TY - JOUR AU - Dobson, Rachel AU - Du, Peter Y. AU - Rásó-Barnett, Lívia AU - Yao, Wen-Qing AU - Chen, Zi AU - Casa, Calogero AU - EI-Daly, Hesham AU - Farkas, Lorant AU - Soilleux, Elizabeth AU - Wright, Penny AU - Grant, John W. AU - Rodriguez-Justo, Manuel AU - Follows, George A. AU - Rashed, Hala AU - Fabre, Margarete AU - Baxter, E. Joanna AU - Vassiliou, George AU - Wotherspoon, Andrew AU - Attygalle, Ayoma D. AU - Liu, Hongxiang AU - Du, Ming-Qing PY - 2022/02/01 Y2 - 2024/03/29 TI - Early detection of T-cell lymphoma with T follicular helper phenotype by RHOA mutation analysis JF - Haematologica JA - haematol VL - 107 IS - 2 SE - Articles DO - 10.3324/haematol.2020.265991 UR - https://haematologica.org/article/view/haematol.2020.265991 SP - 489-499 AB - Angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma with T follicular helper phenotype (PTCL-TFH) are a group of complex clinicopathological entities that originate from T follicular helper cells and share a similar mutation profile. Their diagnosis is often a challenge, particularly at an early stage, because of a lack of specific histological and immunophenotypic features, paucity of neoplastic T cells and prominent polymorphous infiltrate. We investigated whether the lymphoma-associated RHOA Gly17Val (c.50G>T) mutation, occurring in 60% of cases, is present in the early “reactive” lesions, and whether mutation analysis could help to advance the early diagnosis of lymphoma. The RHOA mutation was detected by quantitative polymerase chain reaction with a locked nucleic acid probe specific to the mutation, and a further peptide nucleic acid clamp oligonucleotide to suppress the amplification of the wild-type allele. The quantitative polymerase chain reaction assay was highly sensitive and specific, detecting RHOA Gly17Val at an allele frequency of 0.03%, but not other changes in Gly17, nor in 61 controls. Among the 37 cases of AITL and PTCL-TFH investigated, RHOA Gly17Val was detected in 62.2% (23/37) of which 19 had multiple biopsies including preceding biopsies in ten and follow-up biopsies in 11 cases. RHOA Gly17Val was present in each of these preceding or follow-up biopsies including 18 specimens that showed no evidence of lymphoma by combined histological, immunophenotypic and clonality analyses. The mutation was seen in biopsies 0-26.5 months (mean 7.87 months) prior to the lymphoma diagnosis. Our results show that RHOA Gly17Val mutation analysis is valuable in the early detection of AITL and PTCL-TFH. ER -