Transient abnormal myelopoiesis with extramedullary involvement in a down syndrome preemie leading to an unresponsive course despite chemotherapy.

Introduction: Transient abnormal myelopoiesis (TAM) is a transient, clonal myeloproliferative disorder unique to Down Syndrome (DS) babies. It is characterized by increased peripheral blasts and presence of GATA1 mutation. The clinical spectrum ranges from jaundice and hepatosplenomegaly to multi-organ failure and death. Here we present a case of a premature baby with DS diagnosed to have TAM with extramedullary involvement at birth who had a fatal outcome. Case report: A 30.3-week-old female fetus with DS had leukocytosis (WBC: 187.82 K/uL) with neutrophilia (ANC 27.65 K/uL), macrocytic anemia (RBC: 2.41 m/uL, Hb 8.8 g/dL, MCV 108.3, MCH 36.5, MCHC 33.7) and thrombocytosis (platelet count 361 K/uL) at birth. Liver panels demonstrated normal bilirubin levels with elevated liver enzymes (AST = 239 U/L, ALT = 216 U/L). Results: Peripheral smear showed marked leukocytosis with increased blasts (70%), nucleated RBCs, giant platelets, and megakaryocytic elements. Flow cytometry demonstrated two populations of cells: 20% myeloblasts and 26% dim CD45 CD34- cells. GATA1 mutation was present. Based on these findings a diagnosis of TAM with extramedullary hematopoiesis was made. She received two cycles of cytarabine chemotherapy. Though her WBC levels reached a low of 18.93 K/uL, she developed multi-organ failure, eventually leading to death on day 45. Discussion: TAM is a transient condition resulting in disease resolution in around 80% of cases. Death is reported in 10% of cases. Risk factors associated with early death include prematurity, hyperleukocytosis, elevated bilirubin levels. Management of high-risk babies with chemotherapy is recommended to improve survival.

Study of the Utility of Myeloid Cell Nuclear Differentiation Antigen (MNDA) in the Diagnosis of Marginal Zone Lymphoma.

Myeloid cell nuclear differentiation antigen (MNDA) is normally expressed on myelomonocytic cells and a subset of B lymphocytes. It was found to be differentially expressed between nodal marginal zone lymphoma (MZL) and follicular lymphoma (FL). However, MNDA has not been widely used as a diagnostic marker in clinical practice. To validate its utility, we studied the expression of MNDA by immunohistochemistry in 313 cases of small B-cell lymphomas. Our results showed that MNDA was positive in 77.9% of MZL, 21.9% of mantle cell lymphoma, 28.9% of small lymphocytic lymphoma/chronic lymphocytic leukemia, 2.6% of FL, and 25% of lymphoplasmacytic lymphoma. MNDA positivity varied from 68.0% to 84.0% among the 3 MZL subtypes, with extranodal MZL having the highest percentage. There was a statistically significant difference in MNDA expression between MZL and FL, mantle cell lymphoma, small lymphocytic lymphoma/chronic lymphocytic leukemia, or lymphoplasmacytic lymphoma. CD43 expression was slightly more frequent in MNDA-negative MZL than in MNDA-positive MZL. Combined use of CD43 and MNDA improved the diagnostic sensitivity for MZL from 77.9% to 87.8%. There was a trend of positive correlation between MNDA and p53 in MZL. In conclusion, MNDA is preferentially expressed in MZL among small B-cell lymphomas and it is a useful marker for the differentiation of MZL and FL.

Acquired haemophilia A: successful treatment of a patient using upfront immunosuppressive therapy and haemostatic agents.

Acquired haemophilia A (AHA) is a rare and possibly fatal autoimmune disorder that is challenging to treat. Although a majority of cases are idiopathic, AHA can also be associated with an underlying malignancy, autoimmune disorder, pregnancy, infection or certain medications. The diagnosis and treatment of AHA require a specialist with both clinical and laboratory expertise. The goal of treatment is aimed at achieving haemostasis as well as eradicating factor inhibitors. We present a patient with AHA and life-threatening haemorrhage who was successfully treated with a combination of haemostatic agents and a triple-drug immunosuppressive regimen. In reviewing recent studies and published guidelines, we advocate that a newer agent, emicizumab, can potentially be incorporated into the treatment protocol for AHA given its promising performance in the realm of congenital haemophilia.

Intracranial acute promyelocytic leukemia at presentation-A case-based discussion.

Intracranial disease is a very rare presentation at diagnosis in acute promyelocytic leukemia (APL). The risk associated with this particular presentation is not accounted for when the current risk stratification is based on peripheral counts. Extra medullary disease in general may challenge this risk stratification that commands initial induction treatment of this potentially fatal disease. Here we discuss a case presented at diagnosis with extensive intracranial base of the skull, clivus and sinus infiltration and heavily infiltrated bone marrow yet with low peripheral blood counts and no peripheral blood blasts. Such cases lack evidence of how to treat.

An unusual presentation of Merkel cell carcinoma: a case report.

Merkel cell carcinoma (MCC) is a rare, aggressive carcinoma that usually arises in sun-exposed regions. MCC is a primary neuroendocrine tumor that arises in the skin. This report describes an unusual case of MCC on the buttocks that was treated with excision, radiation and chemotherapy. Physicians should consider MCC as a differential diagnosis when encountering a rapidly growing, painless lesion. Early diagnosis and treatment may improve patient survival rates.