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Highlights • Sertoli-Leydig cell tumor and gynandroblastoma are rare ovarian sex cord-stromal tumors that warrant germline DICER1 testing. • DICER1 mutations are associated with an increased risk of various benign and malignant tumors especially during childhood. • Childhood genetic testing is controversial but provides earlier screening and diagnosis in DICER1 mutation patients., Sex cord-stromal tumors (SCSTs) are ovarian tumors that generally present with an adnexal mass and signs/symptoms of hormone excess. Gynandroblastoma is a rare subtype of SCST with a combination of female and male sex cord differentiation. These tumors typically present in premenopausal women and are diagnosed at early stages with benign clinical courses. Here, we present a rare case of recurrent gynandroblastoma in a premenopausal woman with a DICER1 germline mutation. The patient was referred to our clinic for new symptoms of hormonal imbalance with a history of ovarian juvenile granulosa cell tumor (JGCT). Evaluation revealed a 5x5cm complex right adnexal mass and rising inhibin B. Patient underwent total abdominal hysterectomy with right salpingo-oophorectomy, omentectomy and right pelvic and para-aortic lymphadenectomy. Pathology showed a right ovarian gynandroblastoma. Somatic biallelic mutations in the RNase IIIb domain of DICER1 were identified; a 23-gene germline panel confirmed a germline DICER1 pathogenic variant. Cascade testing of her children documented that both daughters inherited the pathogenic variant. Testing for DICER1 mutations has important implications for individual and familial tumor risk assessment given what we know about DICER1 mutation and increased childhood cancer risk.

The endometrium plays host to a variety of alterations in epithelial differentiation, and all of these alterations display a morphologic spectrum from benign changes to those that are malignant. The best way to conceptualize metaplasias is to consider them as alterations of differentiation and visualize them as running parallel to benign processes, endometrial precancers, and cancer. This chapter will focus on a practical approach to the management of such alterations, specifically those changes that merit the most concern.

This chapter addresses new concepts in the prevention, pathogenesis, diagnosis, and management of endometrial epithelial neoplasia. Superimposed on the traditional two disease system (endometrioid and serous carcinomas) is newly discovered molecular subgroups of tumors that correlate with both improved (POLE mutations) and poor (high copy number variation [CNV]) outcomes. Prevention now focuses on more extensive screening for mismatch repair defects by immunohistochemistry to identify a small percentage of patients with a familial predisposition (Lynch syndrome). In practice, the most common classification issues are (1) the identification of subsets of endometrioid carcinomas that are at higher risk for an adverse outcome, including excluding serous carcinoma and (2) distinguishing clear cell carcinoma from clear cell change. Management issues center on determining the depth of invasion, separating real from artifactual vascular space invasion, interpreting nodal micrometastases, and distinguishing metastatic disease from new primary tumors. Ultimately, the role of radiation merits more scrutiny when balancing quality of life with recurrence risk if survival will not be altered. Chemotherapy beyond hormonal therapy remains an ongoing challenge.