This is a case report of a 10-year-old with Ollier disease and an ovarian mass. Ollier disease, a rare disorder characterized by multiple enchondromas resulting in bone deformities, has been occasionally associated with ovarian juvenile granulosa cell tumor. This patient developed signs of precocious puberty and was found to have an ovarian tumor; however, pathology revealed a mixed sex-cord stromal tumor with components of juvenile granulosa and Sertoli-Leydig cell tumor. Tumor genomic testing revealed an IDH1 mutation. Mixed sex-cord stromal tumors of this type, also called \"gynandroblastomas,\" have been associated with DICER1 mutations and DICER1 tumor predisposition syndrome but never with Ollier disease. Our findings expand the known spectrum of syndromic associations with this tumor type, with implications for tumor screening.

Sertoli-Leydig cell tumors (SLCTs) are rare sex cord-stromal tumors, representing <0.5% of all ovarian tumors. We sought to describe prognostic factors, treatment and outcomes for individuals with ovarian SLCT.
Individuals with SLCT were enrolled in the International Pleuropulmonary Blastoma/DICER1 Registry and/or the International Ovarian and Testicular Stromal Tumor Registry. Medical records were systematically abstracted, and pathology was centrally reviewed when available.
In total, 191 participants with ovarian SLCT enrolled, with most (92%, 175/191) presenting with FIGO stage I disease. Germline DICER1 results were available for 156 patients; of these 58% had a pathogenic or likely pathogenic germline variant. Somatic (tumor) DICER1 testing showed RNase IIIb hotspot variants in 97% (88/91) of intermediately and poorly differentiated tumors. Adjuvant chemotherapy was administered in 40% (77/191) of cases, and among these, nearly all patients received platinum-based regimens (95%, 73/77), and 30% (23/77) received regimens that included an alkylating agent. Three-year recurrence-free survival for patients with stage IA tumors was 93.6% (95% CI: 88.2-99.3%) compared to 67.1% (95% CI: 55.2-81.6%) for all stage IC and 60.6% (95% CI: 40.3-91.0%) for stage II-IV (p < .001) tumors. Among patients with FIGO stage I tumors, those with mesenchymal heterologous elements treated with surgery alone were at higher risk for recurrence (HR: 74.18, 95% CI: 17.99-305.85).
Most individuals with SLCT fare well, though specific risk factors such as mesenchymal heterologous elements are associated with poor prognosis. We also highlight the role of DICER1 surveillance in early detection of SLCT, facilitating stage IA resection.

Mixed sex cord-stromal tumors, which consist of poorly differentiated Sertoli cells and Leydig cells and juvenile granulosa cell tumor tissue, are extremely rare. Most of these tumors are unilateral and stage I at the time of diagnosis; nonetheless, according to the available relevant English-language literature, these tumors maintain a malignant potential. We herein report a case involving a 15-year-old girl diagnosed with a mixed sex cord-stromal tumor (gynandroblastoma with juvenile granulosa cell tumor component). Left salpingo-oophorectomy was initially performed, and the diagnosis of a juvenile granulosa cell tumor was established. Right salpingo-oophorectomy was performed 1 year later, at which time the specimen showed a different growth pattern involving epithelioid cells and tubules, resembling a Sertoli-Leydig cell tumor. Immunohistochemical staining was performed and the specimen was compared with that obtained 1 year earlier. We concluded that the tumors were linked and most likely constituted a gynandroblastoma (mixed form of sex cord-stromal tumor). Although this is an extremely uncommon ovarian tumor, it should be considered when diverse tumor morphology is identified. Bilateral metachronous involvement of the ovaries is possible. The grade of the Sertoli-Leydig cell component may influence the prognosis of such a tumor.

This article focuses on the recent advances in ovarian sex cord-stromal tumors, predominantly in the setting of their molecular underpinnings. The integration of genetic information with morphologic and immunohistochemical findings in this rare subset of tumors is of clinical significance from refining the diagnostic and prognostic stratifications to genetic counseling.

This article focuses on the recent advances in ovarian sex cord-stromal tumors, predominantly in the setting of their molecular underpinnings. The integration of genetic information with morphologic and immunohistochemical findings in this rare subset of tumors is of clinical significance from refining the diagnostic and prognostic stratifications to genetic counseling.

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.

Ovarian gynandroblastoma (GAB) is an extremely rare sex cord-stromal tumor showing morphological evidence of both female (granulosa cell tumor) and male (Sertoli-Leydig cell tumor (SLCT)) components. Almost all GAB cases have been reported in children, adolescents, or women of reproductive age, and most of them typically have adult granulosa cell tumors as the female component. In contrast, GAB with a juvenile granulosa cell tumor (JGCT) component is a very rare condition; to the best of our knowledge, only one case of GAB with JGCT in a postmenopausal woman has been reported. In this report, we present an extremely rare case of ovarian GAB with JGCT in an elderly patient. A 65-year-old woman presented with an abdominal mass. Abdominopelvic magnetic resonance imaging revealed a large multiseptated cystic mass measuring 20 cm. No peritoneal seeding, lymph node enlargement, or hematogenous metastasis was identified. Laboratory test showed a slight elevation of serum CA 125 level (37.1 U/mL). Based on the preoperative clinical impression of ovarian cancer, she underwent a total hysterectomy with bilateral salpingo-oophorectomy. Grossly, the ovarian mass had a smooth and glistening surface without excrescences. The cut sections showed yellow-to-tan solid areas with foci of necrosis, myxoid degeneration, and hemorrhage, as well as multilocular cystic cavities filled with serosanguinous fluid. Histologically, the female component was characterized by JGCT displaying nodular growth patterns with follicle-like structures of various shapes and sizes. Most of the microcysts contained eosinophilic or basophilic secretions. The JGCT cells had indistinct cell borders, an abundant eosinophilic cytoplasm, and round-to-oval hyperchromatic nuclei with many mitotic figures. The SLCT component consisted predominantly of intermediately differentiated Sertoli cells forming lobulated solid nodules. They were arranged in cords, solid tubules, or nests, and possessed oval-to-spindle-shaped darkly stained nuclei and scant cytoplasm. In several foci, well-formed Sertoli cell tubules were loosely aggregated within areas of moderately differentiated SLCT. In summary, we described GAB in a postmenopausal woman with JGCT and SLCT as the female and male components, respectively. This is the second case of GAB with JGCT occurring in an elderly patient. Our findings can help pathologists and clinicians make accurate histological diagnoses of GAB with a JGCT component and plan an adequate treatment strategy for this rare tumor.

Sex cord-stromal tumors of the ovary (SCSTO) comprise a heterogeneous and fascinating group of neoplasms with diverse clinicopathological features, including benign lesions as well as tumors with malignant potential. Clinically, SCSTO may be associated with hyperestrogenic or androgenic function as a result of steroid hormone production by the tumor cells.Histological diagnosis may be challenging due to complex and sometimes overlapping morphological features of the various tumor types. A panel of immunohistochemical sex cord markers (e. g. inhibin-α, calretinin) has proven to be helpful in confirming the cellular lineage of SCSTO and differentiating them from other sex cord-like ovarian lesions. Recently, molecular analysis of SCSTO has led to the discovery of specific molecular events such as FOXL2 and DICER1 mutations. In selected diagnostically challenging cases, mutation analysis of FOXL2 and DICER1 may be helpful in the differential diagnosis. Molecular analysis is also expected to help advance the classification of SCSTO, and it may hold prognostic potential and form the basis for future type-specific therapies.This review focuses on the clinicopathological as well as the molecular features of adult and juvenile granulosa cell tumors (AGCTs and JGCTs) as well as Sertoli-Leydig cell tumors (SLCTs), these being the most relevant lesions with malignant potential in the SCSTO category. In addition, recently published molecular findings among rare ovarian gynandroblastomas (GABs) are described, which may also impact the future classification of SCSTO.

OBJECTIVE: Gynandroblastoma is a rare ovarian sex cord-stromal tumour characterised by the presence of both male (Sertoli and/or Leydig cells) and female (granulosa cells) components. We investigated the mutational status of DICER1, FOXL2 and AKT1 genes at hot-spot regions that are known to be the key driving events in the development of Sertoli-Leydig cell tumour (SLCT), adult granulosa cell tumour (aGCT) and juvenile granulosa cell tumour (jGCT), respectively, to gain insights into the molecular pathogenesis of gynandroblastoma.
RESULTS: Sixteen cases of gynandroblastoma were studied. All contained SLCT or Sertoli cell tumour components. aGCT and jGCT components were identified in seven and 10 cases, respectively, with one presenting both components. Heterozygous hot-spot mutations in the RNase IIIb domain of DICER1 were discovered in three cases, including one case with heterologous mucinous elements, all of which were composed of moderately or poorly differentiated SLCT and jGCT components, and harboured the mutations in both histological components. None of the 16 cases displayed mutations at the p.C134W (c.402C→G) of FOXL2 or within the pleckstrin-homology domain of AKT1. All cases showed FOXL2 immunostaining in both male and female components.
CONCLUSIONS: DICER1 hot-spot mutation is the key-driving event in a subset of gynandroblastomas containing components of SLCT and jGCT. Gynandroblastomas composed of SLCT and jGCT may represent morphological variants of SLCT. The molecular basis of gynandroblastoma containing a component of aGCT is different from pure aGCT.

Ovarian sex cord-stromal tumors (OSCST) include juvenile granulosa cell tumors (JGCT), Sertoli-Leydig cell tumor (SLCT) and gynandroblastoma (GAB) among others. These ovarian sex cord-stromal tumors as well as other tumors including pleuropulmonary blastoma (PPB) may be associated with DICER1 mutations. We sought to describe the clinical and genetic findings from the first 107 individuals enrolled in the International Ovarian and Testicular Stromal Tumor Registry.
Medical and family history were obtained for individuals consecutively enrolled in the International Ovarian and Testicular Stromal Tumor Registry. Pathology was centrally reviewed. DICER1 sequencing was performed on blood and tumor tissue.
Of the 107 participants, 49 had SLCT, 25 had JGCT and 5 had GAB. Nearly all (36/37) SLCTs and 4/4 GAB tested had a DICER1 mutation in an RNase IIIb domain hotspot; approximately half of these individuals had a predisposing germline DICER1 mutation. Metachronous SLCTs were seen in 3 individuals with germline DICER1 mutations. Other DICER1-associated conditions were seen in 19% of patients with SLCT or GAB. Three children of women with SLCT were diagnosed with PPB based on genetic testing and clinical screening during the course of this study. All were diagnosed with PPB in its earliest and most curable form (Type I), were treated with surgery alone, and are alive without evidence of disease.
Recognition of the distinct genetic basis for a group of these tumors improves precise classification in difficult cases and promotes mutation-based screening and early detection.