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.

BACKGROUND: A Phase II Study multinstitutional study by the lymphoma group within the Southwest Oncology Group (SWOG 0213) was performed to determine the 1 year progression free survival of patients with newly diagnosed mantle cell lymphoma (MCL). Previously, this regimen was utilized in a similar group of newly diagnosed MCL patients in a single institution study by Romaguera et al (JCO200523:7013) at the MD Anderson Cancer Center. They reported a 97% response rate, a 87% CR rate, and a 3 year failure free survival rate of 73%. PATIENTS AND METHODS: This study was a prospective phase II trial of rituximab plus fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyperCVAD; considered one cycle) alternating every 21 days with rituximab plus high-dose methotrexate-cytarabine (considered one cycle) for a total of eight cycles per the MD Anderson protocol. Newly diagnosed MCL patients under age 70 with adequate organ function and measurable disease were eligible. All cases were histologically confirmed. RESULTS: 49 eligible patients were enrolled. There was one probable treatment-related death due to colitis. Grade 4 hematologic toxicity was reported for 87% of patients. 40 patients have been evaluated for response. 3 patients had inadequate assessment and are assumed to be non-responders.16 patients (40%) had complete responses, 7 patients (18%) had unconfirmed complete responses, and 12 patients (30%) had partial responses for an overall response rate was of 88% (35/40; 95% CI, 73%–96%). Median follow-up among patients still alive is 1.6 years (range: 0.3–4.1 years). The progression-free survival estimate at 1-year is 89% (95% CI: 80%–98%) and at 2 years is 64% (95% CI: 46%–82%). The overall survival estimate at 1 year is 91% (95% CI: 82%–99%) and at 2 years is 76% (95% CI: 60%–91%). 13 of the 49 eligible patients have progressed or died. One year overall survival was 91% and one year progression free survival is 89%. Two year PFS is 63% (95% CI: 46%–82%). Two year OS is 76% (95% CI: 60%–91%). The 1-year progression-free survival estimate is 89% (95% CI: 80%–98%). The 1-year overall survival estimate is 91% (95% CI: 82%–99%). The overall response rate was 88% (35/40; 95% CI, 73%–96%). CONCLUSIONS: The hyperCVAD + rituximab regimen is active as reported in MCL with a one year progression free survival of 89%. However, similar to the reported MD Anderson experience, this regimen is toxic and a continuous pattern of relapse over time is observed.