeted therapy as in cutaneous melanomas.

The prognosis of sinonasal melanoma is grim with a mean 5-year survival is estimated to be 0–30%. Early diagnosis is challenging but may assist curative approaches. Although a rare pathology, sinonasal melanoma can be a consideration in the differential diagnosis of persistent upper respiratory symptoms even if seemingly innocuous.

#234  Dermatomyositis, the great predictor

C Vaughn*

P Say

LS Engel

S Guillory

LSU Health New Orleans, New Orleans, LA

Case Report

A 59-year-old male with newly diagnosed dermatomyositis four months prior to admission presented with a complaint of left neck swelling that he noticed the morning prior to presentation. The swelling was non-tender and did not affect his swallowing or breathing. Other complaints at this time included skin rash and proximal muscle weakness that the patient stated were improving since he was started on prednisone by his dermatologist. His vital signs were normal, and his physical examination was significant for left sided supraclavicular lymphadenopathy that was non-tender, firm, and mobile. Skin examination was significant for heliotrope rash, gottron papules on both hands, and a rash on the extensor surfaces of both upper extremities. CT imaging of the neck revealed lymphadenopathy of the left supraclavicular and infraclavicular regions. Follow-up CT chest and CT abdomen/pelvis revealed a proximal gastric mass with extensive regional adenopathy. EGD demonstrated a large, fungating, ulcerated, and partially circumferential mass extending from the gastroesophageal junction to the posterior wall of the stomach. These findings were highly suspicious for malignancy. Biopsies of the mass were taken and the pathology is currently pending.

Discussion

Dermatomyositis is an idiopathic inflammatory myopathy that can develop as a paraneoplastic process. In patients with dermatomyositis there is a six-fold higher risk of malignancy compared with the general population. Therefore, following the diagnosis of dermatomyositis, patients, should at minimum, undergo age-appropriate cancer screening. Our patient with recently diagnosed dermatomyositis presented with new lymphadenopathy concerning for malignancy and further work-up revealed that the malignancy was likely gastric in origin. This patient had received age-appropriate cancer screening including colonoscopy yet went undiagnosed. The cancers linked to dermatomyositis may go undiagnosed by only following age-appropriate screening guidelines as these cancers may arise from sites not routinely screened. Therefore, blind screening may be appropriate for patients with newly diagnosed dermatomyositis, who do not have any suspicious clinical findings.

#235  Outcomes of central nervous system lymphoma treated with non-thiotepa based consolidation chemotherapy and autologous stem cell transplant

A Vegel1*

H Safah1

F Socola1

N Ziglar2

J Rink2

S Entwisle2

NS Saba1

1Tulane University School of Medicine, New Orleans, LA

2Tulane Medical Center, New Orleans, LA

Purpose of Study

To investigate and report outcomes for patients with either primary or secondary CNS lymphoma who received a non-thiotepa based consolidation chemotherapy, specifically Busulfan, Cyclophosphamide, and Etoposide (BuCyE), with autologous stem cell transplantation (ASCT). Although recent studies have suggested superior outcomes with thiotepa base regimens, there continues to be difficulty obtaining thiotepa for some patients due to recurrent national shortage, insurance coverage and cost within our patient population. In addition, the doses of BuCyE used at Tulane are higher (Bu:3.2 mg/kg on Day –8 through Day –5, E:30 mg/kg on Day –4, Cy:50 mg/kg on Day –3 and Day –2) than those reported in the literature when compared to thiotepa based regimens (Bu: 3.2 mg/kg on Day –7 to Day-5, E:200 mg/m2 once daily on Day –5 and Day –4 OR 200 mg/m2 twice daily on Day –5 and Day –4, Cy:50 mg/kg on Day –3 and Day –2). With this in mind, we set out to identify and report the outcomes of patients treated within our facility with BuCyE consolidation therapy and ASCT for CNS lymphoma.

Methods Used

We conducted a retrospective case series in which we identified patients who were treated for CNS lymphoma with BuCyE consolidation chemotherapy and ASCT from the year 2005 through 2021 at Tulane University. We obtained clinical information via retrospective chart review.

Summary of Results

We identified a total of three patients, 1 patient with primary CNS lymphoma and 2 patients with secondary CNS lymphoma who were treated with BuCyE consolidation and ASCT within our facility since 2005. To date, all patients remain alive, with follow-up times as follows: 7 years for the patient with primary CNS lymphoma; 7 years for the patient with a secondary CNS lymphoma who achieved complete remission and was discharged from our institution to his local oncologist for routine follow up; 3 years for the second patient with secondary CNS lymphoma who continues to follow up while maintaining clinical remission. In contrast with the literature, our improved outcomes could be linked to the higher doses of BuCyE used which could result in improved CNS penetration and anti-lymphoma effect.

Conclusions

Although a small cohort, our three patient case series suggests that the BuCyE consolidation regimen that our facility protocol follows may extend survival times as compared to initially reported (Median OS reported: 4.9 years). We believe that our extended survival times in these three patients may be due to increased dosing as compared to prior literature. With these findings, we suggest that future investigations, possibly with higher dosing of Busulfan and Etoposide, may further clarify the optimal regimen as compared to thiotepa based regimens for patients with CNS lymphoma.

#236  To err is human: a case of poems syndrome

C Wynn*

T Hilal

University of Mississippi, Jackson, MS

Introduction

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) is a rare plasma cell neoplasm that is often difficult to diagnose. Here we present a case of POEMS syndrome with significant morbidity due to delayed diagnosis.


Case Description

A 53 year-old male presented to his primary care physician with new-onset peripheral edema and numbness and tingling in his extremities. Chest x-ray and echocardiogram were within normal limits, and he was prescribed increasing doses of furosemide. Neuropathic symptoms were initially treated with gabapentin. Several months later he began having shoulder pain. MRI showed focal areas in the right proximal humerus concerning for multiple myeloma. Serum protein electrophoresis showed a small IgA lambda and IgG kappa biclonal gammopathy at 0.5 g/dL. Kappa and lambda light chains were both mildly elevated (kappa 3.1 mg/dL; lambda 2.9 mg/dL). Free light chain ratio was normal at 1.1. On laboratory evaluation he was noted to have thrombocytosis but no anemia, renal insufficiency, or hypercalcemia. CT scans of the chest, abdomen, and pelvis showed multiple sclerotic bone lesions in the axial and appendicular skeleton. PET scan also showed widespread axial and appendicular osseous lesions. Two bone biopsies were nondiagnostic.

During this time his neuropathy progressively worsened to the point where he was having difficulty walking, and he developed bilateral contractures and clawing of his hands. He was unable to work due to his symptoms. MRI spine showed only his known sclerotic bone lesions without evidence of cord compression. Electromyogram showed ongoing very severe sensory motor large fiber primarily axonal neuropathy with demyelinating features. Bone marrow biopsy showed 5–10% polyclonal plasma cells with only a very small kappa (0.1%) and lambda (<0.1%) biclonal population by flow cytometry. Vascular endothelial growth factor (VEGF) level was elevated at 200 pg/mL (upper limit of normal, 96.2 pg/mL). He was diagnosed with POEMS syndrome and is currently undergoing treatment with lenalidomide and dexamethasone.


Discussion

This case illustrates the significant morbidity patients with POEMS syndrome can suffer due to delayed diagnosis. The presence of a monoclonal (M) protein and peripheral neuropathy are required for diagnosis, but the magnitude of the M-protein is usually small (around 1 g/dL). The minor features of the disease are easily overlooked, such as peripheral edema and thrombocytosis as in our patient. Peripheral motor neuropathy typically dominates the clinical picture, and it is not uncommon for patients to be wheelchair-bound at diagnosis. Almost all patients will have osteosclerotic bone lesions. Treatment with lenalidomide-based regimens is first-line and symptoms will improve. Younger, fit patients may be considered for autologous stem cell transplant. Improved knowledge and awareness of this syndrome will aid in faster diagnosis.

#237  Don’t look at my belly, look at my heart – pericardial effusion from an occult malignancy

S Yohannan*

S Alhariri

A Deoker

Texas Tech University Health Sciences Center El Paso, El Paso, TX

Introduction

Malignant pericardial effusion is a serious manifestation of some advanced malignancy. Of this, lung and breast cancer along with leukemia and lymphoma are the most common etiologies of malignant pericardial effusion. Even though most patients have a known malignant tumor before any evidence of pericardial involvement, sometimes malignant pericardial effusion can be the initial presentation. Therefore, malignancy must be excluded in every case of an acute pericardial disease, especially with cardiac tamponade at presentation.

Case Presentation

A 52-year-old male with a history of hyperthyroidism, diabetes mellitus, and hypertension presented with progressively worsening shortness of breath of 2 days duration and fatigue for the past 4 months. He quit smoking 20 years ago. While initial vitals seemed normal, pulsus paradoxus of 10–12 mmHg was noted on physical examination. This was checked due to distant heart sounds, jugular venous distention, and low voltage QRS on EKG. He also had reduced right lower lung breath sounds. His initial labs showed neutrophilic leukocytosis, otherwise no anemia, thrombocytopenia, electrolyte, kidney or liver abnormalities. Chest X Ray revealed moderate loculated right sided pleural effusion and cardiomegaly. Echocardiogram demonstrated a large circumferential pericardial effusion with evidence of cardiac tamponade and he underwent urgent pericardiocentesis, with removal of 1.5L of red, turbid pericardial fluid. Cytological analysis of the pericardial fluid showed metastatic adenocarcinoma of an unknown primary source. CEA, PSA, LDH were within normal limits. CT Abdomen was significant for chronic cholecystitis otherwise no masses. CTA chest was unrevealing of visible masses but rather multiple, enlarged, bilateral mediastinal and hilar lymphadenopathy. Colonoscopy and endoscopy with biopsies were negative for malignancy. In search of the primary malignancy, endobronchial ultrasound-guided biopsy was performed and the cells obtained stained positive for cytokeratin 7, TTF1, NapsinA, and BerEP4, consistent with metastatic adenocarcinoma from primary lung cancer. Similarly, a diagnostic thoracentesis was performed and cytology was consistent with malignant pleural effusion from metastatic adenocarcinoma. All throughout, oncology was consulted and the decision was made to start the patient on palliative chemotherapy.

Discussion

This patient with no known malignancy presented with clinical and echocardiographic signs of tamponade. Pericardial cytology was positive for adenocarcinoma from an unknown source. Interestingly, CT scans were unrevealing of masses but rather hilar lymphadenopathy, and it was only through the endobronchial biopsy that we were able to identify the primary source as lung cancer. Hence the etiology of pericardial effusions should always be investigated as malignancy can be a devastating cause of pericardial effusion.

#238  Vitamin b12 deficiency can be severe enough to mimic ttp

H Yousuf*

OH Al-Jobory

MA Tanbir

Y Al-Hilli

M Khan

F Al-Jubory

S Wright

Texas Tech University Health Sciences Center School of Medicine, Amarillo, TX

Case Report

Microangiopathic hemolytic anemia (MAHA) is one of the presentations of TTP. If not diagnosed early, TTP can have severe complications including ischemic colitis, progression to end-organ failure, and death. However few other conditions can also present as TTP, we report a case of a patient who presented with macrocytic anemia, thrombocytopenia, high lactate dehydrogenase, and bilirubin, schistocytes on peripheral blood smear mimicking TTP but negative ADAMTS13 and low vitamin B12 levels.

64-year-old male patient, with a history of untreated chronic vitamin B12 deficiency, hypertension, hypothyroidism, presented to the ER with shortness of breath, lightheadedness progressively worsening from the past 3 weeks. On initial presentation, the patient was alert and oriented, afebrile with stable vitals. The physical exam was unremarkable except for mild scleral icterus. Lab work was significant for severe anemia with hemoglobin of 5.8 g/dL, MCV:136.7 fL, platelet: 42L K/cumm. The patient received two units of blood on presentation. Further lab studies were significant for WBC of 4.4L K/cumm, HCT 17.0 L%, lactate dehydrogenase level: 2049 IU/L, haptoglobin <8L mg/dL, total bilirubin: 2.5 mg/dL, vitamin B12 level: 67 pg/mL (180 – 914), serum folate level: 11.62 ng/mL (5.2 – >20), reticulocyte count: 3.64H% (0.7 – 2.9). Chemistry profile, direct antiglobulin test, fecal occult blood test, ANA comprehensive panel, hepatitis profile was negative and coagulation profile, thyroid profile, methylmalonic acid levels were all within normal limits. Initially at presentation ADAMTS13 activity was pending, the patient received steroid treatment along with urgent plasmapheresis. Repeat smear on the third day of admission showed 2–3+ schistocytes. Eventually, ADAMTS13 activity came back within normal limits. Intrinsic factor antibody came positive, further strengthening vitamin B12 deficiency diagnosis. Clinical improvement was seen when the patient was provided with intramuscular vitamin B12 therapy with 1000 mcg daily for 1 week followed by 1000 mcg weekly for four weeks. Repeat vitamin B12 levels after 1 month of initial therapy were normal including his MCV and platelet count. The patient was advised to take his vitamin B12 monthly injections and was closely followed up by a hematologist.

Vitamin B12 deficiency is not commonly seen with hemolytic anemia, upon literature review few cases have been reported where vitamin B12 deficiency can mimic hemolytic anemia but thrombotic microangiopathy with the presence of schistocytes on the peripheral smear is rarely seen. With this case, we highlight an unusual presentation of severe vitamin B12 deficiency. If suspicion for TTP is high, prompt and accurate diagnosis of TTP is necessary in order to start emergent plasmapheresis, but at the same time, physicians should also recognize that severe vitamin B-12 deficiency can also present similarly, in which case treatment would simply be vitamin B12 supplementation.

#239  Transient carcinoembryonic antigen elevation in response to chemotherapy for stage II colon cancer

X Zheng1*

A Garcia1,2

1LSU Health New Orleans, New Orleans, LA

2University Medical Center New Orleans, New Orleans, LA

Purpose of Study

Transient carcinoembryonic antigen elevation in response to chemotherapy for stage II colon cancer

Methods Used

Review of Electronic Health Records and literature review

Summary of Results

A 54-year-old female with a history of normocytic normochromic anemia presented with a one-inch colonic mass in the hepatic flexure. The patient underwent a biopsy of the mass lesion, revealing invasive, moderately-differentiated MSI-stable adenocarcinoma. Preoperative Carcinoembryonic Antigen (CEA) was 24. CT scans showed no distant metastases. A right hemicolectomy was performed showing a moderately differentiated adenocarcinoma invasive through muscularis propria into pericolorectal soft tissue. All 15 lymph nodes were negative for metastatic cancer. Post-operative CEA was 3.9. She was started on adjuvant chemotherapy with XELOX (capecitabine plus oxaliplatin). CEA increased progressively during adjuvant chemotherapy to a peak of 9.3 at the end of treatment; however, CT scans of the chest, abdomen, and pelvis and PET/CT at the end of chemotherapy found no evidence of metastatic disease. 2 months after chemotherapy completion, CEA levels decreased to normal. Two years after surgery, the patient remains alive and well, with normal CEA levels and no evidence of recurrence.

Rising CEA following treatment in colorectal cancer is typically considered an indicator of tumor progression. CEA biomarker testing is utilized during a chemotherapy course to assess the effectiveness of treatment; however, chemotherapy may induce transient increases in CEA despite providing clinical benefits. An initial rise in CEA after chemotherapy initiation should not be presumed to indicate tumor progression or ineffective treatment. Repeat tests and imaging should be done to distinguish transient chemotherapy-induced CEA elevation from tumor progression. CEA can transiently increase in up to 30% of patients receiving adjuvant chemotherapy.

Conclusion

This case highlights an important caveat in the use of CEA biomarker testing as an indicator of chemotherapy response and colorectal tumor progression. CEA elevation after initiation of chemotherapy may represent a transient surge versus indicator of tumor progression, requiring additional consideration of clinical context and testing to differentiate.