Endometrial intraepithelial carcinoma in association with polyp: review of eight cases.

BACKGROUND: The uterine endometrial polyp (EMP) has a potential risk of developing malignant tumors especially in postmenopausal women. These malignancies include endometrial intraepithelial carcinoma (EIC). PATIENTS AND METHODS: Eight patients with EIC in the EMP, who were postmenopausal with ages ranging from 49 to 76 years (av. 62), were cytologically reviewed in comparison with histological findings. RESULTS: The endometrial cytological findings were summarized as follows: mucous and watery diathesis as a background lacking or with little necrotic inflammatory changes; micropapillary cluster formation; abrupt transition between carcinoma cells and normal cells; nuclear enlargement; high N/C ratio; and single or a few prominent nucleoli. Histologically, one case had EIC alone in the EMP; three cases had EIC with stromal invasion confined to the EMP; and four cases had EIC in the atrophic endometrium in addition to EIC in the EMP. Seven patients have taken a disease-free course after surgical resection, but one patient died 44 months following the initial diagnosis because of the massive tumor extending over her peritoneal cavity. CONCLUSIONS: Endometrial cytology may be helpful for the detection of early endometrial adenocarcinomas with serous features including EIC. Some early stage endometrial adenocarcinomas represented by EIC exceptionally take an aggressive clinical course irrespective of a lack of extrauterine lesions. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1651876760876449.

Granulosa cell tumor with activated mTOR-HIF-1alpha-VEGF pathway.

The DNA-binding activity of hypoxia-inducible factor-1 alpha (HIF-1alpha) has been analyzed for various gynecological tumors. Among the tumors that were studied, there was a finding of a high level of DNA-binding HIF-1alpha activity, although it was limited to one case of adult type granulosa cell tumor (GCT). In this case a 60-year-old female had marked immunohistochemical expression of HIF-1alpha. The expressions of the mammalian target of rapamycin (mTOR) and phosphorylated-mTOR (p-mTOR) were also marked, and vascular endothelial growth factor (VEGF) was moderately expressed. To compare the expression profiles, 11 consecutive cases with adult type GCT were used. All cases showed marked expressions of HIF-1alpha and mTOR, but p-mTOR expression was moderately to markedly observed in four of the 12 cases. VEGF was expressed in all cases in varying degrees. Based on the evidence that downregulation of the mTOR pathway due to treatment with rapamycin (everolimus) would suppress tumor cell growth, an experimental study using the GCT cell line was designed to clarify whether HIF-1alpha and VEGF expressions decline. As a result, the expressions of p-mTOR, HIF-1alpha and VEGF were suppressed, but those of mTOR were not. It was concluded that mTOR-targeted therapy may represent a promising strategy for some GCT with an activated mTOR-HIF-1alpha-VEGF pathway.