Joseph T Rabban1, W Patrick Devine1, Ankur R Sangoi2, Liina Poder3, Edwin Alvarez4, Jessica L Davis5, Erin Rudzinski6, Karuna Garg1, Gregory R Bean1. 1. Pathology Department, University of California, San Francisco, CA, USA. 2. Pathology Department, El Camino Hospital, Mountain View, CA, USA. 3. Radiology Department, University of California, San Francisco, CA, USA. 4. Gynecologic Oncology Division, University of California, San Francisco, CA, USA. 5. Pathology Department, Oregon Health & Science University, Portland, OR, USA. 6. Pathology Department, Seattle Children's Hospital, Seattle, WA, USA.
Abstract
AIMS: A unique fibrosarcoma-like tumour of the uterine cervix harbouring a rearrangement of a neurotrophic tyrosine kinase receptor (NTRK) gene (NTRK1 or NTRK3) has recently been described in 11 young women, some with recurrence and/or metastasis. The aims of this study were to expand the morphological spectrum of this tumour by reporting three additional cases that showed adenosarcoma-like features not previously described, one of which is the first reported to respond to targeted therapy, and to evaluate 19 conventional uterine adenosarcomas for evidence of NTRK rearrangement. METHODS AND RESULTS: Three patients presented with a polyp or mass confined to the cervix. The constellation of polypoid growth, spindle cell morphology, entrapped endocervical glands and intraglandular stromal projections raised diagnostic consideration for adenosarcoma with stromal overgrowth. Deep cervical wall invasion was present in two cases at hysterectomy, and the third was removed by polypectomy. All three stained for S100 and pan-Trk, but were negative for a spectrum of other diagnostic markers. All three harboured NTRK rearrangements (TPM3-NTRK1, TPR-NTRK1, and SPECC1L-NTRK3). One patient developed pleural metastases at 16 months, received the NTRK inhibitor larotrectinib, and is free of disease 15 months later. Two others are alive without disease. None of the uterine adenosarcomas showed any S100 or pan-Trk staining, or rearrangement of NTRK1, NTRK2 or NTRK3 on next-generation sequencing. CONCLUSIONS: Unusual adenosarcoma-like spindle cell neoplasms of the cervix may represent an NTRK fusion sarcoma, which can be detected by S100 and pan-Trk staining and confirmed by NTRK molecular testing. Conventional uterine adenosarcomas do not harbour NTRK rearrangements.
AIMS: A unique fibrosarcoma-like tumour of the uterine cervix harbouring a rearrangement of a neurotrophic tyrosine kinase receptor (NTRK) gene (NTRK1 or NTRK3) has recently been described in 11 young women, some with recurrence and/or metastasis. The aims of this study were to expand the morphological spectrum of this tumour by reporting three additional cases that showed adenosarcoma-like features not previously described, one of which is the first reported to respond to targeted therapy, and to evaluate 19 conventional uterine adenosarcomas for evidence of NTRK rearrangement. METHODS AND RESULTS: Three patients presented with a polyp or mass confined to the cervix. The constellation of polypoid growth, spindle cell morphology, entrapped endocervical glands and intraglandular stromal projections raised diagnostic consideration for adenosarcoma with stromal overgrowth. Deep cervical wall invasion was present in two cases at hysterectomy, and the third was removed by polypectomy. All three stained for S100 and pan-Trk, but were negative for a spectrum of other diagnostic markers. All three harboured NTRK rearrangements (TPM3-NTRK1, TPR-NTRK1, and SPECC1L-NTRK3). One patient developed pleural metastases at 16 months, received the NTRK inhibitor larotrectinib, and is free of disease 15 months later. Two others are alive without disease. None of the uterine adenosarcomas showed any S100 or pan-Trk staining, or rearrangement of NTRK1, NTRK2 or NTRK3 on next-generation sequencing. CONCLUSIONS: Unusual adenosarcoma-like spindle cell neoplasms of the cervix may represent an NTRK fusion sarcoma, which can be detected by S100 and pan-Trk staining and confirmed by NTRK molecular testing. Conventional uterine adenosarcomas do not harbour NTRK rearrangements.
Authors: Amir Momeni Boroujeni; Elizabeth Kertowidjojo; Xinyu Wu; Robert A Soslow; Sarah Chiang; Edaise M Da Silva; Britta Weigelt; M Herman Chui Journal: Mod Pathol Date: 2022-09-22 Impact factor: 8.209
Authors: Danielle C Costigan; Marisa R Nucci; Brendan C Dickson; Martin C Chang; Sharon Song; Lynette M Sholl; Jason L Hornick; Christopher D M Fletcher; David L Kolin Journal: Am J Surg Pathol Date: 2022-06-20 Impact factor: 6.298
Authors: Dong-Anh Khuong-Quang; Lauren M Brown; Marie Wong; Chelsea Mayoh; Alexandra Sexton-Oates; Amit Kumar; Mark Pinese; Sumanth Nagabushan; Loretta Lau; Louise E Ludlow; Andrew J Gifford; Michael Rodriguez; Jayesh Desai; Stephen B Fox; Michelle Haber; David S Ziegler; Jordan R Hansford; Glenn M Marshall; Mark J Cowley; Paul G Ekert Journal: Cold Spring Harb Mol Case Stud Date: 2020-12-17