Müllerian inhibiting substance as a marker for ovarian sex-cord tumor.
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Biomedical subjects
Publications and source records attributed to R E Scully.
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Three girls, one 14 and two 15 years of age, with the recently described neoplasm that has been designated "intra-abdominal desmoplastic small round cell tumor with divergent differentiation," and ovarian involvement at presentation are described. In two cases the ovarian tumor was initially thought to be the primary neoplasm. In all cases there was extensive extraovarian tumor at the time of presentation. The ovarian involvement was bilateral in two cases and unilateral in the third. Microscopic examination showed prominent nodular growth within the ovaries. The tumors were characterized predominantly by nests of small cells with hyperchromatic nuclei and scant cytoplasm separated by a prominent desmoplastic stroma. A few tubules containing mucinous secretion were present in one case. On immunohistochemical staining many of the tumor cells stained positively for cytokeratin, epithelial membrane antigen, desmin, and vimentin. Staining for neuron-specific enolase was present in two cases but was conspicuous in only one of them. Leu-7 was expressed by the tumor cells in two cases, and S-100 protein by one, giving further support to the possibility of neuroectodermal differentiation within some of these neoplasms. The two cases studied by electron microscopy both showed frequent intercellular junctions, basal lamina, cytoplasmic filaments, and sparse, small dense granules of either neuroendocrine or lysosomal type. Paranuclear aggregates of filaments were found in one case and cellular processes were prominent in the other case. The differential diagnosis in these cases was extensive and included a number of small cell tumors that may involve the ovary, either primarily or secondarily, in young females. The desmoplastic small round cell tumor should be considered in such cases when the appearances on routine examination are consistent with the diagnosis, and appropriate immunohistochemical stains should be performed to confirm the diagnosis.
Three cases of hepatocellular carcinoma with ovarian metastases discovered during the patient's life are reported. A 31-year-old woman presented with back pain, and radiographic studies disclosed massive liver enlargement and bilateral ovarian tumors. The second patient, a 38-year-old woman, had an enlarged liver at the time of laparoscopic tubal ligation, and subsequently underwent right hepatic lobectomy for hepatocellular carcinoma. Three months later a left ovarian tumor was detected and a total abdominal hysterectomy with bilateral salpingo-oophorectomy performed. The third patient, a 68-year-old woman, presented with gastrointestinal symptoms and weight loss, and had bilateral ovarian tumors and widespread tumor at laparotomy. Two patients died of their disease at 18 months and 4 years 7 months; the third patient is alive with residual tumor at 7 months. The ovarian tumors, which were bilateral and multinodular in two cases and focally cystic in one case, ranged from 4 to 11 cm in maximum dimension, and had yellow-green or yellow sectioned surfaces. On microscopic examination, they were composed of cells with moderate to abundant eosinophilic cytoplasm growing diffusely and in nodules, nests, and trabeculae; cysts or glands were conspicuous in two cases. Bile was present in one tumor. The main differential diagnostic considerations were hepatoid yolk sac tumor and hepatoid carcinoma, primary or metastatic in the ovary. A variety of features, including the age of the patient, unilaterality or bilaterality of the ovarian tumors, distribution of disease, and microscopic features of the neoplasm, including the identification of bile, established the diagnosis. Metastatic hepatocellular carcinoma must be included in the differential diagnosis of oxyphil cell tumors of the ovary.
Paraffin-embedded tissue from 38 patients with early- and advanced-stage juvenile granulosa cell tumor (JGCT) of the ovary was analyzed by flow cytometry to investigate whether the DNA content is related to the histologic features, stage, or clinical outcome. Thirty-three cases were suitable for analysis: twenty-seven Stage Ia, two Stage Ic, and four Stage III. Eighteen (55%) tumors were DNA diploid and fifteen (45%) tumors were DNA aneuploid with a mean S-phase fraction (SPF) of 13.6% and a range of DNA indices from 1.0 to 2.2. Neither the DNA ploidy nor the SPF was associated with the stage of the disease. An analysis of the relation between DNA content and histopathologic features revealed that aneuploidy was associated with high mitotic rates and to a lesser extent with high-grade nuclear atypia. DNA aneuploidy was not associated with aggressive behavior of Stage Ia JGCTs. However, among the four patients with Stage III tumors, the two with diploid, low-SPF tumors were alive and well, whereas the two with aneuploid, high-SPF tumors developed recurrences or died. These data suggest that further studies on the prognostic significance of flow cytometric analysis of DNA content in advanced-stage JGCTs are warranted.
Ovarian small cell carcinoma of the hypercalcemic type is a rare cancer of young women of nuclear histogenesis. Although usually lethal, a subset of patients with stage I tumors have survived. Twenty-five cases of small cell carcinoma (17 stage I, 1 stage II, and 7 stage III) were evaluated by flow cytometric analysis performed on paraffin-embedded tissue. Forty classifiable histograms from 23 cases were DNA diploid; histograms from two cases could not be interpreted. The mean S-phase fraction was 10.5% (4.7% to 18.4%), and the mean G2/M fraction was 5% (1.5% to 19.5%) in 22 cases. Mean values of mitotic rate, S-phase fraction, G2/M fraction, and proliferation index (%S + %G2/M) were not associated with stage or outcome, nor did any proliferation variable correlate with interval to death. A comparative review of flow cytometric findings in other types of ovarian cancer that may be confused with small cell carcinoma indicates that flow cytometry is an objective diagnostic aid to distinguish small cell carcinoma of the hypercalcemic type from other forms of small cell carcinoma, malignant germ cell tumors, and sex-cord tumors, and that small cell carcinoma probably does not belong in either the surface epithelial or germ cell categories of ovarian cancer. Finally, the flow cytometric findings in this report exemplify the rare phenomenon of a diploid DNA content in a very lethal tumor and indicate that an accurate diagnosis of tumor type is essential before a prognosis on the basis of flow cytometric data can be made.
We describe 10 uterine leiomyomas with hydropic changes that created problems in differential diagnosis. The patients ranged in age from 41 to 51 years (mean, 45 years). Their presenting symptoms did not differ from those of patients with typical uterine leiomyomas. The follow-up, available for eight patients, was uneventful. Gross and microscopic examination revealed otherwise typical or cellular leiomyomas with focal accumulations of edema fluid (hydropic degeneration), typically associated with variable amounts of collagen ("hyaline degeneration"). Significant accumulations of acid mucins (myxoid degeneration) were present in only one case. These changes resulted in one or more of the following: (a) a characteristic perinodular hydropic change that mimicked intravenous leiomyomatosis on both gross and microscopic examination; (b) hydropic changes extending beyond the confines of the leiomyomas that raised the suspicion of myxoid leiomyosarcoma; and (c) extensive or subtotal obliteration of the usual architecture of the leiomyoma, often accompanied by numerous thick-walled blood vessels, that tended to obscure its smooth-muscle nature. Awareness of these changes combined with mucin stains and immunohistochemical stains for endothelial antigens should facilitate the diagnosis. Hydropic leiomyomas are clinically similar to typical leiomyomas; it is obviously important that they not be confused with intravenous leiomyomatosis or myxoid leiomyosarcoma.
Eleven primary ovarian tumors that resembled small cell carcinoma of the lung are reported. They occurred in women 28-85 (mean 59) years of age, most of whom presented with abdominal swelling. Six of the tumors were unilateral and five bilateral; seven had spread beyond the ovary. The tumors ranged from 4.5 to 26 (mean 13.5) cm in greatest dimension and were mostly solid, with a variable minor cystic component. Microscopic examination showed small to medium-sized round to spindle-shaped cells with scanty cytoplasm, hyperchromatic nuclei, and inconspicuous nucleoli growing in sheets, closely packed nests, and occasionally islands and trabeculae. A component of endometrioid carcinoma was present in four tumors, another tumor showed squamous differentiation, another contained a cyst lined by atypical mucinous cells, and two others were associated with a Brenner tumor. Argyrophil granules were present focally in two of six tumors appropriately stained. Immunohistochemical staining was performed in nine cases: in six there was staining of the small cell component for keratin, in five for epithelial membrane antigen, in seven for neuron-specific enolase, in two for chromogranin, and in one for Leu-7. Vimentin staining was not observed. Flow cytometry was performed on eight tumors: five were aneuploid and three diploid. Five of seven patients with long-term follow-up died of, or with, disease at 1-13 (mean 8) months, one died after an unknown interval, and one was alive at 7.5 years. Two other patients had recurrent or residual disease at 6 and 8 months.
Six uterine adenocarcinomas, one cervical and five endometrial, that simulated microglandular hyperplasia histologically are described. The cervical neoplasm occurred in a 34-year-old woman who had been taking oral contraceptives. The five endometrial cancers occurred in postmenopausal patients 57 to 69 years of age; two of them were receiving, or had been receiving, premarin and provera and two were receiving only premarin. The patient with the cervical neoplasm had an abnormality observed on pelvic examination. The five postmenopausal patients presented because of vaginal spotting, bleeding, or discharge; their carcinomas were discovered in endometrial curettage specimens. On initial pathologic examination two specimens were misinterpreted as benign and in the remaining four cases there was uncertainty as to whether the lesion was benign or malignant. All the neoplasms had conspicuous microglandular patterns, with the gland lumens typically containing eosinophilic mucinous secretion and numerous acute inflammatory cells, which were also characteristically prominent in the stroma. Subsequent hysterectomies in all the cases showed residual adenocarcinoma with more typical features. Three of the endometrial tumors were mucinous adenocarcinomas and two mixed mucinous and endometrioid adenocarcinomas; the cervical tumor was a moderately differentiated adenocarcinoma of endocervical type. These cases illustrate that microglandular hyperplasia should be diagnosed with caution in a postmenopausal patient, particularly if lesional tissue is present in an endometrial curettage specimen, and, rarely, cervical adenocarcinomas have foci that simulate microglandular hyperplasia.
Six adenocarcinomas of the fallopian tube that resembled the female adnexal tumor of probable wolffian origin are described. The tumors, which occurred in patients from 38 to 66 (average 55) years of age, typically formed intraluminal masses. One was an incidental finding on microscopic examination. On microscopic examination, the tumors were characterized by a predominant pattern of small, closely packed cells punctured by numerous glandular spaces, which were typically small but occasionally were cystically dilated. Many of the glands contained a dense colloid-like secretion that was positive with the periodic acid-Schiff stain. Small amounts of intracellular mucin were present in all cases. In the solid areas of three cases, spindle cells that focally formed concentric whorls were present. In all cases, small numbers of tubular glands typical of endometrioid adenocarcinoma were identified. The cytologic atypia and mitotic activity of the tumors were variable, but they exceeded that usually seen in wolffian duct tumors. The evidence indicates that this neoplasm represents an unusual form of endometrioid adenocarcinoma. It is important that it is distinguished from a tumor of wolffian duct origin.
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Three cases of endometrial stromal sarcoma (ESS) with prominent glandular differentiation within the primary or recurrent tumors are described. Each case posed a problem in diagnosis and classification. The patients, who ranged in age from 41 to 47 years, presented with abnormal uterine bleeding, a pelvic mass, or a combination thereof. All the patients underwent hysterectomy with or without bilateral salpingo-oophorectomy. There was no evidence of extrauterine spread of tumor in any case. Polypoid tumors involved the endometrium in two cases, and in one of them, tumor deeply invaded the myometrium. The tumor in the third case was an infiltrative mass that was confined to the myometrium and its vessels. On microscopic examination, the tumors were low-grade ESSs that contained large numbers of endometrioid glands, which were benign appearing in two cases, and in the third varied from atypical to carcinomatous. In one of the cases in the first group, the glandular component was present only in recurrent tumor excised 10 years after hysterectomy; prominent foci of sex-cord-like differentiation were also present in the recurrent tumor. This patient was clinically free of tumor 27 months later; follow-up in the other two patients was uneventful. ESSs with prominent numbers of benign-appearing glands should be distinguished from adenomyosis, endometriosis, ESSs arising in adenomyosis or endometriosis, ESSs with sex-cord-like differentiation, and müllerian adenosarcomas. ESSs with carcinomatous glands should be distinguished from endometrial adenocarcinomas and malignant müllerian mixed tumors (carcinosarcomas). Extrauterine lesions that have been designated "aggressive endometriosis" may be examples of extrauterine ESS with prominent glandular differentiation.
The pathology of epithelial tumors is reviewed in this article, with particular emphasis on new information. Important new data of prognostic significance concerning tumors in the borderline group are emphasized, and the division of mucinous borderline tumors into two groups is discussed. Serous carcinomas of surface type are reviewed, which have recently been the subject of a great deal of study, as well as transitional cell carcinoma, a newly defined subtype of invasive cancer. Finally, the highly aggressive small cell carcinoma is briefly discussed.
Detection of ovarian cancer at an early stage should reduce the mortality associated with this disease. Through the Stockholm Population Registry, 5550 apparently healthy women were enrolled in a study designed in part to define the use of the CA 125 radioimmunoassay (RIA) as an initial test for early detection of ovarian cancer. Women whose CA 125 levels were elevated and an equal number of age-matched controls with normal levels were followed by means of pelvic examinations, transabdominal sonography, and serial CA 125 determinations. Of the 175 women with high CA 125 levels, six were found to have ovarian cancer: two each in stages IA, IIB, and IIIC. Of those with normal-range CA 125 levels, three had ovarian cancer as identified through the Swedish Cancer Registry; all three were under 50 years of age. Ovarian cancer was diagnosed on laparotomy in six of the women age 50 or over. Using thresholds of 30 and 35 U/mL, the rates of specificity for the CA 125 RIA were 97 and 98.5%, respectively, for women age 50 or older, and 91 and 94.5%, respectively, for those younger than 50 years of age. Thus, the specificity of the CA 125 RIA is adequate in postmenopausal women to undertake a larger study to determine whether screening using CA 125 influences survival of patients with ovarian cancer.
Vaginal adenosis and clear cell adenocarcinoma of the vagina occurred in a 44-year-old woman after treatment for condylomata acuminata. She had no known exposure to diethylstilbestrol (DES) in utero. Biopsy-proven vaginal adenosis appeared 8 months after intravaginal 5-fluorouracil application for recurrent urogenital condylomata acuminata. Forty months later, biopsies showed residual adenosis with foci of clear cell adenocarcinoma. Although clear cell adenocarcinoma is associated with vaginal adenosis and cervical ectropion in DES-exposed women, its occurrence in adenosis after 5-fluorouracil therapy has not been reported to the authors' knowledge. In this report, this rare but serious complication of treatment of condylomata acuminata is highlighted, and the literature regarding the development of non-DES-associated vaginal adenosis is discussed.
The immunoreactivity of monoclonal antibody (MoAb) B72.3 with ovarian serous tumors of borderline malignancy from 44 women who were pregnant, were on hormone medication containing a progestin, or were known to be in the secretory phase of the menstrual cycle, was compared with that of similar tumors of 32 patients who were not known to be in any of these three categories. All 76 borderline tumors expressed the tumor-associated glycoprotein (TAG-72) recognized by MoAb B72.3. Striking staining differences (P less than 0.0001) were observed between the hormone-related and the nonhormone-related tumors. Differences were also noticed between the staining of tumors from pregnant patients and that of previous, persistent, or recurrent tumors of the ipsilateral or contralateral ovaries when the same patients were not pregnant. Tumor MoAb B72.3 reactivity increased with progressive gestational age and fell to lower levels at term and during the postpartum period. Although it has been suggested by cell culture studies, enhanced TAG-72 expression in human tumors under hormonal stimulation has not been described before.
The second and third examples of clear cell carcinoma of the inguinal region arising from endometriosis are reported. In one patient a right inguinal mass was excised along with an inguinal lymph node dissection. The tumor recurred in the retroperitoneum and was removed, and postoperative radiation therapy was administered. The patient died of recurrent tumor after 11 years. The other patient was treated by excision of a left inguinal mass and an inguinal lymph node dissection and was alive without recurrence 4 years and 8 months later.
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.