Yutaka Morimura

Production of IL1-beta by ovarian cancer cells induces mesothelial cell beta1-integrin expression facilitating peritoneal dissemination

BackgroundA crucial step in the metastatic spread of ovarian cancer (OC) is the adhesion and implantation of tumor cells to the peritoneal mesothelium. In order to study this step in the cascade, we derived a pro-metastatic human ovarian carcinoma cell line (MFOC3) from the non-metastatic FOC3 line.MethodsMolecular profiling of the isogeneic lines identified differentially expressed genes, and investigation for a role in dissemination for specific factors was achieved by development of a co-culture adhesion assay utilizing monolayers of human mesothelial cells.ResultsAfter murine intraperitoneal inoculation, the FOC3 cell line formed no metastases, but the MFOC3 subline formed metastases in > 80% of SCID mice. MFOC3 cells also adhered 2-3 times more avidly to mesothelial monolayers. This adhesion was inhibited by neutralizing antibodies to IL-1β and enhanced by recombinant IL-1β (p < 0.01). IL-1β induced mesothelial cell β1-integrin, and an antibody to this subunit also inhibited the adhesion of MFOC3 to mesothelial cells in vitro and significantly reduced metastases in vivo. Immunohistochemical analysis of a cohort of 96 ovarian cancer cases showed that negative IL-1β expression was significantly associated with an improved overall survival rate.ConclusionsThese results suggest that a IL-1β/β1-integrin axis plays a role in ovarian tumor cell adhesion to mesothelia, a crucial step in ovarian cancer dissemination.

Ovarian Sertoli‐Leydig cell tumor with heterologous gastrointestinal epithelium as a source of alpha‐fetoprotein: A case report

Ovarian Sertoli‐Leydig cell tumors (SLCT) are rare sex cord stromal neoplasms. To date there have been approximately 25 case reports of ovarian SLCT expressing alpha‐fetoprotein (AFP). In such cases, AFP was immunohistochemically detected in the Sertoli cells, Leydig cells, or hepatocytes. This case report confirms heterologous gastrointestinal epithelium expression of AFP. A 20‐year‐old woman presented with complaints of abdominal enlargement and irregular menstrual cycles over one year. A right ovarian tumor was detected and the patients serum AFP was elevated. A right salpingo‐oophorectomy was performed. On microscopic examination, the tumor was composed of a fibrosarcoma‐like area and a poorly differentiated SLCT area with heterologous gastrointestinal epithelium. Immunohistochemical analysis detected AFP in the gastrointestinal epithelium only. Postoperatively, serum AFP levels fell to normal. A recurrent tumor was discovered in the omentum after adjuvant chemotherapy, but serum AFP remained normal. A second laparotomy was performed and the recurrent tumor showed only fibrosarcoma‐like features. The patient received second line chemotherapy and is currently in remission. This is the first case of AFP production by heterologous gastrointestinal epithelium in SLCT.

Dysgerminoma with syncytiotrophoblastic giant cells arising from 46,xx pure gonadal dysgenesis

Background Dysgerminoma with syncytiotrophblastic giant cells is a rare ovarian tumor. Only ten cases of this tumor have been reported, and all tumors developed in normal ovaries. This report presents a case of dysgerminoma with syncytiotrophoblastic giant cells arising in a patient with 46,XX pure gonadal dysgenesis. Case An 18-year-old phenotypic female of normal height without somatic anomalies with nonfunctional ovaries underwent a bilateral gonadectomy for a right ovarian tumor and left streak gonad. The tumor revealed a dysgerminoma containing scattered syncytiotrophoblastic giant cells. Her serum hCG was elevated, and hCG was demonstrated within syncytiotrophoblastic giant cells immunohistochemically. The clinical diagnosis was stage Ia dysgerminoma with syncytiotrophoblastic giant cells. Her karyotype was 46,XX and the sex-determining region Y gene was not detected in tumor DNA by polymerase chain reaction analysis. Conclusion This rare gonadal tumor may arise from dysgenetic gonads in addition to gonadoblastoma and pure dysgerminoma. It is an example of tumorgenesis in pure gonadal dysgenesis with no identifiable Y chromosome component.

Fetal hepatic hemangioma representing non-reassuring pattern in fetal heart rate monitoring

To the best of our knowledge, this is the first report of a non‐reassuring fetal pattern caused by a hepatic hemangioma that was found during fetal heart rate monitoring. A 37 weeks’ gestation, a 32‐year‐old‐woman was referred to our hospital for evaluation of a rapidly growing fetal abdominal tumor. Fetal heart rate monitoring revealed a non‐reassuring pattern, and a cesarean section was performed as a result. Examination of the 2820 g female infant suggested a hepatic hemangioma accompanying an intratumor hemorrhage and coagulopathy. The infant died 2 days after birth. The autopsy confirmed that the cause of death was a result of a hepatic hemangioma. Frequent monitoring of fetuses and ultrasound examinations are necessary for determining the timing of delivery and for a favorable prognosis.

A case of uterine cervical adenoid cystic carcinoma: Immunohistochemical study for basement membrane material

Background Adenoid cystic carcinoma is a rare neoplasm of the cervix. Only two reports of immunohistochemical studies for basement membrane material in adenoid cystic carcinoma of the cervix have been reported. Case An 80-year-old Japanese woman complained of atypical vaginal bleeding and underwent removal of a cervical polyp; the biopsy specimen revealed a solid variant of adenoid cystic carcinoma. The tumor was composed of nests and nodules of small carcinoma cells, and there were few characteristic cribriform patterns. Immunohistochemical findings for type IV collagen and laminin revealed intercellular cylinders composed of basement membrane material in the solid area without a cribriform pattern. Conclusion The immunohistochemical finding of intercellular cylinders that reacted for type IV collagen was useful for the diagnosis of a solid variant of adenoid cystic carcinoma.

Diagnosing Endometrial Carcinoma with Cervical Involvement by Cervical Cytology

OBJECTIVE To assess the relationship of a cervical cytologic diagnosis based on number, size and degeneration of malignant clusters and necrotic background to cervical involvement of endometrial carcinoma. STUDY DESIGN Cervical smears of 53 women with endometrial carcinoma were evaluated for cervical involvement. The cytologic diagnosis was compared with actual involvement, and accuracy was calculated. Retrospectively, cytologic features, including number, size and degeneration of malignant clusters and necrotic background, were analyzed in involved and noninvolved cases. RESULTS Cervical involvement was confirmed in 15 patients (28.3%). The number and size of malignant clusters in the involved cases were significantly larger than those in the noninvolved cases (P < .001 and < .01, respectively). The proportion of degenerated malignant cells and necrotic background in involved cases were significantly higher than those in noninvolved cases (P < .05). Cytologic diagnosis had a sensitivity and specificity of 62.5% and 86.8%, respectively. CONCLUSION Cervical smears of involved cases revealed a large number and large size of malignant clusters. These findings support cytologic diagnosis based on number, size and degeneration of malignant cells and necrotic background. Cervical cytology is useful to exclude cervical involvement because of its high specificity and can help detect cervical involvement because of its moderately high sensitivity.

Imprint cytology of extraskeletal mesenchymal chondrosarcoma of the perineum: a case report.

BACKGROUND Extraskeletal mesenchymal chondrosarcoma (EMC) is an uncommon soft tissue tumor, occurring mainly in the lower limbs, meninges and retroperitoneum. EMC of the female genital tract is extremely rare, and the cytologic literature is scarce. CASE A 43-year-old female with a growing perineal mass underwent excision of the tumor. Pathologic examination of the rumor revealed a characteristic two-cell pattern of primitive small cells and cartilaginous tissue. A diagnosis of EMC of the perineum was made. Imprint cytology from surgical material showed a cluster of small round cells with a focal hemangiopericytomalike arrangement and islets of cartilage. The cartilaginous cells reacted with S-100 protein immunocytochemically. CONCLUSION The characteristic features of EMC, a hemangiopericytomalike arrangement of small cells and S-100-positive cartilaginous cells, may be helpful in diagnosing EMC and differentiating it from other perineal tumors.

Angiosarcoma of Vagina Successfully Treated with Interleukin‐2 Therapy and Chemotherapy: A Case Report

We report a case of angiosarcoma of the vagina in a 61‐year‐old woman who had undergone radical hysterectomy and pelvic irradiation for uterine cervical adenocarcinoma 14 years previously. Combination chemotherapy (cyclophosphamide, vincristine, doxorubicin and dacarbazine) and interleukin‐2 induced complete remission of the tumor. The patient remained free from disease for 15 months.

Evaluation with MIB1 antibody of proliferative activity in ovarian clear cell adenocarcinoma.

The purpose of this study was to determine whether proliferative activity is a prognostic factor in ovarian clear cell adenocarcinoma. The paraffin-embedded sections from eight cases of ovarian clear cell adenocarcinoma were immunostained with monoclonal antibody MIB1 using microwave oven heating for antigen retrieval. The difference in survival (Kaplan-Meier) between patients with high and low MIB1 expression was estimated with the generalized Wilcoxon test. MIB1 positivity ranged from 1.80 to 27.12% with a mean of 11.43%. A cutoff point of 10% dichotomized patients into two groups. The survival of high (> or = 10%) expressing tumors was worse than that of low (< 10%) expressing tumors (p < 0.05). MIB1 immunostaining may have useful prognostic value in ovarian clear cell adenocarcinoma.

Uterine cervical clear-cell adenocarcinoma with a choriocarcinomatous component: a case report.

A 55‐year‐old woman presented with vaginal bleeding. A tumor was found in the cervix; it was composed of 2 distinctive elements: a clear‐cell adenocarcinoma and a choriocarcinoma. Histologic findings suggested that the choriocarcinomatous element was derived from a preexisting clear‐cell adenocarcinoma through a metaplastic process.