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DICER1 -Associated Gynecologic Neoplasms: An Update and Review.

Hyun-Soo Kim^1,2, Esther Oliva¹, Gulisa Turashvili¹

¹Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.

Advances in Anatomic Pathology

|November 17, 2025

Summary

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.

Keywords:

DICER1 syndrome Sertoli cell tumor Sertoli-Leydig cell tumor adenosarcoma embryonal rhabdomyosarcoma germline mutation gynandroblastoma gynecologic tract juvenile granulosa cell tumor pleuropulmonary blastoma-like peritoneal sarcoma

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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.