Shunichiro Ota

Molecular pathology of atypical polypoid adenomyoma of the uterus

Atypical polypoid adenomyoma (APA) is an uncommon and benign tumor of the uterus. In some patients, however, APA has been found to coexist with or to precede the development of an endometrioid adenocarcinoma similarly to complex endometrial hyperplasia. The molecular changes underlying the progression from APA to adenocarcinoma are unknown. DNA from paraffin-embedded tissue of 6 APAs was evaluated for microsatellite instability (MI), MLH-1 promoter hypermethylation, and CTNNB-1 mutations. Tissue sections were also subjected to MLH-1, MSH-2, and beta-catenin immunostaining. MI was not detected in any case. Two tumors exhibited MLH-1 promoter hypermethylation and showed focal negative MHL-1 immunostaining; 1 of these showed marked architectural complexity and cellular pleomorphism. Five cases presented beta-catenin nuclear immunoreactivity, but none of them had CTNNB-1 mutations. The results of this study suggest that APA and complex endometrial hyperplasia may share some molecular alterations. Some APAs exhibit MLH-1 promoter hypermethylation with focal lack of MLH-1 immunostaining, a molecular abnormality involved in the transition from complex atypical hyperplasia to endometrioid adenocarcinoma.

Fertility-preserving treatment for patients with malignant germ cell tumors of the ovary

Aim:  The aim of this study was to investigate whether fertility preservation influences the clinical outcome in patients with malignant germ cell tumors of the ovary (MGCTO).

Desmoplastic small round cell tumor in the ovary: Report of two cases and literature review.

Desmoplastic small round cell tumor (DSRCT) is a rare intra‐abdominal tumor of uncertain histogenesis that occurs predominantly in young males. We report two cases of DSRCT in young women that presented clinically as ovarian tumor with extensive pelvic and abdominal dissemination. Both patients underwent debulking surgery and combined chemotherapy. After primary therapy, the tumors recurred and both women died of the disease. The clinical presentation and differential diagnosis, as well as the treatment, including surgical debulking and combined chemotherapy are discussed.

Ovarian hepatoid carcinoma without staining for alpha-fetoprotein in the primary site.

An ovarian hepatoid carcinoma associated with minimal alpha-fetoprotein (AFP) production is described. The tumor involved both ovaries, and had metastasized to the omentum, uterus and retroperitoneal lymph nodes. The neoplastic cells were arranged in sheets, had abundant eosinophilic cytoplasm, central nuclei and distinct cellular borders. Despite the morphologic similarity to the histology of a hepatocellular carcinoma, elevation of the serum AFP level was minimal, at 74.0 ng ml−1 (normal range: under 20 ng ml−1), and the value normalized after surgery and subsequent chemotherapy. An immunohistochemical technique revealed focal staining for albumin in the tumor tissue and AFP in the uterine metastasis. Since the primary tumor itself did not stain for AFP, it is suggested that there may be hepatoid ovarian carcinomas without AFP production, a situation found in some hepatocellular carcinomas.

Polypoid endocervical adenomyoma: A case report with clinicopathologic analyses

A case of polypoid endocervical adenomyoma (PEA) in the uterine cervix was encountered in the uterine cervix of a 56‐year‐old woman. Grossly, a well‐circumscribed polypoid tumor was observed protruding from the uterine cervix. Based on the findings of imaging studies, it was assumed to be an adenoma malignum in the uterine cervix. The tumor was composed of a mixture of proliferating glands of endocervical type and fascicles of smooth muscle. No distinct nuclear anaplasia, architectural abnormality or any evidence of destructive stromal invasion was observed. Adenoma malignum, which shows a gastric phenotype with immunoreactivity for HIK‐1083, was a serious diagnostic possibility. In the present case, the tumor was a well‐circumscribed polypoid lesion, with no cytologic or architectural abnormality; however, focal immunoreactivity was shown for HIK‐1083, which thus suggested it to be PEA. Therefore, the results of these ancillary diagnostic modalities should be interpreted with caution and combined with the gross and light microscopy findings.

Weekly 1-h paclitaxel infusion in patients with recurrent endometrial cancer: a preliminary study

Abstract.Background: The aim of this study was to evaluate the toxicity and efficacy of weekly paclitaxel in patients with recurrent endometrial cancer. Methods: Nine patients with recurrent endometrial cancer who had previously received chemotherapy or radiotherapy participated in the study, between May 1999 and August 2001. Paclitaxel was given at a dose of 70 mg/m2 as a 1-h infusion every week for at least 20 consecutive weeks unless lesions became progressive. Intravenous dexamethasone and cimetidine and oral diphenhydramine were administered 30 min before paclitaxel infusion. Results: The nine patients received a total of 149 cycles of therapy. No hypersensitivity reactions were elicited. Grade 3 leukopenia, neutropenia, and anemia occurred in 22%, 33%, and 33% of the patients, respectively. Granulocyte colony-stimulating factor was required for two patients and no patients experienced febrile neutropenia. Neurotoxicity was commonly observed. Grade 1 peripheral neuropathy and myalgias were observed in 78% and 11% of the patients, respectively. No grade 3 or higher nonhematological toxicities were observed. Partial responses were seen in six of the nine patients (67%). The median progression-free interval was 8 months (range, 0–12 months) and the median overall survival was 10 months (range, 4–24 months). Conclusion: Weekly 1-h paclitaxel administration is considered safe and effective as a salvage therapy for recurrent endometrial cancer, with this schedule and delivery making its use more convenient and easier in the outpatient setting. The current results support further evaluation.

Successful treatment of two patients with recurrent endometrial cancer by weekly paclitaxel

OBJECTIVE The aim of this study was to evaluate the toxicity and efficacy of weekly paclitaxel in patients with recurrent endometrial cancer. METHODS Paclitaxel (70 mg/m(2) by 1-h infusion weekly) was administered to two patients with recurrent endometrial cancer of the lung. RESULTS After 5 cycles, both patients with platinum-resistant disease achieved clinical partial responses confirmed by computed tomography (CT) scan. The serum CA125 levels of case 1 decreased to cut-off level. The response duration of both patients was 4 months. The toxicity was acceptable and probably less pronounced than that characterize of the standard tri-weekly schedules. CONCLUSION Although conclusions regarding survival are premature, weekly paclitaxel might offer better quality of life during treatment.

An unusual endometrioid adenofibroma of the uterine cervix: a histologic and immunohistochemical study

An unusual adenofibroma of the uterine cervix is reported. The cervix was bulkily enlarged but did not have a polypoid appearance. The neoplastic epithelium was in continuity with the covering epithelium of the cervix and consisted predominantly of endometrioid cells which proliferated to form numerous glandular structures of irregular size and shape. The glandular component resembled an endometrial hyperplasia, and was set in an abundant fibrous stroma which was moderately cellular and hyalinized. Both the epithelial and mesenchymal cells lacked cytologic atypia. Despite its benign appearance, the tumor occupied almost all the uterine cervix and extended into the upper vaginal wall. The epithelial cells showed diffuse positive staining for CA19-9 and were focally positive for carcinoembryonic antigen. The presence of dense periglandular fibrosis distinguished the present case from a minimal deviation adenocarcinoma of endometrioid type.

Tumor bleeding requiring intervention and the correlation with anemia in uterine cervical cancer for definitive radiotherapy

Background The prognostic impact of tumor bleeding requiring intervention and the correlation with anemia on the survival outcome of cervical cancer radiotherapy is unclear. Methods One hundred and ninety-six patients requiring hemostatic intervention between January 2006 and March 2014 were retrospectively investigated. The correlation between anemia and bleeding during radiotherapy, the prognostic impact of genital bleeding during radiotherapy and the influence of blood transfusion were estimated. Results None of the patients had incomplete or prolonged treatment exceeding 1 week due to bleeding. All tumor bleeding could be controlled by gauze packing, and no patients suffered from fatal genital bleeding. Bleeding significantly correlated with progression-free survival (P = 0.015) and overall survival (P = 0.048). Regarding the risk factors of anemia: age (P = 0.043), FIGO stage (P < 0.001), tumor diameter (P < 0.001), and bleeding (P = 0.002) were significant. Multivariate analysis revealed FIGO stage (Odds Ratio: 2.360; 95% CI = 1.202-4.633; P = 0.013), tumor diameter (Odds Ratio: 2.089; 95% CI = 1.048-4.162; P = 0.036) and Bleeding (Odds Ratio: 2.226; 95% CI = 1.052-4.709; P = 0.036) were independent to anemia. Anemia (Hazard Ratio = 1.894; 95% CI = 1.082-3.318; P = 0.025) was only independently correlated with progression free survival, while bleeding (Hazard Ratio = 1.156; 95% CI = 0.556-2.406; P = 0.698) had no independent correlation. Blood transfusion did not improve progression-free survival in patients with anemia or genital bleeding (P = 0.742). Conclusion We have proved that genital bleeding requiring intervention during cervical cancer radiotherapy is a negligible prognostic factor and is the independent factor for causing anemia. Easily bleeding tumors are potential prognostic markers, which are not effectively treated using existing radiotherapy.

Palliative Colostomy for End-Stage Gynecologic Cancer

Purpose: This study aimed to investigate the use of colostomies to alleviate gastrointestinal symptoms in patients with end-stage gynecologic cancer presenting with malignant bowel obstruction (MBO). Material and Methods: We retrospectively investigated 12 patients undergoing palliative colostomy for MBO due to end-stage gynecological cancer. Two main areas were assessed: i. postoperative complications, the duration of postoperative oral intake, and the postoperative survival; and ii. The effect of the patient’s preoperative general condition and nutritional status on postoperative vital prognosis using the palliative prognostic (PaP) score and the prognostic nutritional index (PNI), respectively. Results: Postoperative oral intake was possible for 10 of the 12 patients. The median length of oral intake was 42 (6-150) days and the median duration of postoperative survival after colostomy was 54.5 (14-217) days. All patients died due to disease progression. For the 8 patients in the group with PaP scores under 5.5, the median durations of postoperative oral intake and postoperative survival were 58 and 85.5 days, respectively. For the 4 patients in the group with PaP scores of ≥ 5.5, the corresponding values were 3 and 25.5 days, respectively. For the 10 patients in the group with PNI of <40, the median durations of postoperative oral intake and postoperative survival were 38.5 and 51.5 days, respectively. For the 2 patients in the group with PNI of ≥ 40, the corresponding values were 88 and 183.5 days, respectively. Conclusion: Colostomy performed on patients for MBO due to end-stage gynecological cancer contributed to improved quality of life. The data suggests that the PaP score and PNI may facilitate the prediction of postoperative outcomes.