Loss of estrogen receptor (ER) expression in endometrial tumors is not associated with de novo methylation of the 5' end of the ER gene.

Normal endometrium, an estrogen-responsive tissue, expresses the estrogen receptor (ER) alpha gene. Loss of ER expression, the basis for which is currently unknown, is often seen in advanced stage, poor prognosis endometrial tumors. The ER gene undergoes de novo methylation with high frequency in a wide variety of human tumors, including ER-negative breast cancers. In this study, we used several bisulfite-based detection methods to assess whether loss of ER positivity in endometrial tumors is associated with aberrant methylation of the ER gene. Although extensive methylation of a 600-bp region at the 5' end of the gene was seen in two endometrial carcinoma cell lines, none of the 55 CpGs in this region was methylated in 25 of 26 ER-deficient endometrial carcinomas.

Diagnostic discrepancies in breast specimens subjected to gross reexamination.

To determine the accuracy of gross examination of breast specimens from a large university pathology service, 1120 breast specimens submitted from 1995 to 1997 that had residual tissue after submission of tissue sections were reexamined for diagnostic discrepancies. A total of 520 mastectomies, 143 wire localization excisions, 156 lumpectomies, and 301 mammoplasties were reexamined. Fifty-three (5%) major and 65 (6%) minor diagnostic discrepancies were detected. Major discrepancies included eight additional positive lymph nodes, 37 missed cancers, four upstagings by size, and four skin invasions. Forty-four of the major discrepancies were in mastectomy specimens. First-year residents accounted for slightly more than one half of all discrepancies. In contrast, review of original slides of 733 breast cancer cases revealed only 11 (1.5%) major discrepancies: three changes of margin status, six missed carcinomas, one positive lymph node, and one upstaging by size. Most discrepancies occurred because a specimen was not thoroughly inspected. The second most common cause was failure to recognize lesions. Our findings suggest that gross dissection performed by first-year residents is more prone to error and that such discrepancies are amenable to instruction and supervision.

Management of twin pregnancies consisting of a complete hydatidiform mole and normal fetus.

OBJECTIVE: To report the clinical features, management, and outcome of twin pregnancies consisting of a complete hydatidiform mole and a coexisting normal fetus. METHODS: Between 1966 and 1997, seven women with complete hydatidiform mole and coexisting normal fetus were treated at the John I. Brewer Trophoblastic Disease Center of Northwestern University Medical School. Clinical features, including presenting symptoms, gestational dates, hCG levels, and complications, as well as route of delivery or evacuation, pregnancy outcome, genetic analysis, and need for chemotherapy were assessed. RESULTS: Four women required uterine evacuation before 20 weeks' gestation because of vaginal bleeding or medical complications, one woman required an emergency hysterotomy because of hemorrhage at 24 weeks, and two women delivered normal, viable infants at 26 and 34 weeks. The pathologic diagnosis of complete hydatidiform mole was confirmed in each case and the chromosome complement was 46,XX in all molar gestations. Four of seven women required chemotherapy for treatment of nonmetastatic gestational trophoblastic tumors, including both women who delivered viable infants and two of the five women whose pregnancies were evacuated before 24 weeks' gestation. All four patients were treated with five to seven cycles of a 5-day methotrexate regimen and achieved complete remission. CONCLUSION: Patients with a twin pregnancy consisting of a complete mole and a normal fetus are at increased risk for hemorrhage and medical complications, as well as the development of persistent gestational trophoblastic tumor.

Leiomyoma causing massive ascites, right pleural effusion and respiratory distress. A case report.

BACKGROUND: Pseudo-Meigs' syndrome, or atypical Meigs' syndrome, occurs when a pelvic mass other than an ovarian fibroma is present with hydrothorax and ascites. Leiomyomas rarely cause this condition. CASE: An otherwise healthy 31-year-old woman presented to the emergency department in acute respiratory distress with massive ascites, pleural effusion and a pedunculated leiomyoma. After receiving mechanical ventilation, she underwent myomectomy and recovered fully within four weeks. CONCLUSION: This unique presentation of pseudo-Meigs' syndrome should be included with malignancy in the differential diagnosis of a pelvic mass with ascites.

Ovarian carcinoma initially presenting as metastatic axillary lymphadenopathy.

BACKGROUND: Ovarian carcinoma usually presents at advanced stage due to diffuse intraabdominal disease. Presenting signs and symptoms often relate to the degree of intraabdominal spread. It is rare to have distant lymph node metastases, in conjunction with minimal intraabdominal disease, at initial presentation. CASE: A 78-year-old woman was noted to have an enlarged axillary lymph node on a routine, screening mammogram. Biopsy revealed metastatic adenocarcinoma, consistent with primary breast cancer. Physical examination, diagnostic mammogram, and magnetic resonance imaging of the breasts were normal. A pelvic computed tomography scan revealed a 7-cm complex, right adnexal mass. At exploratory laparotomy, there was minimal intraabdominal tumor burden; only a 6-cm right ovarian tumor and a single 1.0-cm nodule adherent to the bladder peritoneum were found. After optimal cytoreductive surgery, she received tamoxifen for presumed metastatic breast cancer. One year later, recurrent disease developed in the pelvis. After reexploration and excision of all gross pelvic disease, a revised diagnosis of recurrent ovarian cancer was made, and therapy was changed to carboplatin and paclitaxel chemotherapy. The patient is currently without evidence of disease. CONCLUSION: Ovarian carcinoma usually presents with signs and symptoms related to the tumor burden within the peritoneal cavity. The finding of isolated, distant metastatic lymphadenopathy with minimal intraabdominal disease is very unusual. Immunohistochemical tumor markers can help determine the origin of a metastatic adenocarcinoma when the clinical presentation is atypical.

Late recurrences of vaginal clear cell adenocarcinoma.

Recurrent vaginal clear cell adenocarcinoma was diagnosed in two DES-exposed patients 17 and 19 years after initial therapy. These cases demonstrate the need for continued clinical evaluation, since patients with clear cell carcinoma of the vagina seem to be at greater risk for developing late recurrences than patients with squamous cell carcinomas.

Pilomatricoma-like endometrioid adenosquamous carcinoma of the ovary with neuroendocrine differentiation.

A case of high-grade endometrioid adenosquamous carcinoma of the ovary showing pilomatricoma-like areas and neuroendocrine differentiation is presented. The pilomatricoma-like areas were strongly positive for cytokeratin and vimentin, whereas the poorly differentiated areas of the tumor were positive for cytokeratin, synaptophysin, and neuron-specific enolase. Review of the literature did not show any published report of adenosquamous carcinoma with pilomatricoma-like areas either in the ovary or in the uterus.

Malignant mesonephric neoplasms of the uterine cervix. A report of eight cases, including four with a malignant spindle cell component.

Eight mesonephric adenocarcinomas of the uterine cervix, four of which had a malignant spindle-cell component, occurred in women aged 34 to 71 (median 43, mean 54.5) years, bringing to 14 the number of cervical mesonephric carcinomas in the literature. The tumors with a malignant spindle-cell component ("malignant mesonephric mixed tumors") are, with one possible exception, the first reported examples at this site. The patients, almost all of whom presented with vaginal bleeding, underwent hysterectomy; five also had a pelvic lymph node dissection. The tumors were all stage IB, although microscopic lymph node metastases were found in two cases. Gross examination revealed an invasive cervical mass in each case. On microscopic examination, seven tumors were adjacent to mesonephric hyperplasia, which in five cases was florid and focally atypical; in the remaining case, occasional non-neoplastic mesonephric tubules were found only within the tumor. The adenocarcinomas typically exhibited a variety of patterns, including a ductal pattern resembling endometrioid adenocarcinoma, a small tubular pattern, a retiform pattern, a solid pattern, and a sex-cord-like pattern. These disparate patterns frequently caused diagnostic difficulty. The spindle-cell component generally resembled endometrial stromal sarcoma or a nonspecific spindle-cell sarcoma; one tumor also contained multiple foci of osteosarcoma and another, a single chondroid focus. Immunohistochemical staining for a variety of antigens failed to reveal a distinctive profile, although all the carcinomas were immunoreactive for vimentin. Follow-up in six cases revealed three patients to be alive without evidence of recurrence at postoperative intervals of 2 to 3 years. Recurrent tumor developed in a fourth patient 1 year after hysterectomy; she was treated with chemotherapy and was alive and free of disease at 2 years. Another patient had intra-abdominal recurrences (including liver metastases) at 9 and 11 years and was alive with tumor at 13 years. Death at 8.5 months in a final patient was probably due to an independent stage IIc ovarian clear-cell carcinoma. These and prior observations in the literature suggest that malignant mesonephric tumors of the cervix may be more indolent than their müllerian counterparts, from which they should be distinguished. Mesonephric carcinomas in this site should also be distinguished from florid mesonephric hyperplasia, with which they are usually associated.

Anterior mediastinal endodermal sinus (yolk sac) tumor in a female infant.

The first known case of primary anterior mediastinal endodermal sinus (yolk sac) tumor in a female patient, occurring in a 20-month-old infant, is reported. The child presented with cough, fever, and listlessness. Chest x-ray revealed a right anterior mediastinal mass. At thoracotomy a large anterior mediastinal tumor extending from the neck to the diaphragm was found, and was almost totally resected. Microscopically, the tumor displayed many of the histologic patterns observed in EST. Other neoplastic germ cell elements were not identified. The ultrastructural and immunohistochemical findings further confirmed the diagnosis. Serum alpha-fetoprotein (AFP) level, determined during surgery, was elevated to 65,200 ng/ml, whereas serum beta-human chorionic gonadotropin level was normal. Postoperatively, combination chemotherapy consisting of vinblastine, bleomycin, cisplatin, dactinomycin, cyclophosphamide, and doxorubicin was administered with a maintenance program. After 18 weeks on this regimen all the findings were normal, including serum AFP level. The child is well and disease-free 25 months after diagnosis.

Large-cell calcifying Sertoli cell tumor of the testis: a case report with ultrastructural study.

Large-cell calcifying Sertoli cell tumor (LCCSCT) is a rare histologic variant of Sertoli cell tumor. Recently we observed a case of LCCSCT of the testis with no associated endocrine abnormality. Our ultrastructural findings of rows of tight junctions, numerous intracytoplasmic filaments, and abundant rough endoplasmic reticulum in whorled formations support the Sertoli cell origin of this neoplasm.

Mediastinal yolk sac tumor: ultrastructural and immunofluorescent studies.

Primary mediastinal yolk sac tumor is rare. In this report, a case of a 32-year-old male with a mediastinal yolk sac tumor was studied by light, electron, and immunofluorescent microscopy. A positive immunofluorescent reaction to alpha-fetoprotein (AFP) correlated with the PAS-positive hyaline globules and electron-dense deposits seen in intracellular and extracellular locations. Serum AFP is a useful tumor marker for monitoring the results of therapy. Review of the literature indicates that the prognosis for patients with yolk sac tumor is generally poor.

Myoepithelial differentiation and basal lamina deposition in fibroadenoma and adenosis of the breast.

Sixteen cases of breast fibroadenomas and 11 of adenosis were studied ultrastructurally; emphasis was placed on the patterns of myoepithelial differentiation and the number and appearance of the basal laminae. Ducts of both fibroadenomas and adenosis showed well differentiated, peripherally arranged myoepithelial elements with conspicuous cytoplasmic filaments and numerous hemidesmosomes; focal myoepithelial multilayering occurred. Myoepithelial cells exhibited complex, convoluted cytoplasmic processes extending into the stroma and resulting in the formation of pseudocysts containing stromal material. Basal lamina deposition was invariably found; basal lamina reduplication was extremely frequent. Basal lamina discontinuities with cytoplasmic processes extending directly into the stroma were seen in adenosis. Myoepithelial features and conspicuous basal lamina deposition indicate advanced differentiation and correlate well with the benign prognosis of these lesions. The focal basal lamina gaps in adenosis may be significant in the long-term evolution of this and similar dysplastic processes.

Squamous cell dysplasia and carcinoma in situ of the cervix and vagina after prenatal exposure to diethylstilbestrol.

Squamous cell abnormalities of the vagina and cervix were evaluated in 1424 women exposed to diethylstilbestrol (DES) in utero. The prevalence of dysplasia was 2.1% and the incidence 0.85/100 person-years of followup. The dysplastic epithelial changes were almost always mild in women with no prior history of dysplasia and was slightly more frequent in the cervix than the vagina. Severe dysplasia and carcinoma in situ (CIS) were encountered only in those subjects specifically referred because of those abnormalities. The most common problem in the diagnosis of these squamous cell changes was the misinterpretation of mature and immature metaplastic cells for dysplastic squamous cells. Discordance between biopsy and cytology was common-place in the detection and followup of dysplasia, especially when it was mild. There were no instances in the study where cytology and biopsy samples from the vagina were both abnormal concurrently. Colposcopically directed biopsies did not increase the frequency of confirmation of cytologic findings. These data suggest that both cytology and biopsy of abnormal segments of the vagina and cervix remain an integral part of the examination of the DES-exposed female during long-term follow-up studies.

Urogenital sinus origin of mucinous and ciliated cysts of the vulva.

The origin of mucinous and ciliated cells in the vulva and the pathogenesis of cysts lined by these epithelia were investigated. Small mucinous glands numbering from one to more than a hundred were encountered in 9 of 19 vulvas (53%) that were consecutively examined at autopsy. Eleven other cysts were encountered clinically. Six were lined by mucinous epithelium, three by pseudostratified cells with cilia plus small foci of mucinous epithelium, and two by ciliated epithelium only. Four of the cysts with ciliated epithelium were otherwise typical Bartholin's gland cysts. It is concluded that glands lined by either mucinous or ciliated epithelia are normal constituents of the vulvar vestibule, are derived from urogenital sinus, and develop into cysts when the neck leading to the vulvar surface becomes inflamed and obstructed.

Fetus papyraceus in twin pregnancy.

Three cases of fetus papyraceus in twin pregnancy were seen over a 4-month period. They were associated with an antepartum stillbirth and intrauterine growth retardation of the larger twin. Two of the 3 mothers exhibited hypertension. It is concluded, therefore, that the appearance of a fetus papyraceus frequently indicates the presence of a hostile intrauterine environment. We suggest that serial ultrasonic examinations be performed to confirm the diagnosis of fetus papyraceus. In this way, appropriate therapy may be directed toward a better outcome for the second twin.

Cytology of 575 young women with prenatal exposure to diethylstilbestrol.

The vaginal and cervical cellular changes encountered in 575 postpubertal females exposed prenatally to diethylstilbestrol (DES) were compared with those of an unexposed population with particular reference to the role of cytology in the detection of vaginal adenosis and cervical ectropion (erosion). Several methods of obtaining specimens were utilized, the most effcacious of which was scraping of the vagina, especially the fornices, and the portio vaginalis of the cervix. With this technic, columnar cells of the mucinous type and metaplastic squamous cells were observed in 34% of the vaginal scrapes and 54% of the scrapes of the cervical portio. A higher incidence was apparent among those patients in whom iodine staining of the vaginal mucosa was abnormal or vaginal adenosis was proven by biopsy. Moderate to severe dysplasia of the squamous cells or atypical glandular cells were found in 1% of the exposed subjects. This study indicates that the presence of mucinous columnar or metaplastic squamous cells in vaginal scrapes is suggestive of vaginal adenosis but that vaginal cytology cannot be considered a uniformly reliable screening technic for detecting the presence of this disorder.

Ultrastructure of the basal cell adenoma of parotid gland.

Electron microscopic examination of two classical examples of so-called basal cell adenoma of parotid gland disclosed four distinct cellular types: the squamous epithelial cells with tonofilaments and prominent desmosomes predominantly located at the central portion of neoplastic mass; the basally located secretory cells with numerous secretory granules; the occasional intermediate cells with scanty cytoplasmic microfilaments; and the peripherally situated attenuated myoepithelial cells. The neoplastic clusters are surrounded by highly replicated basal laminae with microfibrils in their interstices. This information about its component cells suggests that basal cell adenoma arises from the secretory duct, in particular the intercalated duct, of the parotid gland. The term basal cell adenoma appears appropriate for its designation. It is interesting that the secretory cells and the multilayered basal laminae illustrated in the present study are reportedly seen in adenoid cystic carcinoma of the salivary gland; this finding would suggest a common cellular origin for these two neoplasms.