Retroperitoneal seminoma as a first manifestation of a partially regressed (burnt-out) testicular germ cell tumor.

Regressed (burnt-out) testicular germ cell tumors (TGCT) are rare clinical situations that are clinically difficult to recognize. This 43-year-old patient was admitted because of a suspicion of prostatic carcinoma, which eventually was followed by transrectal ultrasonography and a CT scan, both of which revealed a large retroperitoneal mass. Surgery showed extensive ureteral and vas deferens infiltration. Pathology was consistent with a classical seminoma. Eventually, testes were normal on palpation but ultrasonography only revealed areas of fibrosis and microcalcifications in the left testis, which was followed by a left orchidectomy. Microscopically, there were extensive areas of fibrosis and only a 2 mm area of seminoma was demonstrated. The few areas of uninvolved testicular tissue lacked lesions of intratubular germ cell neoplasia (IGCNU). Retroperitoneal germ cell tumors are rare in the male and consequently, an origin from an occult testicular tumor should always be discarded by image analysis and eventually a biopsy. Immunologic response may be responsible for tumor involution.

Ultra low dose continuous combined hormone replacement therapy with 0.5mg 17beta-oestradiol and 2.5mg dydrogesterone: protection of the endometrium and amenorrhoea rate.

OBJECTIVES AND STUDY DESIGN: The aim of this open, multicentre study was to demonstrate the endometrial safety and assess the bleeding pattern of ultra low dose continuous combined hormone replacement therapy with 0.5 mg 17beta-oestradiol and 2.5 mg dydrogesterone in 446 healthy, non-hysterectomised, postmenopausal women with symptoms of oestrogen deficiency. MAIN OUTCOME MEASURE: Aspiration endometrial biopsies were performed at baseline and after 1 year of treatment to assess the incidence of endometrial hyperplasia or a more serious endometrial outcome. RESULTS: The only adverse endometrial outcome at the end of the study was one case of simple hyperplasia. This gives an overall incidence of 0.27% (95% CI: 0.01-1.48%) in the per protocol sample (n=395). The overall rate of amenorrhoea in the full sample (n=446) was 68% and 14% had only one or two bleeding/spotting episodes. The rate of amenorrhoea in months 10-12 (n=413) was 88%. The number of bleeding/spotting days per cycle fell during the study. The mean number of bleeding/spotting days was 5.8 and the mean number of days without bleeding was 358.2. Spotting alone was the most prevalent bleeding intensity, whilst heavy bleeding was rare. CONCLUSIONS: In conclusion, 2.5 mg dydrogesterone continuously combined with 0.5 mg 17beta-oestradiol effectively protects the endometrium in postmenopausal women in accordance with the guidelines of the Committee for Medicinal Products for Human Use (CHMP). It has a favourable amenorrhoea rate and is well tolerated by the majority of women.

Uterine adenosarcomas overgrown by sex-cord-like tumour: report of two cases.

Müllerian adenosarcomas are tumours of low malignant potential with proliferation of benign glands and low grade endometrial stromal sarcoma (LGESS). Unusually, the latter may include foci of uterine tumours resembling ovarian sex-cord tumours (UTROSCT). Two cases of uterine adenosarcomas massively overgrown by UTROSCT are reported, for the first time. The patients, aged 71 and 64, one receiving tamoxifen, presented with intracavitary polypoid adenosarcomas; each was overgrown by an immunopathologically characteristic UTROSCT that constituted more than 75% of its volume. Periglandular CD10+LGESS represented less than 25%. Both are alive and well after 5 and 3 years, respectively. Compared to the poor prognosis of adenosarcomas overgrown by high grade sarcomata, the cases reported here had a benign behaviour. Quantitative assessment of volume percentage of the potentially aggressive LGESS, CD10+ areas should be considered as a relevant prognostic histological parameter in these tumours.

Expression of platelet-derived growth factor receptor in low-grade endometrial stromal sarcomas in the absence of activating mutations.

AIMS: To investigate platelet-derived growth factor receptor (PDGFR)alpha and PDGFRbeta expression and a mutational analysis of PDGFRalpha (exons 11, 12, 17 and 18) and PDGFRbeta (exon 12) genes in endometrial stromal sarcomas (ESS). Gastrointestinal stromal tumours (GISTs), which have somatic mutations of the transmembrane tyrosine kinase receptor, respond to tyrosine kinase inhibitors, which act through an inhibitory effect on class 3 receptor tyrosine kinase members such as PDGFRalpha, PDGFRbeta and c-kit. METHODS AND RESULTS: The immunohistochemical expression of PDGFRalpha and PDGFRbeta was investigated in 37 archival c-kit- ESS. Staining was scored as negative (0-10% positive tumour cells) and positive (weakly positive 11-50% positive cells; strongly positive > 50% positive cells). PDGFRalpha was expressed in 24/37 ESS [65%; strongly by 19/37 (51.5%) and weakly by 5/37 ESS (13.5%)]. ESS tumour cells were negative for PDGFRbeta, but endothelial cells stained positive. A mutational analysis of PDGFRalpha (exons 11, 12, 17 and 18) and PDGFRbeta (exon 12) genes on frozen metastatic ESS from three patients detected no mutations leading to amino acid changes in the mature protein. CONCLUSIONS: Patients with PDGFRalpha+ ESS may benefit from treatment with tyrosine kinase inhibitors by blocking autocrine and paracrine stimulation loops, blocking neovascularization and enhancing the effects of chemotherapy.

Mixed epithelial and stromal tumour of the kidney with luteinised ovarian stroma.

We report a case of a 9-cm mixed epithelial and stromal tumour of the kidney in an obese 70-year-old woman with diabetes. The ovarian-type stroma had a spindle cell component that was positive for progesterone receptors and had the hitherto unreported presence of abundant foci of luteinised stromal cells with characteristic immunohistochemical positivity to alpha-inhibin, calretinin, aromatase and gonadotropin-releasing hormone (GnRH) receptors. We conclude that the stromal component is identical to ovarian cortical stroma. We believe that ovarian-type stroma occurs in extragenital tumours as a result of an epithelial-stromal interaction in an environment of hormonal hyperstimulation.

Pure testicular carcinoid associated with intratubular germ cell neoplasia.

This case report describes for the first time a case of pure testicular carcinoid pre-aortic lymph node metastases in a 25 year old patient with carcinoid syndrome. The simultaneous occurrence of intratubular germ cell neoplasia in the surrounding testicular tissue was identified by OCT4 and placental-like alkaline phosphatase positivity. This confirmed that the tumour had a germ cell origin in the testis, rather than being a metastasis from an extragenital carcinoid.

Endometrial coccidiosis.

This report describes a case of granulomatous endometritis caused by coccidiosis in an immunologically uncompromised 63 year old patient. The glandular epithelium of the endometrium contained numerous intracytoplasmic cysts, corresponding to periodic acid Schiff positive and methenamine silver negative sporoblasts. The endometrial glands revealed reactive phenomena, such as eosinophilic and squamous glandular metaplasia and intraluminal desquamation. Non-necrotising epithelioid granulomata, lacking the presence of parasites, were present in the stroma. Although not detected in the stool examination, the organisms were probably Isospora belli. There was no evidence of other foci of the disease. Coccidiosis should be differentiated from the more commonly occurring coccidiomycosis.

Retiform Sertoli-Leydig cell tumours: clinical, morphological and immunohistochemical findings.

AIMS: To determine the morphological and immunohistochemical profile of retiform Sertoli-Leydig cell tumours and to compare the observed profile with that of adult rete ovarii. METHODS AND RESULTS: Nineteen retiform Sertoli-Leydig cell tumours were studied, eight by immunohistochemistry, and five examples of rete ovarii from adult females were also evaluated immunohistochemically. The patients ranged in age from 3 to 74 years with a mean age of 31 years. Four patients were virilized and had an abdominal mass; two were virilized with amenorrhoea and two had amenorrhoea alone. Eight presented with an abdominal mass and one patient was pregnant. Two tumours were incidental findings. Information on stage was available in 16 patients: 14 tumours were stage 1, one was stage 2, and one was stage 3. Fifteen tumours were of intermediate differentiation and four were poorly differentiated. Papillary structures were evident grossly in four cases. Microscopically, all cases had a retiform pattern in addition to varying quantities of sex cord, gonadal stromal and heterologous elements. Heterologous elements were present in 13 cases and consisted of hepatocytes (n = 7), mucinous epithelium (n = 7) and skeletal muscle (n = 2). Immunohistochemical evaluation of eight tumours showed a more intense positivity for keratin in the retiform areas, whereas the gonadal stromal component had a more intense expression of inhibin. Inhibin stains Leydig cells strongly and hepatocytes moderately. Rete ovarii epithelium was positive for keratin and vimentin in the five cases studied, and for inhibin in one case. Follow-up was available on 13 patients. Three tumours behaved in a malignant fashion: one each was stage 1, 2, and 3 at diagnosis. CONCLUSIONS: Immunohistochemistry is useful in distinguishing retiform Sertoli-Leydig cell tumours from other tumours that they may resemble. Inclusion of inhibin is essential in a panel of antibodies to evaluate these tumours. The clinical behaviour of these neoplasms cannot always be predicted from their morphology or clinical stage.

Mesonephric adenocarcinoma of the uterine corpus: CD10 expression as evidence of mesonephric differentiation.

Mesonephric (wolffian) neoplasms of the female genital tract are infrequent and found in sites where embryonic remnants of wolffian origin are usually detected, such as the uterine cervix, broad ligament, mesosalpinx, and ovary. Their diagnosis is difficult because of the absence of specific immunohistochemical markers for mesonephric derivatives. We present the first report of adenocarcinoma of mesonephric type arising as a purely myometrial mass without endometrial or cervical involvement in the uterine corpus of a 33-year-old woman. The tumor showed a combination of patterns, with retiform areas, ductal foci, and small tubules with eosinophilic secretion, which merged with solid sheets of cells with a sarcomatoid appearance. Immunohistochemically, neoplastic cells were diffusely positive for cytokeratin 7, epithelial membrane antigen, and CD15 and focally positive for BerEP4 and vimentin. A hitherto unreported feature was the positivity for CD10 in neoplastic cells, which was also present in a large number of control tissues obtained from male mesonephric derivatives and female mesonephric remnants and tumors. Furthermore, CD10 was negative in controls from müllerian epithelia of the female genital tract and in their corresponding tumors. Therefore, the expression of CD10 by mesonephric remnants may be useful in establishing the diagnosis of tumors with mesonephric differentiation.

Villoglandular adenocarcinoma of the vulva.

BACKGROUND: Only two previous cases of villoglandular adenocarcinoma of the vulva, an entity morphologically similar to tumors found in the uterine cervix and colorectum, have been reported. This paper communicates the first complete immunohistochemical study in villoglandular adenocarcinoma in order to determine its phenotype and histogenesis. CASE: A 69-year-old woman had a 1.5-cm nodule in the right labium majus. Histologically, it corresponded to a minimally atypical, villoglandular adenocarcinoma with a small microinvasion. Immunohistochemically, it was positive to OC125, CEA, and OC19.9 and coexpressed cytokeratins 7 and 20. Chromogranin, nuclear estrogen, and progesterone receptors were negative. CONCLUSION: Phenotypic expression was more consistent with a papillary mucinous ovarian or cervical neoplasm than of a colonic one. Its behavior was similar to that of its morphologic counterpart in the cervix, since the patient had no recurrence 3 years after a wide local excision.

Ovarian endometriosis and clear cell carcinoma, leiomyomatosis peritonealis disseminata, and endometrial adenocarcinoma: an unusual, pathogenetically related association.

A 42 year-old female with a preoperative clinical diagnosis of ovarian cancer underwent laparotomy which revealed leiomyomatosis peritonealis disseminata (LPD) in the peritoneum and omentum and a left ovarian endometriotic cyst associated with a clear cell carcinoma. A grade 1, superfically invasive villoglandular endometrial endometrioid adenocarcinoma was also found. Microscopically, the endometriotic cyst wall contained an extensive peripheral band-like condensation of stromal cells. These cells were strongly positive for alpha inhibin and may have been the hormonal source responsible for the induction of the simultaneous LPD and endometrial adenocarcinoma. It is proposed that endometriosis is not only a precursor of clear cell carcinoma but, through secondary hormonal induction of the surrounding ovarian stroma, may also provide a hormonal stimulus for diverse proliferative processes.

Rectal endometrial stromal sarcoma arising in endometriosis: report of a case.

PURPOSE: Endometriosis of the rectovaginal septum can harbor different types of secondary tumors that may involve the rectal wall and protrude into its lumen, thus making diagnosis difficult. Extrauterine low-grade endometrial stromal sarcoma may rarely arise in endometriosis. The purpose of this article was to present the third case of this association. METHOD: This was a clinicopathologic study. RESULTS: A 42-year-old female presented with abdominal pain and fever. Laparotomy revealed a large pelvic mass involving the rectovaginal septum and the colonic wall and which protruded into the lumen forming endoluminal polypoid masses. Concomitant peritoneal nodules and a metastatic paracolic lymph node were also found. Histopathologically, primary endometriotic foci were found in close relationship with an endometrial stromal sarcoma which invaded the rectal wall. The female genital tract had no endometriotic lesions. The patient was treated by surgery and subsequent chemotherapy and was alive and well 20 months later. CONCLUSIONS: Endometriosis and its possible malignant changes should be taken into account in the differential endoscopic diagnosis of rectal masses in females.

Merkel cell (neuroendocrine) carcinoma of the vulva. A case report with immunohistochemical and ultrastructural findings and review of the literature.

A new case of primary Merkel cell carcinoma (MCC) of the vulva is reported and the literature reviewed for noting its clinical presentation, microscopic, immunohistochemical and ultrastructural features, as well as for establishing the role of immunohistochemistry in the ultimate diagnosis of this uncommon and aggressive tumor. The lesion occurred in a 79 year old patient. Histologically, the tumor was composed of intradermal small cells with high mitotic index and frequent apoptosis. The immunohistochemical study showed positivity for wide spectrum and low molecular weight cytokeratins, epithelial membrane antigen, neurofilaments, neuron specific enolase and chromogranin A. Electron microscopy revealed intermediate filaments in a typical globular paranuclear arrangement. The coexpression of cytokeratins (including cytokeratin 20) and neurofilaments, both in typical globular paranuclear arrangement, made possible the diagnosis of MCC, differentiating it from other malignant small cell tumors such as neuroendocrine metastatic carcinoma.

Pure cystic nephroblastoma of the ovary with a review of extrarenal Wilms' tumors.

A second case of pure ovarian extrarenal Wilms' tumor (EWT) is presented. A clinical stage Ic tumor occurred in the right ovary of a 21-year-old female and corresponded to a 19-cm multilocular mass which histologically was a cystic, partially differentiated Wilms' tumor, closely resembling the highly differentiated metanephric adenoma. This pattern is reported for the first time in an ectopic location. At the interface between epithelial nests and ovarian tissue, plaques of alpha-inhibin positive cells were detected that corresponded to foci of peripheral stromal luteinization. Differential diagnosis with entities such as retiform Sertoli-Leydig cell tumors and with adenosarcoma should be made. The literature on EWT is also reviewed.