Distinguishing Classical Hodgkin Lymphoma, Gray Zone Lymphoma, and Large B-cell Lymphoma: A Proposed Scoring System

The diagnosis of "B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma" represents an indeterminate or equivocal decision in relation to management because there remain differences in the management of Hodgkin and non-Hodgkin lymphomas. We developed a scoring system for this group of lymphomas using markers that are traditionally associated with diagnosis of classical Hodgkin lymphoma (CHL) and immunophenotypic markers associated with the "B-cell program" expressed in normal B cells.

This system emphasized known criteria used to diagnose CHL that are rare in B-cell lymphoma (BCL) [CD15+, CD45-, CD20- or weak/variable, PAX5+ (weak or moderate), CD79a-, OCT-2-/BOB.1- or OCT-2+/BOB.1- or OCT-2-/BOB.1+, EBV+] versus findings that are common in BCL in contrast to CHL (CD15-, CD45+, CD20+ strong, PAX5+ strong, CD79a+, OCT-2+/BOB.1+, EBV-). After a preliminary test trial, MUM1 staining was also added. Results associated with CHL were assigned a score of +1 and score associated with BCL were assigned a score of -1. In the final grading system, a maximum score of +6 is possible for CHL and -6 for BCL.

An initial series of 38 cases was evaluated using a proprietary system that allows analysis of multiple stains on individual cells in a single section. An additional 23 cases were evaluated with results blinded until after scoring was performed. In general there was high concordance among cases originally diagnosed as CHL with high scores (score +4 to +6). Cases originally diagnosed as gray zone lymphomas exhibited a broader range of scores (+3 to -4). Cases of BCLs had low scores (-3 to -6).

The primary goal of this study was to create a scoring system that allows a cumulative quantitative measure of immunohistochemical markers, based on expected results to compare cases that might have overlapping features. In most cases, scores that trend to one extreme or another are likely representative of CHL or BCL and do not lie in the gray zone. This scoring system allows for practical resolution of many borderline cases and provide some guidance in difficult cases.