Abstract PO-34: Subcutaneous panniculitis-like T-cell lymphoma with HAVCR2 mutation shows unique clinicopathologic features and gene expression profile

Recent studies identified germline HAVCR2 (TIM-3) mutations as the specific genetic predisposition to subcutaneous panniculitis-like T-cell lymphoma (SPTCL). However, distinction between HAVCR2-mutated and HAVCR2-wildtype SPTCLs remains elusive. We studied the prevalence of HAVCR2 mutation in a nation-wide cohort of SPTCL and investigated clinical and molecular distinction between HAVCR2-mutated and HAVCR2-wild-type SPTCLs. A multicenter nationwide cohort of 53 SPTCL cases was established; patients were diagnosed at seven Korean institutions between 2003 and 2020. Histologic features were reviewed by experienced hematopathologists and clinical features were retrospectively reviewed. Whole-exome sequencing (WES) and RNA-seq were performed using formalin-fixed, paraffin-embedded (FFPE) samples of 8 patients diagnosed in Seoul National University Hospital (SNUH), with matched non-neoplastic tissue samples from two patients. Direct sequencing of HAVCR2 exon 2 was successfully carried out using FFPE samples from 33 of the remaining 45 patients. Among 41 patients with available HAVCR2 mutation status, 28 (68.3%) were women, and the median age at diagnosis was 30 years (range 11–74). Ten patients (10/40; 25.0%) suffered hemophagocytic syndrome (HPS) or HPS-like systemic illness during the clinical course, and 14 patients (14/40; 35.0%) progressed during the follow-up. Six patients (6/41; 14.6%) died of disease progression or HPS. We found 18 patients (18/41; 43.9%) with HAVCR2 mutation; 15 patients harbored biallelic HAVCR2 Y82C mutation and 3 patients were noted for heterozygous HAVCR2 Y82C mutation. HAVCR2-mutated SPTCLs occurred in younger patients (median age 26.5 versus 37; Mann-Whitney p-value = 0.003), and were more often complicated by HPS or HPS-like systemic illness (10/18 versus 0/22; Fisher9s exact p-value Citation Format: Jiwon Koh, Insoon Jang, Seungchan Mun, Cheol Lee, Hee-Jung Cha, Young Ha Oh, Jin Man Kim, Young Hyeh Ko, Jae Ho Han, Heounjeong Go, Jooryung Huh, Kwangsoo Kim, Yoon Kyung Jeon. Subcutaneous panniculitis-like T-cell lymphoma with HAVCR2 mutation shows unique clinicopathologic features and gene expression profile [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-34.