Adult Granulosa Cell Tumor With High-grade Transformation: Report of a Series With: FOXL2: Mutation Analysis

We report 5 cases of AGCT in patients aged 37 to 88 years composed of areas of typical AGCT with low-grade morphology admixed with areas of high-grade morphology, with marked nuclear atypia, often with bizarre multinucleate cells and high mitotic activity; this is the first reported series of high-grade transformation in AGCTs. The high-grade areas often morphologically closely resembled juvenile granulosa cell tumor with abundant eosinophilic cytoplasm, significant mitotic activity, and intermediate sized follicles. Four cases were FIGO stage IA at diagnosis and 1 was stage IIIC with omental involvement. FOXL2 mutation analysis of both the morphologically low-grade and high-grade areas in 4 of 5 cases confirmed the presence of missense point mutation, c.402C>G, p.(Cys134Trp), providing conclusive evidence that the high-grade component represents transformation of typical AGCT rather than the coexistence of another sex cord-stromal tumor, such as juvenile granulosa cell tumor, which has been suggested for such neoplasms. In 3 of 4 cases where immunohistochemistry was undertaken, there was a striking difference between the p53 staining in the low-grade and high-grade components with wild-type staining in the former and diffuse mutation-type immunoreactivity in the latter, suggesting that TP53 mutation is likely to play a role in high-grade transformation. TP53 mutation analysis covering exons 4 to 10 was undertaken in 4 cases and TP53 mutations were identified in the high-g...
Source: The American Journal of Surgical Pathology - Category: Pathology Tags: Original Articles Source Type: research

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Oncogene, Published online: 19 November 2019; doi:10.1038/s41388-019-1109-7Aberrant granulosa cell-fate related to inactivated p53/Rb signaling contributes to granulosa cell tumors and to FOXL2 downregulation in the mouse ovary
Source: Oncogene - Category: Cancer & Oncology Authors: Source Type: research
The case of a 36-yr-old woman with a pituitary adenoma who was found to have bilateral ovarian masses is reported. The right ovary was removed, measured 15 cm in maximum dimension, and contained multiple cysts which on microscopic examination had the typical morphology of follicle cysts. The left ovary was grossly similar intraoperatively. Subsequent excision of the pituitary adenoma was followed ∼3 mo later by a return to normal size of the left ovary. The case represents an example of multiple luteinized follicle cysts, analogous to the phenomenon seen occasionally in pregnancy, but with a different cli...
Source: International Journal of Gynecological Pathology - Category: Pathology Tags: Pathology of the Upper Tract: Original Articles Source Type: research
Sumaira Qayoom, Malti Kumari, Sameer Gupta, Madhumati GoelJournal of Cancer Research and Therapeutics 2019 15(5):1186-1188 Breast cancer is one of the main sources of ovarian metastasis. Diffuse sheet of lobular carcinoma cells can strongly mimic granulosa cell tumor (GCT) which itself is a rare ovarian neoplasm constituting <5% of all the ovarian neoplasms. A 55-year-old female presented with a painful lump in the right breast associated with nipple discharge for 4 months, which on radiological and cytological findings was suspicious of an epithelial malignancy. During routine work-up, a solid-cystic lesion in th...
Source: Journal of Cancer Research and Therapeutics - Category: Cancer & Oncology Authors: Source Type: research
Authors: Macut D, Ilić D, Mitrović Jovanović A, Bjekić-Macut J Abstract About 1% of ovarian tumors that comprise testicular cell types can cause hyperandrogenism followed by characteristic virilization. Androgenic group of tumors originated mainly from sex-cord stromal ovarian tumors are including steroid cell tumors, Leydig tumors, granulosa cell tumors, Sertoli cell tumors, Sertoli-Leydig cell tumors, gonadoblastomas, and some other rare forms as ovarian metastases from neuroendocrine tumors. Germline or somatic mutations in some genes like DICER1, STK11, and FOXL2 are associated with the development of some ...
Source: Frontiers of Hormone Research - Category: Endocrinology Tags: Front Horm Res Source Type: research
CONCLUSION: Our findings demonstrate that miR-200b and miR-200c suppress the proliferation of KGN cells by targeting PTEN, and this might provide new evidence for abnormal proliferation of GCs in PCOS. PMID: 31421682 [PubMed - in process]
Source: Reproductive Biology - Category: Reproduction Medicine Authors: Tags: Reprod Biol Endocrinol Source Type: research
Targeting TGFβ pathway in Adult Granulosa Cell Tumor: Opening Pandora's Box? Clin Cancer Res. 2019 Jul 11;: Authors: Bonilla L, Oza AM Abstract Adult granulosa cell tumor (AGCT) is a rare malignancy characterized by FOXL2 (C134W) mutation, an inherent component of the TGFβ pathway. Activin A, a TGFβ superfamily member, is a driver of this activity and is a potential target in AGCT. PMID: 31296528 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
ConclusionThis study demonstrates that rAMH is bioactive in the ovary for a limited time, and that pharmacological administration of rAMH during chemotherapy treatment reduces follicle activation and primordial follicle loss and significantly improves reproductive outcomes in a mouse model, and does not interfere with the therapeutic actions of the treatment. Further investigation is necessary to determine whether it has similar protective effects in the human ovary.
Source: Journal of Assisted Reproduction and Genetics - Category: Reproduction Medicine Source Type: research
Conclusion: Adequate knowledge on cytohistological correlation of ovarian scrape cytology may phase out the use of cryostat in intraoperative diagnosis of ovarian neoplasms, and thus be a boon for resource-deprived settings.
Source: Journal of Cytology - Category: Cytology Authors: Source Type: research
ConclusionThis case was the first of its kind that ovarian tumor was contralateral to the side involved by enchondromatosis.
Source: The Journal of Obstetrics and Gynecology of India - Category: OBGYN Source Type: research
MicroRNAs (miRNAs) are small noncoding RNAs that play important roles in gene regulation at post-transcriptional level. In the current study, we examined the effect of miR-126 on granulosa cell tumor (GCT), a subtype of ovarian cancer. miR-126 expression was repressed in tissues from malignant GCT patients. We showed that miR-126 could inhibit cell proliferation, migration/invasion, ovarian hormone production and promote anticancer drug-induced apoptosis in vitro. The ‘tumor suppressor’ role of miR-126 was further validated in an mice GCT model in vivo. By RNA-seq, immunohistochemical staining (IHC), Western bl...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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