Genetic abnormalities assist in pathological diagnosis and EBV-positive cell density impact survival in Chinese angioimmunoblastic T-cell lymphoma patients.

Objective: To explore the application of genetic abnormalities in the diagnosis of angioimmunoblastic T-cell lymphoma (AITL) and the reliable pathological prognostic factors.

Methods: This study included 53 AITL cases, which were reviewed for morphological patterns, immunophenotypes, presence of Hodgkin and Reed-Sternberg (HRS)-like cells, and co-occurrence of B cell proliferation. The Epstein-Barr virus (EBV)-positive cells in tissues were counted, and cases were classified into "EBV encoded RNA (EBER) high-density" group if >50/HPF. Targeted exome sequencing was performed.

Results: Mutation data can assist AITL diagnosis: 1) with considerable HRS-like cells (20 cases): mutated in 14 cases ( co-mutated in 3 cases, 4 cases with rare mutation), was mutated in 5 cases (1 case co-mutated with ), and mutated in 1 case; 2) accompanied with B cell lymphoma (7 cases): mutated in 4 cases (1 case had mutation), mutated in 2 cases and mutated in 1 case; 3) mimic peripheral T cell lymphoma, not otherwise specified (5 cases): mutated in 2 cases ( co-mutated in 1 case), mutated in 3 cases, and mutated in 1 case; 4) pattern 1 (1 case), and co-mutated. Besides (30/35), rare variant included , , , and , co-mutated with in one case. There were recurrent mutations of , and and genes of epigenetic remodeling, T-cell activation, APC and PI3K/AKT pathway. EBER high-density independently indicated adverse overall survival and progression-free survival (P=0.046 and P=0.008, Kaplan-Meier/log-rank).

Conclusions: Over half AITL cases might be confused in diagnosis for certain conditions without mutation data. Targeted exome sequencing with a comprehensive panel is crucial to detect both hot-spot and rare mutation variants for and and other recurrent mutated genes in addition to and . EBER high-density independently indicated adverse survival.