Genetic profiles and clinical features in subcutaneous panniculitis-like T-cell lymphomas

Abstract

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare peripheral T-cell lymphoma characterized by cutaneous lesions and immunologic manifestations. The five-year survival rate of SPTCL has been reported to be over 80%, indicating a favorable prognosis. Recent studies have uncovered recurrent germline variants in HAVCR2, encoding an immunomodulator. In this study, we integrated whole-exome sequencing data from 60 samples collected from 36 SPTCL patients, encompassing six patients of our cohort and 30 patients of publicly available data. We identified 138 somatic mutations in skin tumors of 24 patients and HAVCR2 germline mutations in 23 of 29 patients. HAVCR2 p.Tyr82Cys mutations were identified in four of six Japanese patients. During the clinical courses of four patients, cyclophosphamide, hydroxydaunomycin, vincristine, and prednisone were administered to all patients, but it resulted in incomplete responses in all four patients. However, disease conditions of all patients remained stable with additional treatment, including autologous peripheral blood stem cell transplantation. Over a 7.5-year median follow-up, one patient developed autoimmune-related diseases, while one developed other hematological malignancy, resulting in death. To our knowledge, this is the first report of recurrent HAVCR2 germline mutations in Japanese patients, suggesting the necessity for long-term follow-up.

Keywords: HAVCR2 mutation; germline mutation; hematology; lymphoma; subcutaneous panniculitis‐like T‐cell lymphoma.

FIGURE 1

Landscape of somatic mutations in subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL). Integrated results of current and previous study datasets. Each column represents an individual case, and each row represents a representative mutated gene. Tumor mutational burden (TMB) is shown at the top. The lower part of the figure shows clinicopathological data (HAVCR2 mutations, race, and nationality) for each sample.

FIGURE 2

Histopathological features in subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL). Pathological images of SPTCL patients; (A) SP1, (B) SP2, (C) SP3, (D) SP4, (E) SP5, and (F) SP6. All cases exhibited adipocytic rimming by CD8‐positive T cells. Scale bars, 20 μm.

FIGURE 3

Clinical courses of Japanese patients. The clinical course of the four patients. The day of diagnosis was denoted as day 0 for each patient. The numbers below each CHOP indicate the number of CHOP cycles. auto‐PBSCT, autologous peripheral blood stem cell transplantation; CHOP, cyclophosphamide, hydroxydaunomycin, vincristine, and prednisone; CR, complete response; CyA, cyclosporine A; EBV+ DLBCL, Epstein–Barr virus‐positive diffuse large B‐cell lymphoma; mESHAP, etoposide, carboplatin, methylprednisolone, and cytarabine; PD, progressive disease; PR, partial response; PSL, prednisolone.