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PubMed2003

Overexpression of human chorionic gonadotropin causes multiple reproductive defects in transgenic mice.

Human CG is a pregnancy marker secreted by the placenta, and it utilizes the same receptors as does LH. Human CG is a heterodimer, and its subunits are expressed in tissues other than placenta. Similarly, LH/hCG receptors are also expressed in multiple tissues; however, the physiological significance of this expression is unknown. Free hCGbeta is efficiently secreted in vitro in transfected cells and is highly expressed in many human cancers; however, the biological effects of free hCGbeta in vivo are unknown. To study in vivo consequences of elevated levels of free hCGbeta and hCG dimer in both male and female reproductive physiology, we used mouse metallothionein 1 promoter to generate multiple lines of transgenic mice that overexpressed either one or both subunits of hCG. Although mice expressing the glycoprotein hormone alpha subunit are normal and fertile, both male and female transgenic mice overexpressing only the hormone-specific hCGbeta subunit are infertile. The hCGbeta subunit-expressing transgenic female mice progressively develop cystic ovaries, whereas the male transgenic mice are infertile but otherwise are not phenotypically discernible. In contrast, both the male and female transgenic mice coexpressing high levels of the hCG subunits (i.e., the hCG dimer) demonstrate multiple reproductive defects. The male transgenic mice have Leydig cell hyperplasia, very high levels of serum testosterone, reduced testis size, and dramatically enlarged seminal vesicles and are infertile and display overly aggressive behavior when caged with females. The female transgenic mice are also infertile, have elevated levels of serum estradiol, and progressively develop hemorrhagic and cystic ovaries with thecal layer enlargement and stromal cell proliferation and degenerating kidneys. These results suggest that the in vivo biological effects of ectopically expressed free hCGbeta subunit are distinct from those of the hCG dimer and are gender specific. These transgenic mice are useful models for studying the biology of free hCGbeta subunit, for further analyzing the gain of function effects of hCG during early Leydig cell development, and for studying the roles of hCG in ovarian and kidney pathophysiology and function.

Animals↗
PubMed1990

Equine granulosa-theca cell tumors express inhibin alpha- and beta A-subunit messenger ribonucleic acids and proteins.

The association of equine granulosa-theca cell tumors with atrophied contralateral ovaries and abnormal estrous cycles suggests that these tumors produce hormones that affect pituitary gonadotropin production. Because inhibin, a heterodimer protein secreted by granulosa cells, decreases FSH production, we examined the presence of inhibin alpha- and beta A-subunits and their mRNAs in ovarian tumors obtained from three mares. These tumors contained neoplastic cords and nodules, multiple fluid-filled cysts, and a predominance of neoplastic granulosa cells. Reduced proteins from tumor-conditioned media were analyzed by electrophoresis and immunoblotting using antibodies directed against peptide fragments of the alpha- and beta A-chains of porcine inhibin. Specific bands at 50-kDa and 36-kDa for the inhibin alpha-subunit and at 44 kDa and 13 kDa for the inhibin beta A-subunit were observed in these tumors. Northern blot hybridization of 32P-labeled rat inhibin alpha- and beta A-subunit complementary RNAs to total RNA from each tumor revealed predominant bands of activity in all three tumors at 1.5 and 7 kb for the alpha- and beta A-subunit mRNAs, respectively. These results demonstrate that equine granulosa-theca cell tumors express the mRNAs for inhibin alpha- and beta A-subunits and also secrete inhibin subunits that could potentially affect gonadotropin production in afflicted mares. Furthermore, cells derived from these tumors may provide a useful model for understanding inhibin gene regulation and ovarian tumorigenesis.

Animals↗
PubMed1985

Cellular differentiation in ovarian sex-cord-stromal and germ-cell tumors studied with antibodies to intermediate-filament proteins.

Seventy ovarian sex-cord-stromal and germ-cell tumors were immunohistochemically studied for the presence of intermediate-filament proteins of different types used as markers for cellular differentiation. Cells of ovarian granulosa-cell tumors constantly expressed vimentin and appeared to lack cytokeratin. Two tumors previously classified as granulosa-cell tumors were reclassified as poorly differentiated "common" epithelial tumors based on their cytokeratin positivity, vimentin negativity, and morphologic features. Dysgerminomas and Leydig-cell tumors showed only vimentin positivity. Tubular structures in androblastomas, which are considered to represent Sertoli-cell differentiation, were cytokeratin positive, and thus differed from the majority of normal Sertoli cells that are known to express vimentin and not cytokeratin. Embryonal carcinomas, choriocarcinomas, and endodermal sinus tumors showed cytokeratin positivity in the neoplastic cells whereas vimentin was observed in the stromal cells. In immature teratomas, epithelial differentiation was demonstrated with cytokeratin antibodies, and neural and glial differentiation was also frequently demonstrated by immunostaining with antibodies to neurofilaments and glial fibrillary acidic protein. The results show that antibodies to intermediate filaments can be used in the differential diagnosis between ovarian epithelial and nonepithelial tumors, and they provide a very accurate additional method to characterize the cellular differentiation of ovarian neoplasms.

Animals↗
PubMed1987

Ovarian steroid cell tumors (not otherwise specified). A clinicopathological analysis of 63 cases.

The clinical and pathological features of 63 steroid cell tumors, not otherwise specified, were reviewed. The patients ranged in age from 2 1/2 to 80 years. The most common initial manifestation was virilization (41%); four patients had estrogenic manifestations, and four had hypercortisolemia with Cushing's syndrome. The tumors, 6% of which were bilateral, ranged from 1.2 to 45 cm in greatest dimension. Microscopic examination revealed two types of cells, which had overlapping features: those with abundant eosinophilic cytoplasm and those with vacuolated cytoplasm. Fat stains were positive in 75% of the 16 cases in which they were performed. Follow-up data ranging from 1 to 19 years (average 5.2 years) in duration were available for 50 patients. In 24 cases, the tumor was designated probably benign (no evidence of spread beyond the ovary within 3 or more years postoperatively). In 18 patients, the tumor was clinically malignant. The best pathological correlates of malignant behavior were: the presence of two or more mitotic figures per 10 high power fields (92% malignant); necrosis (86% malignant); a diameter of 7 cm or greater (78% malignant); hemorrhage (77% malignant); and grade 2 or 3 nuclear atypia (64% malignant).

Adolescent↗
PubMed2000

Tc-99m dicarboxypropane diphosphonate uptake in ovarian fibrothecoma.

A 76-year-old woman had a palpable mass in the lower abdomen. Computed tomography showed an abnormal pelvic mass with necrotic areas, probably of ovarian origin. A Tc-99m dicarboxypropane diphosphonate whole-body scan performed to evaluate the extent of the disease (i.e., the presence of bone metastases) revealed only diffuse uptake of the tracer in the pelvis. Histopathologic analysis after surgical excision of the mass revealed a fibrothecoma of the right ovary, which is a benign tumor composed of cells derived from the ovarian stroma and, in some instances, resembles the thecal element of the follicle.

Aged↗
PubMed1983

Sclerosing stromal tumor of the ovary: case report and review of the literature.

A case of sclerosing stromal tumor of the ovary in a Chinese girl of 17 years is reported. She presented with metrorrhagia and an abdominal mass in the right lower quadrant. At operation, a large unilocular cyst was found in the right ovary. Light microscopic and ultrastructural study established the diagnosis of sclerosing stromal tumor of the ovary. To date, 63 cases have been recorded in the literature, 33 of which have been described in detail.

Adolescent↗
PubMed1987

Stromal luteoma of the ovary: a clinicopathological analysis of 25 cases.

The clinical and pathological features of 25 stromal luteomas were reviewed. The patients ranged in age from 28-74 (average 58.4) years. The most common initial manifestation (60%) was abnormal vaginal bleeding; three patients (12%) were virilized. The tumors, only one of which was bilateral, ranged from 0.25-2.9 (average 1.3) cm in greatest diameter. They were all well circumscribed. Microscopic examination revealed unencapsulated nodules composed of rounded polyhedral cells that were arranged either diffusely or in nests and cords. Twenty percent showed degeneration within aggregates of cell resulting in the formation of pseudoacinar structures. The cytoplasm of the neoplastic cells was generally eosinophilic and granular, and lipochrome granules were present in over half the tumors. In 92% of the cases hyperthecosis was present in the adjacent ovarian stroma. Follow-up of 6 months to 17 years was available for 19 patients. Sixteen of them were alive and free of disease; the remaining three died of other causes. The benign course in all the cases in which follow-up data were available was expected in view of the small size of the tumors and their benign microscopic appearance.

Adult↗
PubMedDate not supplied

Fibrothecomas of the ovary: CT and US findings.

OBJECTIVE: Fibrothecomas of the ovary are mesenchymal tumors representing 4-5% of all ovarian neoplasms. The purpose of this study is to describe a large series of CT findings in this type of tumor. MATERIALS AND METHODS: We reviewed retrospectively the CT examinations in 25 unilateral cases confirmed by surgery and pathology. Unenhanced and enhanced CT scans were performed in all cases and dynamic CT scans were performed in nine cases. These findings were compared to ultrasound in all cases. RESULTS: Computed tomography detected all but two small ovarian tumors (< 2 cm). Eighteen of 23 fibrothecomas were solid, with significant (> 10 HU) enhancement between precontrast and delayed CT scans. In all eight uncomplicated cases, nonincremental dynamic CT scan did not visualize arterial vessels; in seven of nine cases examined dynamically, early uptake of contrast material was visualized. Three of 23 fibrothecomas were partly cystic, partly solid. Two cases with torsion were mainly cystic with thickening and hemorrhage of the tube. CONCLUSION: In conclusion, 79% of ovarian fibrothecomas appeared as solid masses with delayed accumulation of contrast medium. On dynamic CT, the absence of arterial vessels and absence or slight early uptake of contrast enhancement could be useful findings for preoperative diagnosis. When partly or mainly cystic (21% of cases), ovarian fibrothecomas could not be easily differentiated from other ovarian masses.

Adolescent↗
PubMed1975

"Living cytology" in the diagnosis of intraabdominal adenocarcinoma.

Cytologic diagnosis of adenocarcinoma metastatic to the peritoneal surface is often hampered by the difficulty of differentiating between reactive mesothelial cells and macrophages from malignant epithelial cells by light microscopy. With in vitro tissue culture technics, the fibroblastic dedifferentiation of mesothelial cells facilitates the recognition of residual neoplastic epithelial cells. Ascitic fliid from 18 patients who ultimately had histologic documentation of intraabdominal adenocarcinomatosis was studied by tissue culture technics. In 15 of the 18 patients, small islets of replicating tumor cells could be identified after the mesothelial cells had dedifferentiated into fibroblasts. With one exception the average time between collection of the specimen and recognition of adenocarcinoma was 6 days. In 14 cases, a definitive diagnosis of malignancy was made by cytologic analysis.

Abdominal Neoplasms↗
PubMed1978

Differential maternal-fetal response to androgenizing luteoma or hyperreactio luteinalis.

Lacl of masculinization in female infants whose virilized mothers have h. luteinalis is in contrast to the common finding of fetal masculinization when maternal virilization occurs with luteoma of pregnancy. From the data at hand, this variation in fetal response cannot be explained by differences in the quantity of androgen production nor by the stage of pregnancy when maternal virilization becomes evident. Steroid analysis from cases of h. luteinalis suggests that the placenta may serve as an androgen barrier by aromatizing steroids before they reach the fetus. Testosterone conversion by the placenta of an anencephalic fetus confirms that conversion to estrogens occurs even without significant fetal adrenal activity. Understanding of the breakdown of this mechanism, with resultant fetal masculinization, will require careful evaluation of the steroid milieu in conditions like luteoma in which fetal masculinization often occurs. Both cystic and solid ovarian hyperplasia are recognized as are complications of pregnancy which require proper identification and conservative management. The significant difference in patients at risk for luteoma and h. luteinalis and the pathological and hormonal differences clearly indicate that these are distinct and separate entities.

Androgens↗
PubMed1998

Granulosa and theca cell tumors in children: a report of 17 cases and literature review.

The files of the Emil Novak Ovarian Tumor Registry (ENOTR) were searched for granulosa and theca cell tumors in children aged 12 years and less. In addition, an extensive literature search was done for English publications on children with these tumors aged 10 years or less. Of the 17 children from the ENOTR, 5 had adult-type granulosa cell tumors, 6 had juvenile granulosa cell tumors, and 1 had a luteinized granulosa cell tumor. In addition, there were three cases with gonadal stomal tumors, one theca cell tumor, and one granulosa-theca cell tumor. Precocious pseudopuberty was present in 70 percent of the children, abdominal pain in 24 percent, and ascites in 18 percent. The literature review revealed a tumor-related mortality rate of 9 percent (based on 163 cases with granulosa cell tumors, including the juvenile type). Some of these tumors are large with acute pain, but nevertheless, the prognosis is good, particularly in cases with precocious puberty. Treatment can be conservative.

Adolescent↗
PubMed2006

Recent advances in the pathology and classification of ovarian sex cord-stromal tumors.

In recent years, our knowledge of ovarian sex cord-stromal tumors has increased, and their classification has evolved. In this review, recent advances in the classification and pathology of ovarian sex cord-stromal tumors are discussed, and the controversy regarding the classification of sex cord tumor with annular tubules is addressed. The current classification is built on those of the past, and future classifications should improve on what is now in place incorporating new knowledge from more sophisticated clinicopathologic studies and advanced molecular techniques. This review emphasizes articles written in the 21st century as well as those that have significantly advanced our knowledge of sex cord-stromal tumors in past decades. The tumors in this group occur over a wide age range and are often unilateral. In difficult cases, immunocytochemistry provides improved diagnostic accuracy. The most useful immunohistochemical marker for their identification is alpha-inhibin, which is positive in most neoplasms in the sex cord-stromal group. The article concludes with a section discussing the pathogenesis of sex cord-stromal tumors.

Biomarkers, Tumor↗