The histological, immunohistochemical and genetic features of classical Hodgkin lymphoma and anaplastic large cell lymphoma with aberrant T-cell/B-cell antigen expression.

Classical Hodgkin lymphoma (cHL) and ALK− anaplastic large cell lymphoma (ALCL) share many morphologic and immunohistochemical features, causing difficulties in differential diagnosis. Aberrant T-cell/B-cell antigen (TCA/BCA) expression in cHL/ALCL has previously been reported, but differences in the broader morphologic and genetic features still remain unclear. We first explored the histologic and immunohistochemical characteristics of cHL and ALCL with or without aberrant expression. Of 68 cHL cases, 10 (14.71%) were found to express 1 or more TCAs, and the frequency was as follows: CD4 > CD2 > CD3 > CD5 = CD7. Only 1 (3.33%) of 30 ALCL cases expressed BCA. Histologically, the main subtypes of cHL with aberrant TCA expression were LD and NS2. These aberrant TCA-expressing cHL tumor cells exhibited some ALCL features, and the aberrant BCA-expressing ALCL tumor cells displayed cHL characteristics. We also performed whole-exome sequencing analysis on cHL and ALCL samples with aberrant expression and compared them with those without aberrant expression. The results of this analysis showed that GNE and CACNB2 mutations, involved in the MAPK signaling pathway, may play an important role in cHL. In addition, 135 mutation sites involved in multiple signaling pathways were identified in ALCL. In the aberrant-expression cases, genetic features were similar between cHL and ALCL, consistent with their morphologic features. Our results broaden the understanding of the histologic and immunohistochemical characteristics of cHL and ALCL with aberrant expression and, for the first time, compare genetic features between cHL and ALCL with and without aberrant expression.