Chronic Myeloid Leukemia with cryptic Philadelphia translocation and extramedullary B-lymphoid blast phase as an initial presentation.

Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative neoplasm (MPN) characterized by the presence of a reciprocal translocation between the long arms of chromosomes 9 and 22, t(9;22)(q34:q11), resulting in fusion of the break point cluster region (BCR) with the ABL gene, which forms an oncogene, the transcript of which is an oncoprotein with a tyrosine kinase function. In the great majority of CML; BCR/ABL1 is cytogenetically visualized as t(9;22); giving rise to the Ph chromosome, harboring the chimeric gene. Cryptic or masked translocations occur in 2-10% patients with no evidence for the BCR/ABL rearrangement by conventional cytogenetics but are positive by Fluorescence in Situ Hybridization (FISH) and/or reverse transcriptase polymerase chain reaction (RT-PCR). These patients are described as Philadelphia negative (Ph negative) BCR/ABL1- positive CML with the chimeric gene present on the derivative chromosome 22, as in most CML cases, or alternatively on the derivative 9 in rare occasions. In the majority of cases, CML is diagnosed in the chronic phase; it is less frequently diagnosed in accelerated crises, and occasionally, its initial presentation is as acute leukemia. The prevalence of extramedullary blast phase (BP) has been reported to be 7-17% in patients with BP. Surprisingly, no extra-medullary blast crises of B- lymphoid lineage have been reported before among cases of CML as the initial presentation. We report an adult male diagnosed as CML- chronic phase when he was shortly presented with treatment-naive extramedullary B-lymphoid blast crises involving multiple lymph nodes, with no features of acceleration or blast crises in the peripheral blood (PB) and bone marrow (BM). In addition the patient had variant/cryptic Philadelphia translocation. This is the first report of CML, on the best of our knowledge, with extramedullary B-lymphoid blast phase, as initial presentation, that showed a cryptic Ph translocation.

Rare aggressive natural killer cell leukemia presented with bone marrow fibrosis - a diagnostic challenge.

Aggressive natural killer cell leukemia is an extraordinary rare aggressive malignant neoplasm of natural killer cells. Although its first recognition as a specific entity was approximately 20 years ago, this leukemia has not yet been satisfactorily characterized as fewer than 200 cases have been reported in the literature and up to our knowledge, this is the first case report in Qatar. Reaching a diagnosis of aggressive natural killer leukemia was a challenging experience, because in addition to being a rare entity, the relative scarcity of circulating neoplastic cells, failure to obtain an adequate aspirate sample sufficient to perform flow cytometric analysis, together with the absence of applicable method to prove NK clonality (as it lack specific clonal marker); our case had atypical confusing presentation of striking increase in bone marrow fibrosis that was misleading and complicated the case further. The bone marrow fibrosis encountered may be related to the neoplastic natural killer cells' chemokine profile and it may raise the awareness for considering aggressive natural killer leukemia within the differential diagnosis of leukemia with heightened marrow fibrosis.