Ph-negative non-Hodgkin's lymphoma occurring in chronic phase of Ph-positive chronic myelogenous leukemia is defined as a genetically different neoplasm from extramedullary localized blast crisis: report of two cases and review of the literature

This report describes two cases of Philadelphia chromosome-negative (Ph(-)) non-Hodgkin's lymphomas (NHLs) recognized in patients with chronic phase P h-positive (Ph(+)) chronic myelogenous leukemia (CML). Lymph node biopsy of patient I was initially diagnosed as diffuse large B cell non-Hodgkin's ly mphoma (NHL, T cell rich variant), but at relapse showed immunoblastic feat ures with a marked decrease of admired lymphocyte components. Patient 2 pre sented with thickened parietal pleura which revealed a CD30-positive anapla stic large cell lymphoma showing null cell phenotype and genotype with abun dant admired neutrophils and lymphocytes. At the time of lymphoma diagnosis , the patients had CML for 33 and 10 months, respectively, DNA obtained fro m bone marrow cells at the time of lymphoma diagnosis showed BCR/ABL gene r earrangements by both Southern blot analysis and reverse transcription poly merase chain reaction (RT-PCR), but lacked both immunoglobulin and T cell r eceptor gene rearrangements. BCR gene rearrangement and BCR/ABL fusion gene were also identified in lymph node and pleural biopsies by Southern blot a nd RT-PCR analysis, respectively. However, both biopsy specimens also conta ined reactive lymphocytes and neutrophils, and no fusion signals between BC R and ABL genes were identified in the hyperdiploid lymphoma cells of eithe r case by fluorescence in situ hybridization (FISH). These data suggest the lymphoma cells in both cases were not genetically associated with BCR/ABL, Therefore, these cases were not diagnosed as an extramedullary localized b last crisis in CML, but as Ph(-) NHLs, This represents the first definitive demonstration of peripheral B cell lymphoma occurring by a separate geneti c pathway, lacking SCR/ABL, in patients with Ph(+) CML. A review of the lit erature identified two different subtypes of malignant lymphomas arising in patients with an antecedent or concurrent diagnosis of ORAL. The most comm on are T cell lymphomas displaying an immature thymic phenotype, while peri pheral B cell lymphomas are more rare. Our study shows, however, that 'Ph() NHL' occurring in CML or acute lymphocytic leukemia (ALL) may represent a n unrelated neoplasm, even if standard cytogenetic analysis reveals a Ph(+) chromosome, and that FISH is required to confirm whether a localized lymph oid neoplasm is either a true extramedullary localized blast crisis or gene tically distinct neoplasm.