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PubMed1976

[Thecal tumors of the ovary. 14 cases].

Out of 524 tumours of the ovary seen over a 20 year period, the diagnosis was that of a thecal tumour in 14 cases. In addition to the symptoms common to all ovarian tumours, in 7 cases there was metrorrhagia, including 4 post-menopausal. Vaginal cytology after the menopause was abnormally young in 6 cases. In 7 cases out of 13 the endometrium was hyperplasic. In only 5 cases were urinary oestrogen levels increased. At operation, the tumour was bilateral in 3 cases and ascites was present in 4. Histological findings were as follows: 6 thecomas, 4 fibro-thecomas, 1 luteinised thecal tumour, 3 tumours with granular cells and 1 case associated with a Brenner tumour. Two of these "mixed tumours" were malignant, with a fatal outcome. All the others were cured by operation. In young women in whom conservative procedures were used there were 4 subsequent pregnancies. The following questions were posed: The coexistence of ascites with tumours totally free of secretory cells (3 cases); The existence in true thecal tumours of signs of hyperoestrogenism (5 out of 6) whilst fibro-thecomas are not associated with any abnormal production of oestrogen.

Adolescent↗
PubMed1997

Value of inhibin in the identification of granulosa cell tumors of the ovary.

Inhibins are peptide hormones that participate in the regulation of the pituitary-gonadal feedback system and are selectively expressed by cells of sex cord-stromal derivation. To determine the efficacy of this marker for distinguishing granulosa cell tumors, 134 primary and metastatic lesions of the ovary were evaluated for expression of the alpha-subunit of inhibin in routinely processed formalin-fixed, paraffin-embedded tissue. A variety of sex cord-stromal tumors (SCST), including 35 adult and juvenile granulosa cell tumors, 14 fibroma-thecomas, and 18 other sex cord-stromal proliferations, were studied. In addition, 33 surface epithelial neoplasms, 12 germ cell tumors, 11 metastases, and 11 miscellaneous ovarian neoplastic proliferations were evaluated. Among the non-granulosa cell neoplasms, special emphasis was placed on primary neoplasms and metastases that histologically simulated granulosa cell tumors. Thirty-three of 35 (94%) granulosa cell tumors were immunoreactive compared with 2 of 12 (17%) primary ovarian endometrioid tumors, one of nine (11%) primary ovarian transitional cell (Brenner) proliferations, and 3 of 17 (18%) other primary and metastatic poorly differentiated (undifferentiated) carcinomas. In 31 of the 35 granulosa cell tumors, inhibin staining was of moderate to strong intensity or was present in at least half of the constituent cells, whereas only 2 of 33 primary surface epithelial neoplasms fulfilled the same criteria, showing weak staining of 70% to 80% of the cells. In contrast, 10 of 14 (71%) ovarian fibroma-thecomas and 17 of 18 (94%) other sex cord-stromal proliferations were positive for inhibin. Nonneoplastic luteinized stromal cells stained for inhibin in 29 of 85 cases in which they could be evaluated. The results of this study show that although it is not completely specific and cannot reliably distinguish granulosa cell tumors from fibroma-thecomas or other ovarian sex cord-stromal proliferations, inhibin can be used to help distinguish sex cord-stromal neoplasms from most primary and metastatic non-SCST. Caution should be exercised in the interpretation of inhibin-positive cells, because a wide variety of primary and metastatic ovarian tumors may contain significant numbers of positively staining luteinized cells.

Adult↗
PubMed1987

Intermediate filaments cytokeratin and vimentin in ovarian sex cord-stromal tumours with correlative studies in adult and fetal ovaries.

The expression of the intermediate filaments cytokeratin and vimentin were studied immunohistochemically in a series of ovarian sex cord-stromal tumours (26 adult and juvenile granulosa cell tumours, 11 thecomas, six fibromas, three Sertoli-Leydig cell tumours and 1 sex cord tumour with annular tubules). Contrary to previous reports, granulosa cell tumours expressed cytokeratins as well as vimentin. Thecomas and fibromas expressed vimentin only. In Sertoli-Leydig cell tumours and the sex cord tumour with annular tubules, both cytokeratins and vimentin were detected. Correlative studies in adult ovaries showed that patterns of expression in non-neoplastic granulosa, thecal and stromal cells correspond to their neoplastic counterparts. Investigation of fetal ovaries demonstrated that these patterns of intermediate filament expression exist from relatively early stages of development. Ovarian surface epithelium and rete ovarii, like granulosa cells, co-expressed cytokeratin and vimentin. The demonstration of cytokeratins in granulosa cells and the reported presence of desmosomes and tonofilaments, suggests the epithelial nature of these cells although not clarifying their histogenesis. The presence of both these intermediate filaments in granulosa and Sertoli-Leydig cell tumours as well as in some ovarian carcinomas which may mimic them, limits their value in differential diagnosis between these tumour groups.

Adult↗
PubMed1989

Alpha smooth muscle actin (alpha-SM actin) in normal human ovaries, in ovarian stromal hyperplasia and in ovarian neoplasms.

An immunohistochemical investigation of alpha-smooth muscle actin (alpha-SM actin) using the monoclonal anti-alpha-SM-1 antibody was carried out in 15 normal ovaries, in three ovaries with stromal hyperplasia and in 27 neoplastic ovaries. In selected cases the pattern of actin isoforms was examined by means of 2 D-gel electrophoresis. In addition, the tissues were stained for vimentin and desmin. In normal ovaries alpha-SM actin was found in the inner cortex and in the theca externa. In ovarian stromal hyperplasia expression of alpha-SM actin was minimal or absent. In primary and metastatic epithelial tumors there was positive stromal staining for alpha-SM actin, especially in the vicinity of epithelial elements. This tended to be more widespread in malignant neoplasms. Thecomas did not express alpha-SM-actin and could thus be differentiated from leiomyomas which stained intensely for alpha-SM actin. Only focal stromal staining of alpha-SM actin was observed in granulosa and germ cell tumors. In all the tissues studied blood vessels were strongly positive for alpha-SM actin. Desmin, although present in the stroma of most of the specimens, was less abundant than alpha-SM actin. We concluded that alpha-SM actin is a component of the normal human ovary where it may contribute to the contractility of its stroma. Its absence in the normal outer cortex and theca interna, and in stromal hyperplasia and thecoma implies that sex hormones do not constitute a stimulus for alpha-SM actin production in the ovary. Among neoplasms it is most widely represented in the stroma of epithelial tumors in which it may reflect stromal stimulation mediated by neoplastic epithelium.

Actins↗
PubMed1989

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.

Aromatase↗
PubMed2000

No evidence of somatic activating mutations on gonadotropin receptor genes in sex cord stromal tumors.

OBJECTIVE: To search for somatic activating mutations of gonadotropin receptor (FSH-R and LH/chorionic gonadotropin receptor [CG-R]) genes as a cause of sex cord stromal tumors. DESIGN: Molecular studies in human tissue. SETTING: University hospital. SPECIMEN(S): Eight granulosa cell tumors collected from paraffin-embedded tissue, eight Leydig cell tumors, and three thecomas collected from fresh-frozen or paraffin-embedded tissue. INTERVENTION(S): Tumor samples were used for DNA extraction. The entire exon 11 of the LH/CG-R gene and a hot spot for gonadotropin receptor activating mutations on exon 10 of the FSH-R gene were amplified by polymerase chain reaction. The former was analyzed by denaturing gradient gel electrophoresis and automatic direct sequencing, and the latter by automatic direct sequencing. MAIN OUTCOME MEASURE(S): Results of denaturing gradient gel electrophoresis and automatic direct sequencing. RESULT(S): No somatic activating mutation was detected in exon 11 of the LH/CG-R gene in eight Leydig cell tumors and three thecomas. In addition, no mutations were detected in eight granulosa cell tumors in the hot spot for activating mutations in exon 10 of the FSH-R gene. CONCLUSION(S): Somatic activating mutations of gonadotropin receptors seem to play no relevant role in the development of sex cord stromal tumors.

Exons↗
PubMed1994

Histogenetic consideration of ovarian sex cord-stromal tumors analyzed by expression pattern of cytokeratins, vimentin, and laminin. Correlation studies with human gonads.

A total of 30 sex cord-stromal tumors including 9 adult type and 5 juvenile type granulosa cell tumors (GCTs), 4 Sertoli-Leydig cell tumors (SLTs), 1 gynandroblastoma, 5 thecomas, 2 fibromas and 3 sclerosing stromal tumors were immunohistochemically evaluated by means of cytokeratins of different molecular weight, vimentin and laminin with regard to the histogenesis of these tumors and to the embryogenesis of the sex cord and stroma of developing gonads. For comparison, 7 embryonic gonads, 9 fetal and 9 adult ovaries, 14 fetal and 5 postnatal testes, and 1 gonadoblastoma were also examined. The coelomic epithelium of all gonads were positive for both cytokeratins (CAM 5.2 and AE1) and vimentin. In fetal ovaries, the granulosa cells of primordial follicles express low molecular weight cytokeratins only and those cells of more maturing follicles did not express any cytokeratin or vimentin. In adult ovaries, the granulosa cells of primordial follicles coexpressed low molecular weight cytokeratins and vimentin, but those cells of more maturing follicles expressed vimentin only. In fetal testes before 20 weeks gestational age, the Sertoli and Leydig cells did not express any cytokeratins and vimentin. After that time, both cells expressed vimentin only throughout life. The rete ovarii and rete testis from fetal to adult life coexpressed both low molecular weight cytokeratins and vimentin. The rete ovarii in all ages and rete testis in prenatal and childhood ages were surrounded by the laminin-positive basement membrane, however, the rete testis in adult were not. In neoplasia, the GCTs, thecomas, fibromas, and sclerosing stromal tumors expressed vimentin only.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Ovarian stromal tumors with minor sex cord elements: a report of seven cases.

Seven ovarian tumors that were predominantly stromal, but contained, in addition, a minor component of sex cord elements, were encountered in patients ranging from 16 to 65 years of age. The tumors varied from 1 to 10 cm in diameter and resembled grossly fibromas or thecomas. On microscopical examination they were predominantly fibromatous, but also contained small nests or tubules composed of cells resembling granulosa cells, Sertoli cells, or indifferent cells of sex cord type. Two tumors also had cells of steroid-hormone-cell type; these cells contained crystalloids of Reinke in one case. These two tumors were classified as luteinized thecoma and stromal-Leydig cell tumor with minor sex cord elements. The other five tumors were designated fibromas with minor sex cord elements. Five-year follow-up, available in three cases, revealed no evidence of recurrence after operative removal. Although the presence of sex cord components has generally resulted in the classification of an ovarian tumor in either the granulosa cell or Sertoli-Leydig cell category, we propose that tumors with only minor sex cord components be placed in a separate category.

Adolescent↗
PubMed1991

Ovarian fibrothecoma: sonographic and histologic findings.

The sonographic and histologic findings observed in 11 cases of ovarian fibrothecoma were compared, and an attempt was made to find a correlation between each histologic type of the tumor (pure thecoma, predominantly fibrous fibrothecoma, mixed fibrothecoma) and its sonographic appearance. The presence of a homogeneous echogenic pattern, with marked posterior acoustic shadowing, in the absence of any calcification, was highly suggestive of a predominantly fibrous ovarian fibrothecoma; the presence of a diffusely hypoechoic ovarian mass, with no posterior echo enhancement, was strikingly correlated with pure thecomas; mixed fibrothecomas were characterized by the presence of an echogenic pattern with no posterior acoustic shadowing. Sonographic findings, even though nonspecific, can provide the clinician with useful information which permits to detect these rare neoplasms preoperatively.

Adult↗
PubMed2003

Meigs' syndrome with elevated CA 125: case report.

CONTEXT: Meigs' syndrome consists of a benign ovarian tumor accompanied by ascites and hydrothorax. Elevated serum CA 125 levels in postmenopausal women with solid adnexal masses, ascites and pleural effusion are highly suggestive for malignant ovarian tumor. However, patients with Meigs' syndrome can also have elevated serum CA 125 levels. The authors report a case of Meigs' syndrome with elevated CA 125 level. OBJECTIVE: This is a case report of Meigs' syndrome with elevated CA 125 level. CASE REPORT: A 65-year-old Brazilian woman had presented progressive dyspnea, weight loss and decline in general condition over the 7 months preceding admission to our service. In another hospital, the patient had been submitted to thoracic drainage due to pleural effusion. With recurrence of the pleural effusion and increase in abdominal volume due to ascites and a pelvic mass, the patient sought our service. Transvaginal ultrasound showed an extensive adnexal solid mass of 16.4 x 10.8 cm located in the pelvis without exact limits, and the serum CA 125 level was elevated. With a preoperative diagnosis of ovarian carcinoma, the patient was submitted to exploratory laparotomy, which revealed a left ovarian tumor. The frozen section diagnosis was thecoma. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. The histology of the specimen confirmed the diagnosis of thecoma. The patient was asymptomatic with a normal serum CA 125 level 20 months after the operation.

Aged↗
PubMed1980

Granulosa-cell and theca-cell tumors. The clinical picture and long-term outcome for the Radiumhemmet series.

Over the period 1923--72 a total of 305 patients with granulosa-cell, theca-cell tumor and mixed tumor were seen at Radiumhemmet. The commonest symptom was abnormal uterine bleeding. Twenty-three per cent of married women were nulliparous. The menarche seems to have occurred earlier in this group than in the general population. Eight of the granulosa-cell tumor group gave birth to 12 children after treatment for the tumor. Nineteen women with granulosa-cell tumor and 4 with thecoma had received radiotherapy earlier in life for benign lesions. The risk of endometrial cancer was approximately 10 times greater for the women with granulosa- or theca-cell tumor than for the general population. Two hundred and fifty-two patients were given both surgical treatment and radiotherapy. Fifty-three received only surgery (37 granulosa-cell and 16 theca-cell tumors). None of the thecoma patients but 21 per cent of those with granulosa-cell tumor died from their disease. The 5-year survival for the latter group, all stages, was 85 per cent.

Adolescent↗
PubMed2001

[Detection of extra chromosomes 12 by fluorescent in situ hybridization (FISH) in ovarian stromal tumors. Study of 12 cases and review of the literature].

Chromosomic aberrations play a major role in the initiation and the progression of benign as well as malignant tumors. In particular, trisomy 12 is frequently observed in female genitourinary tract tumors and constitutes a recurrent and often unique anomaly in stromal ovarian tumors such as fibrothecomas. Today, the genetic analysis of fresh or fixed solid tumors is enabled by the fluorescent in situ hybridization method (FISH). Using FISH and/or conventional cytogenetics, we analysed 12 ovarian stromal tumors (6 fibromas, 3 fibro thecomas and 3 thecomas). All of these tumors were benign and trisomy 12 was observed in all cases. Moreover, 3 cases presented trisomy and tetrasomy for chromosome 12 simultaneously. The high frequency of trisomy 12 in this tumor type suggests that this abnormality might be implicated in ovarian tumorigenesis.

Adult↗
PubMed2003

[Virilism during pregnancy].

We discuss the causes of virilism in pregnancy and the impact of hyperandrogeny on the female foetus. We report a case of virilism in a 28-year-old, gravida 1, para 1 patient with normal pregnancy and review the literature. After conception, the patient had been well until the 18th week of gestation, when she developed signs of virilization; her serum testosterone was markedly elevated. She delivered of a normal male infant at term. After delivery, signs of virilization regressed with normalization of testosterone level but a wide mass of the left ovary that persisted for 8 months. The histological study of the tumor showed luteinized thecoma. Luteomas and hyper-reactio luteinalis were the principal causes of virilism in pregnancy, thecomas are rare.

Adult↗
PubMedDate not supplied

Histochemistry of hormonally active ovarian tumors.

Thirty-five ovarian tumors were examined (7 granulosa-cell tumors, 2 thecomas, 4 dysgerminomas, 6 mucinous cystadenomas, 10 serous cystadenomas, 2 adenocarcinomas, 3 Krukenberg tumors and 1 early embryonic tumor). The granulosa-cell tumors showed high activity of alpha-glycerophosphate dehydrogenase, and the changed cells of their stroma--that of glucose-6 phosphate and isocitrate dehydrogenases. The activity of the latter enzymes was striking also in thecomas. Dysgerminomas showed high alkaline phosphatase, acid phosphatase and nonspecific esterase activities. The authors emphasize the role of stromal cells in the hormonal activity of ovarian neoplasms.

Adenocarcinoma↗
PubMed1981

A morphologic classification and incidence of spontaneous ovarian neoplasms in three strains of mice.

Ovarian tumors were reviewed and classified in 5,404 control inbred BALB/c, C57BL/6, and C3H mice. In descending order of frequency, the most common types in the C3H mice were the tubular mesothelioma (adenoma), thecoma, luteoma, granulosa cell tumor, and cystadenoma. In descending order the most common types in the BALB/c mice were the luteoma, tubular mesothelioma, granulosa cell tumor, thecoma, and cystadenoma. The tubular mesothelioma was the only ovarian tumor of significance in the C57BL/6 mice. Most of the ovarian tumors were rare before 1 year of age, but they increased with age after 1 year.

Animals↗
PubMed2005

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.

Adenocarcinoma↗
PubMed2002

Calretinin, a more sensitive but less specific marker than alpha-inhibin for ovarian sex cord-stromal neoplasms: an immunohistochemical study of 215 cases.

Although inhibin has been shown to be a sensitive marker for ovarian sex cord-stromal and fibrous neoplasms, it may be negative in some cases. Calretinin, a mesothelial marker, has shown promise as a marker for sex cord-stromal neoplasms. The aim of this study was to evaluate and compare calretinin and inhibin as immunohistochemical markers for sex cord-stromal and fibrous neoplasms. A total of 215 ovarian neoplasms were immunostained with commercially available antibodies to calretinin and inhibin. These tumors included 87 sex cord-stromal (39 granulosa cell, 13 Sertoli-Leydig, 4 Sertoli, 9 thecomas, 14 fibrothecomas, and 8 other stromal tumors), 37 fibrous (20 fibromas, 9 adenofibromas, and 8 fibrosarcomas), 65 epithelial, 22 germ cell, and 4 miscellaneous neoplasms. The staining was evaluated on a 0-4 scale based on percentage of neoplastic cells labeling: 0 = none; 1+ = 1-25%; 2+ = 26-50%; 3+ = 51-75%; 4+ = 76-100%. Calretinin reactivity was detected in 100% of sex cord-stromal and 90% of fibrous neoplasms, including 32 that were inhibin negative (2 granulosa cell tumors, 1 Sertoli-Leydig cell tumor, 1 thecoma, 3 fibrothecomas, 16 fibromas, 6 adenofibromas, and 3 fibrosarcomas). All four calretinin-negative fibrous neoplasms were inhibin negative. Calretinin staining was also detected in 22% of epithelial neoplasms but none of the germ cell and miscellaneous neoplasms tested. Inhibin staining was detected in 92% of sex cord-stromal neoplasms, 22% of fibrous neoplasms, 2% of epithelial neoplasms, and none of the germ cell and miscellaneous neoplasms tested. Calretinin has a 97% sensitivity and 85% specificity for sex cord-stromal and fibrous neoplasms, whereas inhibin has a 71% sensitivity and 99% specificity. This study shows that both calretinin and inhibin are useful in the diagnosis of ovarian sex cord-stromal and fibrous neoplasms. Calretinin is a more sensitive but less specific immunohistochemical marker than inhibin. Calretinin is particularly useful in the diagnosis of sex cord-stromal and fibrous neoplasms that are inhibin negative. The high frequency of calretinin in fibrous neoplasms suggests that a subgroup of these neoplasms may be derived from specialized gonadal stromal cells, perhaps thecal cells.

Biomarkers, Tumor↗