'NOT SO CLASSICAL': A STUDY OF THE IMMUNOPROFILE IN CLASSICAL HODGKIN LYMPHOMA, AN EXPERIENCE FROM A REFERRAL CENTER

Abstract

Introduction: According to WHO classification, Classical Hodgkin Lymphoma (CHL) expresses CD15 and CD30 antigens in majority of cases, and CD20 in a small subset of cases. Expression of CD20 may affect the patients' prognosis, relapse, and refractoriness to the therapy. We come across a subset of cases of CHL in our lymphoma consultation cases that exhibit a lack of the ‘positive’ diagnostic marker CD15 and express CD20 in the Hodgkin and Reed-Sternberg (HRS) cells. This observation has important prognostic implication, based on the western studies from the more developed world, and furthermore prompted us for a systematic evaluation of the immunoprofile of South-East Asian CHL patients and to compare those with the Western data. Methods: In this retrospective analysis, 111 cases of CHL diagnosed over a period of six months were studied. Demographics, clinical details, histopathological (including unusual morphologic patterns), and immunohistochemical (IHC) parameters were recorded. The diagnoses were made according to the 2016 WHO classification of lymphoid neoplasms. The cases were further subtyped. The IHC panel included CD45, CD15, CD30, CD3, CD20, PAX5, ALK1, and EBV (LMP-1) in all cases and MUM1, CD21, EMA, PD1, OCT2, BOB.1, and BCL6, in a subset of cases, wherever necessary. A case was designated CD20+, if >10% of HRS cells were strongly positive. Results: The cases of CHL fit into 'textbook phenotype' (WHO 2016 update) of CD15+, CD30+, CD20- in 54% cases. HRS cells were positive for CD30 in all, CD15 in 56%, PAX5 in 96%, CD20 in 18% cases and EBV (LMP1) in 58.3% cases. In majority of instances, morphology and an initial panel of CD3, CD20, CD15, CD30, CD45, and PAX5 were sufficient for diagnosis. When IHC pattern discordance was noted or mimics of CHL were in the differential diagnostic consideration, additional markers supported the diagnosis of CHL. Conclusions: 1. Our study results broaden the understanding of the demographic, histopathologic, and IHC characteristics of CHL cases. 2. The second peak of bimodal distribution occurs two decades earlier as compared to those of the western population in majority cases in our cohort. 3. 56% of our cases expressed CD15 that is lower than the reported positivity rates (75% to 85%). 4. Significant CD20 positivity in HRS cells as seen in our cohort can create diagnostic dilemma. However, CD45 negativity in the presence of weak to barely perceptible PAX5 and moderate to strong expression for EBV aid in arriving at a diagnosis of CHL. 5. Future directions: The management of CHL is essentially based on radiotherapy and chemotherapy, due to lack of information about the clinical outcomes with anti-CD20 antibody therapy or combined drug therapy using a classic regimen. The prognostic impact of lack of CD15 and positive CD20 expression in the cases of CHL requires further research and clinical follow-up studies in a larger cohort of patient to assess the role of CD20 in the pathophysiology and progression of CHL. Keywords: CD20; classical Hodgkin lymphoma (cHL); immunohistochemistry (IHC).