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Mod Pathol. 2020 Jan 3. doi: 10.1038/s41379-019-0436-0. [Epub ahead of print]

Significantly greater prevalence of DICER1 alterations in uterine embryonal rhabdomyosarcoma compared to adenosarcoma.

Author information

1
Department of Human Genetics, McGill University, Montréal, QC, Canada.
2
Lady Davis Institute, Segal Cancer Centre, Jewish General Hospital, Montréal, QC, Canada.
3
Department of Laboratory Medicine and Pathobiology, University of Toronto, University Health Network, Toronto, ON, Canada.
4
Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
5
Department of Pathology, Belfast Health and Social Care Trust, Belfast, UK.
6
School for Women's and Infants' Health, University of Western Australia, Perth, WA, Australia.
7
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada.
8
Department of Pathology, Toronto General Hospital, Toronto, ON, Canada.
9
Department of Human Genetics, McGill University, Montréal, QC, Canada. william.foulkes@mcgill.ca.
10
Lady Davis Institute, Segal Cancer Centre, Jewish General Hospital, Montréal, QC, Canada. william.foulkes@mcgill.ca.
11
Research Institute of the McGill University Health Centre, Montréal, QC, Canada. william.foulkes@mcgill.ca.

Abstract

Embryonal rhabdomyosarcomas (ERMS) account for 2-3% of cancers in pediatric and adolescent populations. They are rarer in adults. We and others have reported that ERMS arising in the uterine cervix may harbor mutations in the gene encoding the microRNA biogenesis enzyme, DICER1, but a large series of cases has not been published. In the uterus, distinguishing ERMS from adenosarcoma can be very challenging, even for expert pathologists, and DICER1 alterations have been identified in a variable subset of uterine adenosarcomas. We hypothesized that DICER1 genetic testing may be useful in distinguishing between ERMS and adenosarcoma. We conducted a central pathology review-based study of 64 tumors initially thought to be uterine ERMS or adenosarcoma; 19 neoplasms had a consensus diagnosis of ERMS, 27 of adenosarcoma and for 18, no consensus diagnosis was reached. The median age at diagnosis was 30 years (range 2.5-69) for ERMS, 57.5 years (range 27-82) for adenosarcoma, and 65.5 years (range 32-86) for no consensus cases. In our series, the DICER1 mutation prevalence differed between the three groups: DICER1 alterations were present in 18/19 (95%) ERMS, 7/27 (26%) adenosarcomas (p < 0.001), and 4/18 (22%) no consensus cases. A germline alteration was present in 6/12 ERMS patients tested versus 0/6 adenosarcoma patients. Thus, although DICER1 mutations are near ubiquitous in uterine ERMS and are significantly less common in uterine adenosarcoma, DICER1 testing is only of value in distinguishing between the two neoplasms when a DICER1 mutation is absent, as this is helpful in excluding ERMS. On review of the clinical and radiological features of the single DICER1 wild-type cervical ERMS, this was thought most likely to be of vaginal origin. Given the significant prevalence of DICER1 germline pathogenic variants in uterine ERMS, all patients with this diagnosis should be referred to a genetics service.

PMID:
31900434
DOI:
10.1038/s41379-019-0436-0

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