United States

Background
Anemia is three times more common in African Americans than in Caucasians. 90% of anemia can be attributed to nutritional deficiencies, chronic inflammation, or bleeding. In young male adults and both males and females above 65 years of age, chronic gastrointestinal loss is the most likely etiology of iron-deficiency anemia. However, malignancies (not limited to gastrointestinal malignancies) should be considered in the absence of obvious bleeding.
Case Presentation
We present a 47-year-old African American incarcerated male patient with a past medical history of hypertension and peptic ulcer disease who presented to our hospital with a 1-month history of nausea, vomiting, fatigue, and alleged two-day history of coffee-ground hematemesis. His hemoglobin had dropped by 5-6 g/dl over two months; red blood cell indices were suggestive of normocytic normochromic anemia. He also complained of dark urine and left flank pain. Gastrointestinal workup, including esophagogastroduodenoscopy and colonoscopy did not reveal
an obvious bleeding source. During the hospital stay, his hemoglobin continued to decrease, and extensive anemia workup was ordered. Lactate dehydrogenase was elevated, reticulocyte count normal, haptoglobin level decreased, and a differential blood count revealed 55.7% “other abnormal cells.” The peripheral smear report revealed acute myeloid leukemia (AML), later confirmed by bone marrow biopsy, and the qualitative glucose-6-phosphate dehydrogenase (G6PD) screen was noted to be deficient. The patient was promptly started on induction chemotherapy for AML: cytarabine 100mg/m2 for 7 days, daunorubicin 90mg/m2 for 3 days, and midostaurin 50 mg twice daily from day 8-21.
Discussion
Acute myeloid leukemia (AML) can present with non-specific symptoms of anemia such as breathlessness, fatigue, and mucosal bleeding. It also commonly presents with fever and bone pain. Our patient’s history of peptic ulcer disease and initial complaints lead us to investigate gastrointestinal bleeding primarily. The concurrent diagnosis of G6PD in the setting of AML is significant since it has been reported to pose a higher risk for developing invasive fungal infections. From our experience, we recommend a broad approach to evaluating anemia, avoiding ascertainment bias, particularly in the African American population where anemia is more prevalent, and the etiology can be more variable.

2022 AMA Research Challenge

Acute Myeloid Leukemia and G6PD deficiency in a 47-year-old African American Male Patient with Suspected Gastrointestinal Bleed

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Ricardo Correa, MD, EdD
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Charles Lopresto, DO

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poster

Background
Acute myeloid leukemia is a hematological malignancy arising from the myeloid cell line and characterized by the proliferation of abnormal, non-functioning blasts in bone marrow. Patients may present with anemia, recurrent infections, increased bleeding, or rarely an extramedullary mass as in myeloid sarcoma. Some patients have no symptoms at all. With fewer surgeons sending otherwise healthy patients for pre-operative screening laboratory tests, concerning findings representing an occult malignancy may be missed.

Case Presentation
A 50-year-old male presented with chronic sinusitis, with his most recent infection lasting three weeks. He underwent endoscopic sinus surgery, during which urgent labs were drawn due to abnormal blood loss (~800 mL), which revealed pancytopenia with lymphocytosis and monocytosis; he was admitted for acute leukemia work-up and treatment. Initial bone marrow biopsy analysis revealed acute myeloid leukemia with 70% blasts; cytogenetics negative for the PML-RARA fusion gene, and positive for inversion of chromosome 16 with presence of CBFB/MYH11 fusion transcripts. He was definitively diagnosed with acute myeloid leukemia with inversion of chromosome 16. He received 7+3 induction chemotherapy plus gemtuzumab ozogamicin, with subsequent bone marrow biopsy demonstrating no evidence of leukemia. This was followed by three cycles of consolidative high-dose cytarabine plus gemtuzumab ozogamicin, resulting in disease remission. Treatment was complicated by hospitalization for neutropenic fever and Streptococcus mitis bacteremia during the second and third treatment cycles. Bone marrow biopsy after the third cycle of consolidative chemotherapy showed an erythroid predominance with increased monocytes and no increase in blasts. There were no chromosomal abnormalities and no CBFB/MYH11 fusion transcripts detected. The patient was determined to be in remission. 

Discussion
Sinusitis is a potential complication in leukopenic patients. Acute myeloid leukemia may present with a rapid onset of persistent infections or excessive bleeding during procedures. With modern pre-operative screening protocols emphasizing fewer routine laboratory tests, it is incumbent on surgeons to recognize unusual bleeding or other abnormal findings intraoperatively and consider rare conditions such as acute myeloid leukemia, and pursue a diagnostic evaluation urgently.


Acute Myeloid Leukemia in a 50-year-old Male With Chronic Sinusitis

Abstract Title: Amiodarone-Induced Thrombocytopenia: Uncommon side effect of a common cardiac drug

Background
Thrombocytopenia is defined as decrease in platelet count below 150 x 103/mm3. Drug-induced thrombocytopenia (DITP) is considered to be due to direct toxicity or immune-mediated effect. Over 200 medications are listed as thrombocytopenia inciting drugs. In 1987, first case of amiodarone-induced thrombocytopenia was reported and there have been few published reports since. Amiodarone is widely known for side-effects on lungs, thyroid, skin, nervous system, and liver. We discuss a case of DITP immediately after receiving amiodarone, commonly used in atrial fibrillation with rapid ventricular response.

Case Presentation
66-year-old female with a past medical history of heart failure with preserved ejection fraction, atrial fibrillation, and hyperlipidemia presented with chest pain and shortness of breath. In the emergency department, she was tachycardic at 150 beats per minute and had blood pressure of 121/88 mmHg. Electrocardiogram showed atrial fibrillation with rapid ventricular response. Home medications were, metoprolol and diltiazem for rate control, and apixaban for anticoagulation. On admission, oral and intravenous amiodarone was administered. Within three days, platelet count drastically decreased to 55 x 103 /mm3 and liver enzymes trended up. She was evaluated for causes of thrombocytopenia and elevated liver enzymes, and tested negative for disseminated intravascular coagulopathy, viral infection, and gallbladder/common bile duct disease. Amiodarone was then discontinued and diltiazem dose was increased. Platelets and liver enzymes gradually improved back to baseline, correlating with the long half-life of amiodarone. She successfully underwent AV node ablation with pacemaker implantation and was discharged home.

Discussion
Amiodarone-induced thrombocytopenia has been investigated to be due to platelet specific antibodies. DITP can take cause within 5-10 days of exposure to the drug. Any signs of thrombocytopenia after amiodarone administration should prompt possibility of drug-induced toxicity. Amiodarone must be discontinued. Another antiarrhythmic should be used while planning for ablation or pacemaker placement. Platelet counts must be followed till resolution to baseline, and amiodarone must be listed as a drug allergy. Given the frequent use of amiodarone, and lack of diagnostic immunoassays timely diagnosis is crucial to prevent life-threatening complications.



Amiodarone-Induced Thrombocytopenia: Uncommon side effect of a commoncardiac drug

Meningioma is the most common primary brain tumor with most of the cases having good prognosis (WHO grade 1). Higher grade meningioma (WHO grade 2) tend to show higher recurrence rate and worse prognosis. Multiple extra-cranial non-pigmented tumors showed melanocytic colonization e.g., dermatofibroma protuberans. However, melanocytic colonization in meningioma has not been reported except in only three cases. In this report, we are presenting a case of atypical meningioma (WHO grade 2) with melanocytic colonization and comparing our findings with the previous reports.

Atypical meningioma with melanocytic colonization: Histopathological, Radiological and Immunohistochemical findings

Background
Vitamin B12 (cobalamin) is a water-soluble vitamin required for normal DNA synthesis, myelination and function of central nervous system and development of hematopoietic cells. B12 isnaturally found in foods from animal but is also supplemented in many foods. However, even in high-income countries, 15-20% of individuals >60 years of age are likely deficient. Risk factors for deficiency include inadequate dietary intake and conditions that limit absorption such as autoimmune disorders, prior gastric surgery and use of metformin. Although most cases of 
deficiency are asymptomatic or mild, ~2.5% of cases result in a hemolytic anemia with pancytopenia termed pseudothrombotic microangiopathy (pTMA). The syndrome is often mistaken for other forms of true hemolytic anemia and therefore accurate diagnosis is imperative,as pTMA can easily managed by supplemental B12.

Case Presentation
A 56-year-old woman presented to the emergency department complaining of two months of lethargy and anorexia. She had no significant medical history and took no medications other than intermittent acetaminophen. Laboratory evaluation revealed pancytopenia and serum markers (total bilirubin, LDH, and haptoglobin) consistent with hemolysis. Peripheral blood smear revealed schistocytes and dacrocytes. Following hospital admission, further work-up demonstrated undetectable serum B12, normal serum folate, a reticulocyte index of 0.43, and a serum methylmalonic acid of 20,701. The patient was transfused packed-RBCs and started on weekly intramuscular B12. Within two days of initial supplementation, the patient’s symptoms improved. Following discharge, direct and indirect antiglobulin and intrinsic factor auto-antibody testing confirmed the diagnosis of pTMA secondary to pernicious anemia.

Discussion
Although bibliometric analysis reveals an increasing proportion of publications over the past decade that discuss this clinical syndrome (n=93, 68%), pTMA continues to confound clinicians, leading to unnecessary diagnostic and therapeutic interventions. A systematic review of published cases found that of 321 patients with pTMA, 50 (16%) underwent bone marrow biopsy, 11 (3%) were treated with plasma exchange therapy, and 7 (2%) were treated with high dose glucocorticoid therapy prior to B12 supplementation. Such interventions are of limited benefit in pTMA and often confound the diagnosis, delaying therapy. Therefore, increased 
awareness is paramount for the practicing clinician in order to promptly recognize and reverse this illusive condition.

B12 Deficiency: A Curious Cause of Pseudo-Thrombotic Microangiopathy

Introduction: Renal oncocytoma (RO) is a highly differentiated tumor that accounts for 4.3% of solid renal masses and 16% of all renal masses. ROs have a benign clinical course with excellent long-term outcomes and 100% disease specific survival. Up to 30% of the small renal masses detected on routine imaging are benign, but most are still treated without a tissue diagnosis. Partial nephrectomy (PN) is suggested for patients with a renal tumor <4 cm, while radical nephrectomy is recommended for tumors 4 cm and larger. The patient is subsequently followed post-partial nephrectomy with active surveillance (AS), which includes routine imaging tailored to the patient’s profile and risk factors to monitor tumor growth after initial complete staging. Biopsy followed by AS can be considered as an alternative in cases of benign tumors as it avoids overtreatment. 
Case Presentation: A 66-year-old man presented with flank pain was diagnosed with bilateral ROs. Patient underwent left partial nephrectomy and received a histological diagnosis of RO. Subsequently, the patient elected to undergo partial nephrectomy to remove the contralateral right renal mass.
Discussion: In patients who have undergone partial nephrectomy with diagnosis of RO, there is an increased likelihood of benign neoplasm and decreased risk of RCC, similar to that of the general population. After our patient’s left partial nephrectomy, given the diagnosis of RO and the absence of constitutional symptoms or gross hematuria, the chance of RCC or hybrid tumor with RO was decreased. Because the left renal mass was 3.3 cm in size and undiagnosed prior to intervention, the mass was more concerning for RCC; however, with the diagnosis of RO in the left kidney and the decreased size of the right renal mass at 2 cm, there was a negligible risk of metastasis, which warranted AS rather than intervention. The patient could have undergone a confirmatory biopsy of the contralateral right renal mass with AS imaging protocols instead of undergoing a right partial nephrectomy. Given advancements in technology, AS with core renal biopsy is a promising approach to accurately diagnose and manage ROs conservatively.

Bilateral Renal Oncocytoma: Active Surveillance vs. Partial Nephrectomy

Introduction
Heart failure is the most common initial manifestation of infiltrative cardiomyopathies, which in many instances can remain underdiagnosed. In patients with oncological history, it can be due to cancer or its treatment complications. The incidence of metastatic disease to the heart is rare at less than <10% (most common with lung, breast, melanoma, and hematological malignancies). We present a rare case of recurrent breast cancer that presented as new-onset heart failure. 
Case description
81 y/o female with a past medical history of hypertension and breast cancer treated with lumpectomy and radiation without adjuvant chemotherapy in remission since 2004, presented with dyspnea on exertion and orthopnea. Noted to have elevated BNP, bilateral pleural effusions, and ejection fraction (EF) of 30 %, was treated for CHF exacerbation. During outpatient follow-up, a new echocardiogram showed an EF 40-45% with an apical thrombus, which resolved with apixaban. On cardiac catheterization, she was noted to have mild nonobstructive coronary disease. Her EF eventually improved to 55%, however, she continued with symptoms despite diuresis and heart failure treatment. She was readmitted 2 months later and found to be in CHF exacerbation, right pleural effusion, for which she had a thoracentesis and was discharged when stable. Cardiac MRI was done and showed normal EF with diffuse late gadolinium enhancement consistent with infiltrative disease. A Technetium pyrophosphate scan was performed and was negative for amyloidosis. The patient presented recurrent symptoms and pleural effusion a month later. She was referred to the hospital for a myocardial biopsy. The procedure was complicated with right ventricle perforation and pericardial effusion with tamponade and cardiogenic shock that warranted an emergent pericardial window. She was in the ICU until improved. Pleural fluid from prior thoracentesis, and myocardial biopsy revealed malignant cells consistent with breast cancer ER+. She was started on letrozole and would continue further oncologic workup with PET/CT as an outpatient. 
Discussion
Detection of Infiltrative cardiomyopathies has led to improved to better outcomes via disease-specific therapy. Heart failure in oncologic patients can be caused by different mechanisms including radiation, chemotherapy, and cancer metastases. Breast cancer gets to the heart by lymphatic spread most commonly in pericardium; myocardium metastases are rare. Treatment is symptomatic. In our case, the recurrent malignant pleural effusions, nonobstructive CAD, MRI suggestive of infiltrative disease, and negative PYP led to the suspicion of cardiac metastasis. Pathology is the gold standard for the diagnosis of cardiac metastasis.
Conclusion
Cardiac metastases should be considered in any individual with new cardiac symptoms and known malignancy. The prognosis of patients with breast cancer with cardiac metastases is poor.

Cardiac Metastases Mimicking Amyloidosis In New- Onset Heart Failure: A Rare Presentation Of Recurrent Breast Cancer 

Carotid sinus syncope in the setting of metastatic disease 

Background
Carotid sinus syncope, also referred to as carotid sinus hypersensitivity is a condition in which the stimulation of the carotid artery baroreceptors results in a greater than expected fall in heart rate and drop in blood pressure. In such cases, activities that stimulate the carotid baroreceptors such as turning the neck or looking upward stimulate the vagus nerve which results in significant reduction of heart rate. 

Case Presentation 
Our case involved a 65-year-old female with an enlarged right cervical lymph node. The lymph node was previously biopsied and found to be SCC with suspected SCC esophageal primary. Patient was admitted to our service for syncope. The patient had unresponsive with some body rigidity while in the car with her daughter who drove her to the ED. A similar event occurred in the ED on arrival and an RRT was called. She had received her second of fifteen fractions of 45 Gy to the lymph node three days prior to this event and after treatment, the swelling of the node had increased. Patient was admitted for syncope workup and continuous video EEG monitoring was negative for seizure activity. She had severe sinus bradycardia down to 43 upon the admission. Vascular imaging was obtained due to concern for carotid artery occlusion secondary to the mass. The lymph node was observed to be necrotic and encasing the carotid sinus. She was started on steroids considering her recent radiotherapy and concern for increased inflammation compressing the carotid sinus triggering a vagal induced syncope. The patient’s heart rate improved to the 70s initially with steroids before settling to between 51-61 prior to discharge. She was started on midodrine to increase blood pressure and maintain brain perfusion during syncopal events under the advisement of cardiology. Diagnosis was determined to be sinus syncope due to metastatic right cervical lymph node enlargement and right carotid sinus encasement.

Discussion
The case illustrates the diagnosis and management of carotid sinus syncope secondary to non-resectable metastatic disease. It further elucidates the importance of educating patients on symptom recognition and modification of daily life activities. 


Carotid sinus syncope in the setting of metastatic disease

Background  

Despite showing remarkable remission rates in patients with refractory hematological malignancy, Chimeric Antigen Receptor T cell (CAR-T) therapy has raised increased concern over its side effects, such as Cytokine release syndrome (CRS) and neurotoxicity. It should be used carefully, especially in hemodynamically unstable patients. This vignette describes a patient with relapsing B Cell-Acute Lymphocytic Leukemia(B-ALL) who was in hemorrhagic shock prior to CAR-T infusion but showed significant improvement after being infused with CAR-T.  

Case Presentation  

A 40-year-old male with an 18-month history of B-ALL was admitted to our hospital due to leukemia relapse, infectious mastoiditis, and pneumonia. Workup suggested extensive liver leukemic infiltration and fungal pneumonia. The following seven hospital days were complicated by severe anemia, thrombocytopenia, neutropenia requiring frequent blood transfusion, and acute hypoxic respiratory failure requiring mechanical ventilatory support. Further, he suffered an episode of hematemesis leading to hemorrhagic shock, which was treated with IV norepinephrine. The CAR-T therapy was planned for refractory leukemia, but the impaired hemodynamic status posed a therapeutic dilemma for us. However, given his poor prognosis and no other option for leukemia, we proceeded with its infusion despite his hemodynamic instability. He continued to require blood product replacements with extensive volume support and norepinephrine infusion to maintain adequate blood pressure. His vitals, inflammatory markers, hemoglobin, and blast cell count started improving six days post-CAR-T. He was extubated to a high-flow nasal cannula and transitioned to hemodialysis from the continuous renal replacement therapy. He maintained adequate BP without any vasopressor and was transferred to the floor. His hospital stay was further complicated by resistant thrombocytopenia, anemia, GI bleeding, and acute renal failure, and increasing circulating blasts limiting treatment options. As such, after a stay in the hospital of more than 30 days, at his family’s request, he was transferred to hospice care, where he died the next day. 

Conclusion 

The case demonstrates the use of CAR-T therapy in a hemodynamically unstable and clinically deteriorating patient. Despite hypotension on therapy initiation, this patient tolerated the infusion well and did not develop severe CRS. In contrast, the patient showed improved hemodynamic stability, decreasing signs of inflammation, and improvements in resistant anemia. The patient was able to be extubated while on the therapy. This case suggests CAR-T therapy may be an option for rapidly progressing patients or when alternative therapies are not an option. 

Case Report: Chimeric Antigen Receptor T Cell Therapy in Patient with B Cell Acute Lymphocytic Lymphoma Shortly after Developing Shock

There is a known relationship between Clostridium septicum bacteremia and colorectal malignancies. C. septicum is a gram-positive, anaerobic, spore-forming bacterium that can survive the acidic colorectal tumor microenvironment, where it is thought to enter the blood by tumor-mediated epithelial tissue damage. While in circulation, C. septicum can release exotoxins which may lead to life-threatening sepsis. The patient in this case presented with a mild fever, abdominal pain, and left handed weakness. Imaging of the head and abdomen revealed a right frontal lucency and wall thickening of the ascending colon. Two colonic adenocarcinomas were found and removed via an exploratory laparotomy and right hemicolectomy. The blood culture was positive for C. septicum. Brain MRI confirmed a right frontal mass concerning for metastasis. Here, we discuss the relationship between colonic cancers and Clostridium septicum bacteremia.


Acute Myeloid Leukemia and G6PD deficiency in a 47-year-old African American Male Patient with Suspected Gastrointestinal Bleed

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Acute Myeloid Leukemia in a 50-year-old Male With Chronic Sinusitis

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