Robert H. Young

The clinical and pathological features of 150 cases of ovarian small cell carcinoma of the hypercalcemic type are described. The patients ranged from 9 to 43 (average 23.9) years of age. The serum calcium level was known to be elevated in 49 of the 79 patients (62%) whose preoperative calcium levels were measured. Four of these patients had symptoms of hypercalcemia, and one of them had undergone neck exploration with negative results before the ovarian tumor was discovered. At laparotomy the tumor was unilateral in 148 cases (99%). Extraovarian spread was present in approximately half the cases. The tumors ranged from 6 to 26 (average 15.3) cm in greatest dimension. Microscopic examination disclosed various patterns, the most common of which was diffuse sheets of cells punctured by variable numbers of follicle-like spaces; the tumor cells also grew in nests, cords, clusters, and singly. The follicle-like spaces, which were present in 80% of the cases, contained fluid that was almost always eosinophilic and rarely basophilic. Glands or cysts lined by mucinous epithelial cells were present in 12% of the neoplasms. The neoplastic cells were typically small and round with hyperchromatic nuclei and brisk mitotic activity. Fifty percent of the tumors, however, also had a variable component of cells with moderate to abundant amounts of eosinophilic cytoplasm, which sometimes contained large hyaline globules and large nuclei that were typically paler and had more prominent nucleoli than the small cells. Immunohistochemical staining confirmed the epithelial nature of the tumors, as did electron microscopy, which characteristically showed abundant dilated rough endoplasmic reticulum. Five of seven tumors investigated by immunohistochemical staining for parathyroid hormone-related protein showed positive results. All 23 tumors examined by flow cytometry with interpretable results were diploid. Fourteen of 42 patients (33%) with stage IA disease for whom follow-up information is available remained well and free of disease 1-13 (average 5.7) years postsurgery; 23 died of their disease, usually within 2 years; and five had recurrences but were alive at last follow-up. Almost all the patients with tumors of a stage higher than IA died of disease, but one patient with stage IIB disease who received intensive chemotherapy and radiation therapy is alive and apparently free of disease at 7 years. Features in stage IA tumors that appeared to be associated with a more favorable outcome included an age > 30 years, a normal preoperative calcium determination, a tumor size < 10 cm, and an absence of large cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Twenty-two cases in which mucinous tumors of the appendix were associated with mucinous tumors of the ovary are reported. The patients ranged from 23 to 83 (average 49) years of age and usually presented with increasing abdominal girth. The appendiceal and ovarian tumors were synchronous in 21 cases. Laparotomy typically disclosed large cystic ovarian tumors that averaged 16 cm in diameter and were usually multiocular, an appendix that was usually dilated and covered with mucus, and abundant intra-abdominal mucus. The ovarian tumors were bilateral in seven cases. The ovarian and appendiceal tumors were typically similar histologically, with features similar to those of ovarian mucinous cystadenomas and cystadenomas of borderline malignancy. In most of the ovarian tumors, mucin dissected through the ovarian stroma (so-called pseudomyxoma ovarii). Eight of the 20 patients with follow-up information were well when last seen, but the duration of follow-up was 3 years or less in six of them. Two patients died of pseudomyxoma peritonei 4 and 5.5 years after presentation. One patient died of a myocardial infarct shortly after laparotomy for recurrent pseudomyxoma peritonei at 11 years. The remaining patients had definite or probable recurrent or residual disease but were alive at the time of the last follow-up information. The typical synchronous presentation of the ovarian and appendiceal tumors, their histologic similarity, the frequency of bilaterality of the ovarian tumors, the predominance of right-sided ovarian involvement, and the usual presence of mucin and atypical mucinous cells on the ovarian surfaces all point toward the probable secondary nature of the ovarian tumors.

Endometrial stromal tumors are reviewed with emphasis on their wide morphologic spectrum and problems in differential diagnosis, highlighting issues that have received particular attention in the recent literature. These neoplasms are divided into two major categories--endometrial stromal nodules and endometrial stromal sarcomas--a distinction made on the basis of the lack of significant infiltration at the periphery of the former. The division of endometrial stromal sarcomas into low-grade and high-grade categories has fallen out of favor and the designation endometrial stromal sarcoma is now considered best restricted to neoplasms that were formally referred to as "low-grade" stromal sarcoma. Endometrial sarcomas without recognizable evidence of a definite endometrial stromal phenotype, designated poorly differentiated "endometrial sarcomas," are almost invariably high grade and often resemble the mesenchymal component of a malignant mullerian mixed tumor. Two features of endometrial stromal tumors that may cause confusion are smooth muscle differentiation and epithelial patterns. Cases in the former category often have a characteristic "starburst" pattern of collagen formation. The most common epithelial patterns resemble those seen in ovarian sex-cord stromal tumors. Much less common is endometrioid gland differentiation. Some endometrial stromal tumors have a prominent fibrous or myxoid appearance and the myxoid tumors should be distinguished from myxoid leiomyosarcoma. Other unusual features of endometrial stromal tumors are also discussed. Lesions in the differential diagnosis of uterine endometrial stromal neoplasms include highly cellular leiomyoma, cellular intravenous leiomyomatosis, adenomyosis with sparse glands, metastatic carcinoma, and lymphoma. Endometrial stromal sarcomas at extrauterine sites may be primary or metastatic from a uterine tumor, the latter sometimes being occult and difficult to definitively establish, particularly if there is a history of a remote hysterectomy for "leiomyomas." Endometrial stromal sarcomas of the ovary, whether primary or metastatic, may be difficult to distinguish from ovarian sex-cord stromal tumors. Extragenital endometrial stromal sarcomas may be confused with diverse lesions such as gastrointestinal stromal tumors, hemangiopericytoma, lymphangiomyomatosis, or mesenchymal cystic hamartoma of the lung. Immunohistochemistry may play a role in evaluating these tumors and in some instances establishing the diagnosis although conventional light microscopic analysis suffices in the majority of cases. The unusual tumor, the "uterine tumor resembling an ovarian sex-cord tumor," is also considered in this review as it is almost certainly of endometrial stromal derivation in many cases. These neoplasms may have a striking resemblance to granulosa cell tumors or Sertoli cell tumors, including those with a retiform pattern, and have recently been shown to be frequently inhibin positive.

Twenty-five primary ovarian neuroectodermal tumors occurred in females from 6 to 69 (average, 23) years of age; they had the usual presenting symptoms of abdominal swelling or pain. The tumors, which varied from cystic to solid, ranged from 4 to 20 cm (average, 14 cm) in diameter. Microscopic examination revealed three histologic categories--differentiated, primitive, and anaplastic--with the tumors in the first group having a better prognosis than those in the other two groups. Five of the six differentiated gliomas were pure ependymomas, and one was an ependymoma with an astrocytoma component; none contained teratomatous elements. Two patients with stage I tumors were alive 4 and 5 years postoperatively. The one patient with stage IIA tumor was free of disease at 3 years; one of the two patients with a stage III tumor died of tumor after 5 years, and one had two recurrences but was alive and well at 5 years. Twelve tumors were primitive, resembling medulloepithelioma, ependymoblastoma, neuroblastoma or medulloblastoma. Seven tumors had teratomatous foci of other types, including three dermoid cysts. Three patients with stage I tumors were alive at 7 months, 3 years, and 9 years postoperatively; six of seven patients with stage III tumors died of tumor 2 to 20 months postoperatively, and one was alive with disease at 1 year. Seven tumors were anaplastic, resembling glioblastoma. All contained foci of squamous epithelium. One patient with stage IA tumor died of tumor at 2 years, but two were free of tumor after 3 and 4 years. One patient with a stage IIA tumor died of disease after 5 years; another was alive with tumor at 1 year. One patient with a stage III tumor died after 4 months. The differential diagnosis of neuroectodermal tumors of the ovary includes many primary and metastatic ovarian neoplasms of diverse types, and distinction among them is important. Neuroectodermal tumors should be considered when examining unusual ovarian tumors, particularly if the patient is young.

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.