Track
Clinical StudiesAbstract
Cutaneous CD30-positive lymphoproliferative disorders (LPD) may harbor t(5;19)(q35;p13), leading to NPM1::TYK2 fusion and activated JAK/STAT signaling. Cutaneous T-cell lymphomas (CTCL)/LPD with variant TYK2 fusion-partners are not characterized. We recently observed TYK2 fusions with variant partners in CD30-low/negative CTCL and hypothesized that these are distinct from CD30+ NPM1::TYK2-driven CTCL/LPD. With IRB approval, we retrospectively reviewed 6 CTCL/LPDs with TYK2-variant partner gene fusions. Pathology reports, flow cytometric (FC) plots, and tissue images/slides were assessed, and data descriptively analyzed. 6/6 cases showed small-medium-sized lymphocytes with irregular nuclear contours at the dermo-epidermal junction. Immunophenotype was CD3+ (5/6), CD4-/CD8+ (2/6), CD4-/CD8- (4/6), TCRαβ+ (2/6), TCRγδ+ (3/6), TCR-silent (1/6), CD30 <5% (5/6). In 2/4 FC-assessed cases, neoplastic cells comprised 23% and 21% T cells (17% and 19% WBC). Clones were CD4-/CD8-/CD5-/CD7-/CD26+bright/δγTCR- and CD4-/CD8+/CD5-/CD7-/CD26+bright/δγTCR-. One of these exhibited a second intraepidermal δγTCR+ population per immunohistochemistry correlating with TYK2 fluorescence in situ hybridization (FISH) signal. Similarly, FC detailed clonal-favored-non-neoplastic CD3+/CD4-/CD8-/CD5dim/CD7dim lymphocytes in a 3rd case also with intraepidermal δγTCR+ lymphocytes correlated to positive TYK-FISH. Non-neoplastic cells by FC included <1% B cells and γδT cells, 20% NK-cells (2-53%), and 80% non-neoplastic/non-clonal T cells (62-99%); CD4:CD8 ratios ranged from 1-12:1; 28% average CD7-/CD4+ cells.TYK2-variant CTCL/LPDs appear characterized by atypical, junctionally-localized CD4-negative innate immune-cell phenotypes, with minimal CD30-positivity, occasional dual-clonality, and distinct non-neoplastic infiltrates with aberrant antigen expression. TYK2 mediation, mixed-cell composition, and variable T-cell receptor expression appear similar to NPM1::TYK2-related CD30+ LPDs. However, small-cell predominance, epidermal localization and minimal CD30 suggest a distinct disease expression demanding further study.
