Track

Clinical Studies

Abstract

Recently it was suggested that JAK2 gene fusions may be specific to aggressive CD8+ cutaneous T-cell lymphomas (CTCL). In our practice, we identified JAK2 fusions in indolent mycosis fungoides (MF) prompting histopathologic analysis for diagnostically distinctive features including stratification by fusion partners. We performed an IRB-approved retrospective database review for indolent MF with fusions including JAK2. Pathology reports and slides were reviewed; data descriptively analyzed. Biopsies revealed epidermal hyperplasia  (10/10), 7/10 with apoptosis. Infiltrates localized to basilar epidermis (9/10) and superficial dermis (7/9). Lymphocytes were small-to-medium sized (10/10); 2/10 with subsets of large-cells (5% and 30%), with irregular nuclei and fine-to-slightly clumped chromatin (9/10). Rare features included folliculotropism (n=1), vasculopathy (n=1), full-thickness necrosis (n=1) and melanophages (n=3). Intermingled cells included histiocytes (10/10) and eosinophils (7/10). CD2+ and/or CD3+, TCR-αβ+ T cells predominated; subsets included CD4-/CD8+ (n=4), CD4+/CD8+ (n=3), and CD4+/CD8- (n=3). ATXN21::JAK2 fusions were CD8+ (3/3) with dyskeratosis (n=2) and vasculopathy (n=1). CLTC::JAK2 fusion cases were CD4+ (2/2), both with eosinophils, granulomas, and CD30+ cells. PCM1::JAK2 fusion cases were CD4+ (n=1) or CD8+ (n=1). CD4+/CD8+ cases represented NUP214::JAK2, STAT3::JAK2, and CAPRIN1::JAK2 fusions.  JAK2 fusions or specific fusion partners may not signify aggressive CTCL. Distinct from aggressive CD8+ CTCLs, smaller-cell, junctional CD4-/CD8+ and CD4+/CD8+ αβ+ T cells with mild cytotoxic features appear common in this molecular subset. Furthermore, fusion partner may correlate with phenotype. Our findings underscore complexity of genetic alterations in CTCL, cautioning the need to integrate clinical, pathologic, and molecular data for each patient in diagnosis and therapeutic planning.