Page 147 - 2022_02-Haematologica-web

Non-Hodgkin Lymphoma
Early detection of T-cell lymphoma with T follicular helper phenotype by RHOA mutation analysis
Rachel Dobson,1 Peter Y. Du,1 Lívia Rásó-Barnett,2 Wen-Qing Yao,1 Zi Chen,1 Calogero Casa,2 Hesham EI-Daly,2 Lorant Farkas,2,3 Elizabeth Soilleux,1,4 Penny Wright,4 John W. Grant,4 Manuel Rodriguez-Justo,5 George A. Follows,6 Hala Rashed,7 Margarete Fabre,6,8 E. Joanna Baxter,6 George Vassiliou,6,8 Andrew Wotherspoon,9 Ayoma D. Attygalle,9 Hongxiang Liu2
and Ming-Qing Du1,4
1Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge, UK; 2The Haematopathology and Oncology Diagnostic Service, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; 3Department of Pathology, Akershus University Hospital, Lorenskog, Norway; 4Department of Histopathology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; 5Department of Pathology, Royal Free and University College Medical School, London, UK; 6Department of Haematology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; 7Department of Cellular Pathology, University Hospitals of Leicester, East Midlands Pathology Services, Leicester, UK; 8Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK and 9Histopathology Department, The Royal Marsden Hospital, London, UK
ABSTRACT
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 spe- cific 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 muta- tion 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 fre- quency 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 com- bined histological, immunophenotypic and clonality analyses. The muta- tion 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.
Introduction
Angioimmunoblastic T-cell lymphoma (AITL), peripheral T-cell lymphoma with T follicular helper phenotype (PTCL-TFH) and follicular T-cell lymphoma are a group of complex clinicopathological entities that originate from T follicular helper (TFH) cells. These lymphomas are the most common among various T-cell malig- nancies in Western countries. Patients with these lymphomas commonly show an aggressive clinical course, with a median 3-year survival rate of only 30%
Ferrata Storti Foundation
Haematologica 2022 Volume 107(2):489-499
Correspondence:
MING-QING DU
mqd20@cam.ac.uk
Received: July 9, 2020.
Accepted: January 22, 2021. Pre-published: February 11, 2021.
https://doi.org/10.3324/haematol.2020.265991 ©2022 Ferrata Storti Foundation
Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or inter- nal use. Sharing published material for non-commercial pur- poses is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for com- mercial purposes is not allowed without permission in writing from the publisher.
haematologica | 2022; 107(2)
489
ARTICLE