Chronic Myeloid Leukemia with Cryptic Philadelphia Translocation Presenting Initially As Extramedullary Lymphoid Blast Phase

Abstract

Abstract We report an adult male diagnosed as chronic myeloid leukemia (CML) - chronic phase when he was shortly presented with treatment-naive extramedullary 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 has Philadelphia negative (Ph -ve) BCR/ABL-1 - positive CML. Up to our knowledge; this is the first report of CML with extramedullary lymphoid blast phase (as initial presentation) that shows cryptic Ph translocation. This is a 45 year- old male who presented with one month history of swelling of medial canthus of his left eye, and left sided neck swelling for three days. His initial physical examination showed bilateral cervical lymphadenopathy and splenomegaly. CBC showed marked leukocytosis (WBC: 159x10^3/ul (4.0-10.0), with Hb of 12.2gm/dl (13.0-17.0) and thrombocytopenia (123x10^3/ul (150-400)). BM biopsy was markedly hypercellular with granulocytic hyperplasia and prominent eosinophils. Reticulin stain showed focal increase reticulin fibrosis (grade 1-2 out of 3). FISH analysis revealed BCR/ABL1 rearrangement, t(9;22) in 97% of the cells analyzed with deletion of ABL1 as confirmed by metaphase FISH analysis: der(9)t(9;22),del(9)(q34q34)(ABL1+,BCR+),der(22)t(9;22)(BCR+,ABL1-)[10]. (fig 1 B). The fusion signal was formed on chromosome 9 instead of 22. Conventional cytogenetics confirmed the presence of cryptic BCR/ABL1 rearrangement. and normal karyotype: 46,XY. (fig1 c). BCR/ABL1 transcript confirmed by PCR.The overall findings consistent with CML- chronic phase. Immunohistochemical studies showed positivity for CD45, CD20, CD79a and BCL2 with strong and diffuse positive staining for Tdt. Ki67 shows high expression of about 90% of cellular nuclei. T-cell markers including CD3, CD5, CD4 and CD8 are negative in tumor cells. The morphological and immunohistochemical features are consistent with nodal involvement by precursor B-cell lymphoblastic lymphoma. FISH analysis performed on nodal tissue and confirmed the presence of BCR/ABL-1 rearrangement confirming that nodal involvement is lymphoid blast phase (BP) of CML and excluding the possibility of denovo ALL as second pathology. The patient started on hyper CVAD chemotherapy and Dasatinib .Still under treatment . In the great majority of CML; BCR/ABL is cytogenetically visualized as t(9;22); giving rise to the Ph chromosome, harboring the chimeric gene. Cryptic or masked translocation occurs in 2-10% patients with no cytogenetic evidence for the BCR/ABL rearrangement but are positive by FISH and/or (RT-PCR. Cryptic BCR/ABL rearrangements can be found in cases with a normal karyotype and in cases with complex karyotype in which the t(9;22) is not detected by conventional cytogenetics. These latter patients are described as CML Ph-ve/ BCR/ABL1 +ve with the chimeric gene present on the derivative chromosome 22, as in most CML cases, or alternatively on the rivative 9 as in our case. The prognostic significance of cryptic Ph translocations has been discussed in previous reports, some authors reported a worse prognosis associated with location of BCR/ABL on the der (9). Data regarding the outcome of Ph-neg CML patients treated with TKIs are limited, only 10 Ph-neg CML cases treated with imatinib have been described in 6 previous reports . The prevalence of extramedullary blast phase (BP) has been reported to be 7-17% in patients with BP . Extramedullary BP in the newly diagnosed patients is extremely rare as the prevalence of an accelerated phase and BP as initial presentations has been reported to be only 5-10% in CML patients . Conclusion: This is a report of a case of (CML) with a combination of a couple of unusual events including cryptic Philadelphia (Ph) translocation together with extramedullary lymphoid blast crisis as an initial presentation We aim in this report to highlight this case with unusual features, to describe clinical features and disease out come and to focus that the absence of hematologic blast proliferation in PB or BM in cases of CML doesn't by all means exclude the possibility of concomitant extramedullary blast crisis as an initial event. The combined cytogenetic, molecular and clinical studies in CML cases can bring to light the frequency of this event and disease out come. Although rare; this possibility should be raised and thoroughly investigated whenever clinically suspected. Download : Download high-res image (336KB) Download : Download full-size image Disclosures No relevant conflicts of interest to declare.