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Lymphoma

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

Leukemia volume 14, pages 169–182 (2000)Cite this article

Abstract

This report describes two cases of Philadelphia chromosome-negative (Ph(−)) non-Hodgkin's lymphomas (NHLs) recognized in patients with chronic phase Ph-positive (Ph(+)) chronic myelogenous leukemia (CML). Lymph node biopsy of patient 1 was initially diagnosed as diffuse large B cell non-Hodgkin's lymphoma (NHL, T cell rich variant), but at relapse showed immunoblastic features with a marked decrease of admixed lymphocyte components. Patient 2 presented with thickened parietal pleura which revealed a CD30-positive anaplastic large cell lymphoma showing null cell phenotype and genotype with abundant admixed neutrophils and lymphocytes. At the time of lymphoma diagnosis, the patients had CML for 33 and 10 months, respectively. DNA obtained from bone marrow cells at the time of lymphoma diagnosis showed BCR/ABL gene rearrangements by both Southern blot analysis and reverse transcription polymerase chain reaction (RT-PCR), but lacked both immunoglobulin and T cell receptor gene rearrangements. BCR gene rearrangement and BCR/ABL fusion gene were also identified in lymph node and pleural biopsies by Southern blot and RT-PCR analysis, respectively. However, both biopsy specimens also contained reactive lymphocytes and neutrophils, and no fusion signals between BCR and ABL genes were identified in the hyperdiploid lymphoma cells of either 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 blast crisis in CML, but as Ph(−) NHLs. This represents the first definitive demonstration of peripheral B cell lymphoma occurring by a separate genetic pathway, lacking BCR/ABL, in patients with Ph(+) CML. A review of the literature identified two different subtypes of malignant lymphomas arising in patients with an antecedent or concurrent diagnosis of CML. The most common are T cell lymphomas displaying an immature thymic phenotype, while peripheral B cell lymphomas are more rare. Our study shows, however, that ‘Ph(+) NHL’ occurring in CML or acute lymphocytic leukemia (ALL) may represent an unrelated neoplasm, even if standard cytogenetic analysis reveals a Ph(+) chromosome, and that FISH is required to confirm whether a localized lymphoid neoplasm is either a true extramedullary localized blast crisis or genetically distinct neoplasm.

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Acknowledgements

This study was supported in part by a Grant-in-Aid from the Gonryo Medical Foundation. The authors are grateful to Jerome B Myers, Dr Jerome Ritz, and Dr Chris Pickett for the pathologic and molecular analysis, and to Ms Shizue Mochizuki, and Mitsuru Inoue for morphologic and phenotypic analysis, to Mr Yoshito Tsurukubo, Mr Satoshi Iwai, Mr Toshikazu Yamaguchi and Mr Tsurukubo for genotypic and cytogenetic examination and to Mr Atsushi Abe for photographic work.

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Authors and Affiliations

  1. Department of Oral Pathology, Tohoku University School of Dentistry, Sendai, Japan

    R Ichinohasa ma & K Ooya

  2. Third Department of Internal Medicine, Akita University School of Medicine, Akita, Japan

    I Miura & N Takahashi

  3. Division of Internal Medicine, Furukawa City Hospital, Furukawa, Japan

    T Sugawara & E Tamate

  4. Division of Internal Medicine, Sendai City Hospital, Sendai, Japan

    K Endoh, F Endoh & H Naganu ma

  5. Department of Pathology, Royal University Hospital, University of Saskatchewan, Saskatoon, Canada

    JF DeCoteau

  6. Division of Hematologic Malignancies, Dana-Faber Cancer Institute and Harvard Medical School, USA

    JD Griffin

  7. Department of Pathology, Beth Israel Deaconess Hospital and Harvard Medical School, Boston, USA

    ME Kadin

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Ichinohasa, R., Miura, I., Takahashi, N. et al. 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. Leukemia 14, 169–182 (2000). https://doi.org/10.1038/sj.leu.2401606

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