Embryonal carcinoma of the ovary: a six-year survival.

We report a case of embryonal carcinoma, stage II, arising in the right ovary of an 18-year-old woman. The elevated serum levels of alpha-fetoprotein (AFP) and urinary human chorionic gonadotropin (hCG) rapidly normalized after conservative surgery followed by combination chemotherapy. The tumor was composed of large primitive cells and some multinucleated giant cells. AFP and hCG were demonstrated immunohistochemically in each type of cells. She has been disease-free for 6 years.     

Serous carcinoma of the endometrium with choriocarcinomatous differentiation: a case report and review of the literature indicate the existence of 2 prognostically relevant tumor types.

Nongestational choriocarcinomas rarely occur outside the gonads or teratomas. We report a serous carcinoma of the endometrium with a choriocarcinomatous component and review of the literature. A 61-year-old woman underwent hysterectomy and bilateral salpingo-oophorectomy for a serous carcinoma with choriocarcinomatous component. Immunohistochemistry showed a strong p53 staining of the serous component and the cytotrophoblastic cells of the choriocarcinomatous component; the syncytiotrophoblast was negative. The initial serum human chorionic gonadotropin (hCG) was 225,000 IU/L. Postoperatively, the patient developed diffuse pulmonary metastatic disease. Despite chemotherapy, the patient died 2 months after initial diagnosis. Abstracting the data from the reported cases and from the literature, it can be assumed that 2 different tumor types exist. The first one is morphologically and clinically more related to the gestational choriocarcinoma with strongly elevated serum hCG levels, early onset of (distant) metastatic disease, and consecutively rapid and often fatal clinical course. The second type presents as an endometrial carcinoma with single syncytiotrophoblast-like cells, associated with low serum hCG, no distant metastatic disease, and, consequently, a better prognosis. The prognostically relevant component for long-time survival in the latter variant is the nontrophoblastic component.     

Adenocarcinoma of the uterine cervix with choriocarcinomatous and hepatoid differentiation: report of a case.

A case of adenocarcinoma of the uterine cervix that showed choriocarcinomatous and hepatoid differentiation was encountered in a 65-year-old woman. She presented with genital bleeding and had multiple metastatic nodules in the lungs. At operation, a large, hemorrhagic, and necrotic tumor was found in the uterine cervix. The major portion of the tumor consisted of typical choriocarcinoma admixed with minor areas of hepatoid carcinoma and endocervical adenocarcinoma. Human chorionic gonadotropin and alpha-fetoprotein were detected in tumor cells in the choriocarcinomatous and hepatoid areas, respectively. The patient died of pulmonary metastasis 4 months after the operation. The coexistence of choriocarcinomatous and hepatoid carcinoma in an endocervical adenocarcinoma has not been reported previously. Both heterotopic components were probably derived from aberrant differentiation (or neometaplasia) of the somatic epithelial cells of the endocervical adenocarcinoma.     

Malignant ovarian tumor composed of endometrioid adenocarcinoma, clear cell adenocarcinoma, squamous cell carcinoma, yolk sac tumor and immature teratoma with prominent neuroectodermal and rhabdomyosarcomatous differentiation: a case study

BACKGROUND: Cases of malignant ovarian tumor composed of müllerian-type epithelial tumor and malignant germ cell tumor are extremely rare. CASE: We herein report the case of a 34-year-old woman with an ovarian tumor which was composed of endometrioid adenocarcinoma (EAC), clear cell adenocarcinoma (CCC), squamous cell carcinoma, yolk sac tumor (YST) and immature teratoma with prominent neuroectodermal and rhabdomyosarcomatous differentiation. Even after systemic chemotherapy, this intriguing tumor recurred again and again, which is in contrast to pure germ cell tumor which is known to be sensitive to chemotherapy. CONCLUSION: No previous cases with an identical composition have been found in the literature. Correct diagnosis of this complex and aggressive tumor is paramount.     

Ovarian Mixed Germ Cell Tumor Composed of Polyembryoma and Immature Teratoma

We report the case of a 41-year-old woman with ovarian mixed germ cell tumor which was composed of polyembryoma and immature teratoma and who had high serum levels of α-fetoprotein (AFP) and human chorionic gonadotropin (hCG). By immunohistochemical methods, AFP was found in yolk sac cells of the embryoid bodies and immature hepatoid tissues, and hCG was found in giant syncytiotrophoblastic cells. She was treated with surgery followed by cisplatin-based combination chemotherapy. She is well, and her serum levels of AFP and hCG have not been elevated for more than 4 years after the treatment.     

Endometrioid adenocarcinoma with a functioning stroma

A case of a 70-year-old woman with endometrioid adenocarcinoma of the ovary with functioning stroma is presented. The symptom was postmenopausal bleeding. The preoperative level of serum estradiol was as high as 162.4 pg/mL, and serum gonadotropin levels were suppressed. The endometrial tissue showed hyperplastic changes. The surgical specimens consisted of a multilocular cystic ovarian tumor of 95 mm in diameter and an enlarged uterus. Histologically, the tumor was composed of proliferating, atypical, columnar cancer cells resembling early secretory endometrial cells, and condensation of plumed stromal cells resembling theca lutein cells. The diagnosis of endometrial adenocarcinoma of the ovary with functioning stroma was made. After surgery, the serum levels of estradiol decreased and of follicle-stimulating hormone increased. Almost all types of ovarian tumor have been reported to be associated with endocrine abnormalities. Mucinous epithelial ovarian tumors most commonly present with estrogenic stroma, although the frequency of endometrioid adenocarcinoma with functioning stroma is very low. Here, a rare case with the patient's clinical course and histopathologic findings is reported.     

Human chorionic gonadotropin and alpha-fetoprotein in sera and tumor cells of a patient with pure dysgerminoma of the ovary. A case report with radio-immunoassay and immunoperoxidase

One of 7 patients with pure dysgerminoma had slightly elevated serum human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) levels as determined by radio-immunoassay before operation. The values returned to the normal range after the removal of the tumor. The cells that produced the HCG or AFP were identified by immunohistochemical staining of the tumor tissues. HCG proved positive both in the multinucleated giant cells with eosinophilic cytoplasm and in the spindle-shaped cells with a hyperchromatic nucleus. AFP was positively stained in the round cells. These results suggest that HCG and AFP are produced by the cells which constitute pure dysgerminoma.     

Ductal adenocarcinoma of the prostate with endometrioid features in a 69-year-old man.

We describe a case of ductal adenocarcinoma of the prostate with endometrioid characteristics presenting as painless hematuria and intraurethral tumor. A 69-year-old man had intermittent painless hematuria for 2 months. The serum prostate-specific antigen concentration was elevated (22.0 ng/mL). An enlarged prostate with a necrotic tumor was noted in the right lobe of the prostate on computerized tomography and magnetic resonance imaging studies. A polypoid and worm-like tumor was found within the prostatic urethra near the verumontanum. The tumor had a distinctly papillary configuration with a focal glandular structure on microscopy. Radical prostatectomy was performed and histology of the tumor specimen revealed it to be composed of a closely packed glandular structure lined by single layers of high columnar cells with focal stratification. Frequent papillary projections of glandular epithelium and intraglandular bridging were noted, with a histopathologic appearance similar to endometrioid carcinoma of the uterus. Androgen deprivation therapy was started immediately following surgery. No evidence of recurrence or metastasis was found at follow-up 27 months postoperatively. Distinct features of ductal adenocarcinoma of the prostate include intraurethral papillary tumor close to the verumontanum, urethral obstruction, and easy bleeding of the tumor. Its more aggressive behavior than classical microacinar adenocarcinoma of the prostate makes early recognition of this type of prostatic malignancy important.     

A high-grade uterine leiomyosarcoma with human chorionic gonadotropin production.

Ectopic human chorionic gonadotropin production has been described in a wide variety of non-germ cell tumors, particularly in epithelial tumors, but rarely in sarcomas. In this report, we describe the case of 49-year-old woman with a history of "uterine fibroids," who presented with vaginal bleeding and a positive urine pregnancy test. After pregnancy was ruled out by ultrasound, the patient underwent a laparotomy and hysterectomy for a presumptive diagnosis of "fibroids" and was found to have carcinomatosis at the time of the surgery. Therefore optimal debulking of tumors was performed. Two weeks later, the patient developed a small bowel obstruction, which apparently was due to rapid recurrence of tumors in the abdomen, and soon afterwards she died. Microscopically, the resected pelvic mass was composed of highly atypical and pleomorphic spindle cells admixed with many multinucleated giant cells. The tumor had a high mitotic rate along with areas of hemorrhage and necrosis. Immunohistochemically, the tumor cells were positive for vimentin, desmin, smooth muscle actin, and beta-human chorionic gonadotropin, and were negative for epithelial membrane antigen, keratin AE1/3, S-100, CD31, CD117, Ber-EP4, WT-1, estrogen and progesterone receptors. The majority of cells, including the multinucleated giant cells, were strongly immunoreactive for beta-human chorionic gonadotropin. Only three cases of leiomyosarcomas with beta/human chorionic gonadotropin production have been described in the literature, and all three cases had extrauterine origin. Our case, to the authors' best knowledge, is the first uterine leiomyosarcoma with prominent beta/human chorionic gonadotropin production.     

Pure dysgerminoma of the ovary with elevated serum human chorionic gonadotropin: diagnostic and therapeutic considerations

Pure ovarian dysgerminomas with associated elevation of human chorionic gonadotropin (hCG) are rare, and their optimum management is unclear. We report here a 24-year-old woman with stage III dysgerminoma of the ovaries, with bulky intrapelvic disease, paraaortic adenopathy, and elevated pre- and postsurgical serum beta-hCG titers. Following administration of whole abdominal-pelvic and mediastinal irradiation therapy, the patient's adenopathy regressed, her serial beta-hCG titers returned to normal, and she has remained free of disease for the past 30 months. Histopathological studies revealed a pure dysgerminoma with scattered giant cells which were negative for hCG by immunoperoxidase staining. The literature is reviewed with reference to the significance of elevated hCG levels, the presence of giant cells in association with dysgerminoma of the ovary, and therapeutic implications. Serial determinations of beta-hCG titers may prove to be as valuable in the management of these patients as they are in patients with testicular tumors.     

Pelvic malignant mixed mesodermal tumor of uncertain origin: a case report.

Extra-uterine, and especially extragenital, malignant mixed mesodermal tumors (MMMT) are very rare. A large intrapelvic tumor resected from a 56-year-old woman was investigated with morphological and immunohistochemical methods. A large, soft and fragile tumor was located in the pelvic space. The tumor showed high cellularity and was biphasic; it consisted of an admixture of adenocarcinoma and various kinds of sarcomas. The latter were comprised of high-grade endometrial stromal sarcoma, pleomorphic sarcoma, and chondrosarcoma. The pleomorphic sarcoma showed a storiform pattern. The periodic acid-Schiff-positive eosinophilic hyaline droplets and globules in multinucleated giant cells revealed a typical ring-like or peripheral staining for alpha-1-antitrypsin and alpha-1 antichymotrypsin. We considered this case to be pelvic MMMT of uncertain origin, heterologous type.     

The relationship between trophoblast differentiation and the production of bioactive hCG

We previously showed that a significant number of failing pregnancies are associated with production of human chorionic gonadotropin (hCG) having relatively low bioactivity. The present study was designed to compare the secretion of intact, immunoreactive hCG to the secretion of bioactive hCG during trophoblast differentiation, and to test the hypothesis that the lower bioactive: immunoreactive hCG ratios in failing pregnancies are related to reduced or impaired trophoblast differentiation. Cytotrophoblast cells were isolated from term placentas and cultured under conditions that induced or did not induce syncytiotrophoblast formation. Culture media were collected at regular intervals up to 72 h and levels of immunoreactive and bioactive hCG were measured. The differentiation of cytotrophoblast cells to multinucleated syncytiotrophoblast was monitored by immunocytochemistry and electron microscopy. During the 72 h culture period, concentrations of immunoreactive and bioactive hCG increased in both differentiating and non-differentiating cells. However, the concentrations of immunoreactive and bioactive hCG were higher under culture conditions that promoted trophoblast differentiation. Furthermore, the ratio of bioactive hCG to immunoreactive hCG was higher in differentiating cultures. When differentiation was inhibited by dimethyl sulfoxide, the secretion of bioactive hCG was reduced and the bioactive: immunoreactive hCG ratio did not change. These findings are consistent with the idea that production of bioactive hCG accompanies syncytiotrophoblast formation.     

Changes in the serum levels of human chorionic gonadotropin and the pulsatility index of uterine arteries during conservative management of retained adherent placenta

OBJECTIVE: Our purpose was to assess the natural course of retained adherent placenta at term. METHODS: Five cases of retained adherent placenta, clinically diagnosed as placenta accreta, were managed conservatively without methotrexate. To assess the biochemical and circulatory changes in the placentas, the serum levels of human chorionic gonadotropin (hCG) and the pulsatility index (PI) of the uterine arteries were examined. RESULTS: Serum hCG levels decreased spontaneously; the half-life of serum hCG was calculated to be 5.2 +/- 0.26 days (mean +/- SEM). The PI of the uterine arteries remained at the level of pregnant women at term, but became elevated within a few days after the removal of the placentas. All the placentas were successfully removed transvaginally within 6 weeks postpartum. CONCLUSIONS: The changes in serum hCG observed in this study indicated the spontaneous degeneration of the placenta. Such changes might be similar to those reported to occur during treatment with methotrexate. In contrast, the PI of the uterine arteries did not reflect degeneration of the placenta.     

Synchronous ovarian endometrioid adenocarcinoma with a functioning stroma and endometrial endometrioid adenocarcinoma by different loss of heterozygosity findings

Purpose  

Mucinous epithelial ovarian tumors generally have estrogenic stroma, although the frequency of endometrioid adenocarcinoma with functioning stroma is very low. And while synchronous development of carcinomas in the endometrium and ovaries is a fairly common phenomenon, the distinction of a single clonal tumor with metastasis from two independent primary tumors may present a diagnostic challenge. We present a rare case of a 31-year-old woman with endometrioid adenocarcinoma of the ovary with functioning stroma and endometrial endometrioid adenocarcinoma who showed symptoms of virilization. Her preoperative levels of serum testosterone and estradiol were as high as 553 ng/dL and 177 pg/mL, respectively, and her serum gonadotropin levels were suppressed. After surgery, the serum levels of testosterone and estradiol decreased and that of follicle-stimulating hormone increased.     

Desensitization of both luteal and pituitary function in baboons with nafarelin, a potent LH-RH agonist

Acute responsiveness in vivo of the baboon corpus luteum to a course of twice daily injections of human chorionic gonadotropin (hCG) has been studied with and without concomitant injections of nafarelin, a potent luteinizing hormone-releasing hormone (LH-RH) agonist. HCG injection alone caused an acute (1 hour) rise in circulating levels of progesterone (P), confirmed to be a direct effect at the luteal level, since no change in circulating levels of endogenous LH was detected. When hCG was coadministered with a low dose of nafarelin (50 micrograms per injection), circulating levels of LH rose, but the rise in serum P levels was blunted. However, when hCG was coadministered with a high dose of nafarelin (250 micrograms per injection), serum LH levels rose only in response to the first injection and serum levels of P were not elevated, suggesting a desensitization of the pituitary to the LH-RH agonist and of the corpus luteum to the hCG. The profile of luteal P during the luteal phase in response to combined treatment with hCG and nafarelin also reflected these effects, being intermediate between vehicle controls and hCG treatment alone. This first demonstration of a luteal desensitization to gonadotropin by an LH-RH agonist in primates may account for previously noted successful interception of pregnancy in baboons treated with these agents.     

Ovarian endometrioid carcinoma with diffuse pigmented peritoneal keratin granulomas: a case report and review of the literature

The presence of keratin granulomas in peritoneal cavity associated with ovarian endometrioid carcinoma, which might be related to leakage from the ovarian tumor, is rarely reported. Its clinical significance has not yet been well investigated. We report a case presenting with intermittent abdominal pain after an acute episode 1 month before a complex adnexal tumor was noted. Comprehensive cytoreductive surgery was performed. The ovarian tumor was an endometrioid adenocarcinoma with squamous differentiation. There were diffuse brownish flecks over the omental surface and pelvic peritoneum, which contained fragments of degenerated squamous cells, keratin, and numerous foreign body giant cells. Extensive multiple sections were examined for these implants. DNA flow cytometry and various immunostaining studies (HER-2/neu, p53, CK-7, and cytokeratin [AE1/AE3]) were performed. Since viable epithelial cells in the implants could be differentially identified against mesothelial or granulomatous components by CK-7 staining and DNA aneuploidy was demonstrated on primary ovarian tumor, four courses of chemotherapy were administered. The patient has been free of disease for 18 months since diagnosis.     

Antibody to human chorionic gonadotropin detected choriocarcinoma

Persistently elevated levels of serum human chorionic gonadotropin (hCG) in women call for a tumor investigation, if pregnancy can be ruled out. We present a case of increased hCG concentrations for 1 1/2 years. Radiolabelled antibody directed against the hCG molecule indicated the source of production to be a choriocarcinoma. The patient was cured by multiagent chemotherapy.     

Eccrine adenocarcinoma of the vulva producing isolated alpha-subunit of glycoprotein hormones

A rare case of adenocarcinoma of the sweat glands of the vulva producing isolated alpha-subunit of glycoprotein hormones is reported. By an immunohistochemical method, eccrine gland adenocarcinoma tissues obtained from the right vulva and from its metastatic lesion in the right subclavicular lymph nodes were found to react with human chorionic gonadotropin (hCG), alpha-hCG but not beta-hCG. The concentrations of alpha-subunit in the serum and urine were markedly elevated to 6000 ng/mL and 55,000 ng/mL, respectively, just before the death of the patient.     

Epithelioid trophoblastic tumor of the lung

Epithelioid trophoblastic tumor (ETT) is a rare type of gestational trophoblastic disease and only 25 cases have been reported so far. It was first proposed by Mazur and Kurman in 1994 as an unusual type of trophoblastic tumor that is distinct from placental site trophoblastic tumor and choriocarcinoma and has features resembling carcinoma. A case of ETT of the lung in a 38-year-old Japanese woman is reported. The patient had suffered from a hydatidiform mole at the age of 27 years, and had four normal deliveries at the ages of 24, 31, 35 and 37 years. Because no tumor lesions were detected in the uterus, the patient was suspected of having metastatic choriocarcinoma with multiple lesions in the lung accompanied by an elevated level of human chorionic gonadotropin (hCG). In order to make an exact diagnosis, a partial resection of metastatic foci in the lung was performed. Microscopically, the tumor showed hemorrhagic necrotic foci and was composed of mainly mononuclear tumor cells and some giant tumor cells resembling trophoblastic cells. Immunohistochemical examination showed that a few large cells were stained positively for hCG, and that other cells were positive for human placental lactogen, pregnancy-specific beta1-glycoprotein, cytokeratin 7 and inhibin-alpha. In the ultrastructure, the tumor cells contained large nuclei and rich organella with desmosomes and well-formed filaments. The diagnosis of ETT was confirmed from the findings as described above.     

Pleomorphic Rhabdomyosarcoma of the Uterus in a Postmenopausal Woman with Elevated Serum CA125

BACKGROUND: Pure rhabdomyosarcoma of the uterus is an exceedingly rare tumor. While there are no commonly associated tumor markers, a previously reported case confirmed CA125 production by a pure uterine rhabdomyosarcoma. CASE: We describe a postmenopausal woman who presented with vaginal bleeding and was diagnosed with pleomorphic rhabdomyosarcoma of the uterus. Of particular interest was an elevated serum CA125 level at presentation. Immunohistochemical staining with CA125 antibody, however, showed no activity within the tumor. Despite aggressive therapy, the patient experienced distant nodal metastases and succumbed to the disease within 25 months of diagnosis. CONCLUSION: Our patient illustrates the typical presentation and aggressive behavior of this rare neoplasm. While serum CA125 may be a useful tumor marker in selected patients, elevated levels do not directly reflect tumor burden when associated with negative immunohistochemical staining.