Satoshi Amada

Large cell neuroendocrine carcinoma of the uterine cervix: a clinicopathological study of six cases.

&NA; Six cases of cervical large cell neuroendocrine carcinomas (LCNEC) were found among 972 patients (0.6%) with invasive cervical carcinoma. The patients, who were from 27 to 51 (mean 38) years of age, presented with vaginal bleeding or an abnormal Papanicolaou smear. Five tumors were stage Ib and one was IIa. All patients underwent radical hysterectomy and received adjuvant chemotherapy and pelvic radiotherapy. Four patients died of tumor 6 to 19 months (mean 14 months) postoperatively. On histologic examination, the tumor cells were arranged in an organoid growth pattern and were larger than those of typical small cell carcinoma. Glandular differentiation was present in one case. Mitotic figures ranged from 15 to 45 (mean 29) per 10 high‐power fields. Prominent vascular invasion and necrosis was seen in all of the tumors. Each tumor was immunoreactive for chromogranin A and/or synaptophysin. The results of this study confirm the aggressive nature of cervical LCNECs. The recognition of LCNECs is necessary to establish the most effective treatment for these aggressive tumors.

Increased nuclear localization of transcription factor YB-1 in acquired cisplatin-resistant ovarian cancer

Abstract Purpose. Nuclear expression of Y box-binding protein (YB-1), a member of the DNA-binding protein family, was recently reported to have a much higher concentration in cisplatin-resistant cancer cell lines than in their drug-sensitive parental counterparts, suggesting the ability to induce cisplatin resistance. Ovarian cancer has been generally treated with cisplatin-based chemotherapy and often recurs due to acquired cisplatin resistance. The aim of our study is to elucidate the association between nuclear YB-1 and cisplatin resistance in human ovarian cancer using cultured cell lines and surgical specimens. Methods. Intracellular YB-1 localization was examined by Western blot analysis for both cisplatin sensitive and resistant human ovarian cancer cell lines. Moreover, 35 pairs of surgical specimens derived from primary and matched recurrent ovarian cancers of the same patient were evaluated for their nuclear YB-1 expression by immunohistochemical staining. Results. Western blot analysis for nuclear and cytoplasmic extracts indicated that cisplatin-resistant cells showed much higher nuclear YB-1 expression than sensitive parental cells. Immunohistochemical analysis showed that ten paired cases turned from negative nuclear YB-1 in primary lesions to positive nuclear YB-1 in recurrent lesions, whereas only two paired cases showed a reverse turn from positive to negative. Conclusions. The expression of YB-1 in the nucleus seems to be associated with acquired cisplatin resistance in ovarian cancers. Nuclear YB-1 might be a useful predictive marker indicating cisplatin sensitivity and/or a target molecule to treat recurring ovarian cancers by cisplatin-based second-line chemotherapy.

Leiomyosarcoma versus bizarre and cellular leiomyomas of the uterus : a comparative study based on the MIB-1 and proliferating cell nuclear antigen indices, p53 expression, DNA flow cytometry, and muscle specific actins

There is still controversy over the criteria for malignancy of smooth muscle tumors (SMTs) of the uterus. We examined 51 cellular SMTs using immunohistochemistry for MIB-1, proliferating cell nuclear antigen (PCNA), p53, HHF35, alpha-smooth muscle actin (SMA), and flow cytometry. Morphologically, the 51 cases were classified into 24 leiomyosarcomas (LMS), two uncertain malignant potential, four bizarre leiomyomas, and 21 cellular leiomyomas. The mean values of the MIB-1 and PCNA indices showed significant differences between LMS and benign SMTs. p53 cells were positive in eight of 24 leiomyosarcomas, and 12 of 22 were aneuploid. HHF35 and alpha-SMA showed a diffuse positivity in almost all the benign SMTs. In contrast, 10 of the 24 LMS were either focally positive or negative for SMA. Using a logistic regression model, at cut-off points of 3.6 on the MIB-1 index and 15.6 on the PCNA index, the LMS and the benign SMTs were classified with an overall accuracy of 92% and 82%, respectively. Moreover, by combining the MIB-1 index and alpha-SMA positivity, the cut-off point could be established at 0.492 on the probability scale with the highest overall accuracy of 96%. Regarding the prognosis of LMS, p53 positivity was correlated with survival (p = 0.0357). A combination of the MIB-1 index and alpha-SMA was helpful in distinguishing between LMS and benign SMT. Moreover, p53 positivity was considered to be a good marker for predicting the prognosis of LMS.

Metastatic adenocarcinoma to the uterine cervix from gastric cancer. A clinicopathologic analysis of 16 cases

Background. Metastatic adenocarcinoma to the uterine cervix from gastric cancer is rare, and the clinicopathologic features of this metastasis are unclear.

Genetic origin of malignant trophoblastic neoplasms

The genetic origin of three trophoblastic neoplasms (two choriocarcinomas and a placental site trophoblast tumor (PSTT)] was determined by analysis of the restriction fragment length polymorphism (RFLP) pattern. One choriocarcinoma, which was believed not illogically to have developed from an antecedent complete mole, contained both paternal and material RFLP alleles and thus was probably the product of a normal fertilization. The other choriocarcinoma was not of gestational origin but had RFLPs homozygous at some loci and heterozygous at others, compatible with the parthenogenic origin of this tumor from a germ cell after meiosis I. The PSTT required amplification of DNA sequences by polymerase chain reaction (PCR) because of the small amount of tumor material available. This tumor contained RFLP alleles from both parents and appeared to have resulted from a previous unrecognized (and abnormal) pregnancy.

Malignant mixed müllerian tumor of the fallopian tube: Report of two cases and review of literature

Malignant mixed Müllerian tumors are usually found in the endometrium, vagina, cervix, and ovary. It is extremely rare for this tumor to arise in the fallopian tube, and to date only 37 tubal cases have been reported. We recently experienced 2 such cases. The clinical features, pathologic findings, diagnosis, therapy, and outcome of these 39 cases were reviewed. The clinical features and diagnosis were similar to those of primary carcinoma of the fallopian tube. Correct preoperative diagnosis was difficult. Histologically, 18 patients had homologous elements and 21 had heterologous elements in the sarcomatous components. The most common type of heterologous element was cartilage, followed by striated muscle and bone. The clinical stage (FIGO staging of ovarian carcinoma) was stage I in 15 cases, stage II in 11 cases, stage III in 8 cases, stage IV in 3 cases, and unknown in 2 cases. In all the patients except 1, the tumor was surgically removed. Postoperatively, radiotherapy was given to 9 patients, chemotherapy to 9 patients, and both to 2 patients. Sixteen patients died of the disease, after a mean period of 16.1 months. Of the 15 stage I patients, 10 survived more than 12 months. The most important prognostic factor was spread of the tumor at diagnosis.

Prognostic value of histologic grading of ovarian carcinomas

Histologic grading of ovarian carcinomas has prognostic and therapeutic relevance, but although several grading systems have been proposed, no universal grading system has been established. Silverbergs group has recently proposed a simple histologic grading system of ovarian carcinomas. We studied its prognostic value in 70 patients with invasive ovarian carcinomas and compared it with that of histologic typing and clinical staging. Kaplan-Meier survival curves showed the following 5-year survival rate using the Silverberg grading system: grade I (n=21) 91%, grade II (n=20) 64%, grade III (n=29) 38% (p<0.001). Multivariate analysis indicated that the histologic grade, the clinical stage, and clear cell histologic type were significant prognostic factors. The Silverberg histologic grade correlated well with prognosis for all histologic types of ovarian carcinomas except for clear cell carcinoma. It is simple, reproducible, and provides useful prognostic information.

Inhibin‐producing ovarian granulosa cell tumor as a cause of secondary amenorrhea: Case report and review of the literature

We report the case of 31‐year‐old patient with an inhibin B‐secreting granulosa cell tumor of the left ovary who presented with secondary amenorrhea. Preoperative serum hormonal levels were as follows: follicle‐stimulating hormone (FSH) 0.3 mIU/mL, luteinizing hormone (LH) 9.81 mIU/mL, estradiol 142.0 pg/mL and inhibin B 2429 pg/mL. Gonadotropin‐releasing hormone (GnRH) test revealed no FSH response and a normal LH response. After removal of the tumor, the levels of FSH and inhibin B returned to within the normal range, and regular menses resumed 27 days postoperatively. In premenopausal women, secondary amenorrhea may be the initial manifestation of granulosa cell tumor. A low FSH level coupled with normal levels of E2 and LH, the inhibition of the FSH response to GnRH and an elevated inhibin level suggest the presence of an inhibin‐secreting ovarian tumor and also rule out the possibility of isolated FSH deficiency.

Relationship between age, histological type, and size of ovarian tumors

Objective: To clarify the relationship between age, histological type, and size of ovarian tumors. Method: A review was made of 1648 cases of histopathologically diagnosed ovarian tumors and tumor‐like lesions, and information on the age of the patients and size of the tumor was obtained. Statistical analysis was performed using Kruskal–Wallis tests or Mann–Whitney U‐tests. Results: There were 840 (51%) cases of benign tumors, 73 (4%) cases of tumors of low malignant potential (LMP), 268 (16%) cases of malignant tumors and 467 (28%) cases of tumor‐like lesions. The age of the patients was significantly different among tumor‐like lesions (34.6±8.1 years), benign tumors (39.8±16.4 years), LMP tumors (45.2±18.3 years) and malignant tumors (51.9±13.0 years) (P<0.0001). The maximum diameter of the tumors was significantly different among tumor‐like lesions (7.1±3.3 cm), benign tumors (10.9±5.6 cm), malignant tumors (13.6±6.5 cm) and LMP tumors (18.5±6.8 cm) (P<0.0001). Conclusion: The distribution of tumor histological type (tumor‐like lesions, benign, LMP and malignant) was correlated against patient age and lesion diameter, with tumors in older patients or larger tumors more likely to be malignant.

Efficacy of selective venous sampling to localize a small ovarian androgen-producing tumor.

Two cases of androgen‐producing tumors, including a Sertoli‐Leydig cell tumor in a woman of reproductive age and a Leydig cell tumor in a postmenopausal woman, are reported herein. In both cases, only selective venous sampling was able to detect the presence of the androgen‐producing ovarian tumors.