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R. Dobson et al.
investigate RHOA and other lymphoma-associated muta- tions in patients with advanced age and biopsies showing EBV-positive polymorphous infiltrates, to explore how such mutation analyses can help to circumvent this diag- nostic pitfall. At the genetic level, the high number of TET2 mutations and their frequent presence in non-neo- plastic T cells suggest that the patient most likely had an underlying CHIP with TET2 and DNMT3A mutations that occurred in hematopoietic stem cells, consequently extending to the progenies of these cells.
In general, patients with AITL typically have an aggres- sive clinical course and respond poorly to currently avail- able therapies. Case 7 appeared to be an exception to this rule, showing slow disease progression in the absence of any treatment, although it is not possible to rule out a response to the R-GCVP (rituximab, gemcitabine, cyclophosphamide, vincristine, prednisolone) that was aimed at treating the EBV-associated proliferations (Table 1). An indolent clinical course has been previously report- ed for some patients with AITL showing pattern-1 histol- ogy, including those treated only with steroids.22,32 It remains to be investigated how to identify such indolent cases at the time of diagnosis and stratify their clinical management accordingly, particularly in view of the advance in early detection of AITL.
In summary, we have shown that RHOA mutation is specifically associated with AITL, PTCL-TFH and their related lesions, and investigation of the mutation is highly valuable in early detection of these T-cell lymphomas and their extranodal involvement.
Disclosures
No conflicts of interest to disclose.
Contributions
RD, PD, WQ, and CC designed the experiments and collected and analyzed data; WQ and ZC performed the Illumina sequencing analysis and variant calling; LRB, HED, LF, ES, PW, JWG, MRJ, GAF, HR, AW, ADA, HL, MF, EJB, and GV contributed cases and pathology review; MQD and RD wrote and prepared the manuscript; MQD was responsible for research funding, study design and coordination. All authors commented on the manuscript and approved its submission for publication.
Acknowledgments
The authors thank Shubha Anand and Yuanxue Huang for their assistance with using TapeStation, Graeme Clark and Ezequiel Martin for their assistance with Illumina sequencing and Fangtian Wu for carrying out DNA extraction on a control case.
Funding
The research in MQD's laboratory was supported by grants from Blood Cancer UK (13006, 15019), CRUK (C8333/A29707), and the Kay Kendall Leukaemia Fund (KKL582) UK. WY was supported by a research fellowship from the China Scholarship Council, and an International Collaborative Award from the Pathological Society of Great Britain and Ireland, UK. The Human Research Tissue Bank is supported by the NIHR Cambridge Biomedical Research Centre.
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