Non-alcoholic Wernicke's Encephalopathy Masquerading As CNS Relapse of Acute Myeloid Leukemia.

While Wernicke's encephalopathy (WE) is mostly caused by thiamine deficiency secondary to chronic alcohol use, other conditions that may affect one's nutritional status, such as bariatric surgery, hyperemesis gravidarum, chronic gastrointestinal disease, HIV/AIDS, and certain malignancies, may also lead to this outcome. We are discussing one such case, WE, in a young man with acute myeloid leukemia (AML) who underwent chemotherapy. The patient presented with blurred vision, paresthesia, weakness, and vomiting. Although he denied alcohol abuse, his symptoms, physical exam findings, and MRI results were consistent with WE. Treatment with thiamine resulted in a significant improvement in his visual disturbances and mental status. The authors highlight the importance of recognizing WE in non-alcoholic patients, particularly those undergoing prolonged hospitalization and chemotherapy, as nutritional deficiencies can develop. They recommend thiamine supplementation for patients receiving chemotherapy and those with poor oral intake. The case underscores the need for high clinical suspicion and early intervention in atypical cases of WE.

Dystrophic Nails: An Unusual Clue to Recurrent Lymphoma.

Nail changes are a well-known phenomenon in T-cell lymphoma but have not been reported as widely in B-cell lymphomas and Hodgkin lymphomas. We describe a patient with a history of diffuse large B-cell lymphoma in a background of nodular lymphocyte predominant Hodgkin lymphoma treated eight years prior who developed new nail changes that were noted on a routine surveillance visit. He had developed symptoms of painful fingertips that became white and required him to wear gloves even in warm weather, suggestive of Raynaud phenomenon. Due to a suspicion of a paraneoplastic phenomenon, a positron emission tomography-computed tomography was obtained, which showed fluorodeoxyglucose avid uptake involving the spleen and retroperitoneal, para-aortic, and right inguinal lymph nodes. Right inguinal lymph node biopsy was non-diagnostic and a splenectomy was performed. Pathology evaluation of the spleen revealed recurrent nodular lymphocyte-predominant Hodgkin lymphoma. Treatment was initiated with rituximab-based systemic therapy. The Beau lines grew out eventually with normal new nail growth and there was an improvement in Raynaud phenomenon after systemic treatment.

Successful Treatment of Central Nervous System Post-Transplant Lymphoproliferative Disease With a Reduced Dose of High-Dose Methotrexate.

Post-transplant lymphoproliferative disease (PTLD) is a complication of solid organ and hematopoietic stem cell transplantation that occurs as a result of immunosuppression. PTLD isolated to the central nervous system (CNS) is a rare disease and it presents with nonspecific signs and symptoms. Optimal therapy guidelines have not yet been established for CNS PTLD. Here, we report a case of successful treatment of CNS PTLD in an adult female following two subsequent kidney transplants. Initial management was with immunosuppression reduction and a trial of rituximab. There were concerns regarding using methotrexate (MTX) given the patient's fragile transplant status. Magnetic resonance imaging of the brain following four cycles of rituximab revealed the progression of the disease. Subsequently, high-dose MTX (HD-MTX) was considered within the constraints of potential kidney toxicities given her transplant status and chronic kidney disease. Potential toxicities from other therapies, such as brain radiation, also factored into the final decision. The patient was treated with one cycle of a combination of rituximab and HD-MTX 1 g/m2. The patient tolerated HD-MTX and did not have evidence of renal toxicity in laboratory studies. Following that, she was started on a reduced dose of HD-MTX at 2 g/m2 every two weeks instead of the higher MTX dose range of 3.5 to 8 g/m2, which was a shared decision with the patient and nephrology after weighing the risk of kidney dysfunction with the possibility of a less than optimal response with regards to her lymphoma. She was followed with a magnetic resonance imaging of the brain, which demonstrated a complete response after four cycles. Further consolidation treatments with HD-MTX 2 g/m2 every four weeks were administered to complete one year of treatment. Following the completion of chemotherapy, the patient was able to achieve and maintain a complete response without affecting her kidney function. She continues to do well one year following treatment. This case highlights the significance of tailoring therapy to each individual based on their comorbidities and clinical response, as well as the possible merit in exploring the use of a reduced dose of HD-MTX in the treatment of CNS PTLD in patients at high risk for renal toxicity.

Desperate times, desperate measures: successful use of chemotherapy in treatment of haemophagocytic lymphohistiocytosis (HLH) due to disseminated histoplasmosis.

We describe a case of haemophagocytic lymphohistiocytosis (HLH) secondary to disseminated histoplasmosis, which was treated with chemotherapy in addition to standard antifungal therapy. While HLH in the setting of infections is very well described, its treatment in this setting is controversial, with some physicians treating only the underlying infection, whereas others using immune suppression in addition to antimicrobials. To the best of our knowledge, this is the first report documenting the successful treatment of an adult patient with HLH due to disseminated histoplasmosis using etoposide chemotherapy after initial antifungal therapy failed to show improvement.

Hematology/Oncology Fellowship Emergency Restructuring in Response to the COVID-19 Pandemic-Henry Ford Hospital, Michigan.

The COVID-19 pandemic has wreaked havoc and created challenges in various subspecialty training programs, including hematology/oncology fellowship programs. The challenge of social distancing, providing care for those infected by COVID-19, continuing appropriate treatment of time-sensitive diseases, and the looming threat of health care worker infections required swift planning and restructuring of training programs. The Accreditation Council for Graduate Medical Education provided leeway to tackle the challenges faced by institutions and training programs in the setting of the COVID-19 pandemic. Currently, there is no established guideline specific to hematology and oncology fellowship programs. While understanding that there is no one-size-fits-all, shared experiences can assist training programs to incorporate best practices and customize their programs to provide an active educational environment that balances patient care needs, didactics, scholarly activities, and wellbeing during the process of rapid changes and adaptation. We share our hematology/oncology fellowship program's restructuring approach in response to the COVID-19 pandemic.

The role of a low erythropoietin level for the polycythemia vera diagnosis.

A low erythropoietin (EPO) level is a minor diagnostic criterion for polycythemia vera (PV). Controversies exist regarding the diagnostic value of a low EPO level when considering increasing availability of advanced molecular testing. We assessed the role of low EPO level for PV diagnosis in the context of positive JAK2 mutation status as well as other diagnostic parameters. Of 138 patients, 75 patients had PV and 63 had secondary erythrocytosis. Of the 75 patients with PV, 32% had EPO levels within the normal range. EPO level positively correlated with obesity and smoking status, making it an unreliable diagnostic marker in those patients. Although EPO level below normal as a standalone diagnostic modality was significantly associated with PV (odds ratio [OR] 0.857; p < 0.001), when JAK2V617F mutation status was included in the prediction model, the association of low EPO was not statistically significant (OR 0.962, p = 0.269). Positive JAK2V617F demonstrated a strong predictive value for PV (OR 670.5, p = 0.006) either alone or in combination with other variables. Results show that EPO level is not a reliable diagnostic marker due to physiologic variation in association with obesity and smoking.

Paraneoplastic Syndrome in Splenic Marginal Zone Lymphoma: A Rare Phenomenon of Paraplegia as an Atypical Presenting Manifestation.

We describe a case presenting complaint of complete lower body paraparesis, which was discovered to have splenic marginal zone lymphoma (SMZL). While paraneoplastic syndromes are more common in tumors, such as small cell lung cancer, very few reports exist on this condition with SMZL. We describe such a rare entity with a clinical course spanning twenty-four months after diagnosis.

Spontaneously recovered severe thrombocytopaenia following zoledronic acid infusion for osteoporosis.

Zoledronic acid is widely used for the treatment of various skeletal disorders. While acute phase reactions are commonly seen, hypocalcaemia, femoral shaft fractures, osteonecrosis of the jaw and renal failure are rare. Two cases of fatal thrombocytopaenic purpura have been reported following zoledronic acid infusion. We report a case of non-fatal thrombocytopaenia with spontaneous recovery. A 70-year woman with osteoporosis participated in a research study. Complete blood and platelet counts prior to zoledronic acid infusion were normal (138,000/µL), but had declined slightly from 185,000/µL 2 years ago. One year after the first zoledronic acid infusion, her platelet count declined to 50,000/µL without any clinical manifestations, and rose slowly returning to normal (156,000/µL) over the next 1 year. Extensive evaluation did not reveal any specific abnormalities, and the pathogenesis of her transient severe thrombocytopaenia after two infusions of zoledronic acid remains unclear.

Predictors of Venous Thromboembolism in Patients with Glioblastoma.

To evaluate different risk factors associated with development of venous thromboembolism (VTE) in patients with Glioblastoma (GBM). A retrospective chart review was performed to include patients diagnosed with GBM from 2001 to 2011. Cases (n = 162) were defined as patients with GBM who developed VTE after diagnosis of GBM. Controls (n = 840) were defined as patients with GBM with no history of VTE. Data was collected for multiple variables including age, gender, race, length of hospital stay after brain biopsy, total number of hospital admissions unrelated to VTE, Karnofsky Performance Status (KPS), use of Bevacizumab and any bleeding episodes. Patients with GBM who had VTE had poorer KPS scores, with the majority (57%) being in between 40 and 70, as compared to the controls where majority (82%) had better performance (KPS 80-100). For every one year increase in age, the odds of developing VTE increased by 3% (OR 1.03, 95%CI 1.02-1.04, p < 0.001) with the mean age being 61.8 ± 11.4 years. GBM patients who developed a VTE were found to have greater number of hospital admissions (OR 1.43, 95%CI 1.33-1.53, p < 0.001) and longer stays in hospital after GBM biopsy (OR 1.14, 95%CI 1.09-1.18, p < 0.001). Patients receiving Bevacizumab were more likely to develop VTE (OR 1.79, 95%CI 1.21-2.64, p < 0.001) and were more likely to have a bleed (OR 3.78, 95% CI 2.70-5.30, p < 0.001). Patients with GBM are at a higher risk of developing VTE. The risk is higher in older patients who require multiple hospital admissions, longer duration of hospital stays related to GBM biopsy, and in patients with lower KPS scores. Bevacizumab use is related to a higher incidence of VTE as well as bleeds. This study suggests that a more aggressive strategy for VTE prophylaxis should be considered in GBM patients with risk factors for VTE.

Isolated Ocular Manifestation of Relapsed Chronic Myelogenous Leukemia Presenting as Myeloid Blast Crisis in a Patient on Imatinib Therapy: A Case Report and Review of the Literature.

Blast phase in chronic myelogenous leukemia (CML) has rarely been reported to involve extramedullary sites like skin, lymph nodes, and central nervous system. Clinical history, characteristic hematologic findings (elevated leukocyte counts, myelocytic predominance, and basophilia), and Philadelphia chromosome are of high diagnostic significance especially in isolated extramedullary presentations. We describe a unique case of CML relapse with blast phase involving the eye. A 66-year-old man with a known diagnosis of CML on imatinib and in molecular remission for 3 years presented with a painful blind eye. Histologic examination revealed diffuse involvement of choroid, iris, vitreous humor, and the optic nerve by blast cells. The blasts expressed CD34, aberrant TdT, and a myeloid phenotype (CD13, CD33, and CD117). Fluorescence in situ hybridization (FISH) of vitreous fluid detected BCR-ABL1 gene rearrangement. Additionally, trisomy 8 and gains of 9 and 22 were seen which were not present in the initial diagnostic marrow study 3 years ago. At relapse, the bone marrow, peripheral blood, and the cerebrospinal fluid were not involved by CML. Patient received induction chemotherapy and single dose prophylactic intrathecal methotrexate and was maintained on antityrosine kinase therapy and eventually underwent allogenic stem cell transplantation.

Non-Hodgkin's lymphoma: a cause of paraneoplastic cholestasis.

We describe a 79-year-old gentleman with a longstanding history of chronic lymphocytic leukaemia who presented with subacute onset of cholestatic jaundice. Comprehensive review of the patient's data and medications failed to reveal any obvious causes. Exhaustive testing including abdominal CT and magnetic resonance cholangiopancreatography failed to reveal any obstruction. A liver biopsy demonstrated scattered non-caseating granulomas. The patient was diagnosed with granulomatous hepatitis and treated with oral steroids and eventually improved. It was thought to be due to paraneoplastic cholestasis as an extrahepatic manifestation of non-Hodgkin's lymphoma.

'Tumour-induced osteomalacia'.

A 60-year-old man presented 2 years before his diagnosis with long-standing muscle cramping, progressive generalised weakness and chronic hip pain. The patient was found to have bilateral femoral neck pathologic fractures therefore, underwent reamed intramedullary nailing of both femurs. Laboratory studies showed hypophosphataemia. Bone marrow biopsy was negative for malignancy. Positron emission tomography demonstrated fludeoxyglucose uptake only in the posterior neck. Bone scan showed innumerable foci of increased activity throughout the skeleton consistent with pseudofractures seen in osteomalacia. Fine needle aspiration from the mass in the neck revealed a phosphaturic mesenchymal tumour of mixed connective tissue type. Resection of the mass in the neck resulted in resolution of generalised complaints with no evidence of recurrence with a follow-up of 12 months.

Prospective study to determine the volume of pleural fluid required to diagnose malignancy.

BACKGROUND: The optimal volume of pleural fluid to diagnose a malignant effusion is unknown. Our study was designed to demonstrate if a minimum pleural fluid volume (10 mL) is equivalent to a large volume thoracentesis to make a cytopathologic diagnosis of malignancy. METHODS: A total of 121 thoracentesis samples were obtained from 102 patients with suspected or known malignant effusions. Pleural fluid was collected in three aliquots for cytologic examination (10 mL, 60 mL, > or = 150 mL). The pathologist was blinded to patient identifiers and aliquot volume. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were calculated for each volume for the diagnosis of malignancy. RESULTS: Pleural malignancy was diagnosed in 90 patient encounters (74.4%). For direct smear/cytospin, there was increased sensitivity and NPV for 60 mL (P = .0058 and P = .045, respectively) and for > or = 150 mL (P < .001 and P = .009, respectively) compared with 10 mL. For combined direct smear/cytospin and cell block preparations, statistical significance for sensitivity and NPV existed only between the 10 mL and > or = 150 mL specimens (P = .0099 and P = .033, respectively). No statistical difference existed for specificity or PPV for any aliquot volume. CONCLUSIONS: The sensitivity for diagnosis of pleural malignancy is dependent on the pleural fluid volume extracted during thoracentesis. Volumes of 10 mL do not perform as well as larger volumes. When both direct smear/cytospin and cell block preparations are used, we recommend > or = 150 mL, whereas when only direct smear/cytospin is used, 60 mL is adequate for the diagnosis a malignant pleural effusion.