Uterine tumors resembling ovarian sex cord tumors: A retrospective analysis of 7 cases from a single institution.

To investigate the clinicopathological features, diagnosis, surgical treatment and prognosis of uterine tumors similar to ovarian sex cord tumors (UTROSCT). The clinical data, surgical approach, histopathological, and immunohistochemical features of 7 cases of UTROSCTs were retrospectively reviewed and followed up. All 4 patients were premenopausal women. The most common clinical presentation was menorrhagia (n = 4) followed by postmenopausal lower abdominal mass (n = 2) and postmenopausal bleeding (n = 1). Gynecological ultrasonography suggested uterine fibroids in 4 cases, adenomyosis with uterine fibroids in 2 cases, and an intrauterine mass in 1 case. Pelvic MRI was performed preoperatively in only 2 cases, and both indicated uterine fibroid degeneration, including 1 patient with suspected malignancy. Preoperative serum tumor markers were measured in 6 patients, and only 1 patient had elevated CA125 levels, up to 158 U/mL. Total hysterectomy with bilateral adnexectomy or salpingectomy was the most common treatment pattern (n = 6). The tumors were located within the myometrium (n = 4), submucosa (n = 1), and isthmus to external cervical os (n = 1), with a range of 2 to 12 (mean = 8) cm. Edema and degeneration were observed in 2 cases, and necrosis in 1 case. Postoperative follow-up ranged from 31 to 82 (mean = 43) months. Unfortunately, 1 patient died at 54 months of follow-up without undergoing hysterectomy. The remaining 6 cases showed no tumor recurrence or metastasis after surgery. Histological examination revealed a tumor composed of epithelioid tumor-like cells arranged in cords, trabeculae, and nests. All 7 tumors showed expression of 2 sex cord differentiation markers. Furthermore, all tumors expressed the smooth muscle marker, while epithelial marker CK (4/7). endometrial stromal marker CD10(0/7). The Ki-67 proliferation index was found to be <5% (5/7). The option of total hysterectomy may be considered for women who do not have any fertility requirements. However, for young women who desire to maintain their reproductive capacity, surgery to preserve the uterus may be an alternative, although it necessitates careful postoperative monitoring. In terms of follow-up monitoring, MRI is more suitable than ultrasound. The diagnosis of UTROSCT heavily relies on histopathological examination and immunohistochemical analysis.

Ovarian sclerosing stromal tumor mimicking malignancy: case series and literature review.

BACKGROUND: Sclerosing stromal tumors (SST) are rare ovarian neoplasms that often appear as solid unilateral tumors of the ovary with no specific clinical or radiological presentation. The definitive treatment is surgical removal. CASE PRESENTATION: Our article presents four cases of female patients with sclerosing stromal ovarian tumor with clinical characteristics mimicking malignant ovarian lesions. Interestingly, two of our cases had elevated levels of inhibin B. All patients were treated with surgery (oophorectomy) and had no disease recurrence. CONCLUSION: Tumors' macroscopic features are usually non-specific and often suggestive of possible malignancy, therefore diagnosis is always based on histopathological report.

Microscopic sex cord-stromal proliferations in extraovarian heterotopic sites: Report of a rare case and review of the literature.

Microscopic heterotopic extraovarian sex cord-stromal proliferations were first reported in the literature in 2015 by McCluggege. Afterwards, few similar cases have been described. Herein, we report the fourteenth case of microscopic heterotopic sex cord-stromal proliferation and the third case sited in the pelvic peritoneum. The clinical history of these rare cases suggests their benign nature. Knowledge of this histological pattern is important for differential diagnoses such as malignant pathologies and metastatic diseases.

Outcomes in ovarian Sertoli-Leydig cell tumor: A report from the International Pleuropulmonary Blastoma/DICER1 and Ovarian and Testicular Stromal Tumor Registries.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Exceptional lymph node recurrence of an unusual ovarian tumor 16 years later: a case report.

BACKGROUND: Sex cord-stromal tumors with annular tubules are a rare tumor accounting for less than 1% of all ovarian malignancies. However, they are characterized by very late recurrence, which can be as late as 30 years after diagnosis and treatment. CASE PRESENTATION: A 16-year-old female Caucasian patient was treated in our department for a stage IA ovarian sex cord-stromal tumors with annular tubules. She underwent a left salpingo-oophorectomy and ipsilateral pelvic node biopsy with no adjuvant treatment. She was seen for amenorrhea after being lost to follow up for 16 years. The diagnosis of recurrence was made by radiology and the elevation of serum inhibin B level. The patient underwent resection of the tumor, left segmental colectomy, and paraaortic lymphadenectomy because the mass was massively adherent to the left mesocolon. Histology confirmed the diagnosis with no metastatic lymph nodes. No adjuvant therapy was indicated. The patient was lost to follow-up again for 4 years and re-presented for amenorrhea. Serum inhibin B level was high. A second recurrence was suggested, and the patient underwent a laparoscopic surgery. We performed left pelvic and paraaortic lymphadenectomy, and 3 months after surgery the patient was pregnant. CONCLUSION: Sex cord-stromal tumors with annular tubules is a slow-growing ovarian tumor with a high potential for recurrence and metastasis. Surgery is the mainstay of treatment. Due to the rarity of these tumors, they are often unsuspected and thus incompletely staged before primary surgery; the diagnosis is made by histological examination. The prognosis of these patients is unknown, and they require long-term follow-up.

The Malignant Potential of Ovarian Steroid Cell Tumors Revisited: A Multi-institutional Clinicopathologic Analysis of 115 Cases.

Steroid cell tumors (SCTs) of the ovary are rare and understudied, and as such, uncertainties remain about their malignant potential, as well as clinicopathologic predictors of patient outcome. Based on a multi-institutional cohort of cases, we present findings from the largest study of SCT reported to date. Clinicopathologic data were documented on 115 cases of SCT that were assembled from 17 institutions. The median patient age was 55 years (range: 9 to 84). When measured, preoperative androgen levels were elevated in 84.2% (48/57) of patients. A total of 111 (96.5%) cases were classified as stage I (103 stage IA; 2 stage IB; 6 stage IC). The stage distribution for the remaining 4 patients was as follows: stage II (n = 1), III (n = 3; 1 IIIA, 1 IIIB, 1 IIIC). The median tumor size was 3 cm (range: 0.2 to 22). Cytologic atypia, microscopic tumor necrosis, microscopic tumor hemorrhage, and a mitotic index of >1 mitotic figure/10 high-power fields were present in 52% (60/115), 9.6% (11/115), 37% (43/115), and 19% (22/115) of cases, respectively. Of 115 patients, 7 (6.1%) recurred postexcision, 4 (3.5%) ultimately died of disease, and 10 (8.7%) either recurred, died of disease, or were advanced stage at presentation. The median duration to recurrence postresection was 33 months (range: 23 to 180). Four of the 7 recurrences were stage IA at baseline. Tumor size >4 cm, International Federation of Gynecology and Obstetrics (FIGO) stage ≥IB, tumor necrosis, and tumor hemorrhage were each significantly associated with reduced recurrence-free survival in log-rank tests and univariable Cox models, with age older than 65 years being of marginal significance (hazard ratio [HR]: 5.4, 95% CI: 1.0-30.0, P = 0.05). Multivariable analyses suggested that FIGO stage ≥IB (HR: 27.5, 95% CI: 2.6-290.5), and age older than >65 years (HR: 21.8, 95% CI: 1.6-303.9) were the only parameters that were independently associated with recurrence. Cross-section analyses showed that tumor necrosis, tumor hemorrhage, and larger tumor size were significantly associated with a FIGO stage ≥IB status, which bolstered the conclusion that they are not independent predictors of recurrence. In summary, <10% of SCTs are clinically malignant, a substantially lower frequency than has previously been reported in the literature. Clinicopathologic predictors of patient outcomes that are prospectively applicable in practice could not be definitively established. Recurrences may occur many years (up to 15 y in this study) after primary resection, even in stage IA cases.

The detailed histopathological characteristics of ovarian fibroma compared with thecoma, granulosa cell tumor, and sclerosing stromal tumor.

BACKGROUND: Ovarian fibromas are benign tumors that can present peculiar morphological features not studied sufficiently. MATERIAL AND METHODS: In this retrospective study, 75 consecutive cases of ovarian fibroma were morphologically compared with 46 thecomas, 16 granulosa cell tumors, and 5 sclerosing stroma tumors for the following factors: the growth pattern as diffuse or nodular, the presence of hyaline plaques, necrosis, keloid-like sclerosis, calcifications, cystic degeneration, fibrous or edematous stroma, prominent vascularity, lutein cells, cellularity, scant or abundant cytoplasm, prominent cell membranes, nuclear grooves, atypia, and mitotic activity. RESULTS: The tumors differed significantly in terms of hyaline plaques presence, nuclear grooves, growth pattern, stroma type, tumor cellularity, cytoplasm, prominence of cell membranes, atypia, mitotic activity, and prominent vascularity. CONCLUSION: Ovarian fibromas can present some maybe unexpected features rather frequently, such as cystic degeneration, hyaline plaques, prominent vascularity, increased cellularity, and some mitotic activity, thus their presence should not always prompt to an alternative diagnosis.

Sex Cord-Stromal Tumors of the Ovary: An Update and Review. Part I - Pure Ovarian Stromal Tumors.

In two separate reviews, we review the time-honored but still frequently challenging features of ovarian sex cord-stromal tumors, and also emphasize new developments including unusual morphologic appearances that, despite the relative rarity of many of the tumors, result in a disproportionate number of differential diagnostic problems, variant immunohistochemical profiles, and specific molecular and syndromic associations. These neoplasms are also of historical interest as current knowledge is still based in significant part on the contributions of 2 giants of gynecologic pathology, Dr Robert Meyer and Dr Robert E. Scully. In part I, we present the major clinical, pathologic, and genomic features of the pure ovarian stromal tumors including comments on differential diagnosis and briefly note significant historical contributions. In part II we will discuss pure sex cord and sex cord-stromal tumors.

Sex Cord-Stromal Tumors of the Ovary: An Update and Review. Part II - Pure Sex Cord and Sex Cord-Stromal Tumors.

We review the time honored but still frequently challenging features of ovarian sex cord-stromal tumors and also emphasize new developments, including unusual morphologic appearances that, despite the relative rarity of many of the tumors, result in a disproportionate number of differential diagnostic problems, variant immunohistochemical profiles, and specific molecular and syndromic associations. These neoplasms are also of historical interest as current knowledge is still based in significant part to the contributions of 2 giants of gynecologic pathology, Dr Robert Meyer and Dr. Robert E. Scully. In part I, we reviewed the pure ovarian stromal tumors. Now, in part II, we present the major clinical, pathologic, and genomic features of pure sex cord and sex cord-stromal tumors.

An unreported case of intraoperative frozen section diagnosis of a sclerosing stromal tumor of the ovary- A report with a review.

ABSTRACT: Sclerosing stromal tumor is a benign sex cord-stromal tumor, that commonly occurs in the second and third decades of age. Intraoperative diagnosis of this entity poses a great challenge because of the rare occurrence and can mimic malignant lesions. A 15-year-old female presented with a right ovarian mass. Serum markers were within normal limits. The radiological evaluation showed a large heterogeneously enhancing solid cystic abdominopelvic mass of size 16 × 14 × 9 cm with non-visualization of both ovaries separately and a few areas of calcification with mild ascites. An open cystectomy was performed. A part of the cyst wall was sent for an intraoperative frozen section. It was reported as sclerosing stromal tumor, and the post-operative specimen also confirmed the same. Areas of calcification and ossification were also identified as additional findings. We reported this case because of the uncommon occurrence, highlighting additional histological features, and also did a literature review, especially focussing on the intra-operative diagnosis.

Myoid gonadal stromal tumor of the testis-the novel subtype of testicular gonadal stromal tumors: a case report and review of the literature.

BACKGROUND: Sex cord gonadal stromal tumors compose less than 10% of all testicular neoplasms and consist of a variety of histological subtypes. In 2016, the World Health Organization introduced a novel subtype, the myoid gonadal stromal tumor, that consists of spindle-shaped cells with immunohistologic features of muscle cells. Only few cases have been reported to date. Due to its rarity and owing to its only recent introduction, the current knowledge about myoid gonadal stromal tumor is limited, and particularly, appropriate clinical management is still ill-defined. CASE PRESENTATION: A 47-year-old man of Caucasian descent presented with nonspecific scrotal discomfort. A roundish and well demarcated hypoechoic mass of 8.5 mm in diameter was detected in the cranial region of the left testis. Serum tumor marker levels were within normal ranges. Testis-sparing surgery revealed a 9-mm whitish, hard mass with sharp surgical margin. Histologically, the neoplasm consisted of microfibrillar tissue with spindle-shaped cells harboring elongated nuclei. Immunohistochemical work-up disclosed expression of desmin, small muscle actin, and S100 protein giving evidence for the myogenic nature of the neoplastic cells. There was no indication of malignancy, neither histologically nor clinically. Follow-up of 1 year was uneventful. CONCLUSION: A literature survey revealed 22 previous cases of myoid gonadal stromal tumor. The median age was 37 years, the median size of the neoplasm was 20 mm, and there was no side-preponderance. Myoid gonadal stromal tumor is not much different from other subtypes of gonadal stromal tumors nor from testicular gem cell tumors regarding age and laterality; however, tumor size is smaller in myoid gonadal stromal tumors than in germ cell tumors. Although rarely performed so far, testis-sparing surgery probably constitutes an appropriate treatment of this neoplasm. Myoid gonadal stromal tumor represents an emerging novel entity of benign testicular new growths that caregivers of patients with testicular tumors should be aware of.

Review on Sertoli-Leydig Cell Tumours of the Ovary.

Sertoli-Leydig cell tumours (SLCTs) represent a subset of mixed sex cord-stromal tumours (SCSTs), a rare form of non-epithelial ovarian tumours comprising less than 7% of malignant cases. Among other types of SCSTs, SLCTs are one of the more prevalent types observed in young adults. SLCTs are classified into 5 histologic categories based on differentiation levels and histological variants. Diverse chromosomal and genetic mutations have been identified in SLCTs, with the most well-studied being the genetic mutations observed in the Dicer 1, Ribonuclease III (DICER1) and the Forkhead Box L2 (FOXL2) genes. These mutations have important clinical implications and their mechanisms are discussed. Particularly, this review emphasizes the correlation between tumour differentiation, mutation status and virilization. Current common methods and difficulties in the clinical diagnosis of SLCTs are also considered, and the usefulness of immunohistochemistry is highlighted. Patient stratification for treatment is done according to the patient's age, stage of disease and prognostic factors. The gold standard of treatment is surgical resection and adjuvant chemotherapy is administered based on the risk of recurrence. The management of recurrence remains a major challenge. Apart from recurrence, there is also a risk of the development of a metachronous tumour, especially in patients with DICER1 syndrome. Hence, the diagnosis of a SLCT has important implications for genetic testing and patient surveillance even if the management of the tumour is successful. This scoping review serves to consolidate current knowledge on SLCTs and advocates for future research advancements to refine diagnosis, management, and prognosis.

18F-FDG PET/CT features of Meigs syndrome induced by ovarian sex cord stromal tumors: a retrospective clinical study.

The objective of this study was retrospectively to analyze the clinical characteristics and 18F-FDG PET/CT findings in Meigs syndrome (MS) patients. A total of 21 patients with MS induced by ovarian stromal tumors and 69 patients with pseudo-MS caused by ovarian cancer (OC-PMS) were subjected to evaluation using 18F-FDG PET/CT. Visual and semi-quantitative methods were employed to analyze the PET/CT findings. Visual analysis included recording whether the density of the primary tumor was uniform, whether there were cystic changes and calcifications, and the location of serous fluid accumulation. Semi-quantitative analysis involved the measurement of the tumor size, SUVmax, and SUVmean. No significant difference was observed in the size and density of primary tumors between the MS group and the OC-PMS group. However, the SUVmax and SUVmean of tumors in the MS group were found to be significantly lower than those in the OC-PMS group. The amount of serous cavity effusion caused by ovarian sex cord stromal tumors was found to be unrelated to the size of the tumor, SUVmax, and SUVmean but was positively correlated with the level of Ca125. MS patients have both benign ovarian tumors and ascites and/or pleural effusion, which may be accompanied by elevated Ca125 levels. This should be considered as one of the differential diagnoses for ovarian cancer. Understanding the PET/CT features of MS can facilitate the attainment of an accurate diagnosis before surgery.

Oncological and endocrinological outcomes for children and adolescents with testicular and ovarian sex cord-stromal tumors. Results of the TGM13 National Registry.

RATIONALE: Sex cord-stromal tumors (SCST) are hormonally active and rare. The aim was to describe their endocrinological presentation and outcomes. METHOD: Patients (< 19 years) registered in the TGM13 registry between 2014 and 2021 for SCST were selected. RESULTS: Sixty-three ovarian SCST (juvenile granulosa tumor (JGT) n = 34, Sertoli-Leydig cell tumor (SLCT) n = 17, other SCST n = 12) were included. Median age was 13.1 years (0.4-17.4). Germline DICER1 pathogenic variant was present in 9/17 SLCT. Sixty-one were FIGO stage I (IC n = 14). Adjuvant chemotherapy was administered for 15. Seven had recurrence (FIGO IA n = 3, IX n = 2, III n = 2), leading to one death. With a median follow-up of 42 months (2.5-92), the 3-year progression-free survival (PFS) was 89% (95% CI 76%-95%). Median age was 6.4 years (0.1-12.9) among the 15 testicular SCST (Leydig cell tumor n = 6, JGT n = 5, Sertoli cell tumor n = 3, mixed SCST n = 1). Tumor-nodes-metastases (TNM) stage was pSI in 14. Eight underwent a tumorectomy, 7 an orchiectomy. None experienced recurrence. Endocrinological data were reviewed for 41 patients (18 prepubescent). Endocrine symptoms were present at diagnosis in 29/34 females and 2/7 males (gynecomastia). After a median follow-up of 11 months, 15 patients had persistent endocrine abnormalities: gynecomastia/breast growth (2 males, 1 prepubescent female), precocious/advanced puberty (4 prepubescent females), and hirsutism/menstruation disorders/voice hoarseness/hot flashes (8 pubescent females). The mean height at the last follow-up was within normal ranges (+0.3 standard deviation). CONCLUSIONS: SCSTs have a favorable prognosis. Tumorectomy appears safe with testicular primary. Endocrinological disorders, common at diagnosis, may persist warranting endocrinological follow-up.

[Fundamentals in the pathology of testicular tumours]. / Grundlagen der Pathologie seltener Hodentumoren.

The most common group of testicular tumours comprises germ cell tumours. Other primary testicular tumours are rare, but it is important to be aware of the wide variety of other, much rarer testicular tumours for the differential diagnosis. These tumours include sex cord stromal tumours and testicular adnexal tumours, which must be distinguished from metastases or somatic-type malignancies in germ cell tumours. Immunohistochemical markers and molecular alterations can help to correctly diagnose these tumours.

Uterine Tumors Resembling Ovarian Sex Cord Tumors (UTROSCTs): A Scoping Review of 511 Cases, Including 2 New Cases.

Uterine Tumors Resembling Ovarian Sex Cord Tumors (UTROSCTs) are rare uterine mesenchymal neoplasms with uncertain biological potential. These tumors, which affect both premenopausal and postmenopausal women, usually have a benign clinical course. Nevertheless, local recurrences and distant metastases have been described. By analyzing 511 cases retrieved from individual reports and cases series, we provide here the most comprehensive overview of UTROSCT cases available in the literature, supplemented by two new cases of UTROSCTs. Case 1 was an asymptomatic 31-year-old woman who underwent a laparoscopic resection of a presumed leiomyoma. Case 2 was a 58-year-old postmenopausal woman with abnormal vaginal bleeding who underwent an outpatient hysteroscopic biopsy of a suspicious endometrial area. In both cases, immunohistochemical positivity for Calretinin and Inhibin was noted, typical for a sex cord differentiation. In both cases, total laparoscopic hysterectomy with bilateral salpingo-oophorectomy was performed. In light of the available literature, no pathognomonic clinical or imaging finding can be attributed to UTROSCT. Patients usually present with abnormal uterine bleeding or pelvic discomfort, but 20% of them are asymptomatic. In most cases, a simple hysterectomy appears to be the appropriate treatment, but for women who wish to become pregnant, uterus-preserving approaches should be discussed after excluding risk factors. Age, tumor size, lymphovascular space invasion, nuclear atypia, and cervical involvement are not reliable prognostic factors in UTROSCT. The current research suggests that aggressive cases (with extrauterine spread or recurrence) can be identified based on a distinct genetic and immunohistochemical phenotype. For instance, UTROSCTs characterized by GREB1::NCOA1-3 fusions and PD-L1 molecule expression appear to be predisposed to more aggressive behaviors and recurrence, with GREB1::NCOA2 being the most common gene fusion in recurrent tumors. Hence, redefining the criteria for UTROSCTs may allow a better selection of women suitable for fertility-sparing treatments or requiring more aggressive treatments in the future.