Postmenopausal androgen-secreting ovarian tumors: challenging differential diagnosis in two cases.

Postmenopausal hyperandrogenism constitutes a very rare condition of tumoral or non-tumoral origin primarily residing either in the ovary or in the adrenal glands. We present herein two cases with this condition; one with abnormal postmenopausal genital bleeding and mild increase in facial hair, and the second with slow-developing hirsutism and virilization. Both cases shared a notorious increase in libido. The laboratory tests showed high levels of testosterone (>100 ng/ml). A normal value of dehydroepiandrosterone sulfate and a normal cortisol level at 9 am after 1 mg of dexamethasone administered at midnight (Nugent test) made an adrenal etiology very unlikely. On the other hand, a high level of inhibine B oriented to an ovarian source. Transvaginal sonography failed to demonstrate an ovarian tumor, but an abdominal and pelvic computed tomography scan or magnetic resonance imaging detected an ovarian tumor and normal adrenal glands. A laparoscopic oophorectomy was performed, and the histological study demonstrated a steroidal cell tumor in the first case and a Leydig cell tumor in the second.

Lipophilic but not hydrophilic statins selectively induce cell death in gynaecological cancers expressing high levels of HMGCoA reductase.

Recent reports have suggested that statins induce cell death in certain epithelial cancers and that patients taking statins to reduce cholesterol levels possess lower cancer incidence. However, little is known about the mechanisms of action of different statins or the effects of these statins in gynaecological malignancies. The apoptotic potential of two lipophilic statins (lovastatin and simvastatin) and one hydrophilic statin (pravastatin) was assessed in cancer cell lines (ovarian, endometrial and cervical) and primary cultured cancerous and normal tissues. Cell viability was studied by MTS assays and apoptosis was confirmed by Western blotting of PARP and flow cytometry. The expressions of key apoptotic cascade proteins were analysed. Our results demonstrate that both lovastatin and simvastatin, but not pravastatin, selectively induced cell death in dose- and time-dependent manner in ovarian, endometrial and cervical cancers. Little or no toxicity was observed with any statin on normal cells. Lipophilic statins induced activation of caspase-8 and -9; BID cleavage, cytochrome C release and PARP cleavage. Statin-sensitive cancers expressed high levels of HMG-CoA reductase compared with resistant cultures. The effect of lipophilic statins was dependent on inhibition of enzymatic activity of HMG-CoA reductase since mevalonate pre-incubation almost completely abrogated the apoptotic effect. Moreover, the apoptotic effect involved the inhibition of synthesis of geranylgeranyl pyrophosphate rather than farnesyl pyrophosphate. In conclusion, lipophilic but not hydrophilic statins induce cell death through activation of extrinsic and intrinsic apoptotic cascades in cancerous cells from the human female genital tract, which express high levels of HMG-CoA reductase. These results promote further investigation in the use of lipophilic statins as anticancer agents in gynaecological malignancies.

Simvastatin interferes with cancer 'stem-cell' plasticity reducing metastasis in ovarian cancer.

Cell plasticity of 'stem-like' cancer-initiating cells (CICs) is a hallmark of cancer, allowing metastasis and cancer progression. Here, we studied whether simvastatin, a lipophilic statin, could impair the metastatic potential of CICs in high-grade serous ovarian cancer (HGS-ovC), the most lethal among the gynecologic malignancies. qPCR, immunoblotting and immunohistochemistry were used to assess simvastatin effects on proteins involved in stemness and epithelial-mesenchymal cell plasticity (EMT). Its effects on tumor growth and metastasis were evaluated using different models (e.g., spheroid formation and migration assays, matrigel invasion assays, 3D-mesomimetic models and cancer xenografts). We explored also the clinical benefit of statins by comparing survival outcomes among statin users vs non-users. Herein, we demonstrated that simvastatin modifies the stemness and EMT marker expression patterns (both in mRNA and protein levels) and severely impairs the spheroid assembly of CICs. Consequently, CICs become less metastatic in 3D-mesomimetic models and show fewer ascites/tumor burden in HGS-ovC xenografts. The principal mechanism behind statin-mediated effects involves the inactivation of the Hippo/YAP/RhoA pathway in a mevalonate synthesis-dependent manner. From a clinical perspective, statin users seem to experience better survival and quality of life when compared with non-users. Considering the high cost and the low response rates obtained with many of the current therapies, the use of orally or intraperitoneally administered simvastatin offers a cost/effective and safe alternative to treat and potentially prevent recurrent HGS-ovCs.

[Silent adenoma type 3: the importance of the ultrastructural study in the differential diagnosis of pituitary adenoma associated with hyperprolactinemia in a case]. / Adenoma silente subtipo 3: importancia del estudio ultraestructural en el diagnóstico diferencial del adenoma hipofisiario asociado a hiperprolactinemia en un caso.

The association of hyperprolactinemia over 100 ng/ml and a pituitary adenoma is usually diagnostic of prolactinoma. However type 3 pituitary adenomas can occur with similar serum prolactin values. We report a 31 years old woman that consulted due to headache and photopsiae. She had a serum prolactin level of 148 ng/ml and imaging studies showed a solid tumor that occupied the sellar region and most of the left temporal fossa. The tumor was partially resected and the patient recovered her lost visual field. Light microscopy showed an acidophilic and in part chromophobe adenoma. Immuno-histochemistry was positive for prolactin and growth hormone. Electron microscopy disclosed features of a silent type 3 adenoma such as big cells with cytoplasmic prolongations, pleomorphic nuclei and a greatly developed rough endoplasmic reticulum.

Temporal lobe epilepsy surgery with limited resources: results and economic considerations.

This study evaluates the surgical outcome of patients with medically refractory temporal lobe epilepsy (TLE) who underwent anterior temporal lobe lobectomy (ATL) based on data derived from noninvasive studies and assesses the economic costs entailed at a newly created epilepsy program in Chile. Seventeen ATL candidates underwent a presurgical evaluation. This included outpatient brain MRI and neuropsychological testing and inpatient scalp/sphenoidal prolonged video-EEG monitoring. There were 10 females and 7 males, with a mean age of 23.8 years and a mean duration of seizure disorder of 12 years. Patients with congruent data localizing the seizure focus to one anterotemporal region underwent ATL. Seven patients underwent a left-side ATL and 10 patients a right-side ATL. The histopathological findings showed a low grade tumor in six patients, hippocampal sclerosis in five, neuronal migration disorder in four, and cavernous angiomas in two patients. The mean follow-up period was 29.1 months. Seizure outcome was assessed with Engel's classification: class I, no seizures or only auras; class II, rare seizures; class III, >90% seizure reduction; class IV, <90% seizure reduction. Fifteen patients are now in class I, one patient in class II, and one in class IV. The total cost, including evaluation and surgery, was equivalent to US$ 5,020. Thus, well-selected TLE patients can derive maximal benefit from ATL after a noninvasive presurgical evaluation. This finding is of great significance for the creation of epilepsy surgery programs in developing countries.