ABSTRACT
Reactive immunoblastic proliferations can histologically mimic classical Hodgkin lymphoma (CHL), and show diffuse CD30 expression in large cells. The lack of expression of CD15 in a subset of CHL further complicates their separation from immunoblastic proliferations. Loss of expression of B-cell transcription factors is frequently exploited in making a diagnosis of CHL; however, the staining patterns of B-cell transcription factors in immunoblastic proliferations have not been extensively studied. Thirty-three cases of reactive immunoblastic proliferations were evaluated using a panel of immunohistochemistry for CD30, CD15, CD20, CD3, κ, λ, CD45RB, MUM1, PAX5, OCT2, and BOB.1, as well as Epstein-Barr virus (EBV)/EBV-encoded ribonucleic acid in situ hybridization. A newly developed dual-color chromogenic in situ hybridization technology for detection of κ/λ mRNAs was also used. The majority of immunoblasts expressed CD30 in 14 of 33 (42%) cases; none expressed CD15. Loss or weak expression of at least 1 transcription factor in B immunoblasts, most commonly PAX5, was noted in 24 of 29 (83%) cases. A polytypic light chain expression pattern was detected by immunohistochemistry in 14 of 22 (63.6%) cases and by dual-color chromogenic in situ hybridization in 9 of 10 (90%) cases studied. EBV-encoded ribonucleic acid was detected in 8 of 33 (24.2%) cases, 5 of which were clinically unrelated to infectious mononucleosis. We conclude that B-cell transcription factors can show loss or weak expression in a significant proportion of reactive immunoblastic proliferations, and, therefore, staining for B-cell transcription factors together with CD30 should be interpreted with caution before a diagnosis of CHL is made.
Subject(s)
B-Lymphocytes/pathology , Diagnosis, Differential , Hodgkin Disease/diagnosis , Pseudolymphoma/diagnosis , Transcription Factors/biosynthesis , Adolescent , Adult , Aged , B-Lymphocytes/metabolism , Biomarkers, Tumor/analysis , Child , Female , Humans , Immunohistochemistry , In Situ Hybridization , Male , Middle Aged , Pseudolymphoma/metabolism , Transcription Factors/analysis , Young AdultABSTRACT
Randomized trials suggest improved disease-free survival in low-grade non-Hodgkin's lymphoma (LGNHL) when interferon is combined with multiagent chemotherapy. This phase II trial was conducted to investigate the feasibility of combining fludarabine monophosphate (fludarabine) and IFN in a regimen for treatment of LGNHL. Twenty-one patients were evaluable. Median age was 55 years, and patients had been treated with an average of 1.7 chemotherapy regimens before enrollment. Patients received 25 mg/m2 of fludarabine intravenously on days 1 through 5 followed by 2 x 10(6) U/m2 of interferon-alpha-2a subcutaneously on days 22 through 26. Cycles were repeated every 4 weeks with delays and dose modifications for significant cytopenias. Patients were restaged after cycles 4 and 8, and those with at least a partial response to therapy were given maintenance therapy consisting of 2 x 10(6) U/m2 interferon-alpha-2a subcutaneously three times per week for 6 months. The overall response rate was 76% with a 25% complete response (CR) rate. Overall response rates were 75% (3/4 with 2 CR's) for chemotherapy-naive patients and 76% (13/17 with 3 CR's) for previously treated patients. Median time to progression was 12 months, and currently two patients are without evidence of progression at a median follow-up of 55 months. Grade III or greater toxicities included neutropenia (39%), anemia (17%), thrombocytopenia (5%), fevers/chills (5%), and fatigue (5%). Fludarabine and interferon can be effectively and safely combined in a regimen with significant activity against LGNHL. A modification of this regimen may be suitable for further study.