Uterine and vaginal sarcomas resembling fibrosarcoma: a clinicopathological and molecular analysis of 13 cases showing common NTRK-rearrangements and the description ... View Full Text


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Article Info

DATE

2019-03-16

AUTHORS

Sabrina Croce, Isabelle Hostein, Teri A. Longacre, Anne M. Mills, Gaëlle Pérot, Mojgan Devouassoux-Shisheboran, Valérie Velasco, Anne Floquet, Frédéric Guyon, Camille Chakiba, Denis Querleu, Emmanuel Khalifa, Laetitia Mayeur, Flora Rebier, Sophie Leguellec, Isabelle Soubeyran, W. Glenn McCluggage

ABSTRACT

Mesenchymal neoplasms of the uterus (corpus and cervix) encompass a heterogeneous group of tumors with differing morphologies, immunophenotypes and molecular alterations. With the advent of modern molecular techniques, such as next generation sequencing, newly defined genetic abnormalities are being reported in this group of neoplasms. Herein we report the clinicopathological and molecular features of a series of 13 spindle cell sarcomas of the uterus and vagina (10 cervix, 2 uterine corpus, 1 vagina) with morphology resembling fibrosarcoma. After targeted RNA-sequencing, dual FISH fusion and array-CGH analysis, 7 of 13 tumors exhibited NTRK rearrangements (6 TPM3-NTRK1 and 1 EML4-NTRK3) and 3 a COL1A1-PDGFB fusion; in the other 3 neoplasms, all of which were positive with S100 (2 diffuse, 1 focal), we identified no rearrangement. All the NTRK fusion-positive sarcomas were located in the cervix and exhibited diffuse staining with Trk while all the other neoplasms were negative. CD34 was diffusely positive in all 3 of the COL1A1-PDGFB fusion sarcomas. The latter molecular abnormality is identical to that commonly found in dermatofibrosarcoma protuberans and has not been reported previously in uterine mesenchymal neoplasms. We suggest that uterine sarcomas with a morphology resembling fibrosarcoma (and in which leiomyosarcoma and the known molecularly confirmed high-grade endometrial stromal sarcomas have been excluded) can be divided into 3 groups:- an NTRK fusion group, a COL1A1-PDGFB fusion group and a group containing neither of these molecular abnormalities which, on the basis of positive staining with S100, could be tentatively classified as malignant peripheral nerve sheath tumor, although additional molecular studies may identify specific genetic alterations necessitating a nomenclature change. We suggest a diagnostic algorithm when reporting such neoplasms. Identification of these newly described fusion-associated sarcomas is important given the potential for targeted treatments. More... »

PAGES

1-15

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  • Identifiers

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    http://scigraph.springernature.com/pub.10.1038/s41379-018-0184-6

    DOI

    http://dx.doi.org/10.1038/s41379-018-0184-6

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1110837745

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30877273


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