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International Journal of Cancer Dec 1996To define the involvement of p16/CDKN2 and p15/MTS2 inactivation in ovarian tumorigenesis and the association of these inactivation events with histological types and...
To define the involvement of p16/CDKN2 and p15/MTS2 inactivation in ovarian tumorigenesis and the association of these inactivation events with histological types and clinical stages of ovarian tumors, we analyzed homozygous deletion and somatic mutation of p16/CDKN2 and p15/MTS2 genes, as well as hypermethylation of the 5'-CpG island of the p16/CDKN2 gene, in 49 primary ovarian tumors and 6 ovarian carcinoma cell lines. We found homozygous deletions of p16/CDKN2 and p15/MTS2 in 6 (12%) and 5 (10%) primary tumors, respectively. Somatic mutation of p16/CDKN2 was found in only 1 primary tumor, but mutation of p15/MTS2 was not detected in any sample. None of the 28 primary tumors or 6 cell lines was hypermethylated at the 5'-CpG island of p16/CDKN2. The incidence of inactivation of p16/CDKN2 in primary tumors was significantly higher in the advanced stages (7 of 29) than in the early stages (0 of 14). Seven of 9 alterations in p16/CDKN2 and p15/MTS2 were observed in serous (3 of 12), endometrioid (3 of 9) and clear-cell (1 of 4) carcinomas. However, only normal sequences of these genes were detected in mucinous carcinomas. Loss of heterozygosity (LOH) at the IFNA locus was detected in 1 of 19 (5%) tumors, but no change at the D9S171 locus was observed in 17 tumors. These results suggest that: (i) homozygous deletion is the main mechanism of inactivation of p16/CDKN2 and p15/MTS2 in ovarian tumorigenesis; (ii) inactivation of p16/CDKN2 and p15/MTS2 may be the histological type-specific events involved in ovarian tumorigenesis; and (iii) inactivation of p16/CDKN2 is potentially involved in the progression of ovarian tumors in advanced stages.
Topics: Carcinoma; Carrier Proteins; Cell Cycle Proteins; Cyclin-Dependent Kinase Inhibitor p15; Cyclin-Dependent Kinase Inhibitor p16; Disease Progression; Enzyme Inhibitors; Female; Heterozygote; Humans; Mutation; Neoplasm Staging; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Thecoma; Tumor Cells, Cultured; Tumor Suppressor Proteins
PubMed: 8980248
DOI: 10.1002/(SICI)1097-0215(19961220)69:6<466::AID-IJC8>3.0.CO;2-2 -
Journal of Obstetrics and Gynaecology... Oct 2011The sex cord stromal tumors (SCST) account for approximately 7% of all malignant ovarian tumors. They are endocrinologically active tumors of which granulosa cell tumors...
OBJECTIVES
The sex cord stromal tumors (SCST) account for approximately 7% of all malignant ovarian tumors. They are endocrinologically active tumors of which granulosa cell tumors are the commonest. We describe an analysis of all cases of SCST managed, in our department over the last five years and discuss two cases of unusual presentation of these tumors.
METHODS
Ten cases of SCST which were managed in the Department of Gynecology and Obstetrics at University College of Medical Sciences (UCMS) & associated Guru Teg Bahadur hospital, Delhi from Jan. 01 to Dec. 05 were analyzed.
RESULTS
Of the total 312 ovarian tumors which were operated in these 5 years, 73 (23.3%) were malignant, 10 cases (13.6%) out of the malignant ovarian tumors were SCST. The age of presentation varied from 4 to 70 years. Four women presented with lump abdomen as their chief complaint, 2 had postmenopausal bleeding, 2 presented with irregular bleeding per-vaginum, 1 woman had secondary amenorrhea and one young girl who was only 4½ years old developed precocious puberty. The majority of cases (70%) were granulosa cell tumors, 10% were fibromas and 20% thecomas. Maximum patients 9 (90%) were stage I at the time of surgery and only 1 case was stage IV with tumor infiltrating into omentum and gut.
CONCLUSION
SCST tumors are rare endocrine active tumors that are essentially unilateral, benign or with a low malignant potential. Though most patients present with one or a combination of symptoms ranging from abnormal vaginal bleeding, abdominal distention and abdominal pain, the signs of Paraneoplastic syndrome (PNS) may be the first indication of the presence of an ovarian malignancy and can even facilitate its diagnosis.
PubMed: 23024526
DOI: 10.1007/s13224-011-0087-7 -
Advanced Biomedical Research 2014Leiomyoma is benign mesenchymal tumor, that frequently occur in uterus but it rarely happens in ovary. Ovarian leiomyomas are seen concomitantly with uterine leiomyoma...
Leiomyoma is benign mesenchymal tumor, that frequently occur in uterus but it rarely happens in ovary. Ovarian leiomyomas are seen concomitantly with uterine leiomyoma in about 78% of cases. They often discover incidentally but their most clinical manifestations are abdominal pain and palpable mass. Herein, we reported a large ovarian leiomyoma in a 22-year-old woman with abdominal pain and palpable mass at lower abdominal region. Computed tomography scan revealed large adnexal mass. Microscopic appearance was typical for leiomyoma but because its rarity in ovary the immunohistochemical staining was done. Major differential diagnostic considerations for this tumor in ovary are fibroma/thecoma, sclerosing stromal tumor, and leiomyosarcoma. The immunohistochemical staining with desmin, inhibin, and α-smooth muscle actin are helpful to rule out this differential diagnosis.
PubMed: 24761396
DOI: 10.4103/2277-9175.128001 -
Modern Pathology : An Official Journal... Jun 2013A single, recurrent somatic point mutation (402C→G) in FOXL2 has been described in almost all adult-type granulosa cell tumors but not other ovarian neoplasms....
A single, recurrent somatic point mutation (402C→G) in FOXL2 has been described in almost all adult-type granulosa cell tumors but not other ovarian neoplasms. Histopathological features of adult-type granulosa cell tumors can be mimicked by a variety of other tumors, making diagnosis of adult-type granulosa cell tumor challenging. It has been suggested that molecular testing for FOXL2 mutation might be a useful tool in the diagnosis of adult-type granulosa cell tumors. The aim of this study was to demonstrate how testing for the FOXL2 mutation can be used in a gynecological pathology consultation service and to establish clear procedural guidelines for FOXL2 testing. Immunohistochemistry for FOXL2 was done using an anti-FOXL2 polyclonal antiserum. If immunohistochemistry was positive, FOXL2 mutation status was subsequently analyzed using a TaqMan assay. A dilution experiment was done to assess the sensitivity and minimum tumor cellularity requirements for our TaqMan assay. Twenty problematic cases were assessed, where the differential diagnosis after the initial investigations included adult-type granulosa cell tumors. Differential diagnoses included: thecoma, Sertoli-Leydig cell tumor, juvenile granulosa cell tumor, endometrial stromal sarcoma and others. In all cases, FOXL2 immunohistochemistry was positive and in six samples the FOXL2 mutation was detected, thus confirming a diagnosis of adult-type granulosa cell tumor. The TaqMan assay was able to reliably detect the FOXL2 mutation with input DNA in the range of 2.5-20 ng, and with a minimum of 25% tumor cell nuclei. The analysis of the FOXL2 mutational status in clinical samples is a useful diagnostic tool in situations where the differential diagnosis is between adult-type granulosa cell tumor and other ovarian tumors. The TaqMan assay requires a minimum of 2.5 ng DNA, with optimal assay performance for 5 to 10 ng DNA input. Laser capture or needle-macrodissection should be undertaken to enrich samples with tumor cell content below 25%.
Topics: Algorithms; Animals; Biomarkers, Tumor; DNA Mutational Analysis; Diagnosis, Differential; Female; Forkhead Box Protein L2; Forkhead Transcription Factors; Genetic Testing; Granulosa Cell Tumor; Immunohistochemistry; Ovarian Neoplasms; Point Mutation; Polymerase Chain Reaction; Practice Guidelines as Topic; Predictive Value of Tests; Reproducibility of Results
PubMed: 23348906
DOI: 10.1038/modpathol.2012.226 -
Journal of Clinical and Diagnostic... Nov 2014Ovarian leiomyoma is one of the rare solid tumours of ovary, accounting for 0.5-1% of the benign tumours of the ovary. We report one such case which presented in a...
Ovarian leiomyoma is one of the rare solid tumours of ovary, accounting for 0.5-1% of the benign tumours of the ovary. We report one such case which presented in a postmenopausal woman. The differential diagnosis includes ovarian fibroma, thecoma, cellular fibroma and sclerosing stromal tumour. Masson's trichrome staining helps to distinguish fibrous and smooth muscle components of the lesion and confirms the diagnosis of ovarian leiomyoma. Hence, ovarian leiomyoma should be considered in the differential diagnosis of ovarian spindle cell tumours.
PubMed: 25584274
DOI: 10.7860/JCDR/2014/10369.5204 -
Journal of Mid-life Health Oct 2014A unique case of unilateral ovarian luteinized thecoma with sclerosing peritonitis is reported because the association between these two conditions is extremely rare....
A unique case of unilateral ovarian luteinized thecoma with sclerosing peritonitis is reported because the association between these two conditions is extremely rare. Etiology is not clearly known. A 50-year-old post-menopausal woman presented with pain abdomen and huge swelling. Pelvic contrast-enhanced computed tomography (CECT) revealed a heterogenous enhancing mass arising possibly from ovary and adherent to uterus, bowl loops, and omentum. A spindle cell neoplasm without definite features of malignancy was reported in computed tomography (CT)-guided fine-needle aspiration cytology (FNAC). Ascitic fluid was negative for malignancy. Her serum carcinoembryonic antigen (CEA) (1.1ng/ml) and CA125 (27.6μ/ml) level was within normal limits. Total abdominal hysterectomy with bilateral supracolic omentectomy, resection of part of colon, and supracolic omentectomy was done. Histopathological diagnosis was luteinized thecoma with sclerosing peritonitis. Tumor cells were immunoreactive to smooth muscle antigen (SMA) and CD 99 and non- reactive to ER, PR, Calretinine, and Cytokeratin. Patient developed post-operative sepsis and enterocutaneous fistula, which was managed conservatively and was kept in follow-up. According to current concept, in spite of its large size, wide-spread involvement, mitotic activity, and complications due to peritoneal involvement, behavior of this rare clinical entity is benign.
PubMed: 25540572
DOI: 10.4103/0976-7800.145173 -
Proceedings of the Royal Society of... Jan 1972
Topics: Female; Humans; Ovarian Neoplasms; Pregnancy; Pregnancy Complications; Thecoma
PubMed: 4335590
DOI: No ID Found -
Gynecologic Oncology Reports Nov 2020Elevated serum inhibin B is a classic marker of adult granulosa cell tumors. Here we discuss an extremely rare and informative case of elevated inhibin B associated with...
INTRODUCTION
Elevated serum inhibin B is a classic marker of adult granulosa cell tumors. Here we discuss an extremely rare and informative case of elevated inhibin B associated with an ovarian thecoma.
CASE
A 57 year-old postmenopausal female presented with recurrent bleeding and was found to have an adnexal mass with an elevated serum inhibin B level of 1,915 pg/mL (normal range 10-200 pg/mL). With a preoperative diagnosis of adult granulosa cell tumor, she underwent surgical management for what was ultimately a benign ovarian thecoma. The diagnosis of thecoma was confirmed by a pericellular pattern of reticulin staining and the lack of a mutation by molecular testing.
CONCLUSION
This case demonstrates that inhibin B lacks specificity as a tumor marker for adult granulosa cell tumor, even at very high levels. Knowledge of benign alternative explanations for this finding can facilitate improved preoperative patient counseling. Pertinent literature is reviewed, with an emphasis on proposed hypotheses for inhibin overproduction.
PubMed: 33204793
DOI: 10.1016/j.gore.2020.100658 -
Human Pathology Dec 1997Inhibins are peptide hormones that participate in the regulation of the pituitary-gonadal feedback system and are selectively expressed by cells of sex cord-stromal...
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.
Topics: Adult; Biomarkers, Tumor; Carcinoma, Adenoid Cystic; Carcinoma, Endometrioid; Female; Granulosa Cell Tumor; Humans; Inhibins; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Retrospective Studies; Sex Cord-Gonadal Stromal Tumors
PubMed: 9416696
DOI: 10.1016/s0046-8177(97)90229-x -
International Journal of Surgery Case... May 2024Fibroma, thecoma, and fibrothecoma collectively denote a range of non-cancerous sex cord-stromal tumors distinguished by the presence of fibroblastic stromal cells...
INTRODUCTION AND IMPORTANCE
Fibroma, thecoma, and fibrothecoma collectively denote a range of non-cancerous sex cord-stromal tumors distinguished by the presence of fibroblastic stromal cells and/or cells resembling luteinized theca cells.
CASE PRESENTATION
In this report, we present a case study of a 52-year-old patient in whom this uncommon tumor was identified via MRI, highlighting the distinctive diagnostic and treatment considerations associated with it.
CLINICAL DISCUSSION
Ovarian fibrothecoma tumors are infrequent, constituting less than 4 % of all ovarian tumors. Although they may manifest at any age, they are more commonly observed in elderly and post-menopausal individuals. Diagnosis hinges on clinical and paraclinical data, yet definitive confirmation is predominantly achieved through anatomopathological examination. For younger patients, conservative surgery is usually favored, whereas peri- or post-menopausal individuals may undergo radical treatment.
CONCLUSION
Ovarian Fibrothecoma, though rare, are typically benign tumors frequently found in older patients. Diagnosis primarily relies on histological examination. Fortunately, the prognosis for these tumors is generally favorable.
PubMed: 38810296
DOI: 10.1016/j.ijscr.2024.109771