Ovarian serous cystadenoma associated with Sertoli-Leydig cell tumor--a case report.

We Describe a case of ovarian serous cystadenoma having Sertoli-Leydig cell tumor, well differentiated, in the cystic septum. Well differentiated Sertoli-Leydig cell tumor coexisting with other tumor, including serous tumor, has not yet been described. In all cases of Sertoli-Leydig cell tumor with heterologous components or other tumors, the androblastomatous components are intermediately or poorly differentiated. The present case revealed a well differentiated Sertoli-Leydig cell tumor arising in a septum of serous cystadenoma, as a circumscribed nodule. With these findings, we discuss the possibility of this Sertoli-Leydig cell tumor, considered a mural nodule, which is well established in cystic common epithelial tumors of the ovary.     

Sertoli-Leydig cell tumor of the ovary with alpha-fetoprotein production

A case of poorly differentiated Sertoli-Leydig cell tumor with elevated serum alpha-fetoprotein (AFP) levels occurred in a 17-year-old girl. No germ cell component and no heterologous elements were identified, but a retiform pattern was present. Immunohistochemical studies demonstrated immunoreactivity for AFP and testosterone in Leydig's cells only. Secretion of AFP by Sertoli-Leydig cell tumors has rarely been mentioned previously, and its mechanism is difficult to explain. Non-germ cell tumors must be considered in the differential diagnosis of ovarian tumors with elevated serum AFP levels.     

Sertoli-Leydig cell tumor associated with a mature cystic teratoma in a single ovary

Sertoli-Leydig cell tumors of the ovary are rare neoplasms of young women and are best known for their frequent virilizing effects. They have very rarely been reported in association with other ovarian neoplasms. We report such a tumor associated with a mature cystic teratoma in the same ovary. The wide variety of histologic patterns seen in many Sertoli-Leydig cell tumors including the present case, often causing difficulty in diagnosis, is reviewed.     

Clinicopathologic features of ovarian Sertoli-Leydig cell tumors

Background: Ovarian Stertoli-Ledig cell tumor (SLCT) is a rare type of sex cord-stromal tumor of the ovary. The present study was to evaluate clinicalopahologic features and prognosis of patients with Sertoli-Leydig cell tumor treated by surgery and adjuvant chemotherapy during short term follow-up. Methods: A total of sixteen patients with ovarian Sertoli-Leydig cell tumor treated at the Obstetrics and Gynecology Hospital, Shanghai, China, between Jan 2001 and Dec 2011 were reviewed. The clinical data, treatment and prognosis were obtained from medical records. Results: The median age of the patients with ovarian Sertoli-Leydig cell tumor was about 27.5 years old in non-menopausal women, while the median age of menopausal women was about 63 years old. The most common complaint was with hormonal-related symptoms in the form of secondary amenorrhea and infinity, features of virilization, abdominal mass or irregular vaginal bleeding. All of sixteen patients underwent surgical staging and all were found to have stage I disease at the time of diagnosis. Eleven patients with intermediate and two patients with poorly differentiated tumors received adjuvant chemotherapy. There were differences found in operative time, blood loss and postoperative recovery time between laparotomy and laparoscopy. There were no disease-related deaths and all patients were under complete remission at the last follow-up. Conclusions: Ovarian Sertoli-Leydig cell tumors could happen in any period age of women. However, the tumors typically occur in the single side while still at the early stage, a favorable outcome could be achieved by surgery and adjuvant chemotherapy. Laparoscopy has similar surgical effects as laparotomy, but has a number of advantages.     

Sertoli-Leydig cell tumor of the ovary with heterologous elements and carcinoid: an immunohistochemical and ultrastructural study

A Sertoli-Leydig cell tumor of the ovary is described in which there were heterologous elements consisting of enteric cysts and an evolving carcinoid. Endocrine cells in the cysts and carcinoid were found to contain gastrin and other polypeptide hormones. Aspects of the organization of the enteric epithelium, its histogenesis, and the possible relationship of this tumor to other cystic ovarian neoplasms are discussed.     

Ovarian Sertoli-Leydig cell tumor of intermediate grade with heterologous elements of rhabdomyosarcoma. A case report and a review of the literature

Ovarian Sertoli-Leydig cell tumors (SLCTs) are rare sex cord-stromal tumors, and among them, tumors with heterologous mesenchymal elements are exceptional and mainly associated with poorly differentiated tumors and are often fatal. We present the fourth case of an ovarian SLCT of intermediate differentiation with rhabdomyosarcoma and a review of the literature. Surgical treatment was conservative with preservation of the contralateral adnexa and uterus. No adjuvant treatment was given. At 4 years control post surgery, the patient was without evidence of disease. Extensive sampling of SLCTs is important because heterologous elements may be sparse. Immature skeletal muscle cells in SLCTs often reveal only moderate pleomorphism, and as they are closely admixed with the Sertoli cells or immature gonadal stroma, they can be rather difficult to differentiate from the latter ones. Immunohistochemical analysis with a panel of antibodies including antibodies against myogenin and alpha-inhibin is very important to diagnose the rhabdomyosarcoma and to grade the SLCT accurately.     

Hepatocytic differentiation in retiform Sertoli-Leydig cell tumors: distinguishing a heterologous element from Leydig cells.

Sertoli-Leydig cell tumors (SLCT) of the ovary are rare sex cord-stromal neoplasms. A minority of SLCT are characterized by a pattern resembling that of the rete ovarii and frequently have a range of homologous and heterologous tissues. Approximately 20 cases of SLCT have been reported to have elevation of serum alpha-fetoprotein (AFP) levels, or tissue immunoreactivity for AFP, a protein usually associated with germ cell neoplasms, especially yolk sac tumor. We identified hepatocytic differentiation in five cases of retiform SLCT (RSLCT), and confirmed immunohistochemically that these cells are hepatocytes rather than Leydig cells. Hepatocytes are positive for keratins (AE1/3 and Cam 5.2), AFP, and ferritin, negative for vimentin, and show weak to moderate staining for inhibin. Leydig cells are negative for keratins, positive for vimentin, and intensely positive for inhibin. Immunohistochemistry is needed to distinguish hepatocytic differentiation from Leydig cells with certainty. Including the cases in this report, hepatocytic differentiation has been associated with a retiform pattern in SLCT in 14 of 25 cases (56%). The association of these two patterns appears to be characteristic of a relatively primitive sex cord-stromal neoplasm.     

Mucinous adenocarcinoma as heterologous element in intermediately differentiated Sertoli–Leydig cell tumor of the ovary

Sertoli–Leydig cell tumor (SLCT) is a rare tumor involving the ovary. Approximately 20% of SLCT are associated with heterologous elements that are either of endodermal or mesodermal origin. The gastrointestinal-type epithelium is the most commonly described endodermal heterologous element. SLCT with benign and borderline mucinous neoplasm has been reported in the literature. However, SLCT with mucinous adenocarcinoma as heterologous element has been rarely documented. Herein, we describe a rare case of intermediately differentiated Sertoli–Leydig cell tumor with mucinous adenocarcinoma as the heterologous element in a 21-year-old woman. She presented with throbbing lower abdominal pain and was found to have a large, complex left ovarian mass on imaging studies. She underwent left salpingo-oophorectomy, appendectomy and lymph node staging. Gross examination of the surgical specimen showed a large, encapsulated, solid-cystic mass completely replacing the ovary. Microscopically, the tumor was composed of intermediately differentiated Sertoli–Leydig cell tumor and well-differentiated mucinous adenocarcinoma. Interestingly, the bulk of the tumor (more than 90%) was composed of mucinous adenocarcinoma, whereas the SLCT component comprised less than 10% of the total tumor. The mucinous adenocarcinoma expressed positivity for CK20, CEA, CDX2 and CK7, and the SLCT component was positive for inhibin expression. The histopathological features and results of immunostaining were consistent with the diagnosis of the intermediately differentiated SLCT with mucinous adenocarcinoma as the heterologous element. This case was a diagnostic challenge as more than 90% of the tumor was composed of mucinous adenocarcinoma and SLCT constituted only the minor part of the tumor. This feature was in contrast to the previously described two cases, where mucinous adenocarcinoma as heterologous element was present as microscopic foci. This case highlights the importance of identifying the SLCT component in a case of an apparently pure mucinous adenocarcinoma in a young patient.     

Immunohistochemical studies of steroidogenic enzymes (aromatase, 17 alpha-hydroxylase and cholesterol side-chain cleavage cytochromes P-450) in sex cord-stromal tumors of the ovary

Aromatase, 17 alpha-hydroxylase, and cholesterol side-chain cleavage P-450 cytochromes (P-450AROM, P-450(17 alpha,) and P-450SCC, respectively) were immunohistochemically localized in nine granulosa cell tumors, 15 thecomas, ten Sertoli-Leydig cell tumors, two steroid cell tumors, five fibromas, and five sclerosing stromal tumors. In the thecomas, P-450SCC and P-450(17 alpha) were positive in luteinized theca cells and in cells with vacuolated cytoplasm, while P-450AROM was not observed. In the steroid cell tumors, all the P-450 cytochromes were intensely stained. P-450SCC and P-450(17 alpha) were present in cells with vacuolated cytoplasm in two cases of sclerosing stromal tumor. P-450AROM was weakly demonstrated in one of the granulosa cell tumors. P-450(17 alpha,) P-450SCC, and P-450AROM were all faintly stained in the Sertoli-Leydig cell tumors. No P-450 cytochrome immunoreactivity was observed in any fibroma.     

The utility of calretinin, inhibin, and WT1 immunohistochemical staining in the differential diagnosis of ovarian tumors

Calretinin has been proposed as a novel marker of ovarian sex cord-stromal tumors (SCST); this study aims to determine whether calretinin can complement or supplant the established utility of inhibin in the differential diagnosis of SCST. WT1 has been shown to be expressed in ovarian serous, but not mucinous neoplasms; its expression in a variety of ovarian tumors is also examined. Formalin-fixed, paraffin-embedded archival tissues from 111 primary ovarian tumors were analyzed with commercially available antibodies using semi-automated immunohistochemistry. Results were graded on a 4-tiered scale with staining of more than 0 but less than 5% of cells considered focal. Of 27 SCST, 56% were calretinin and 56% inhibin positive overall; 90% of granulosa cell tumors, 57% of Sertoli-Leydig cell tumors, 33% of thecomas, and 14% of fibromas were calretinin positive. Inhibin was expressed in 60% of granulosa cell tumors, 71% of Sertoli-Leydig cell tumors, 43% of fibromas, and 33% of thecomas. Of 35 surface epithelial tumors (SET), 8% of serous papillary tumors were calretinin positive, whereas 8% of serous papillary tumors and 13% of poorly differentiated carcinomas expressed inhibin. WT1 was expressed in 29% of all endometrioid carcinomas, 10% of borderline mucinous tumors, and no mucinous carcinomas; however, most of the other SETs were positive (77% serous papillary and 88% poorly differentiated carcinomas). Among the SCST, WT1 stained only granulosa cell tumors (75%), though often weakly or variably. Calretinin has only slightly greater sensitivity (76% versus 65%) and equal specificity to inhibin (92%) in the differential staining of granulosa or Sertoli-Leydig cell tumors, that is, nonstromal SCST. Hence, calretinin cannot replace but could complement inhibin as part of an immunohistochemical panel used for diagnostically challenging SCST. Although WT1 should be reliably positive in non-mucinous SET, staining of granulosa cell tumors and lack of expression in a sizable subset of endometrioid carcinomas may confound interpretation.     

Sertoliform endometrioid carcinoma of the ovary: a potential diagnostic pitfall

Sertoliform endometrioid carcinoma of the ovary (SEC) is an uncommon variant that bears histologic similarity to Sertoli and Sertoli-Leydig cell tumors (SLTs). Clinically, SEC affects an older population (60-70 years), while patients with SLT have an average age of 25 years and may exhibit endocrine manifestations. A number of histologic features can be used to distinguish the 2 entities, the most important ones being (1) the presence of areas with the usual pattern of endometrioid carcinoma, and (2) the presence of mucin at the apical borders of the tumor cells. Cytokeratin stains positively, while inhibin and calretinin stain negatively in SEC; the converse is true for SLTs. Based on the clinicopathologic behavior of this entity, SEC should be considered a well-differentiated carcinoma with relatively good prognosis if limited to the ovary.     

Immunohistochemical and ultrastructural analysis of a poorly differentiated pediatric age Sertoli-Leydig cell tumor

Ovarian Sertoli-Leydig cell tumors (SLCT) are rare in young women. They are divided into six categories based on the degree of differentiation and the presence of heterologous elements. Less than 15% of these tumors are poorly differentiated. A 14-year-old obese African-American girl presented with amenorrhea, progressive abdominal pain, and increasing abdominal girth. Pelvic CT revealed a 10 x 9 x 9 cm right adnexal mass which was resected successfully. The gross appearance was dark tan and red with central hemorrhage and necrosis. Microscopically, this was poorly differentiated with compact aggregates of moderate size oval to elongated cells separated by zones of edematous stroma containing scattered spindle shape cells. Areas of ill-formed tubules and primitive cords were present. Clusters of Leydig cells were observed. The oval and spindle cells showed multiple mitoses and were diffusely positive for inhibin and patchy but strong positivity for calretinin. Both preoperative and postoperative studies revealed no metastases. Serum alpha-fetal protein (AFP), androgen, and dihydroepiandrosterone sulfate (DHEA-S) were elevated.     

Ovarian heterologous Sertoli-Leydig cell tumors with gastrointestinal-type epithelium. An immunohistochemical analysis

Eight ovarian heterologous Sertoli-Leydig cell tumors containing gastrointestinal-type cells, including two tumors that contained carcinoids, were stained for argyrophilia and argentaffinity; in addition, these specimens were stained by immunohistocytochemical techniques for the demonstration of chromogranin, serotonin, and a variety of peptide hormones. Intestinal- and gastric-type epithelial and carcinoid cells within the tumors were focally argyrophilic and chromogranin-positive, but only intestinal-type epithelial and carcinoid cells contained argentaffin granules, serotonin, and corticotropin. Somatostatin, gastrin, neurotensin, and glucagon were demonstrated additionally in varying numbers of specimens containing intestinal-type epithelium and carcinoid, and somatostatin was present in gastric-type epithelium in one case. Staining for calcitonin and insulin was negative. Despite the frequent identification of serotonin and peptide hormones in the tumors in the present series, evidence of the carcinoid syndrome or syndromes associated with peptide hormone excess was lacking on review of the patients' records.     

Sertoli-Leydig Cell Tumor of the Ovary with Heterologous Elements and Carcinoid: An Immunohistochemical and Ultrastructural Study

Our thanks are due to Dr Michael Cullen, St. James's Hospital, Dublin, for clinical data in this case and to Dr Sean O'Briain, Central Pathology Laboratory, St. James's Hospital, and Dr Fred Bosman, Rijksuniversiteit, Leiden, who supplied the various antisera. James Dunne and Derek Cullen provided expert technical assistance in electron microscopy and staining techniques.

A Sertoli-Leydig cell tumor of the ovary is described in which there were heterologous elements consisting of enteric cysts and an evolving carcinoid. Endocrine ceils in the cysts and carcinoid were found to contain gastrin and other polypeptide hormones. Aspects of the organization of the enteric epithelium, its histogenesis, and the possible relationship of this tumor to other cystic ovarian neoplasms are discussed.     

Overexpression of the BCL2 gene in a Sertoli-Leydig cell tumor of the ovary: a pathologic and cytogenetic study

A case of virilizing ovarian Sertoli-Leydig cell tumor overexpressing the BCL2 gene and including a novel clonal chromosomal rearrangement of chromosome 18, der(5)t(5;18)(p13;q12),+6,+12, der(18)r(5;18)(p15.3p13;p11.3q12) is described. Further studies of these rare tumors are necessary to ascertain the significance of the findings.     

Sertoli-Leydig Cell Tumor of the Ovary with Heterologous Elements and Carcinoid: An Immunohistochemical and Ultrastructural Study

Our thanks are due to Dr Michael Cullen, St. James's Hospital, Dublin, for clinical data in this case and to Dr Sean O'Briain, Central Pathology Laboratory, St. James's Hospital, and Dr Fred Bosman, Rijksuniversiteit, Leiden, who supplied the various antisera. James Dunne and Derek Cullen provided expert technical assistance in electron microscopy and staining techniques.

A Sertoli-Leydig cell tumor of the ovary is described in which there were heterologous elements consisting of enteric cysts and an evolving carcinoid. Endocrine ceils in the cysts and carcinoid were found to contain gastrin and other polypeptide hormones. Aspects of the organization of the enteric epithelium, its histogenesis, and the possible relationship of this tumor to other cystic ovarian neoplasms are discussed.     

Clinicopathologic and immunohistochemical study on 8 cases of malignant mixed müllerian tumor

The clinico-pathological features of eight cases of malignant mixed müllerian tumor, a rare neoplasm composed of an admixture of epithelial and stromal elements, are reported. Four of the tumors located in the endometrium, three in the cervix and one in the ovary. Microscopically, the epithelial elements ranged from poorly to well differentiated adenocarcinoma. Homologous stromal sarcoma cells were present in six tumors and heterologous elements were also seen in the other two tumors. Immunohistochemical studies showed diffuse cytoplasmic staining of keratin in the epithelial elements of all the eight cases. Sarcomatous cells were positive focally for keratin in four spindle cell sarcoma cases. Desmin immunoreaction was moderately positive in the sarcomatous element of four neoplasms. Follow-up result was available in 7 patients of whom 3 survived and 4 died from recurrence or metastasis. Immunohistochemical findings support the stem cell origin of this tumor.     

Cervical embryonal rhabdomyosarcoma and ovarian Sertoli-Leydig cell tumour: a more than coincidental association of two rare neoplasms?

A case in which an embryonal rhabdomyosarcoma of the cervix and an ovarian Sertoli-Leydig cell tumour of intermediate differentiation occurred in a 13-year-old girl is described. Although initially considered as a chance association, a review of the literature showed the co-occurrence of these two uncommon neoplasms in three previous cases. The reason for this association, which is thought to be more than coincidental, is not known, although an underlying genetic abnormality is a possibility. The ovarian tumour in this case was characterised by the presence of foci of cells with extremely pleomorphic nuclei, which initially raised the possibility of metastatic rhabdomyosarcoma. These were interpreted as foci of bizarre nuclei within the Sertoli-Leydig cell tumour.     

Endometrioid-like yolk sac and Sertoli-Leydig cell tumors in a carrier of a Y heterochromatin insertion into 1qh region: a causal association?

We describe the case of a young woman showing yolk sac tumors (YST) and a Sertoli-Leydig cell tumor (SLCT) in the right ovary, with recurrences in the right adnexum and with hepatic metastasis. To our knowledge, YST and SLCT have never been described as components of the same tumor or reported as associated in the same patient. The patient's karyotype showed the presence of Y chromosome inserted into the 1qh region; the inserted region corresponded to Yq12 heterochromatin. LOH analysis revealed 1p36 paternal allele loss in the proband tumor, thus supporting a germ cell origin for the tumor. The presence of Y heterochromatin in 1qh DNA might induce disturbances in the normal regulation of oncogenes located in 1q.     

Inhibin immunohistochemical staining: a practical approach for the surgical pathologist in the diagnoses of ovarian sex cord-stromal tumors

Through a brief introduction of inhibin history, characteristics of the antibody against inhibin, and normal tissue distribution of alpha-inhibin expression, this comprehensive review focuses on a practical approach to using alpha-inhibin in the differential diagnosis of ovarian sex cord-stromal tumors (SCSTs). Alpha-inhibin has become a most useful immunohistochemical marker of gonadal SCST, regardless if the tumors are primary, recurrent, or metastatic. However, pathologic diagnosis of individual SCST is still based largely on morphologic criteria. Alpha-inhibin immunohistochemical (IHC) staining should be used only when a difficult morphologic diagnosis is encountered. In this perspective, alpha-inhibin and other properly selected markers should be ordered at the same time. This is simply because alpha-inhibin is not specific for SCSTs. Caution should be exercised in the interpretation of alpha-inhibin-positive cells, because a wide variety of primary and metastatic ovarian tumors may contain significant numbers of alpha-inhibin-positive stromal cells. As with other immunohistochemical stains, a panel of stains and comparison with the corresponding hematoxylin and eosin (H&E) slides is necessary, especially when staining patterns and cellular localization are in question. The antibody will not help to differentiate tumors within the category of SCST. The pattern or the intensity of staining in SCSTs does not predict tumor behavior, although there is a tendency of loss of alpha-inhibin expression in poorly differentiated Sertoli or Sertoli-Leydig cell tumors. In cases where metastatic granulosa or Sertoli-Leydig cell tumors are a concern, positive alpha-inhibin staining is diagnostic, but a negative result does not rule out metastatic disease. Calretinin has been recently recognized as a more sensitive, but less specific marker for SCSTs and it may be used to recognize an inhibin-negative SCST. In this review, we have listed nine of the most commonly encountered clinical scenarios where alpha-inhibin and other markers could be used in diagnostic surgical pathology of ovarian tumors.