PMID- 37988282 OWN - NLM STAT- MEDLINE DCOM- 20240115 LR - 20240115 IS - 1365-2559 (Electronic) IS - 0309-0167 (Linking) VI - 84 IP - 3 DP - 2024 Feb TI - Pan-TRK immunohistochemistry in gynaecological mesenchymal tumours: diagnostic implications and pitfalls. PG - 451-462 LID - 10.1111/his.15082 [doi] AB - AIMS: NTRK-rearranged sarcomas of the female genital tract mainly occur in the uterus (more commonly cervix than corpus) and are characterized by a "fibrosarcoma-like" morphology and NTRK gene rearrangements. These neoplasms may exhibit histological overlap with other entities and can present diagnostic difficulties without molecular confirmation. Pan-TRK immunohistochemistry was developed to identify tumours harbouring NTRK rearrangements. The aim of this study was to characterize pan-TRK immunohistochemical expression in a large cohort of gynaecological mesenchymal neoplasms and investigate the utility of pan-TRK immunohistochemistry to distinguish NTRK-rearranged sarcoma from its mimics. METHODS AND RESULTS: A total of 473 gynaecological mesenchymal tumours (461 without known NTRK fusions and 12 NTRK-rearranged sarcomas) were selected. Pan-TRK immunohistochemistry (EPR17341, Abcam) was performed on whole tissue sections and tissue microarrays. Molecular interrogation of pan-TRK positive tumours was performed by RNA sequencing or fluorescence in situ hybridization (FISH). Of the 12 NTRK-rearranged sarcomas, 11 (92%) exhibited diffuse (>/=70%) cytoplasmic pan-TRK staining with moderate/marked intensity, while the other was negative. Eleven (2.4%) additional tumours also exhibited pan-TRK immunohistochemical expression: three low-grade endometrial stromal sarcomas, seven high-grade endometrial stromal sarcomas, and an undifferentiated uterine sarcoma. Molecular confirmation of the absence of NTRK rearrangements was possible in nine of these tumours. Of these nine neoplasms, seven exhibited focal/multifocal (<70%) pan-TRK cytoplasmic staining with weak/moderate intensity. CONCLUSION: Even though pan-TRK immunohistochemical expression is not entirely sensitive or specific for NTRK-rearranged sarcomas, these neoplasms tend to exhibit diffuse staining of moderate/strong intensity, unlike its mimics. Pan-TRK should be performed in monomorphic uterine (corpus and cervix) spindle cell neoplasms that are negative for smooth muscle markers and hormone receptors and positive for CD34 and/ or S100. Ultimately, the diagnosis requires molecular confirmation. CI - (c) 2023 John Wiley & Sons Ltd. FAU - Moura, Madalena Souto AU - Moura MS AD - Department of Pathology, Portuguese Institute of Oncology-Porto, Porto, Portugal. FAU - Costa, Joao AU - Costa J AUID- ORCID: 0000-0002-9506-9662 AD - Department of Pathology, Portuguese Institute of Oncology-Porto, Porto, Portugal. FAU - Velasco, Valerie AU - Velasco V AD - Department of Biopathology, Institut Bergonie, Comprehensive Cancer Centre, Bordeaux, France. FAU - Kommoss, Felix AU - Kommoss F AD - Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany. FAU - Oliva, Esther AU - Oliva E AD - Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. FAU - Le Loarer, Francois AU - Le Loarer F AUID- ORCID: 0000-0001-8582-9819 AD - Department of Biopathology, Institut Bergonie, Comprehensive Cancer Centre, Bordeaux, France. AD - Inserm U1312, Universite de Bordeaux, Bordeaux, France. AD - Universite de Bordeaux, Talence, France. FAU - McCluggage, W Glenn AU - McCluggage WG AUID- ORCID: 0000-0001-9178-4370 AD - Department of Pathology, Belfast Health and Social Care Trust, Belfast, UK. FAU - Razack, Rubina AU - Razack R AD - Division of Anatomical Pathology, National Health Laboratory Service, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg Academic Hospital, Cape Town, South Africa. FAU - Treilleux, Isabelle AU - Treilleux I AD - Department of Pathology, Centre Leon Berard, Lyon, France. FAU - Mills, Anne AU - Mills A AD - Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA, USA. FAU - Longacre, Teri AU - Longacre T AD - Department of Surgical Pathology, Stanford University School of Medicine, Stanford, CA, USA. FAU - Devouassoux-Shisheboran, Mojgan AU - Devouassoux-Shisheboran M AUID- ORCID: 0000-0003-3296-0957 AD - Department of Pathology, CHU Lyon Sud, Pierrebenite, France. FAU - Hostein, Isabelle AU - Hostein I AD - Department of Biopathology, Institut Bergonie, Comprehensive Cancer Centre, Bordeaux, France. FAU - Azmani, Rihab AU - Azmani R AD - Bioinformatics, Data and Digital Health Department, Institut Bergonie, Comprehensive Cancer Centre, Bordeaux, France. FAU - Blanchard, Larry AU - Blanchard L AD - Department of Biopathology, Institut Bergonie, Comprehensive Cancer Centre, Bordeaux, France. FAU - Hartog, Cecile AU - Hartog C AD - Department of Biopathology, Institut Bergonie, Comprehensive Cancer Centre, Bordeaux, France. FAU - Soubeyran, Isabelle AU - Soubeyran I AD - Department of Biopathology, Institut Bergonie, Comprehensive Cancer Centre, Bordeaux, France. FAU - Khalifa, Emmanuel AU - Khalifa E AD - Department of Biopathology, Institut Bergonie, Comprehensive Cancer Centre, Bordeaux, France. FAU - Croce, Sabrina AU - Croce S AUID- ORCID: 0000-0002-6487-5418 AD - Department of Biopathology, Institut Bergonie, Comprehensive Cancer Centre, Bordeaux, France. AD - Inserm U1312, Universite de Bordeaux, Bordeaux, France. LA - eng PT - Journal Article DEP - 20231121 PL - England TA - Histopathology JT - Histopathology JID - 7704136 RN - 0 (Biomarkers, Tumor) RN - 0 (Oncogene Proteins, Fusion) RN - EC 2.7.10.1 (Receptor, trkA) SB - IM MH - Female MH - Humans MH - Biomarkers, Tumor/genetics MH - *Endometrial Neoplasms MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - *Neoplasms, Connective and Soft Tissue MH - Oncogene Proteins, Fusion/genetics MH - *Sarcoma/diagnosis/genetics/pathology MH - *Sarcoma, Endometrial Stromal MH - *Soft Tissue Neoplasms MH - Receptor, trkA OTO - NOTNLM OT - NTRK OT - fibrosarcoma OT - immunohistochemistry OT - pan-TRK OT - sarcoma OT - uterine neoplasm EDAT- 2023/11/21 18:43 MHDA- 2024/01/10 06:42 CRDT- 2023/11/21 12:52 PHST- 2023/09/22 00:00 [revised] PHST- 2023/06/30 00:00 [received] PHST- 2023/10/14 00:00 [accepted] PHST- 2024/01/10 06:42 [medline] PHST- 2023/11/21 18:43 [pubmed] PHST- 2023/11/21 12:52 [entrez] AID - 10.1111/his.15082 [doi] PST - ppublish SO - Histopathology. 2024 Feb;84(3):451-462. doi: 10.1111/his.15082. Epub 2023 Nov 21.