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Biomedical subjects

S J Robboy

Publications and source records attributed to S J Robboy.

At least 73 records · Page 4Linked to original sources

Nuclear DNA content of clear cell adenocarcinoma of the vagina and cervix and its relationship to prognosis.

A study was performed to determine if ploidy levels of nuclear DNA content could be used as a prognostic index of the biologic behavior of clear cell adenocarcinoma of the vagina and cervix in young females. Forty tumors were examined. Four patterns of nuclear DNA distribution were identified: (1) peridiploid stem cell lines (2N to 3N); (2) peritetraploid stem cell lines (3N to 5N); (3) hypertetraploid stem cell lines (greater than 5N); and (4) highly aneuploid without detectable stem cell lines. Tumors having peridiploid and peritetraploid stem cell lines (low ploidy group) were most often clinical Stage I or II (87%) and were in general associated with a favorable prognosis. Tumors having hypertetraploid stem cell lines and highly aneuploid distribution (high ploidy group) were usually clinical Stage III or IV (65%). Clinically advanced tumors (Stage III or IV) had poor prognosis irrespective of ploidy level. Among the clinical Stage I and II tumors, the low ploidy group had a slightly better prognosis than the high ploidy group. This difference, however, was not statistically significant.

Adenocarcinoma↗

Experimental study of the effect of diethylstilbestrol on the development of the human female reproductive tract.

Female genital tracts from human embryos and fetuses 5-17 weeks post fertilization were grown for 1-3 months in vivo as grafts to athymic female nude mice. The nude mice were either untreated or treated with diethylstilbestrol (DES). In control (untreated) hosts, anticipated normal development occurred with a high degree of precision. Müllerian ducts fused and proliferated, forming a solid uterovaginal canal that later canalized and formed a normal vaginal mucosa. Uterine glands appeared, and the uterine tube developed its highly plicated mucosa. Under the influence of DES, many of these normal developmental processes were adversely affected. Müllerian epithelium was largely obliterated in the fallopian tube and uterine corpus, mesenchymal stratification into endometrial stroma and myometrium was suppressed, plical development in the fallopian tube was inhibited, cervicovaginal epithelial development was abnormal, and vaginal adenosis was observed in several specimens. This in vivo model of human development is discussed in terms of its potential for resolving the mechanisms of normal human genital development and understanding the teratogenic action of DES on the developing human genital tract.

Animals↗

Hepatoid yolk sac tumor of the ovary (endodermal sinus tumor with hepatoid differentiation): a light microscopic, ultrastructural and immunohistochemical study of seven cases.

Seven cases of ovarian yolk sac tumor (endodermal sinus tumor) with patterns resembling those of hepatocellular carcinoma were encountered in patients 7-43 years of age. Two of the patients had gonadal dysgenesis with a 46XY karyotype. At operation three tumors were confined to the ovary and four were associated with intra-abdominal metastases. Two of the Stage I tumors recurred within one year. The hepatoid pattern was a prominent feature of all the tumors and was exclusive in four of them. In one specimen it merged almost imperceptibly with a polyvesicular vitelline pattern. The hepatoid component of the tumors was characterized by discrete masses, nests and/or broad bands of large polyhedral cells with central nuclei and prominent nucleoli; gland-like spaces, some of which contained mucin, were occasionally evident. Each tumor contained numerous PAS-positive, diastase-resistant intracytoplasmic and extracytoplasmic hyaline bodies. Alpha-fetoprotein and alpha-1-antitrypsin were identified by immunoperoxidase and immunofluorescence techniques in four tumors and albumin in two. Immunoperoxidase stains for chorionic gonadotropin were negative in four cases. Ultrastructural analysis of two specimens disclosed features similar to those of hepatocellular carcinoma.

Adolescent↗

Neurohormonal peptides in ovarian carcinoids: an immunohistochemical study of 81 primary carcinoids and of intraovarian metastases from six mid-gut carcinoids.

Eighty-one primary ovarian carcinoids and intraovarian metastases from six mid-gut carcinoids were examined for the presence of tumor cells immunoreactive with antisera raised against various neurohormonal peptides, mostly of gastroenteropancreatic (GEP) origin. Twenty of the primary and two of the metastatic carcinoids contained such tumor cells. The incidence of tumors with any kind of neurohormonal peptide immunoreactive tumor cells was 53% in the trabecular carcinoids, and 42% in the strumal carcinoids, whereas the incidence was much lower (7%) in the insular type. Immunoreactive pancreatic polypeptide (PP), glucagon, enkephalin, and somatostatin were those neurohormonal peptides most commonly observed in the tumor cells of the primary carcinoids. Those less commonly found were substance P, calcitonin, VIP, neurotensin, beta-endorphin, and ACTH. Four metastatic carcinoids were nonreactive with all the antisera used. Cells storing immunoreactive insulin, glucagon, PP, VIP, gastrin, substance P, or enkephalin were found in one of the two remaining metastatic carcinoids; in the other only gastrin-immunoreactive tumor cells were observed. The occurrence and distribution of tumor cells storing the neurohormonal peptides in ovarian carcinoids are discussed in relation to their possible origin in the ovary and to carcinoids in the gut.

Carcinoid Tumor↗

Autoradiographic analysis of nuclear estrogen binding sites during postnatal development of the genital tract of female mice.

Autoradiographic analysis of [3H]-estrogen nuclear binding sites was performed on developing genital tracts (uterus, cervix and vagina) of mice 1 to 90 days postpartum. During days 1 to 15 postpartum, nuclear estrogen binding sites were observed exclusively within mesenchymal cells; epithelial cells did not exhibit nuclear labelling. At 18 days postpartum vaginal and cervical epithelial cells exhibited nuclear estrogen binding sites for the first time, whereas the initial appearance of estrogen receptor activity in the epithelium of the uterus was detected at 20 days postpartum. Thereafter, nuclear estrogen binding sites were maintained in both epithelial and stromal cells into adulthood. The acquisition of nuclear binding sites within epithelium of female genital organs at 18 days is discussed in terms of epithelial-mesenchymal interactions and the acquisition of growth responsiveness.

Animals↗

Normal development of the human female reproductive tract and alterations resulting from experimental exposure to diethylstilbestrol.

An in vivo model is described for the study of human uterovaginal development in the presence and absence of the teratogenic drug diethylstilbestrol (DES). Intact reproductive tracts from fragments of 29 human embryos and fetuses 5.0 to 17.7 weeks of age obtained after dilatation and curettage were grown for four weeks in vivo in athymic (nude) mice that were either untreated (control) or implanted subcutaneously with a DES pellet. Control specimens grown in vivo continued their anticipated morphogenesis for equivalent in-utero ages; the normal processes observed included fusion of the paired embryonic müllerian ducts into a single uterovaginal canal, stratification of endometrial and tubal mesenchyma into inner (presumptive endometrial stroma) and outer (presumptive myometrium) layers; plication of tubal and endometrial mucosa; uterine gland formation; and stratification (transformation) of the simple columnar epithelium of the vagina and cervix into a stratified squamous plate. Specimens exposed in vivo to DES exhibited anomalies, many of which mimicked those observed clinically in young women exposed prenatally to DES. Glandular epithelium (adenosis) was found in the vagina. The upper genital tract was malformed; its growth was stunted, and the inner and outer stromal layers of the uterine corpus and fallopian tubes failed to segregate. The authors conclude that the in vivo model that they describe, with its built-in controls, provides a valid approach for examining the dynamics of morphogenesis and cytodifferentiation in developing human genital tracts under experimentally regulated conditions.

Animals↗

Dysgenesis of testicular and streak gonads in the syndrome of mixed gonadal dysgenesis: perspective derived from a clinicopathologic analysis of twenty-one cases.

The clinical and pathologic aspects of 21 cases of mixed gonadal dysgenesis (MGD) were studied. The gonads in 15 patients consisted of a macroscopic testis and a streak gonad; six patients had variants, including two with bilateral testes and four with bilateral streak gonads or tumors. Functionally, the gonads were incompetent. Testes 1) failed to completely inhibit müllerian development, 2) failed to support full differentiation of mesonephric duct structures, 3) failed to adequately masculinize development of the external genitalia, or 4) often failed to mediate their own descent, resulting in asymmetry of the internal and external genitalia. None of the streak gonads mediated normal female adolescent development or fertility. Microscopic examination revealed that every gonad, regardless of its gross appearance, was morphologically abnormal. Although gonads with seminiferous tubules usually developed to a moderately advanced state, macroscopically resembling testes, the hilar zone remained architecturally disorganized; the cortex invariably lacked more than a rudimentary tunica albuginea or exhibited partial ovarian differentiation, sometimes even with a rare primordial follicle. Over time, the seminiferous tubules atrophied and hyalinized. Gonads that grossly resembled streak gonads were observed microscopically to be composed of a stroma resembling that of normal ovarian cortex. In patients more than several years of age, the entire complement of germ cells in streak gonads disappeared. It is suggested that patients with MGD be raised as females. Early removal of gonads will prevent the development of gonadoblastoma and dysgerminoma. If the uterus is retained and the patient is subsequently given exogenous estrogen, care should be taken to detect early any signs of the development of endometrial carcinoma or its precursor, to which these patients may be prone.

Adolescent↗

Topographic relation of cervical ectropion and vaginal adenosis to clear cell adenocarcinoma.

Twenty specimens of uterus and vagina removed because of clear cell adenocarcinoma of the cervix or vagina in women exposed prenatally to diethylstilbestrol were serially blocked and sectioned to study the topographic relation between the carcinoma and the cervical ectropion and vaginal adenosis. Three tumors were cervical; 17 were vaginal. Iodine staining performed on 8 specimens indicated that the carcinoma developed consistently just above the distal limit of the cervical or vaginal surface that failed to stain with iodine, a location that usually corresponds to the distal limit of abnormality visible by colposcopic examination. Microscopic examination disclosed the presence of both cervical ectropion and vaginal adenosis in all the specimens. Mucinous glands were abundant above the tumor. In 18 of the 20 cases, tuboendometrial glands were intimately related to the carcinoma, either surrounding it or abutting its inferior border. These data, in addition to other evidence, suggest that tuboendometrial epithelium, whether in the ectocervix or vagina, provides the bed from which clear cell adenocarcinoma develops.

Adenocarcinoma↗

Histopathologic distinctions in the relationship of estrogens and endometrial cancer.

The slides of 233 patients included in a case-control study of estrogens and endometrial cancer were reviewed to determine how often endometrial cancer was misdiagnosed and whether patients with uterine cancer had other coexistent endometrial diseases. Reasonably close agreements were found among the original diagnoses and those of three additional reviewers (the total range of disagreements among all pathologists was from 2% to 16%). Proliferative and hyperplastic endometrium coexisted in many specimens from patients with endometrial cancer, and especially in those who had used estrogen replacement therapy. In contrast, estrogen therapy had seldom been used by patients whose cancers were not accompanied by these proliferative and hyperplastic lesions. In addition, these changes were found significantly more often in women with grade 1 cancers than grade 2 or 3 cancers. We conclude from these data that diagnostic misclassification is uncommon and that coexistent proliferative and hyperplastic lesions occur frequently, especially among women with grade 1 cancers. The data also suggest that the frequent finding of grade 1 cancer in estrogen users is due to bleeding that results from the stimulated coexistent benign proliferating endometrium.

Endometrial Hyperplasia↗

Breast carcinoma masquerading as primary ovarian neoplasm.

Metastases which present as palpable masses in the pelvis occasionally masquerade as primary neoplasms of the ovary. Although most such cancers originate in the stomach and large intestine, the histories of two patients are presented in whom the ovarian tumors were discovered prior to the detection of the breast primary. Three similar cases were found in the literature and are reviewed.

Adenocarcinoma↗

Dysplasia and cytologic findings in 4,589 young women enrolled in diethylstilbestrol-adenosis (DESAD) project.

This report presents the cytologic findings and the rates of dysplasia for 4,589 young women enrolled in the National Cooperative Diethylstilbestrol-Adenosis (DESAD) Project. Mucinous columnar cells and/or metaplastic squamous cells with or without mucinous droplets were encountered in 22% of vaginal scrape smears from all diethylstilbestrol (DES)-exposed participants identified by review of prenatal records and in 43% of women in whom vaginal epithelial changes (VEC) were observed by colposcopy or by iodine staining. The frequency of cellular findings in the vaginal scrape smears was closely related to the timing of the administration of the DES to the mother. With increasing age of the daughters, the overall frequencies of both the mucinous and metaplastic cells decreased; relative to each other, an increasing proportion was metaplastic squamous cells. These data suggest that, as the women grow older, vaginal adenosis regresses by the process of squamous metaplasia. Endometrial type cells were found in 2% of vaginal scrape smears. Their cyclical occurrence during the menstrual cycle and lack of correlation with the presence of VEC indicated an origin from the uterine corpus rather than the tuboendometrial type of adenosis. Squamous cell dysplasia of the vagina and cervix was detected by biopsy or scrape smear specimens in 1.8% of DES-exposed women in the record review group. The rate of unexposed women was twice as high. In general, the rates of dysplasia were higher in the cervix than vagina, and the more severe degrees of dysplasia were encountered only in those women who were referred to the DESAD Project or who themselves requested entry. Four patients who were referred or who themselves requested entry were found to have clear cell adenocarcinoma of the vagina. The vaginal smear provided the first clue to the presence of an abnormality in three of them.

Adenocarcinoma↗

Retrieval in a Computer-assisted Pathology Encoding and Reporting System (CAPER).

A previous report described an online computer-assisted pathology encoding and reporting system (CAPER) developed at the Massachusetts General Hospital that accessions specimens, monitors their state of completion, produces all log books, and permits instantaneous display of all diagnoses rendered within a three-year period. The present report updates the functions currently available and describes a new function that enables the pathologist, independent of computer programmer support, to request complex, in-depth searches of the entire accumulated pathology data base, which at present contains in excess of 150,000 cases and 5,000,000 pieces of information. The pathologist can instruct the system to compare more than 30 types of data items through the development of Boolean expressions. The report also describes the test codes that were developed to reflect the work product of the surgical pathology division, form the basis for automated billing and compilation of monthly and yearly statistics, and are an integral part of the long-term data base for in-depth searches.

Cost-Benefit Analysis↗