- Case report: an identical twin with Sertoli-Leydig cell tumor. [Journal Article]
- GEGynecol Endocrinol 2018 Jan 24; :1-4
- Our report details the workup and management of a 43-year-old woman with an identical twin who presented with 2 years of virilization and secondary amenorrhea. Serum total testosterone was elevated. ...
Our report details the workup and management of a 43-year-old woman with an identical twin who presented with 2 years of virilization and secondary amenorrhea. Serum total testosterone was elevated. An MRI did not identify adnexal or adrenal pathology. Subsequent ovarian vein sampling demonstrated unilateral testosterone elevation. The patient underwent laparoscopic unilateral oophorectomy resulting in the diagnosis of Sertoli-Leydig cell tumor (SLCT). Although SLCT is a rare sex-cord ovarian tumor, it is associated with endometrial hyperplasia and malignancy. Our goals are to review the workup of androgen-secreting tumors and discuss the clinical importance of the DICER1 mutation in the context of SLCT. In this case, an identical twin underwent DICER1 testing which was one of the essential steps in her clinical management.
- DICER1 and associated conditions: Identification of at-risk individuals and recommended surveillance strategies. [Journal Article]
- CCClin Cancer Res 2018 Jan 17
- Pathogenic germline DICER1 variants cause a hereditary cancer predisposition syndrome with a variety of manifestations. In addition to conferring increased cancer risks for pleuropulmonary blastoma (...
Pathogenic germline DICER1 variants cause a hereditary cancer predisposition syndrome with a variety of manifestations. In addition to conferring increased cancer risks for pleuropulmonary blastoma (PPB) and ovarian sex cord-stromal tumors, particularly Sertoli-Leydig cell tumor, individuals with pathogenic germline DICER1 variants may also develop lung cysts, cystic nephroma, renal sarcoma and Wilms tumor, nodular hyperplasia of the thyroid, nasal chondromesenchymal hamartoma, ciliary body medulloepithelioma, genitourinary embryonal rhabdomyosarcoma and brain tumors including pineoblastoma and pituitary blastoma. In May 2016, the International PPB Registry convened the inaugural International DICER1 Symposium to develop consensus testing, surveillance and treatment recommendations. Attendees from North America, Europe and Russia provided expert representation from the disciplines of pediatric oncology, endocrinology, genetics, genetic counseling, radiology, pediatric surgery, pathology and clinical research. Recommendations are provided for genetic testing, prenatal management, and surveillance for DICER1-associated pulmonary, renal, gynecologic, thyroid, ophthalmologic, otolaryngologic, central nervous system tumors and gastrointestinal polyps. Risk for most DICER1-associated neoplasms is highest in early childhood and decreases in adulthood. Individual and caregiver education and judicious imaging-based surveillance are the primary recommended approaches. These testing and surveillance recommendations reflect a consensus of expert opinion and current literature. As DICER1 research expands, guidelines for screening and treatment will continue to be updated.
- CRISPR/Cas9‒Mediated Tspo Gene Mutations Lead to Reduced Mitochondrial Membrane Potential and Steroid Formation in MA-10 Mouse Tumor Leydig Cells. [Journal Article]
- EEndocrinology 2018 02 01; 159(2):1130-1146
- The outer mitochondrial membrane translocator protein (TSPO) binds cholesterol with high affinity and is involved in mediating its delivery into mitochondria, the rate-limiting step in hormone-induce...
The outer mitochondrial membrane translocator protein (TSPO) binds cholesterol with high affinity and is involved in mediating its delivery into mitochondria, the rate-limiting step in hormone-induced steroidogenesis. Specific ligand binding to TSPO has been shown to initiate steroid formation. However, recent studies of the genetic deletion of Tspo have provided conflicting results. Here, we address and extend previous studies by examining the effects of Tspo-specific mutations on steroid formation in hormone- and cyclic adenosine monophosphate (cAMP)-responsive MA-10 cells, using the CRISPR/Cas9 system. Two mutant subcell lines, nG1 and G2G, each carrying a Tspo exon2-specific genome modification, and two control subcell lines, G1 and HH, each carrying a wild-type Tspo, were produced. In response to dibutyryl cAMP, the nG1 and G2G cells produced progesterone at levels significantly lower than those produced by the corresponding control cells G1 and HH. Neutral lipid homeostasis, which provides free cholesterol for steroid biosynthesis, was altered significantly in the Tspo mutant cells. Interestingly, the mitochondrial membrane potential (ΔΨm) of the Tspo mutant cells was significantly reduced compared with that of the control cells, likely because of TSPO interactions with the voltage-dependent anion channel and tubulin at the outer mitochondrial membrane. Steroidogenic acute regulatory protein (STAR) expression was induced in nG1 cells, suggesting that reduced TSPO affected STAR synthesis and/or processing. Taken together, these results provide further evidence for the critical role of TSPO in steroid biosynthesis and suggest that it may function at least in part via its regulation of ΔΨm and effects on STAR.
- Incidental Gynecologic Tract Neoplasms in Women Undergoing Anterior Pelvic Exenteration for Urothelial Carcinoma. [Journal Article]
- IJInt J Gynecol Pathol 2017 Dec 18
- Urothelial carcinoma (UC) invasive into the muscularis propria or tumors unresponsive to treatment are indications for cystectomy. In females, with the goal of achieving complete cancer eradication a...
Urothelial carcinoma (UC) invasive into the muscularis propria or tumors unresponsive to treatment are indications for cystectomy. In females, with the goal of achieving complete cancer eradication and for concerns of UC extension into the adjacent pelvic organs, this may also warrant resection of the gynecologic organs. This study is aimed to assess the prevalence of unanticipated gynecologic neoplasms in anterior pelvic exenteration specimens. A retrospective review of pathology reports to identify women undergoing anterior pelvic exenteration for UC was performed (N=221), and incidentally discovered gynecologic tract neoplasms were recorded. Concomitant malignant or premalignant lesions of the gynecologic tract were identified in 8 patients (3.6%). These included endometrial adenocarcinoma [endometrioid type, International Federation of Gynecology and Obstetrics grade 1 (n=2, 0.9%)], cervical high-grade squamous intraepithelial lesion (n=2, 0.9%), Sertoli-Leydig cell tumor of intermediate differentiation (n=1, 0.5%), endometrioid adenocarcinoma of the ovary (n=1, 0.5%), and high-grade serous carcinoma of the ovary (n=1, 0.5%) and fallopian tube (n=1, 0.5%). Benign uterine neoplasms included leiomyomas (n=81, 37%), adenomyoma (n=3, 1.4%), and adenomatoid tumors (n=2, 0.9%). Benign ovarian neoplasms included serous cystadenoma (n=7, 3%), serous cystadenofibroma (n=4, 2%), benign Brenner tumor (n=5, 2.3%), mature teratoma (n=4, 2%), stromal luteoma (n=2, 0.9%), mucinous cystadenoma (n=1, 0.5%), thecoma (n=1, 0.5%), and endometrioid cystadenoma (n=1, 0.5%). Involvement of the gynecologic tract by UC was identified in 11 patients (5%). Spread of UC to the reproductive organs is rare in anterior pelvic exenteration specimens. Coexisting neoplasms of the gynecologic tract are occasionally identified, therefore careful evaluation of these organs is necessary.
- Familial multinodular goiter and Sertoli-Leydig cell tumors associated with a large intragenic in-frame DICER1 deletion. [Case Reports]
- EJEur J Endocrinol 2018; 178(2):K11-K19
- CONCLUSIONS: Patients with DICER1 syndrome usually present a combination of a typically truncating germline DICER1 mutation and a tumor-specific hotspot missense mutation within the sequence encoding the RNase IIIb domain. The in-frame deletion found in this family suggests that the germline absence of p.E1705 and p.D1709, which are crucial for RNase IIIb activity, may be enough to permit DICER1 syndrome to occur.
- Sertoli-Leydig cell tumor of the ovary masquerading as a mucinous adenocarcinoma: a frozen section pitfall. [Journal Article]
- RTRare Tumors 2017 Oct 03; 9(3):6861
- Sertoli-Leydig cells tumors are rare ovarian neoplasms that can be managed with conservative resection given their generally excellent prognosis. Here we report a case of Sertoli-Leydig cell tumor mi...
Sertoli-Leydig cells tumors are rare ovarian neoplasms that can be managed with conservative resection given their generally excellent prognosis. Here we report a case of Sertoli-Leydig cell tumor mistakenly diagnosed as an invasive mucinous adenocarcinoma at time of intraoperative consultation because of its blue-mucinous appearance in the frozen section material. The patient subsequently underwent an extensive staging procedure revealing unilateral, ovarian confined disease. The mucinous features seen on frozen section were lost on the slides prepared from formalin fixed tissues. Immunohistochemical work up confirmed the diagnosis of a pure Sertoli-Leydig cell tumor. No heterologous elements were identified in this tumor. This case illustrates a hitherto unrecognized frozen section pitfall in evaluation of ovarian neoplasms. To the best of our knowledge, this is the first well documented case of pure Sertoli-Leydig cells tumor which resembled a well differentiated mucinous adenocarcinoma during frozen section.
- Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for disseminated intraabdominal malignancies in children-a single-institution experience. [Journal Article]
- JPJ Pediatr Surg 2017 Oct 02
- CONCLUSIONS: CRS-HIPEC for children with disseminated intraabdominal malignancies performed in a dedicated institution and with guidance by a leading international center can be performed safely.
- DICER1-related Sertoli-Leydig cell tumor and gynandroblastoma: Clinical and genetic findings from the International Ovarian and Testicular Stromal Tumor Registry. [Journal Article]
- GOGynecol Oncol 2017; 147(3):521-527
- CONCLUSIONS: Recognition of the distinct genetic basis for a group of these tumors improves precise classification in difficult cases and promotes mutation-based screening and early detection.
- Germ Cell Neoplasia in Situ and Preserved Fertility Despite Suppressed Gonadotropins in a Patient With Testotoxicosis. [Case Reports]
- JCJ Clin Endocrinol Metab 2017 Dec 01; 102(12):4411-4416
- CONCLUSIONS: The case illustrates that absence of gonadotropins but high intratesticular testosterone concentration is sufficient for spermatogenesis and to allow fatherhood. Our study is also the first description, to our knowledge, of GCNIS in a patient with testotoxicosis. We recommend regular clinical examination and ultrasonic evaluation of the testes in these patients due to potential increased risk of malignancy.
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- Immunophenotypic comparison of testicular sclerosing Sertoli cell tumors and Sertoli cell tumors not otherwise specified. [Multicenter Study]
- HPHum Pathol 2017; 68:99-102
- Testicular Sertoli cell tumors (SCTs) are rare, and most fall into the category of SCT-not otherwise specified (SCT-NOS). Only a few additional types of SCT are recognized. Sclerosing SCT (S-SCT), or...
Testicular Sertoli cell tumors (SCTs) are rare, and most fall into the category of SCT-not otherwise specified (SCT-NOS). Only a few additional types of SCT are recognized. Sclerosing SCT (S-SCT), originally described in 1991, comprises a small fraction of SCTs and was considered a specific entity until the 2016 revision of the World Health Organization classification of non-germ cell tumors, where it was classified as a morphologic variant of SCT-NOS. In a recent study, differences in expression of PAX2/PAX8, inhibin, androgen receptor, and S100 protein between SCT-NOS and S-SCT were noted in a small number of cases. In this interinstitutional study, we compared the expression of these markers and β-catenin in 11 cases each of SCT-NOS and S-SCT to determine if differences exist that could justify keeping a separate classification of these neoplasms. PAX2/PAX8 cocktail was the only marker that was significantly overexpressed in S-SCT. Expression of androgen receptors was strong in S-SCT and variable in SCT-NOS but did not reach statistical significance. Expression of β-catenin was common in both, whereas inhibin was infrequent. The available material was insufficient for a conclusive evaluation of S100 protein expression. Overall, our results support the inclusion of S-SCT as a morphologic variant of SCT-NOS. Expression of PAX2/PAX8 in S-SCT may reflect an overactive epithelial-to-mesenchymal transition as has been shown in experimental models of acute and chronic seminiferous tubular injury and might be related to the process generating the stroma in these tumors.