Enteropathy-associated anaplastic large T cell lymphoma ALK-positive (EA-ALCL-ALK+): variant of T cell lymphoma with possible two-hit pathogenesis

Abstract

Enteropathy-associated T cell lymphoma (EATL) and anaplastic large T cell lymphoma ALK-positive (ALCL-ALK+) are two well-defined and recognized T cell lymphoma entities. We report a case of primary ileal lymphoma in a 68-year-old male with a well-established long-standing history of celiac disease. In addition to the typical clinical presentation and histopathologic aspects of EATL, this lymphoma displayed an ALK-gene rearrangement detected by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Although ALK-gene rearrangements may be encountered in other neoplasms, its presence in an otherwise T cell lymphoma is thus far unique to ALCL-ALK+ category in the WHO classification. Furthermore, primary intestinal ALCL-ALK+ arising in the context of celiac disease or other chronic inflammatory or immune gastrointestinal disorders, has not been described. This case combines, therefore, features specific to two different lymphoma types with distinct pathophysiological pathways: (1) EATL, which derives from transformed intraepithelial lymphocytes during the course of untreated or refractory celiac disease, and (2) ALCL-ALK+ driven by ALK-gene rearrangement. Consequently, this lymphoma seems to best pertain to an “enteropathy associated”-ALCL-ALK+ (EA-ALCL-ALK+), which might represent a T cell lymphoma variant with two-hit pathogenesis. Cases of EA-ALCL-ALK+ might have been historically misclassified as usual EATLs in a subset of celiac disease-associated lymphomas, if ALK-gene rearrangement was not pursued. Identifying such cases is particularly crucial with the current availability of targeted therapies, given the dismal outcome of the disease. Performing ALK-gene rearrangement studies by IHC and FISH in newly diagnosed EATLs, regardless of their subtype, is therefore recommended. Retrospective ALK-gene studies in EATLs may provide greater insight in that regard.