Impact of World Health Organization (WHO) Revised Criteria-2016 on the Diagnosis of Polycythemia Vera.

The diagnosis of polycythemia vera (PV) requires the integration of clinical and laboratory findings, bone marrow morphologic features, and JAK2 analysis. JAK2V617F (exon 14) mutation is found in 95% of PV cases. In PV, addition of characteristic bone marrow morphology as one of three major diagnostic criteria allowed reduced hemoglobin/hematocrit threshold for diagnosis to 16.5 g/dL/49% in men and 16 g/dL/48% in women. JAK2 mutation is still the third major diagnostic criterion in PV. Low serum erythropoietin level is now considered as minor criterion in PV and is used to detect cases, which are negative for JAK2 mutation. In this retrospective study, cases diagnosed as PV from January 2013 to December 2015 were reclassified using WHO 2016 criteria. Their clinical and laboratory parameters along with treatment and outcome were studied. Out of 26 patients of previously diagnosed PV, either definitively or provisionally, twenty-one were found to comply with the new 2016 revision of the WHO Criteria. Median age was 55.5 years, with a male preponderance. The median values of hemoglobin, hematocrit and platelets were 17.5 gm/dL, 56.7% and 493 × 109/L, respectively. JAK2V617F was mutated in 17 cases. Bone marrow showed hypercellularity, panmyelosis and marked megakaryocyte dyspoiesis in all patients. All patients had normal oxygen saturation, confirming the primary nature of the disease. Our study, first of its kind in India, underscores the importance of the 2016 revision of the WHO document in detecting cases of masked PV.

Multiparametric Flow Cytometry in Mixed Phenotype Acute Leukemia.

Mixed phenotype acute leukaemia (MPAL) is a diverse group of leukemia of ambiguous lineage diagnosed when blasts in peripheral blood and/or bone marrow have antigens of more than one lineage or a mosaic of blasts belonging to more than one lineage. Retrospective analysis of 218 consecutive cases of acute leukaemia diagnosed by multiparametric flow cytometry (FCM) was done. MPAL cases were identified in accordance with European Group for the Immunological Classification of Leukaemias Criteria and World Health Organization 2008/2016 guidelines for lineage assignment. Nine out of 218 (4.1%) cases were classified as MPAL. Eight out of nine patients (88.8%) were male and 4/9 (44.4%) were < 20 years of age. There were three cases of B/T and T/myeloid MPAL each. Two cases were B/myeloid MPAL and one case was chronic myeloid leukaemia (CML) in B/myeloid blast crisis. B/myeloid MPAL and CML in B/myeloid blast crisis cases were Philadelphia chromosome positive. The latter case had a complex karyotype as well. Seven cases were treated with acute lymphoblastic leukaemia treatment regimen; two of them achieved complete remission (CR). The patient with CML in B/myeloid blast crisis was treated with imatinib based regimen, attained CR, underwent allogenic bone marrow stem cell transplantation, but developed graft versus host disease. Five patients died due to complications of febrile neutropenia early in the course of treatment (62.5%). The last patient (B/T MPAL) refused therapy and was lost to follow-up. Early accurate diagnosis of MPAL requires FCM. It may be misdiagnosed if a limited panel of antibodies is used.

Hemosiderin tubulopathy-induced acute kidney injury - A rare initial manifestation of paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by episodes of intravascular hemolysis, infections, and thromboembolic complications. Renal abnormalities are rare which occur either due to hemolytic crisis or repeated thrombotic episodes involving small venules. Acute kidney injury (AKI) requiring hemodialysis due to toxic effects of hemoglobinuria, with a stable disease is exceptional. We describe a case of an elderly gentleman presenting with features of severe AKI requiring hemodialysis due to hemosiderin tubulotoxicity as the first manifestation of PNH. The diagnosis was challenging because of the rarity and unfamiliarity with this entity. The outcome was complete recovery of renal function with hemodialysis.

Blastoid Variant of Mantle Cell Lymphoma with Leukemic Presentation - A Rare Case Report.

Mantle Cell Lymphoma (MCL) is a type of Non-Hodgkin's lymphoma and has a wide spectrum of histopathological subtypes of which the blastoid or the blastic variant constitutes 10-15% of all cases. It is difficult to diagnose blastoid variant of MCL on the basis of morphology alone as it mimics lymphoblastic lymphoma and centroblastic large cell lymphoma, hence additional analysis like immunophenotyping and molecular studies aid in its diagnosis. We present a case of 45-year-old male who presented to medicine OPD with chief complaints of fever, fatigability and inguinal swelling. Complete blood count, peripheral smear and bone marrow examination was performed. Peripheral smear showed thrombocytopenia along with 53% abnormal cells. On bone marrow examination 43% abnormal lymphoid cells were seen. This case was diagnosed as blastoid variant of MCL on the basis of routine morphology and immunohistochemistry on bone marrow biopsy and flow cytometric immunophenotyping on peripheral blood.

Hemophagocytic lymphohistiocytosis: An unusual presentation of tuberculosis in hemodialysis patients.

We report a series of three patients with end-stage renal disease on maintenance hemodialysis presenting with hemophagocytic lymphohistiocytosis (HLH) as an unusual manifestation of extrapulmonary tuberculosis. All three patients were middle-aged men. They presented with fever, pancytopenia, varying degrees of hepatosplenomegaly, abnormal liver function tests, coagulopathy, increased serum ferritin, and triglycerides. Tests for fever work-up were negative. Bone marrow examination revealed hemophagocytosis and caseating granuloma. Acid fast bacilli were demonstrated in two patients. The HLH-2004 diagnostic criteria suggested by the histiocytic society were followed to arrive at the diagnosis. All of them succumbed to death even before the definitive diagnosis could be made. We suggest that aggressive diagnostic work-up must be done when hemodialysis patients present with fever and pancytopenia. Priority should be toward early diagnosis and appropriate treatment to improve the prognosis.

Discrepancy in optical & mechanical method in coagulation tests in a turbid sample.

Automated coagulation analyzers have replaced manual methods to meet the ever-increasing test load in many laboratories. Of the different methods, two distinct methods exist based on optical and mechanical clot detection (magnetic steel ball method). In optical method the detection of clot formation is measured by a change in optical density (OD) of a test sample. Mechanical clot detection technology, involves monitoring the movement of a steel ball within the test solution using a magnetic sensor. There are limited studies comparing both these methods and they have conflicting results regarding the effect of plasma turbidity on the final result. We report a case where a plasma factor (lipemia) caused prolongation of both PT and APTT, as measured by the photo optical method.

Correlation of morphologic and cytochemical diagnosis with flowcytometric analysis in acute leukemia.

INTRODUCTION: The classification of acute leukemias has revolutionized over the years. Immunophenotyping of acute leukemia has gained popularity because of its influence on treatment and prognosis of the disease. The various antigens expressed by the leukemic cells can be assessed by flowcytometry (FCA) and can be used in rendering specific treatment and predicting the outcome of the different types of acute leukemia. AIMS: The main aim of this study was to compare the morphologic and cytochemical diagnoses with flowcytometric diagnoses in acute leukemia and to analyze the usefulness of FCA over morphology. RESULTS: In this study we analyzed 50 cases of acute leukemia and found concordance rate as high as 86% between morphologic/cytochemical diagnosis and flowcytometric diagnosis. Of these, complete concordance was seen in 58% of the cases and partial concordance was seen in 22% of the cases. Non-concordance was seen in only 4% of our cases. In remaining 16% of our cases FCA helped in sub classifying the acute leukemia where morphology and cytochemistry had failed to do so. CD19 and 20 were found to be consistent B-cell markers and CD3 was a very specific marker for T-cell leukemia. CD13 and 33 were important myeloid markers and were aided by other secondary panel of markers like CD14, CD117 and CD41. CONCLUSION: FCA not only helps in confirming morphologic diagnosis in acute leukemia but also helps in assigning specific lineage to the blasts, particularly in acute lymphoid leukemia. Immunophenotyping is of utmost importance in classifying acute leukemia as it greatly influences the treatment and the prognosis.

Chronic myeloid leukemia with hyperdiploidy: a case report with review of literature.

Chronic myeloid leukemia (CML) is a common marrow stem cell neoplasm characterized by the presence of the Philadelphia (Ph) chromosome in more than 90% of patients. Studies have shown that CML can be associated with various other cytogenetic abnormalities. 5-10% of these cases can show complex translocations involving other chromosomes in addition to Ph chromosome. Here, we report a Ph-positive CML patient with a hyperdiploid karyotype who presented clinically in chronic phase but progressed to blast crisis in spite of treatment with Imatinib. This case highlights the significance of cytogenetic abnormalities on the prognosis in CML.

Glucose 6 phosphate dehydrogenase deficiency unmasked by diabetic ketoacidosis: an underrated phenomenon.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked disease responsible for moderate to severe hemolytic anaemia. Despite being the most common erythrocyte enzyme disorder, it is often overlooked in the regular diagnostic parlance. A 40-year-old male patient admitted to the casualty with an acutely exacerbated diabetic ketoacidosis, showed features of hemolytic anaemia on peripheral smear examination. Crucially, the spherocytes and bite cells suggested a possibility of G6PD deficiency. This was substantiated by an increased reticulocyte count (6.8%) and a reduced quantitative G6PD enzyme assay (7.2%). There was no significant family or prior medical/ drug history. Interestingly, the hemolytic features were evidenced when blood glucose levels were returning to normal values. The insulin mediated NADPH loss may have resulted in an increased erythrocyte oxidant sensitivity and a loss of sulfhydryl group availability; causing hemolysis to manifest. G6PD deficiency is conventionally affiliated with drug induced oxidative stress. But an association with a diabetes mellitus is seldom reported. This case is being presented as it highlights the lesser known complication of diabetic crisis such as hemolysis secondary to a G6PD deficiency.

Pure red cell aplasia following thymothymectomy: a case report.

Thymoma, a rare epithelial neoplasm, is the most common anterior-superior mediastinal tumour. Thymoma can occur sporadically or in association with other conditions, such as myasthenia gravis, pure red cell aplasia (PRCA), and hypogammaglobulinemia. Only 5% of thymoma cases develop PRCA; however, 10-50% of patients presenting with PRCA have an associated spindle cell type thymoma. Thymoma complicated by PRCA is associated with a poor outcome. We report the case of a 38-year-old female who presented with chest pain, and was diagnosed with an anterior mediastinal mass. A thymectomy was performed, and histopathological examination revealed mixed thymoma; two months later, the patient developed PRCA. The present case reinforces the need for clinicians to be vigilant with thymoma patients, even following thymectomy.

Rosette formation in non Hodgkin's lymphoma in the bone marrow--a case report.

This is a case report of rosette formation in non-Hodgkin's lymphoma in the bone marrow. A 66 year old female on treatment for metastatic papillary carcinoma thyroid and non-Hodgkin's lymphoma of the nodular small cleaved cell type was found to have bone marrow infiltration by a low grade B cell lymphoma. Bone marrow aspirate, imprint and trephine biopsy showed rosettes of the abnormal lymphoid cells. The associations of papillary carcinoma thyroid, hyperglobulinemia and retroperitoneal fibrosis in this case which explain the histogenesis of rosette formation are discussed.