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DICER1 -Associated Gynecologic Neoplasms: An Update and Review
Hyun-Soo Kim1,2, Esther Oliva1, Gulisa Turashvili1
1Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Abstract:
DICER1 plays a crucial role in the biogenesis and maturation of microRNAs. Germline mutations in the DICER1 gene are associated with an increased risk of developing a wide range of benign and malignant neoplasms. The same tumors may also arise sporadically due to somatic DICER1 mutations. In syndromic patients, a germline loss-of-function DICER1 mutation is usually followed by a somatic hotspot mutation in the tumor as a second hit. In the gynecologic tract, DICER1 -associated neoplasms include most commonly embryonal rhabdomyosarcoma and moderately to poorly differentiated Sertoli-Leydig cell tumor, and less frequently pleuropulmonary blastoma-like peritoneal sarcoma, adenosarcoma, gynandroblastoma, juvenile granulosa cell tumor, and Sertoli cell tumor. Irrespective of the primary site of origin, DICER1 -associated neoplasms frequently share characteristic morphology, including primitive mesenchyme, fetal-type epithelium, fetal-type cartilage, rhabdomyoblastic and/or neuroectodermal differentiation, osteoid formation, and anaplasia. Recognition of these distinctive features in gynecologic tumors should prompt consideration of a DICER1 -associated neoplasm followed by genetic testing, thereby facilitating surveillance for patients and their families. As illustrated in this review, the morphologic spectrum of most DICER1 -mutant gynecologic neoplasms (eg, DICER1 -related Wilms-like uterine tumor) appears to be wider than that of any known type of sarcoma. Therefore, we propose that the term " DICER1 -related primitive polyphenotypic neoplasm" may be more inclusive of the diverse histologic features and thus more appropriate for these unique neoplasms.
Insights
Germline and somatic DICER1 gene mutations increase cancer risk. DICER1-associated gynecologic neoplasms exhibit diverse morphology, suggesting a new classification: DICER1-related primitive polyphenotypic neoplasm.
Area of Science:
- Genetics
- Oncology
- Pathology
Background:
- The DICER1 gene is vital for microRNA biogenesis and maturation.
- Germline and somatic DICER1 mutations are linked to various benign and malignant neoplasms.
- Syndromic cases often involve a germline DICER1 mutation followed by a somatic second hit.
Purpose of the Study:
- To review DICER1-associated neoplasms in the gynecologic tract.
- To highlight the shared and diverse morphology of these tumors.
- To propose a more inclusive classification for these neoplasms.
Main Methods:
- Literature review of DICER1-associated gynecologic neoplasms.
- Analysis of morphologic features across different tumor types.
- Evaluation of current and proposed nomenclature.
Main Results:
- Common gynecologic tumors associated with DICER1 mutations include embryonal rhabdomyosarcoma and Sertoli-Leydig cell tumors.
- Less frequent tumors include peritoneal sarcoma, adenosarcoma, gynandroblastoma, and others.
- DICER1-mutant neoplasms share distinctive features like primitive mesenchyme, fetal-type tissues, and various differentiations.
Conclusions:
- Recognition of specific morphologic features in gynecologic tumors warrants consideration of DICER1 association and genetic testing.
- The broad morphologic spectrum of DICER1-mutant gynecologic neoplasms supports a broader classification.
- The term "DICER1-related primitive polyphenotypic neoplasm" is proposed as a more inclusive and appropriate designation.
