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.

Therapeutic management of uterine tumours resembling ovarian sex cord tumours including a focus on fertility: A systematic review.

OBJECTIVE: Uterine tumours resembling ovarian sex cord tumours (UTROSCTs) are extremely rare. To date, most patients with UTROSCTs have undergone hysterectomy and had a benign clinical course. Fertility-preserving surgery should be considered because some patients with UTROSCTs are aged < 40 years. This paper reviews the treatment and prognosis for patients with UTROSCTs, with a focus on fertility. METHODS: PubMed, MEDLINE and Scopus were searched systematically for case reports and case series of UTROSCTs published in English from inception to December 2022, and initial treatment and recurrence rates were compared. The following data were extracted: age; symptoms; initial therapy; metastasis at diagnosis; disease-free survival (DFS); and recurrence. RESULTS: In total, 147 patients (72 studies) reporting the clinical course of UTROSCTs were analysed. The median age at diagnosis was 50 years, and 28 (19.0 %) patients were aged < 40 years. Most patients (n = 125, 85.0 %) underwent hysterectomy as the initial surgery, with a recurrence rate of 17.6 % (n = 22). The recurrence rate was 30 % (n = 6) in patients who underwent mass resection (n = 20). Among the 15 patients who underwent mass resection aged < 40 years, seven went on to achieve pregnancy (46.7 %) and six had successful deliveries (40.0 %). No significant differences in 5- and 10-year DFS were found between the hysterectomy and mass resection groups (p = 0.123 and 0.0612, respectively). Bilateral salpingo-oophorectomy in addition to hysterectomy was not significantly associated with 10-year DFS (p = 0.548). CONCLUSION: While total hysterectomy is the recommended treatment for UTROSCTs based on recurrence rates, mass resection is an acceptable treatment option for patients who wish to retain their childbearing potential. It is recommended that these women should plan for pregnancy and delivery as soon as possible after mass resection, and should undergo hysterectomy within 5 years.

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.

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.

[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.

Contemporary Updates on Sex Cord-stromal Tumors of the Testis.

Testicular sex cord-stromal tumors (TSCSTs) are relatively rare, representing ~5% of testicular neoplasms overall. Historically, TSCSTs have been classified into 3 major entities: Leydig cell tumor, Sertoli cell tumor, and granulosa cell tumor. In recent years, immunophenotypic and molecular analyses have led to a more detailed understanding of the biological and genomic features of these neoplasms, resulting in the description of new entities, some of which have been included in the latest WHO classification. This review summarizes novel histopathologic, clinical, and molecular findings that may lead to a reappraisal of established concepts and help improve the diagnosis and clinical management of TSCSTs in the coming years.

FOXL2 Mutation Status in Sex Cord-stromal Tumors Cannot be Predicted by Morphology.

Granulosa-cell tumors (GCTs) are the most common type of malignant ovarian sex cord-stromal tumor (SCST). The histopathologic diagnosis of these tumors can be challenging. A recurrent somatic mutation of the forkhead box L2 (FOXL2) gene has been identified in adult GCT. In this retrospective single-center study of 44 SCST, a morphologic review together with analysis of FOXL2 C134W was evaluated in relation to tumor morphology. In addition, TERT promoter mutation testing was performed. Twelve of 36 cases got an altered diagnosis based on morphology alone. The overarching architectural growth pattern in 32/44 (72.7%) tumors was diffuse/solid with several tumors showing markedly heterogeneous architecture. In correlation to FOXL2 C134W mutation status, cytoplasmic color, and nuclear shape, differed between the FOXL2 C134W positive and FOXL2 C134 W negative groups, but these differences were not significant when comparing them separately. Nineteen of 44 cases underwent TERT promoter sequencing with a positive result in 3 cases; 2 adult GCTs and 1 cellular fibroma. Three patients developed a recurrence of which 2 were FOXL2 C134W positive adult GCTs and the third was an unclassified SCST. In conclusion, the morphologic and immunohistochemical diagnosis of different SCSTs is challenging and one cannot reliably identify FOXL2 mutation-positive tumors solely by morphologic features. Therefore, broad use of molecular analysis of the FOXL2 C134W mutation is suggested for SCSTs, and further studies are needed to evaluate the clinical outcome of these tumors as well as the diagnostic and prognostic implications of TERT promoter mutations.

A Case of Uterine Tumor Resembling Ovarian Sex Cord Tumor With Prominent Myxoid Features.

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare tumor with low malignant potential that commonly occurs in middle age. Although more than 100 cases have been reported to date, myxoid morphology is not well documented. Here, we present a 75-yr-old woman with abnormal vaginal bleeding, with an 8-cm mass in the uterine corpus detected by irregular, high-intensity signaling on T2-weighted imaging. The uterine mass had a glistening mucinous appearance on gross examination. Microscopically, most of the tumor cells were floating in the myxoid stroma. The tumor cells formed clusters or nests with abundant cytoplasm, while some exhibited trabecular or rhabdoid appearances. Immunohistochemically, tumor cells were positive for pancytokeratin (AE1/AE3), α-smooth muscle actin, CD10, progesterone receptor, and some sex cord markers such as calretinin, inhibin, CD56, steroidogenic factor-1. Electron microscopy demonstrated epithelial and sex cord differentiation. This tumor was negative for JAZF1-JJAZ1 fusion gene that is frequently found in low-grade endometrial stromal sarcoma. Fusion genes related to UTROSCT, including NCOA2/3 , were not detected by reverse transcription polymerase chain reaction. The present case suggests that UTROSCT should be included in the differential diagnosis of myxoid uterine tumors.

Testicular fibroma of gonadal stromal origin in an adult male / Fibroma testicular de origen gonadal estromal en un varón adulto

Para-testicular masses are a rare entity, and therefore the diagnosis and management nearly always lead to clinical doubts. Aside from the doubts that arise from these masses being uncommon, it is always necessary to rule out the malignancy process of them. Sexual cord tumors are extremely rare. Testicular fibroma of gonadal stromal origin is a proliferative process that can develop in para-testicular structures. The objective of our study is to present a rare case report of testicular fibroma of gonadal stromal origin as well as the well-documented diagnostic process and the successful therapeutic management that was subsequently carried out. We report a case of a 68-year old male who came in for a consult due to the casual finding of a nodule in his left testicle with normal tumor markers. Ultrasonography showed a nodular image that was well-defined with a diffusely homogeneous echotexture; it was also hypoechoic, vascularized and demonstrated hydrocele. MRI revealed a solid tumor with extrinsic growth to the left testicle and epididymis, and the lesion was relatively hyperintense in T1-weighted image and hypointense in T2. A surgical exeresis of the para-testicular tumor and hydrocelectomy was performed. The pathological anatomy and immunohistochemistry revealed a fibroma of gonadal stromal origin. Histopathological analysis made a diagnosis, although its clinical and radiological characteristics make it one of the differential diagnoses to consider in testicular tumors. Its characteristics, radiological and histopathological, allow for conservative management in clinical practice. (AU)

Las masas paratesticulares son una entidad rara, por lo que su diagnóstico y tratamiento casi siempre dan lugar a dudas clínicas. Más allá de las dudas que surgen por el hecho de que estas masas sean poco comunes, siempre hay que descartar el proceso de malignidad de las mismas. Los tumores del cordón sexual son extremadamente raros. El fibroma testicular de origen estromal gonadal es un proceso proliferativo que puede desarrollarse en estructuras paratesticulares. El objetivo de nuestro estudio es presentar un reporte de un caso raro de fibroma testicular de origen del estroma gonadal así como el proceso diagnóstico bien documentado y el manejo terapéutico exitoso que se llevó a cabo posteriormente. Presentamos el caso de un varón de 68 años que acude a consulta por el hallazgo casual de un nódulo en el testículo izquierdo con marcadores tumorales normales. La ecografía mostró una imagen nodular bien definida con una ecotextura difusamente homogénea; además era hipoecoico, vascularizado y demostraba hidrocele. La resonancia magnética reveló un tumor sólido con crecimiento extrínseco en el testículo izquierdo y el epidídimo, y la lesión era relativamente hiperintensa en la imagen potenciada en T1 e hipointensa en T2. Se realizó exéresis quirúrgica del tumor paratesticular e hidrocelectomía. La anatomía patológica y la inmunohistoquímica revelaron un fibroma de origen estromal gonadal. El análisis histopatológico permitió establecer el diagnóstico, aunque sus características clínicas y radiológicas lo convierten en uno de los diagnósticos diferenciales a considerar en los tumores testiculares. Sus características, radiológicas e histopatológicas, permiten un manejo conservador en la práctica clínica. (AU)

Hypoxia-associated genetic signature in ovarian steroid cell tumor NOS.

Steroid cell tumors, not otherwise specified (SCT-NOS), are uncommon ovarian neoplasms accompanied by virilization symptoms due to hyperandrogenism, which are malignant in approximately one-third of the cases. Given the rarity of SCT-NOS, their molecular underpinnings have not yet been studied in depth. In this case series, we performed the first comprehensive analysis of the genetic landscape of this rare ovarian tumor. A detailed clinicopathological description of an index case is also provided. Over a 20-year period, a total of eight patients were seen at our institution. Total nucleic acids (RNA and DNA) were extracted from evaluable formalin-fixed, paraffin-embedded tumor specimens (n = 7) and subjected to TruSight Oncology 500 testing and/or exome sequencing. The results identified pathogenic variants in several hypoxia-related genes - including HIF1A, VHL, SDHB, SRC, IDH2, and FOXO4. As the first comprehensive genetic analysis of SCT-NOS, this study shows that dysregulation in the hypoxia signaling pathway is a key molecular feature of this rare tumor. Clinically, long-term follow-up with periodic measurements of androgen levels should be pursued in all cases since recurrences may occur several years after the initial diagnosis.

TFE3 nuclear expression as a novel biomarker of ovarian sclerosing stromal tumors and associated with its histological morphology.

Sclerosing stromal tumors of the ovary are benign and tend to occur in youthful women with lobular structures at low frequencies. Three types of cells, including luteinized cells, short spindle myoid cells, and intermediate cells, are found in the lobules which abundant in the blood vessels. Currently, immunohistochemistry is used to detect normal follicles, sclerosing stromal tumors, granulosa cell tumors, and fibromas/thecomas. Our research results showed that transcription factor enhancer 3 (TFE3) was moderate to strong positive in the theca interna layer of normal follicles. TFE3 was expressed in seven out of eight sclerosing stromal tumors, mainly in luteinized cells. It did not express in 20 granulosa cell tumors. Of the nine fibromas/thecomas, TFE3 was weakly staining in 2 cases and negative in the remaining 7 cases. The expression of TFE3 was also weak in only one microcystic stromal tumor. 8 cases of sclerosing stromal tumors were analyzed by FISH using a TFE3 separation probe, and the results were negative. In short, as a nuclear transcription protein, TFE3 specifically expressed in sclerosing stromal tumors and could serve as a new marker for the diagnosis and differential diagnosis of sclerosing stromal tumors. Moreover, we speculate that TFE3 will promotes the formation of the vascular plexus after entry into the nucleus, which can further explain why sclerosing stromal tumors are different from other ovary sex-cord stromal tumors.

Mixed sex cord-stromal tumor (gynandroblastoma) with malignant morphology involving both ovaries: a case report.

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.

Update on Ovarian Sex Cord-Stromal Tumors.

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.

The sclerosing sertoli cell tumor of the testis: a case report.

BACKGROUND: Testicular Sertoli cell tumor (SCT) is very rare sex cord-gonadal stromal tumor, and sclerosing SCT (SSCT) is even rarer. So far, no more than 50 cases of SSCT have been reported. 80% of SSCTs are less than 2 cm in diameter, large volume mass is pretty unusual. SSCT is usually benign with very low malignant potential. However, it is easily misdiagnosed as a malignant tumor resulting in the removal of the entire testicle. CASE PRESENTATION: A 55-year-old Chinese male patient presented with a six months' history of right testis progressively enlargement and negative tumor markers. The physical examination was nothing special except for swelling in the right testicle. Imaging identified a large mass in right testicle with rich blood. A right radical orchiectomy was performed on suspicion of malignancy. However, the tumor was postoperatively diagnosed as SSCT, which pathologically consisted of a tubular pattern with regular nuclei and embedded in a densely collagenous stroma, as well as diffusely positive for vimentin, ß-catenin and synaptophysin. After 7 months of follow up, no evidence of local recurrence and metastasis has been observed. CONCLUSION: This rare case is helpful to expand the knowledge of the testicular tumor and alert us fully understand the rare variant of SCTs in order to choose the optimal management when they encounter SSCT.

Myoid Gonadal Stromal Tumor: A New Case Report with a Review of the Literature.

The myoid gonadal stromal tumor is a very rare testicular spindle cell tumor. Few cases have been reported in the literature from 1977 to 2022. It was an emerging entity in the fourth edition of the WHO Classification of Tumors of the Urinary System and Male Genital Organs and has been instated as a full benign entity in the new edition of 2022. We report herein an additional case of a myoid gonadal stromal tumor. It was a 27-year-old man who presented with an asymptomatic mass in his left testicle for 2 months. The mass was confirmed by ultrasound as a 3 cm solid well-circumscribed lesion for which orchiectomy has been performed. The histological analysis of the specimen and the immunohistochemistry staining was consistent with a myoid gonadal stromal tumor. The characteristics of this tumor are summarized in well-circumscribed, nonencapsulated masses of uniform spindle cells, and immunohistochemically, tumor cells coexpress SMA and S-100 protein. The benign behavior of this tumor is demonstrated by our results and those presented in the previous cases reported in the literature.

Ovarian steroid cell tumor (not otherwise specified) with subsequent spontaneous pregnancy after tumor removal: a case report and literature review.

Steroid cell tumors not otherwise specified are rare sex cord-stromal tumors of the ovary that may produce various steroids and are associated with hirsutism and virilization. We report a rare case of ovarian steroid cell tumor with subsequent spontaneous pregnancy after tumor removal. A 31-year-old woman presented with secondary amenorrhea, hirsutism, and inability to conceive. Clinical and diagnostic evaluations revealed a left adnexal mass and elevated serum total testosterone and 17α-hydroxyprogesterone levels. She underwent a left salpingo-oophorectomy, and histopathological examination confirmed the diagnosis of a steroid cell tumor not otherwise specified. Her serum total testosterone and 17α-hydroxyprogesterone normalized one month after surgery. Her menses resumed spontaneously one month after the operation. She spontaneously conceived 12 months after the surgery. The patient had an uncomplicated pregnancy and delivered a healthy male infant. In addition, we reviewed the literature on steroid cell tumors not otherwise specified with subsequent spontaneous pregnancies after surgery and data regarding pregnancy outcomes.