ALK-Positive Diffuse Large B-Cell Lymphoma: Report of Four Cases from Peru

Abstract

BACKGROUND: Anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma (ALK-DLBCL) is a rare lymphoma with several differences from ALK-positive anaplastic large cell lymphoma (ALCL). ALK-DLBCL appears as a defined disease entity characterized by the expression of the ALK protein, usually in a granular cytoplasmic fashion. These cells are usually CD20-negative but express plasma cells markers. The most common chromosomal abnormality is a fusion between the ALK and the clathrin gene. Clinically, ALK-DLBCL presents as lymph node-based disease affecting mostly middle-aged men, frequently showing aggressive behavior, a negative prognosis at advanced stage and a strikingly rare bone marrow involvement. Only 44 cases are currently reported in the English and non-English literature.METHODS: This is a retrospective study with data collected on four patients with ALK-DLBCL between 2002 and 2008 in a general hospital from Peru. Immunohistochemical studies were performed to detect expression of B-cell, T-cell, plasma cell markers and oncoviruses (i.e. EBV and HHV8). FISH cytogenetic studies were attempted but were unsuccessful. Clinical characteristics of the cases included age, sex, primary site of involvement, IPI score, Ann Arbor stage, therapy, survival in months and final outcome.RESULTS: The male:female ratio was 1:1; one 13-year-old girl and three adults of 27, 41, and 70 years of age were identified. Two patients had primary extranodal disease (multifocal bone lesions and right nasal fossa involvement) and the remaining two patients had exclusively nodal disease. Stages were I (n=1), II (n=1), III (n=1) and IV (n=1). Two patients had increased LDH levels and three patients reported B symptoms. IPI scores were 0 (n=1), 2 (n=1) and 3 (n=2). All cases exhibited immunoblastic/plasmablastic morphology. By immunohistochemistry the cases showed positive expression of cytoplasmic ALK-1, CD138, monoclonal cytoplasmic light chain, CD45 and EMA. All cases lacked expression of the CD3, CD20 and CD30 antigens. HHV8 and EBV were not expressed. The survival times ranged from 11 to 72 months; the latter was observed in a patient who presented with stage III disease and is still alive without evidence of lymphoma.CONCLUSIONS: ALK-DLBCL is a distinct subtype of B-cell lymphoma, which does not express CD20 and is characterized by marked plasmacytic differentiation. This lymphoma has clinically aggressive behavior and more effective therapies are warranted. However, some cases can have prolonged survival with intensive regimens.Table 1. Clinical characterisitics of the reported casesCaseAgeSexPrimary siteIPIStageTherapySurvival (months)Outcome141FNasal fossa0IARadiotherapy13Alive, free of disease213FCervical lymph node2IIBFrance NHL 96–2002*62Alive, free of disease370MCervical lymph node3IIIBCHOP72Alive, free of disease427MBone3IVBHyperCVAD11Alive, with disease*This regimen is based on induction with vincristine, prednisone, cyclophosphamide, daunorubicin, L-asparaginase and methotrexate, followed by consolidation based on cyclophosphamide, cytarabine, metrotexate, then intensification with vincristine and doxorubicin and manteinance based on metrotexate and mercaptopurine.