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Context.—: Steroidogenic acute regulatory (StAR) protein is a mitochondrial transport protein with a critical regulatory role for steroid hormone production. The tissue distribution of StAR expression is limited to few human normal tissues., Objective.—: To assess the diagnostic and prognostic value of StAR immunohistochemistry analysis., Design.—: A tissue microarray containing 19 202 samples from 152 different tumor types and subtypes and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry., Result.—: StAR immunostaining occurred in 198 (1.2%) of the 17 135 analyzable tumors. StAR expression was observed in 27 of 152 tumor categories, 9 of which included at least 1 strongly positive case. The highest rate of StAR positivity occurred in Leydig cell tumors of the testis and the ovary (100%), steroid cell tumors of the ovary (100%), adrenocortical carcinomas (93%) and adenomas (87%), Sertoli-Leydig cell tumors (67%) and granulosa cell tumors of the ovary (56%), as well as seminomas (7%). Nineteen other tumor entities showed-a usually weak-StAR positivity in less than 6% of cases. A comparison with preexisting Melan-A (a melanocyte antigen) data revealed that StAR was more often positive in adrenocortical neoplasms and in Leydig cell tumors while StAR (but not Melan-A) was negative in Sertoli cell tumors., Conclusions.—: Our data provide a comprehensive overview on the patterns of StAR immunostaining in human tumors and suggest a diagnostic utility of StAR immunohistochemistry for supporting a diagnosis of Leydig cell tumors or of normal or neoplastic adrenocortical tissue., Competing Interests: The rabbit recombinant StAR antibody, clone MSVA-740R, was provided from MS Validated Antibodies GmbH (owned by a family member of Sauter). The other authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

Ovary microcystic stromal tumor (MCST) is an extremely rare subtype of sex cord-stromal neoplasm, and only 57 cases have been reported. We herein report a unique case of ovarian MCST with positive nestin expression in a 39-year-old Chinese woman. The tumor showed microcystic stromal histological structures and characteristically expressed the CD10, WT-1, and Ki67 proteins. A molecular analysis identified a point mutation (c.110C > T) in exon 3 of the CTNNB1 gene. To our knowledge, no report has described a case of ovarian MCST with positive staining for nestin protein. Our study provides new insights into the tumor biology of ovarian MCST.

Background: Stathmin, a cytosolic microtubule-destabilizing phosphoprotein involved in the regulation of mitosis, is widely expressed in various malignancies and acts as an adverse prognostic factor. Our research analyzed its immunohistochemical expression on a large cohort of ovarian sex cord-stromal tumors, evaluating its potential utility in differential diagnosis, prognosis, and therapeutic application., Methods: We examined 390 cases of ovarian sex cord-stromal tumors including 281 adult granulosa cell tumors (AGCT), 5 juvenile granulosa cell tumors (JGCT), 33 Sertoli-Leydig cell tumors (SLCT), 50 fibromas/thecomas (F/T), 11 Leydig cell tumors/steroid cell tumors (LCT/SterCT), 5 sex-cord stromal tumors NOS (SCST-NOS), 3 Sertoli cell tumors (SCT), and 2 sclerosing stromal tumors (ScST). Immunohistochemical analysis was performed using TMAs., Results: Strong expression (> 50%) was observed in all cases of AGCT, JGCT, SLCT, SCST-NOS, SCT and 1 ScST. The other case of ScST exhibited mild expression (5-10%). The negative cases included exclusively F/T and LCT/SterCT, with F/T showing 24% of negative cases and LCT/SterCT comprising 64% of negative cases., Conclusion: The results of our study indicate that stathmin is neither a prognostic marker nor suitable for the differential diagnosis of challenging cases of ovarian sex cord-stromal tumors. However, its predictive value may be theoretically significant, as a decrease in stathmin expression potentialy influences response to chemotherapy treatment., (© 2024. The Author(s).)

Special AT-rich sequence-binding protein 2 (SATB2) is a nuclear transcription factor that shows consistent nuclear staining in colorectal adenocarcinoma and osteosarcoma. Following the observation of cytoplasmic staining with this marker in luteinized ovarian stromal cells, we studied the expression of SATB2 in ovarian stromal cells, various types of follicular cysts, and sex cord-stromal tumors. Eighty-five cases were stained for SATB2. Ovarian hilar Leydig cells (n = 12), luteinized stromal cells (n = 10), corpora lutea (n = 4), luteinized follicular cysts (n = 4), and stromal hyperthecosis (n = 6) exhibited consistent, usually diffuse, granular cytoplasmic staining. In addition, Leydig cell tumors (n = 1) and steroid cell tumors (n = 4) showed diffuse cytoplasmic staining. SATB2 also exhibited cytoplasmic staining in most Sertoli-Leydig cell tumors (n = 16) and gynandroblastomas (n = 3) confined to the Leydig cell component. Adult granulosa cell tumors (n = 14), juvenile granulosa cell tumors (n = 3), sex cord tumors with annular tubules (n = 3), cellular fibromas (n = 3), sclerosing stromal tumors (n = 1), and thecomas (n = 1) were negative apart from cytoplasmic staining in associated luteinized stromal cells. SATB2 cytoplasmic staining has not been previously described in these lesions but is characteristic of a variety of ovarian stromal cells and sex cord-stromal tumors, in particular, those exhibiting luteinization or a Leydig or steroid cell component. SATB2 staining may be of value in identifying luteinized or Leydig cells when these are morphologically inconspicuous., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 by the International Society of Gynecological Pathologists.)

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., (© 2024 Wiley Periodicals LLC.)

A subset of testicular sex cord-stromal tumors (SCST), which includes neoplasms with mixed histology, cannot be classified into a specific histologic subtype. This study evaluated the clinicopathologic, immunophenotypic and molecular features of 26 SCST not amenable to specific classification by expert uropathologists. Median age at diagnosis was 43 years and median tumor size was 2.4 cm. Follow-up information was available for 18 (69%) patients, with evidence of an aggressive clinical course in 6 patients (4 alive with disease, 2 dead of disease 3 months and 6 months after orchiectomy). Microscopically, SCST not amenable to specific classification demonstrated monophasic epithelioid (9/26, 35%), monophasic spindle cell (5/26, 19%), and biphasic or mixed histology (12/26, 46%). One or more aggressive histopathologic features were seen in 11 cases. DNA sequencing was successful in 22 tumors. Pathogenic CTNNB1 and APC alterations were seen in 7 (33%) and 2 (10%) cases, respectively, with additional variants (e.g., CDKN2A, RB1, TP53, BRCA2) being identified in individual cases. Combined evaluation of morphology, sequencing data and beta-catenin immunohistochemistry resulted in reclassification of 6 (23%) tumors as Sertoli cell tumor, not otherwise specified. This was supported by comparing the methylation profiles of a subset of these tumors and those of typical Sertoli cell tumors. Additionally, a subset of 5 neoplasms (19%) with spindle cell or biphasic histology and SMA expression was characterized by hyperdiploid genomes with recurrent chromosomal gains and absence of driver mutations, possibly representing a distinct tumor type. The SCST that remained not amenable to specific histologic classification (15/26, 58%) were enriched for aggressive histologic features and malignant clinical behavior. In conclusion, this study demonstrated that a subset of testicular SCST that were originally not amenable to specific classification could be reclassified by combined evaluation of morphology, immunohistochemistry and molecular data., (© 2022. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.)

Myoid gonadal stromal tumor represents a rare testicular neoplasm displaying smooth muscular and gonadal stromal differentiation. This entity has very few cases reported in the literature that describe heterogeneous clinical and pathological characteristics. Bayesian statistics provides a useful framework to combine information from diverse sources. We here presented a case series-the largest so far reported-of myoid gonadal stromal tumor (4 cases) with extensive morphologic, immunohistochemical, and molecular characterization, performed a systematic review of the literature (that identified 9 papers), and used a Bayesian data analysis to understand the characteristics of this disease. Our study collectively described 16 cases. This neoplasm is mainly found in adults (mean age about 40 years) and often has a size of about 3 cm. By morphology, the tumor can infiltrate testicular tubules and is composed of spindle cells; few mitoses can be seen (usually 2/10 HPF). Neoplastic cells are diffusely positive with α-smooth muscle actin with a tram-track staining pattern. S100 protein, FOXL2, and SF1 are also characteristically positive. Moreover, this neoplasm can display epithelial differentiation, in about half of the cases. In conclusion, we foresee the use of this statistical approach in pathology: our analysis allowed a more precise description of this rare entity.

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a uterine mesenchymal tumor defined histologically by showing sex cord-like growth patterns, such as sheets, nests, trabeculae, cords, or tubules, with/without Sertoli-like or Leydig-like components, and immunohistochemically by exhibiting variable sex cord markers in addition to epithelial, myogenic, and sex hormone markers. Recent years have seen the emergence in UTROSCT of novel fusion genes that involve key genes in sex hormone pathways, including ESR1 and GREB1 as the 5' partner, and (co)activator oncogenes, particularly NCOA1-3, as the 3' partner. While the identification of similar fusions in the majority of cases serves as a strong argument for UTROSCT to be a distinct entity, there is no denying significant clinicopathologic heterogeneity within the disease spectrum, which might to some extent correlate with the different fusion types. The current review gives a summary of the recently identified fusions in UTROSCT, along with their possible clinicopathologic relevance. Also discussed are unsolved issues including the relationship between UTROSCT and so-called GREB1-rearranged uterine sarcoma as well as other uterine mesenchymal tumors harboring similar fusions., (© 2020 Wiley Periodicals LLC.)

Steroid cell tumors occur usually in the ovaries with very few reported cases of extra-ovarian origin. Our patient was a fifteen year old female, complaining from secondary amenorrhea and voice deepening. Values of serum cortisol, DHEA, FSH & LH were normal. Serum Testosterone was elevated while ACTH-pm was markedly elevated. MRI described bilateral solid para-ovarian masses. Exploration revealed two bilateral tubal extraluminal cysts & a right broad ligament cyst which were all excised. Pathological examination led to the diagnosis of steroid cell tumor. Serum testosterone & ACTH returned to normal levels after surgery with subsequent regression of the virilizing symptoms. We can conclude that extra-ovarian steroid cell tumors are extremely rare. They are usually presented with virilizing symptoms and hormonal abnormalities. Surgery is the main line of treatment.

Prostate cancer is well known to metastasize to the testis and is not an uncommon finding on castration performed for advanced disease. Although germ cell tumors make up the majority of testis neoplasms, there are more rare tumors, such as rete testis adenocarcinoma, that can mimic metastatic disease. NKX3.1 and prostein (P501S) are antibodies highly specific for prostate origin. Relatively little is known of the expression of these markers in testicular tissue. We investigated the expression of NKX3.1 and P501S in testicular tissues, sex cord-stromal tumors, germ cell tumors, and rete testis adenocarcinoma. We found strong diffuse nuclear staining for NKX3.1 in Sertoli cells of the testis. Expression of NKX3.1 was seen in 0/3 ovarian Sertoli cell tumors, 1/4 testicular Sertoli cell tumors, and in the Sertoli cell component of 1/12 ovarian Sertoli-Leydig cell tumors. We found moderate, diffuse cytoplasmic positivity for P501S in rete testis epithelium and in testicular Leydig cells. P501S also highlighted Leydig cells in 9/12 Sertoli-Leydig cell tumors of the ovary. Two of 3 Leydig cell tumors of the testis showed weak to moderate, diffuse cytoplasmic staining for P501S. All cases of embryonal carcinoma and pure seminoma were negative for both NKX3.1 and P501S. One case of rete testis adenocarcinoma showed patchy positivity for both NKX3.1 and P501S. In conclusion, NKX3.1 shows routine expression in Sertoli cells and P501S shows routine expression in Leydig cells and rete testis epithelium. In addition, these markers can be positive in sex cord-stromal tumors and rete testis adenocarcinoma.

Ovarian tumours in children and adolescents are rare diseases. Although the majority of tumours are benign, the diagnosis and management present various challenges that require a wide range of expertise. The multidisciplinary team ensures not only accurate diagnosis and correct and minimally invasive management, but also minimal psychological impact and the preservation of fertility. This article outlines the multidisciplinary team approach to ovarian masses in children and adolescents. The team includes paediatric oncologists, gynaecological surgeons, pathologists, radiologists, fertility experts, geneticists and psycho-social services., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Microcystic stromal tumor (MCST) is a rare subtype of sex cord-stromal neoplasm. Tumors from all 31 previously reported cases were located in the ovary. Herein, we present a unique case of a right-side testicular tumor in a 33-year-old Chinese male. The tumor is composed of predominantly lobulated cellular nodules separated by hyalinized fibrous stroma and they expressed CD10, β-catenin (nuclear), and cyclin D1. Molecular analysis identified a point mutation (c.110C>G) in exon 3 of CTNNB1. The histopathological features, immunohistochemistry profiles, and molecular analysis of this tumor were consistent with MCST of the ovary. Therefore, a diagnosis of MCST of the right testicle was determined. To the best of our knowledge, this is the first case of MCST occurring in the testicles. The study may provide new insights to the tumor biology of MCST and a better understanding of this rare entity.

Sclerosing stromal tumours (SSTs) are rare benign tumours and are generally observed in individuals in their teens to 20 s. Many cases are suspected as malignant tumours pre-operatively, owing to their high vascularity on diagnostic imaging. Herein, we aimed to evaluate the expressions of various angiogenic factors in SSTs. The expressions of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF) were examined by immunohistochemical staining. Upon immunohistochemistry, overexpressions of VEGF, bFGF, and HGF in the ovarian stroma were observed in SSTs. In the normal ovary, the expressions were strong around the vessels and weak in the stroma of the ovary, while a Sertoli-Leydig cell tumour showed weak staining with VEGF, locally strong staining with bFGF and negative staining with HGF. This is the first report about angiogenic factors such as bFGF, and HGF in SST. Impact statement What is already known on this subject? Sclerosing stromal tumour (SST) is a rare benign tumour with high vascularity. The high vascularity of SSTs are reported to be related to the overexpression of vascular endothelial growth factor (VEGF). But there is no study on the expressions of other angiogenic factors in SST. What do the results this study add? In the immunohistochemical analysis, VEGF, bFGF and HGF were found to be widely stained in SSTs. This results suggest the possibility that the high vascularity seen on diagnostic imaging, and the many small vessels observed microscopically may be related to the expressions of VEGF, bFGF and HGF in SSTs. What are the implications of these findings for clinical practice and/or further research? Our results suggest the possibility that the combined expression pattern of VEGF, bFGF, and HGF may be used as marker of SSTs.

Objective: To examine the potential of ARX as a novel biomarker of ovarian endometriosis and other ovarian pathologies., Methods: The mRNA level of ARX in ovarian endometriosis and normal endometrium samples was determined by real-time PCR, while the protein level was determined by Western blotting and immunohistochemical staining. Immunohistochemical analysis was performed on nearly 200 tissue samples of different ovarian pathologies. GraphPad Prism was used for statistical analysis., Results: The expression of ARX was significantly increased in ovarian endometriosis samples as compared to normal endometrium. Also Western blotting data showed higher ARX levels in the ovarian endometriosis samples versus normal endometrium. Immunohistochemical analysis revealed that the protein is localized in the ovarian stroma and does not originate from endometriosis. Further immunohistochemical analysis performed on several different non-neoplastic and neoplastic ovarian tissue samples revealed that in the non-neoplastic ovary ARX protein is present only in the stromal cells and their derivates (luteinized stromal cells, theca and Leydig cells) and not in granulosa cells, oocites, surface epithelium or rete ovarii, while all stromal and sex cord tumors showed strong nuclear staining for ARX. All other primary or metastatic epithelial tumors of the ovary were ARX negative., Conclusions: ARX is not associated with endometriosis and cannot be used as a biomarker for ovarian endometriosis. ARX is present in ovarian stroma and cells derived from ovarian stroma as well as in all types of sex cord-stromal tumors of the ovary and could thus be used as a marker for sex cord-stromal differentiation in ovarian tumors., (Copyright © 2017. Published by Elsevier Inc.)

Ovarian germ cell tumors (OGCTs) and sex cord stromal tumors (SCSTs) are rare gynecologic tumors that are derived from germ and stromal cells, respectively. Unlike their epithelial counterparts, molecular pathogenesis of these tumor types is still poorly understood. Here, we characterized microRNA (miRNA) expression profiles of 9 OGCTs (2 malignant and 7 benign) and 3 SCSTs using small RNA sequencing. We observed significant miRNA expression variations among the three tumor groups. To further demonstrate the biological relevance of our findings, we selected 12 miRNAs for validation in an extended cohort of 16 OGCTs (9 benign and 7 malignant) and 7 SCSTs by reverse transcription-quantitative polymerase chain reaction. Higher expression of miR‑373‑3p, miR‑372‑3p and miR‑302c‑3p and lower expression of miR‑199a‑5p, miR‑214‑5p and miR‑202‑3p were reproducibly observed in malignant OGCTs as compared to benign OGCTs or SCSTs. Comparing with benign OGCTs, miR‑202c‑3p and miR‑513c‑5p were more abundant in SCSTs. Additionally, we examined Beclin 1 (BECN1), a target of miR‑199a‑5p, in the clinical samples using western blot analysis. Our results show that BECN1 expression was higher in malignant OGCTs than benign OGCTs, which is concordant with their lower miR‑199a‑5p expression. This study suggests that these miRNAs may have potential value as tumor markers and implications for further understanding the molecular basis of these tumor types.

Rationale: An accessory ovary is a rare structure containing normal ovarian tissue, which has a direct or ligamentous connection with a normal and eutopic ovary., Patient Concerns: In the study, we reported a 46-year-old woman presented with secondary amenorrhea and virilization symptoms for 1 year., Diagnoses: Endocrine evaluation revealed slightly elevated serum cortisol, extremely elevated 24-hour urinary-free cortisol and serum testosterone. Clinical assessment exhibited a large solid mass with heterogeneous enhancement in the left adnexauteri compounded with hypercortisolism and hyperandrogenemia. An accessory ovarian tumor attached to the infundibulum of the left fallopian tube was found, and a separate normal ovary was present on the same side., Interventions: The patient underwent a left adnexectomy., Outcomes: During surgery, a 12 cm × 8 cm, gray-red, and well-circumscribed solid mass was be identified. The tumor had ligamentous attachment with the infundibulum of left fallopian tube. The sectioned surface was gray-brown, lobulated and did not exhibit either significant necrosis or hemorrhage. Pathological findings demonstrated that tumor cells had small round nuclei, mild atypia, no mitosis were arranged in a diffuse pattern of columns or nests separated by a rich vascular network and no crystals of Reinke were found. It was diagnosis ovarian steroid cell tumor (NOS) without malignant behavior by immunohistochemical staining. The patient was finally diagnosed as accessory ovarian steroid. The patient was discharged from the hospital on the seventeenth day after surgery. During postoperative follow-up, the first postoperative menstrual flow recovered and blood pressure regained 1 month after surgery. Furthermore, her Cushing syndrome regressed and hirsutism disappeared completely 4 months after surgery cell tumor., Lessons: It is vitally important to establish a final diagnosis according to the clinical manifestations and laboratory values in addition to imaging studies and laparoscopic examination of a rare coexistence of hyperandrogenemia and Cushing syndrome based on the accessory ovarian pathology.

We report 3 cases of primary extraovarian unclassifiable malignant sex cord-stromal tumors. In all cases, the tumors involved the pelvis, peritoneum, and/or omentum and the morphologic features were essentially those of a poorly differentiated malignant neoplasm. A diagnosis of sex cord-stromal tumor was made on the basis of expression of several markers of ovarian sex cord-stromal tumors and exclusion of other neoplasms. In 1 case, an elevated serum testosterone was present at tumor progression. In reporting these cases, we draw attention to the problems in establishing a diagnosis that can be attributed to the extreme rarity of sex cord-stromal tumors in an extraovarian location and the rarity of unclassifiable malignant sex cord-stromal tumors in general, resulting in pathologists not considering this diagnosis. We review sex cord-stromal tumors occurring in an extraovarian location.

This descriptive study was carried out at Pathology Department, Shifa International Hospital from 2007 to 2016; all sex cord stromal tumours diagnosed during this time period were included. Epithelial, germ cell and metastatic tumours were excluded from the study. A total of 1254 Ovarian tumours were brought to Shifa of which47 (4%) were labeled as sex cord stromal tumours. Of these 36( 76 %)were granulosa cell tumour (adult33, juvenile3), 7 were labeled as sertoli leydig cell tumours (15%), 3 as thecoma/ fibroma group (7%)and only one case was labeled as microcystic stromal tumour of the ovary (2%). Overall age range for sex cord stromal tumours was 42 (12-71). Immunohistochemistry was done in 41 out of 47 cases. Sex cord stromal tumours of the ovary are rare tumours comprising 4% of the total. Adult Granulosa cell tumour is the commonest tumour seen in our study.

Background/aim: Adult granulosa cell tumor of the ovary is usually diagnosed at an early stage. However, most patients with advanced or recurrent disease will die of the disease due to limited treatment options. Data on the stromal p16 expression of ovarian adult granulosa cell tumors are limited. The aim of this study was to analyze the immunohistochemical p16 expression in the peritumoral stroma of primary and recurrent adult granulosa cell tumors and investigate whether there were significant differences in stromal p16 expression among nonpathological ovaries, benign sex cord-stromal tumors, and adult granulosa cell tumors., Materials and Methods: This study included 13 and 11 cases of primary and recurrent adult granulosa cell tumors, respectively. Non-pathological ovaries and benign sex cord-stromal tumors showed negative or weak positive expression, whereas most of the adult granulosa cell tumors showed diffuse and moderate-to-strong immunostaining., Results: Primary adult granulosa cell tumors had significantly higher stromal p16 expression levels than nonpathological ovaries and benign sex cord-stromal tumors (p<0.001). Moreover, recurrent adult granulosa cell tumors showed significantly elevated levels of stromal p16 expression compared to primary adult granulosa cell tumors (p=0.032). In contrast, the difference in stromal p16 expression between non-pathological ovaries and benign sex cord-stromal tumors was not statistically significant (p=0.522)., Conclusion: Our observations suggest that stromal p16 expression may be involved in the development and progression of ovarian adult granulosa cell tumors., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The WHO classification of testis tumours includes the group of sex cord-stromal tumours. They are divided into several histological types, i.e. Leydig cell (LCT) and Sertoli cell tumours (SCT). Based on the physiological expression of β-catenin in normal testis/Sertoli cells, it was previously shown that SCT can carry a β-catenin mutation, causing a nuclear positivity for β-catenin and cyclin D1. Furthermore, it could be shown that the stabilization of β-catenin in Sertoli cells causes the loss of the Sertoli cell marker SOX9. We wanted to know whether the stabilization of β-catenin in sex cord-stromal tumours influences SOX-9 expression and thus could be used in the diagnosis of sex cord-stromal tumours. Therefore, 53 cases of sex cord-stromal tumours and tumour-like lesions were investigated for their immunohistochemical expressions of β-catenin, cyclin D1 and SOX9. In addition, mutation analyses of the β-catenin gene (exon 3; CTNNB1) were performed. β-catenin mutation in SCT results in nuclear β-catenin and cyclin-D1 expressions on immunohistochemical analysis. The nuclear expression/stabilization of β-catenin causes the loss of SOX9 in these tumours. In contrast, SOX9 is considerably expressed in non-mutated SCT as well as in Sertoli cells of non-neoplastic testes. In summary, immunohistochemical analyses of β-catenin and SOX9 are useful to distinguish SCT from other sex cord-stromal tumours of the testis. Furthermore, the presence of SOX9 indicates that the cells of origin may be Sertoli cells.

Microcystic stromal tumors (MCST), first described in 2009 by Irving et al., are rare ovarian neoplasms. The entity was introduced into the 2014 WHO classification of tumors of female reproductive organs in the group of sex cord-stromal tumors, which is rather heterogeneous. We studied three cases of ovarian tumor with the characteristic morphological features and immunohistochemical marker profiles of MCST. The three tumors showed micro, and macrocystic patterns with solid areas, and were composed of small round to spindle-shaped cells, without atypia. The tumors diffusely and strongly expressed CD10, FOXL2, and nuclear β-catenin, but without immmunoreactivity for hormone receptors, calretinin, or inhibin. Genome analyses showed no somatic mutation of exon 1 of the FOXL2 gene and of exons 24 and 25 of DICER1 gene, the latter not having been reported previously. The patients are well, without evidence of tumor progression 1 to 10 years after diagnosis.The absence of FOXL2 and DICER1 gene mutation, along with strong FOXL2 immunoreactivity provides additional evidence to place MCST within pure gonadal stromal rather than sex cord ovarian tumors.

Sclerosing stromal tumor (SST) is a rare ovarian neoplasia deriving from the sex cord stromal tumor, which occurs usually in the sec- ond and third decades of life. However, the authors report a 46-year old multiparous woman who presented with a cystic-solid left pelvic mass, a large amount of ascites, and elevated serum CA-125, all suggesting a malignant tumor. Surgery was performed and final histopathological diagnosis of the specimen was diagnosed with SST. The authors herein report an extremely rare case of SST with a cystic-solid pelvic mass and a large amount of ascites, which is useful to demonstrate the possibility of SST in multiparous woman.

We performed a detailed morphologic, immunophenotypic, and endocrine characterization of neoplastic and non-neoplastic lesions of androgen-producing cells known to harbor or lack Reinke crystals (RCs) with an aim to provide further insight into the nature of these cells and crystals. Study cases were selected from the files of participating hospitals and subclassified according to current classifications: 20 with Leydig cell tumors (LCTs), 2 with testicular adrenal rest tumors (TARTs), 2 with testicular tumors of adrenogenital syndrome (TTAGS), and 2 with androgen insensitivity syndrome (AIS). An extensive immunophenotypic panel including markers used in sex cord-stromal cell tumors, androgen hormones, enzymes, and receptors was applied to the cases and 10 non-tumoral adrenal glands. Non-tumoral tissues were scored separately. RCs were present in 90 % of LCT cases and all cases with normal Leydig cells; RCs stained specifically with calretinin and 3β-hydroxysteroid dehydrogenase (3BHSD) and were present only in cells with high concomitant expression of both proteins, a phenotype unique to Leydig cells and LCTs. Leydig cells from AIS cases lack RCs due to decreased expression of 3BHSD. Calretinin is decreased in testicular adrenal-like tumors and absent in normal adrenocortical cells, which explain why they lack RCs. Calretinin expression in androgen-producing cells is independent from androgen receptors and androgen synthesis. RCs represent for the most part, if not exclusively, crystallized forms of a 3BHSD/calretinin complex. Androgen-producing cells containing and lacking RCs differ mainly in the level of expression of these proteins and androgen receptors.

Aims: Sex cord stromal tumours (SCSTs) of the ovary encompass several histological tumour subtypes that are defined by characteristic histological features. Some can show morphological overlap with other subtypes of SCSTs, as well as with non-SCSTs. The E-cadherin/catenin complex constitutes the adherens junction, which is well developed in epithelial tissue, but the constituent molecules are also expressed in several non-epithelial tumours. The aim of this study was to determine whether the expression patterns of E-cadherin and catenins in ovarian SCSTs can be of diagnostic utility., Methods and Results: We studied the expression of E-cadherin, α-, β- and γ-catenin in 55 tumours using immunohistochemistry. We found that all tumour subtypes showed nuclear expression of E-cadherin, while only microcystic stromal tumours (MCSTs) displayed a distinct profile, with nuclear localization of all three catenins in almost all cases., Conclusions: We conclude that the E-cadherin expression profile in SCSTs can assist in distinguishing between SCSTs and non-SCSTs in which there is no nuclear expression of E-cadherin. The nuclear localization of catenins may be of potential use in distinguishing MCST from other subtypes of SCST., (© 2016 John Wiley & Sons Ltd.)

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare neoplasm which morphologically and immunohistochemically exhibits overlap with an ovarian sex cord tumor. Although many of these neoplasms are positive with markers of ovarian sex cord-stromal tumors, staining is often limited and the pathogenesis of UTROSCT is unknown. To further explore the sex cord lineage of UTROSCT, we studied 19 of these neoplasms and examined the expression of 2 recently described markers of ovarian sex cord-stromal tumors, FOXL2, and steroidogenic factor-1. We also undertook FOXL2 and DICER1 mutation analysis in these cases; a somatic missense mutation in codon C134W (402C→G) of FOXL2 gene has been demonstrated in the vast majority (>95%) of ovarian adult granulosa cell tumors and somatic DICER1 mutations are found in approximately 60% of ovarian Sertoli-Leydig cell tumors. Ten of 19 cases (53%) exhibited nuclear immunoreactivity with FOXL2 and 11 of 19 (58%) exhibited nuclear staining with steroidogenic factor-1. Neither FOXL2 nor DICER1 mutations were identified in any case where there was sufficient tumor tissue for analysis (18 and 9 cases, respectively). Despite exhibiting an immunophenotype characteristic of a sex cord-stromal tumor, mutations in FOXL2 and DICER1, the 2 most common mutations hitherto reported in ovarian sex cord-stromal tumors, are not a feature of UTROSCT.

A 12-yr-old girl presented with lordosis and an intraperitoneal mass that revealed a tumor attached to the uterine fundus. The fallopian tubes and ovaries were spared. The mass was completely excised, and a patch of the uterine fundus and the proximal one third of the fallopian tubes were resected. The lesion was composed of bland spindle cells that were positive for sex cord-stromal markers, with particularly strong staining for inhibin and CD56, as well as patchy staining for calretinin, WT1, and steroidogenic factor 1. Thus, the patient was diagnosed with a sex cord-stromal tumor, specifically a fibroma, arising from the uterine corpus. The pathogenesis of this tumor is unclear. An ovarian origin in the context of adherence or a tumor arising from sex cord-stromal ectopic tissues cannot be excluded, but seem unlikely. The tumor might appear as a particular form of uterine tumor resembling an ovarian sex cord tumor. However, this tumor would differ from the presently described classical form of uterine tumor resembling an ovarian sex cord tumor owing to a pure stromal differentiation instead of a pure sex cord differentiation. Finally, because of the low risk for recurrence, long-term follow-up was prescribed for the patient.

Aims: To analyse the clinicopathological, immunohistochemical and β-catenin (CTNNB1) mutation characteristics of six cases of microcystic stromal tumour of the ovary (MCST)., Methods and Results: Six Chinese patients with MCST who ranged in age from 29 to 69 years (mean 50 years) were included in the study. Five patients were detected with a pelvic mass during routine health examinations and one patient presented initially with opsomenorrhoea. All tumours involved the left ovary, with solid-cystic cut surface in five cases and cystic cut surface in one case. Microscopically, microcysts, solid nests and hyaline degenerated fibrous stroma were variably mixed. Immunohistochemically, the tumour cells in all cases were diffusely positive for CD10, vimentin and WT-1 and negative for α-inhibin and calretinin. β-catenin expression was observed in both the nucleus and the cytoplasm in five cases and only in the cytoplasm in one case. The results of CTNNB1 mutation analysis revealed four missense point mutations in four cases, which were c.97T>C, c.101G>A, c.110C>G and c.122C>T., Conclusions: MCST shows a unique morphology with characteristic immunophenotype. β-catenin expression in the nucleus and β-catenin mutations were identified in the majority of cases, which suggests that the Wnt/β-catenin pathway may play a crucial role in the tumorigenesis of MCST., (© 2015 John Wiley & Sons Ltd.)

Background: Testicular stromal tumors (TSTs) are rare. In adult men with TSTs, various pathologic risk factors have been identified in patients with clinically localized disease that increase the risk of occult metastatic disease (OMD). We systematically reviewed existing literature to analyze the impact of these risk factors on OMD in prepubertal (0 to 12 y) and postpubertal (13 to 21 y) patients., Methods: A literature search was conducted using the combination of terms: "testicular stromal tumors," "testicular leydig cell tumors," "testicular sertoli tumors," "testicular interstitial tumors," "testicular granulosa tumor," and "testicular sex cord tumors." Studies of patients 0 to 21 years with clinical stage I TSTs were included., Results: A total of 100 patients from 31 publications were included with a median age at diagnosis of 5.7 years (range, 1.2 mo to 21 y). Seventy-nine patients were 12 years and below (median 7.2 mo) and 21 patients were 13 to 21 years (median 16 y). No patients in either group were identified to have OMD at retroperitoneal lymph node dissection or during follow-up surveillance (median follow-up 45.6 y; range, 4 to 360 mo). 99% of those 12 years and below versus 95% of those above 12 years had 0 to 1 pathologic risk factors, and 1% versus 5% had 2+ pathologic risk factors (P=0.38)., Conclusions: Clinical stage I TSTs in adolescent, postpubertal patients appear to behave in a benign manner with few pathologic risk factors, similar to prepubertal patients. Given the low risk of relapse in this population, low-impact surveillance strategies are paramount. Prospective study of these patients is needed, and entry into a tumor registry such as the International Ovarian and Testicular Stromal Tumor Registry is important to learning more about this rare disease.

Computed tomography obtained as part of a urinary tract assessment in a 68-year-old woman incidentally detected a solid adnexal mass. Bilateral salpingo-oophorectomy revealed a unilateral, 4-cm, white to tan-yellow colored, focally calcified, left ovarian mass. Microscopically, the tumor was composed of bland fibroblasts, abundant collagen, and areas of calcification with a minor component composed of nests of epithelial cells with nuclear clefts focally evident, some of which contained central lumens with eosinophilic secretions. The major considerations were fibromatous overgrowth in a Brenner tumor or ovarian fibroma with minor sex cord elements. Immunostains for cytokeratin 7 showed diffuse positivity in the epithelial nests, whereas cytokeratin 20 and inhibin were negative, further supporting the diagnosis of a Brenner tumor.

Primary fibrosarcoma arising from ovarian sex-cord stroma is a very rare neoplasm, with only a few reports in the literature. These tumors have been reported to express inhibin which allows their distinction from fibrosarcomas of soft tissue. Here, we report a case of a fibrosarcoma arising in the broad ligament. Despite being totally separate from the ovary, the tumor was diagnosed as sex-cord stromal type on the basis of inhibin expression. Furthermore, this patient suffered a recurrence of her tumor in the pelvis, which showed both the fibrosarcomatous, as well as other sex-cord elements, confirming the sex-cord stromal differentiation of the sarcoma. To our knowledge, this is the first case of a sex-cord stromal fibrosarcoma arising from an extraovarian site. Furthermore, this is also the first case of a recurrent fibrosarcoma, which showed redifferentiation of the tumor into other sex-cord components.

Ovarian tumors encountered during pregnancy can pose a diagnostic challenge due to an abundance of luteinized cells and other changes. We report 8 sclerosing stromal tumors with massive luteinization discovered in pregnant patients. The tumors ranged from 3.1 to 21 cm (mean=8.8 cm) in size and were typically solid and yellow; the neoplasm was bilateral in 1 case. On microscopic examination, the lutein cells, a feature of sclerosing stromal tumor, had more copious eosinophilic cytoplasm and were more numerous than is usually seen in nonpregnant patients and to varying degrees obscured the typical pseudolobular pattern. This resulted in particular diagnostic difficulty in 3 cases, especially when associated with other changes including irregular shapes of tumor cell nests, edema, and/or myxoid change. However, classic features of these tumors: ectatic vessels and admixed luteinized and nonluteinized cells were still focally evident, allowing for accurate classification. The tumors were cytologically bland and with 1 exception had rare mitoses. As sclerosing stromal tumors have been invariably benign, it is important that they not be confused with other tumors, such as steroid cell tumor, which can occasionally be malignant.

The significance of steroidogenic factor-1 (SF-1) in human ovarian tumor has not been fully investigated. The purposes of this study are to provide a meta-analysis for SF-1 and to determine whether SF-1 is associated with ovarian tumor progression and clinicopathological characteristics. A detailed literature search was made for related research publications written in English. Methodological quality of the studies was also evaluated. The data were extracted and assessed by two reviewers independently. Analysis of pooled data was performed, and odds ratio (OR) and corresponding confidence intervals (CIs) were calculated and summarized respectively. Final analysis from seven eligible studies was performed. Aberrant SF-1 expression was significantly lower in ovarian cancer compared to that of normal ovarian tissue (OR = 0.02, 95% CI = 0.00-0.16, p = 0.0002). However, SF-1 protein expression was not significantly different between benign and malignant ovarian tumors (p = 0.35). Interestingly, aberrant SF-1 expression was significantly higher in ovarian sex cord stromal tumors than that of ovarian cancer (OR = 0.00, 95% CI = 0.00-0.01, p < 0.00001). The results of this meta-analysis suggest that SF-1 may play an important role in ovarian cancer initiation and progression. Moreover, SF-1 expression may serve as a marker in the differential diagnosis between ovarian sex cord stromal tumors and ovarian cancer.

Germline mutations in identified breast cancer susceptibility genes account for less than 20% of Chinese familial breast cancers. Dicer is an essential component of the microRNA-producing machinery; germline mutations of DICER1 have been confirmed in familial pleuropulmonary blastoma, ovarian sex cord-stromal tumors, and other cancers. Low expression of DICER1 is frequently detected in breast cancer. However, whether germline mutations of DICER1 occur in familial breast cancers remain unknown. Sixty-five breast cancer probands from BRCA1/BRCA2-negative Chinese breast cancer families were screened for germline mutations in DICER1. In addition, 100 unrelated healthy females were enrolled as controls. A polymerase chain reaction sequencing assay was used to screen for mutations in coding regions and at the exon-intron boundaries of DICER1. All variants in introns were evaluated using the NNSplice software to determine the potential splicing effect. A total of 12 germline variants were found, including 11 variants in introns and 1 variant in the 3'-non-coding region. Four variants (IVS8-205 C>T, IVS11+131 delGAAA, IVS16+42 delTA, and IVS19+160 T>C) were novel. Three variants (IVS11+105 C>T, IVS16+42 delTA, and 6095 T>A) may affect splice sites. None of the observed variants appeared to be disease-related, suggesting that germline mutations in DICER1 are rare or absent in familial breast cancer patients.

Background: Sclerosing stromal tumors are extremely rare sex cord stromal tumors of the ovary, with approximately 100 cases reported since first described in 1973. These tumors present predominantly in the 2nd and 3rd decades of life, typically present with pelvic/abdominal pain and tenderness, mass, and/or abnormal menses, and with hormonal activity reported predominantly in postmenarchal females. Only 5 cases of these tumors have been reported in premenarchal girls, with age ranging from 7 months to 12 years. Only 2 demonstrated hormonal manifestations, with vaginal bleeding due to hyperestrogenism in the 7 month old, and virilization in an 11-year-old female., Case: We report a 9-year-old female who was diagnosed with this ovarian tumor, and who presented with virilization., Summary and Conclusion: This report is remarkable as our patient not only was diagnosed with an ovarian tumor that is extremely rare in this age group but is the youngest reported patient with this tumor who presented with virilization., (Copyright © 2014 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)

Sclerosing stromal tumor (SST) is a distinctive benign ovarian stromal neoplasm first reported in 1973. Although its initial description supports its characterization as an ovarian stromal tumor, its exact pathogenesis remains uncertain. It is usually hormonally inactive, but occasional tumors are estrogenic or androgenic, and virilization can occur during pregnancy. We report 11 cases of SST, 6 of which were associated with another type or other types of ovarian stromal tumor. In 4 of these, a transition from thecoma of either typical or luteinized type to SST was observed. Our index case was that of a 16-yr-old girl who had a typical thecoma that underwent involutional changes in an extensive subserosal portion of the tumor with conversion to SST. In our series, 3 cases of SST underwent transformation to ovarian myxoma, one of which also contained a component of thecoma. The active SST components stained for inhibin, steroidogenic factor 1, and α-smooth muscle actin, but were negative or occasionally weakly positive for desmin.

Microcystic stromal tumor is a recently described rare subtype of ovarian tumor for which there has been no previously reported ultrastructural study. We report a case with the characteristic histological and immunohistochemical features and the first ultrastructural study. The immunohistochemical findings of strong and diffuse nuclear staining for beta catenin and P27 are suggestive of dysregulation of more than one genetic pathway. The ultrastructural findings are supportive of the previous postulation of an ovarian stromal origin of the neoplastic cells.

Uterine tumors resembling ovarian sex cord tumors (UTROSCT) are rare neoplasms of unknown etiology. Only 67 cases have been reported in the literature, to our knowledge, so far. The neoplasm usually occurs in middle-aged women. Most patients present with abnormal uterine bleeding and/or abdominal pain, along with an enlarged uterus or a palpable uterine mass. There is no specific imaging finding, and the diagnosis is made exclusively on histopathologic examination. A multitude of architectural patterns are described, which include plexiform cords, anastomosing trabeculae, watered-silk, microfollicle, macrofollicle, tubules, retiform, solid cellular islands, and diffuse pattern of growth. The neoplastic cells are usually small with round to ovoid nuclei, nuclear monotony, mild nuclear hyperchromasia, and inconspicuous nucleoli with scant eosinophilic cytoplasm. Nuclear grooves are rare. Mitotic figures are infrequent, and necrosis is mostly absent. This tumor depicts a diverse immunohistochemical profile with expression of sex cord, epithelial, and smooth muscle lineages markers. Sex cord markers, such as inhibin, calretinin, CD99, WT1, and MART-1; epithelial markers, such as pancytokeratin and epithelial membrane antigen; smooth muscle markers, such as smooth muscle actin, desmin, and histone deacetylase 8; and miscellaneous markers, such as CD10, estrogen receptor, progesterone receptor, S100, and CD117, are often coexpressed. Immunoexpression for calretinin and at least for one of the other sex cord markers is required to establish a diagnosis of UTROSCT. Hysterectomy with or without bilateral salpingo-oophorectomy is usually the treatment for UTROSCT. Although most UTROSCTs behave benignly, some do recur, and thus, this entity should be considered as a tumor of low malignant potential. In this review, we discuss the current knowledge on UTROSCT and its clinical relevance.

Most ovarian sex cord-stromal tumors (SCSTs) can be categorized on the basis of conventional histology, but approximately 10% of cases are unclassified because they present indeterminate or overlapping morphologic features. Immunohistochemical and molecular studies of unclassified ovarian SCST are very limited, but recently, it has been demonstrated that 2 major subgroups of SCST, adult-type granulosa cell tumor and Sertoli-Leydig cell tumor, are characterized by somatic mutations in FOXL2 and DICER1, respectively. In this study, 12 diagnostically problematic ovarian SCST, including 9 unclassified tumors, were investigated for FOXL2 and DICER1 mutations and for immunohistochemical expression of calretinin, CD56, CD99, estrogen receptor α, estrogen receptor β, FOXL2, inhibin, progesterone receptor, and steroidogenic factor-1. Four of 11 tumors with satisfactory analysis showed a FOXL2 mutation; 3 of these cases were reported initially as unclassified SCST and 1 as Sertoli-Leydig cell tumor. Conversely, 3 cases with an original diagnosis of granulosa cell tumor were FOXL2 mutation-negative, and none of 7 tumors with satisfactory analysis demonstrated a DICER1 mutation. All tumors expressed at least 4 of the immunomarkers examined, although staining was often focal and there was no consistent correlation with tumor morphology. In conclusion, molecular analysis is useful in the assessment of diagnostically challenging ovarian SCST. The absence of FOXL2 and DICER1 mutations in most unclassified SCST suggests that these could represent a distinct tumor subgroup with different molecular pathogenesis. Immunohistochemical profiles overlap with those of better categorized SCST, but staining may be focal or negative emphasizing the requirement for antibody panels in diagnostic assessment., (© 2013.)

Gonadoblastoma is a rare gonadal neoplasm composed of primordial germ cells and sex cord-stromal cells and usually occurs in patients with dysgenetic gonads. When patients with gonadoblastoma develop an invasive germ cell tumor, the invasive germ cell component can take the form of dysgerminoma/seminoma, embryonal carcinoma, or yolk sac tumor. In this study, we performed immunohistochemical analysis for SALL4 and steroidogenic factor-1 (SF-1) on 4 cases of gonadoblastoma to examine the expression patterns of these proteins. All of the patients were phenotypically female. One patient had Swyer syndrome, the rest had Turner syndrome. The primordial germ cell component was histologically similar to cells in dysgerminoma/seminoma in these 4 cases. Two patients showed the invasive component-dysgerminoma. As expected, SALL4 stained the germ cells and SF-1 stained the sex cord-stromal cells. There was a clear distinction between the staining patterns of these 2 cell populations. This study demonstrates the utility of SALL4 and SF-1 in determining whether or not there is an invasion in the primordial germ cell component.

Sclerosing stromal tumours are rare benign ovarian neoplasms of the sex cord stromal that occur predominantly in the second and third decades of life. Herein, we report two cases of sclerosing stromal tumour of the ovary. The two patients were 16 and 45 years old and both presented with pelvic pain. Ultrasonography demonstrated a heterogeneous solid mass of the left and right ovary, respectively, with some cystic foci in the second tumour. Laboratory tests including tumour markers and serum hormonal assays were normal in both cases. The two patients underwent left and right salpingo-oophrectomy, respectively. Microscopically, the tumours showed a pseudolobular pattern with cellular areas separated by oedematous and collagenous areas. The cellular areas were richly vascularized, with a hemangiopericytic pattern, and were composed of an admixture of theca-like and spindle-shaped cells. Immunohistochemical studies showed that the tumour cells were positive for smooth muscle actin, inhibin and vimentin, but negative for cytokeratin. The final pathological diagnosis was sclerosing stromal tumour. Postoperative course was uneventful for both patients.

5-Fluorouracil is a well know drug for chemotherapy of various types of cancer. In the present study, we radiolabeled 5-fluorouracil with (99m)Tc for a diagnostic study of cancer. After successful labeling of the drug we performed an animal study to evaluate the potential of this radiopharmaceutical as a tumor diagnostic agent. The results showed 98.1 ± 1.2% labeling efficacy of 5-fluorouracil with (99m)Tc. The in vitro stability of the radiolabeled drug at room temperature at 4 hr of post-labeling was >96.5 ± 0.4%. The binding of the radiolabeled drug with plasma proteins was 66.6 ± 3%. Partition coefficient results showed that this drug is hydrophilic in nature. Biodistribution study in rabbit models displayed faint uptake in liver. Both kidney and bladder were prominent as excretory route of the labeled drug. Bioevaluation was performed in Swiss Webster mice having naturally developed tumor. Mice were dissected, uptake of drug in various organs was studied and results showed prominent uptake in liver and tumor. Tumor was further investigated by histopathological study.

Immunohistochemistry can be useful in the diagnosis of ovarian germ cell tumours and sex cord-stromal tumours. A wide variety of markers are available, including many that are novel. The aim of this review is to provide a practical approach to the selection and interpretation of these markers, emphasizing an understanding of their sensitivity and specificity in the particular differential diagnosis in question. The main markers discussed include those for malignant germ cell differentiation (SALL4 and placental alkaline phosphatase), dysgerminoma (OCT4, CD117, and D2-40), yolk sac tumour (α-fetoprotein and glypican-3), embryonal carcinoma (OCT4, CD30, and SOX2), sex cord-stromal differentiation (calretinin, inhibin, SF-1, FOXL2) and steroid cell tumours (melan-A). In addition, the limited role of immunohistochemistry in determining the primary site of origin of an ovarian carcinoid tumour is discussed., (© 2012 Blackwell Publishing Limited.)

Ovarian cancer is the leading cause of death in gynecological cancer. Studies suggested Rab25 is involved in the pathogenesis of ovarian cancers. We here investigated the expression of Rab25 is in all ovarian cancers and whether the expression of Rab25 is associated with peritoneal metastasis. Fifty-nine ovarian cancer patients were included and the levels of Rab25 measured by immunohistochemistry. Our data showed Rab25 was highly expressed in all subtypes of epithelial ovarian cancers, and two subtypes of germ cell tumors, but not in sex cord stromal tumors. Furthermore, the Rab25 expression was not correlated with peritoneal metastasis of ovarian cancer.

This study evaluates the immunoreactivity of 12 sex cord-stromal tumors of nonhuman primates (11 granulosa cell tumors and 1 luteoma). The markers selected are used in the characterization of gonadal tumors in dogs and other species, including cytokeratins AE1/AE3, GATA-4, inhibin-α, neuron-specific enolase, protein gene product 9.5, and vimentin. A normal nonhuman primate ovary was used as a control and to optimize immunolabeling. Staining was graded as follows: 0 (nonstaining), 1+ (< 10% positive cells), 2+ (10%-50% positive cells), and 3+ (> 50% positive cells). Calretinin, GATA-4, neuron-specific enolase, and vimentin were the most consistently expressed markers (12 of 12). Cytokeratins AE1/AE3 were also consistently expressed (11 of 12). Inhibin-α and protein gene product 9.5 were expressed in 8 and 10 sex cord-stromal tumors, respectively. Results indicate that immunoreactivity of nonhuman primate sex cord-stromal tumors is similar to that observed in other species and that calretinin, GATA-4, and neuron-specific enolase are the most consistently expressed markers in nonhuman primate sex cord-stromal tumors.