Parallel evolution of two distinct lymphoid proliferations in clonal haematopoiesis

Autor:	Ayoma D Attygalle, Rachel Dobson, Pui Kwan Chak, Katherine M Vroobel, Dorte Wren, Hood Mugalaasi, Yvonne Morgan, Manmit Kaur, Raida Ahmad, Zi Chen, Kikkeri N Naresh, Ming‐Qing Du
Přispěvatelé:	Attygalle, Ayoma D [0000-0001-5034-8150], Naresh, Kikkeri N [0000-0003-3807-3638], Du, Ming-Qing [0000-0002-1017-5045], Apollo - University of Cambridge Repository
Rok vydání:	2022
Předmět:	Male Proto-Oncogene Proteins B-raf Histology T Follicular Helper Cells CD8 Antigens General Medicine clonal haematopoiesis Lymphoma T-Cell Pathology and Forensic Medicine angioimmunoblastic T-cell lymphoma DNA Methyltransferase 3A Dioxygenases DNA-Binding Proteins Diagnosis Differential secondary lymphoid neoplasm Immunoblastic Lymphadenopathy Mutation Humans TET2 and DNMT3A mutation Female Clonal Hematopoiesis rhoA GTP-Binding Protein Aged Cell Proliferation T-Lymphocytes Cytotoxic
Zdroj:	Histopathology. 80(5)
ISSN:	1365-2559
Popis:	AIMS: Angioimmunoblastic T-cell lymphoma (AITL) is genetically characterized by TET2 and DNMT3A mutations occurring in haematopoietic progenitor cells, and late events (e.g. the RHOA-G17V mutation) associated with malignant transformation. As TET2/DNMT3A-mutated progenitor cells can differentiate into multilineage progenies and give rise to both AITL and myeloid neoplasms, they may also have the potential to lead to other metachronous/synchronous neoplasms. We report two cases showing parallel evolution of two distinct potentially neoplastic lymphoid proliferations from a common mutated haematopoietic progenitor cell population. METHODS AND RESULTS: Both cases presented with generalized lymphadenopathy. In case 1 (a 67-year-old female), an initial lymph node (LN) biopsy was dismissed as reactive, but a repeat biopsy showed a nodal marginal zone lymphoma (NMZL)-like proliferation with an increase in the number of T-follicular helper (TFH) cells. Immunohistochemistry, and clonality and mutational analyses by targeted sequencing of both whole tissue sections and microdissected NMZL-like lesions, demonstrated a clonal B-cell proliferation that harboured the BRAF-G469R mutation and shared TET2 and DNMT3A mutations with an underlying RHOA-G17V-mutant TFH proliferation. Review of the original LN biopsy showed histological and immunophenotypic features of AITL. In case 2 (a 66-year-old male), cytotoxic T-cell lymphoma with an increase in the number of Epstein-Barr virus-positive large B cells was diagnosed on initial biopsy. On review together with the relapsed biopsy, we identified an additional occult neoplastic TFH proliferation/smouldering AITL. Both T-cell proliferations shared TET2 and DNMT3A mutations while RHOA-G17V was confined to the smouldering AITL. CONCLUSIONS: In addition to demonstrating diagnostic challenges, these cases expand the potential of clonal haematopoiesis in the development of different lineage neoplastic proliferations.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1134f39efcb52ec91c75a22dbc30d940 https://pubmed.ncbi.nlm.nih.gov/35064935 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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