Early detection of T-cell lymphoma with T follicular helper phenotype by RHOA mutation analysis
Rachel Dobson,
Peter Y. Du,
Lívia Rásó-Barnett,
Wen-Qing Yao,
Zi Chen,
Calogero Casa,
Hesham EI-Daly,
Lorant Farkas,
Elizabeth Soilleux,
Penny Wright,
John W. Grant,
Manuel Rodriguez-Justo,
George A. Follows,
Hala Rashed,
Margarete Fabre,
E. Joanna Baxter,
George Vassiliou,
Andrew Wotherspoon,
Ayoma D. Attygalle,
Hongxiang Liu,
Ming-Qing Du
Affiliations
Rachel Dobson
Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge
Peter Y. Du
Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge
Lívia Rásó-Barnett
The Haematopathology and Oncology Diagnostic Service, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge
Wen-Qing Yao
Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge
Zi Chen
Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge
Calogero Casa
The Haematopathology and Oncology Diagnostic Service, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge
Hesham EI-Daly
The Haematopathology and Oncology Diagnostic Service, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge
Lorant Farkas
The Haematopathology and Oncology Diagnostic Service, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; Department of Pathology, Akershus University Hospital, Lorenskog
Elizabeth Soilleux
Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge, UK; Department of Histopathology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge
Penny Wright
Department of Histopathology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge
John W. Grant
Department of Histopathology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge
Manuel Rodriguez-Justo
Department of Pathology, Royal Free and University College Medical School, London
George A. Follows
Department of Haematology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge
Hala Rashed
Department of Cellular Pathology, University Hospitals of Leicester, East Midlands Pathology Services, Leicester
Margarete Fabre
Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Department of Haematology, University of Cambridge, Cambridge
E. Joanna Baxter
Department of Haematology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge
George Vassiliou
Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Department of Haematology, University of Cambridge, Cambridge
Andrew Wotherspoon
Histopathology Department, The Royal Marsden Hospital, London
Ayoma D. Attygalle
Histopathology Department, The Royal Marsden Hospital, London
Hongxiang Liu
The Haematopathology and Oncology Diagnostic Service, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge
Ming-Qing Du
Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge, UK; Department of Histopathology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge
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.
