Synoptic reports in gynecologic pathology.
Explore the source record for details and available documents.
Female↗
Biomedical subjects
R J Zaino
Publications and source records attributed to R J Zaino.
Histopathologic predictors of the behavior of surgically treated stage IB squamous cell carcinoma of the cervix. A Gynecologic Oncology Group study.
Disagreement persists about the superiority of Reagan and Ng's method over that of Broders' for the histologic grading of squamous carcinoma of the cervix. Uncertainty about the predictive value and reproducibility of any of the grading methods prompted a comparison of factors previously suggested as indicating the biologic behavior for cervical squamous carcinoma. One hundred ninety-five women, who were enrolled in a Gynecologic Oncology Group treatment protocol of Stage IB squamous carcinoma of the cervix and underwent radical hysterectomy with pelvic and paraaortic node sampling, formed the study population. The tumors were graded first by participating institutional pathologists, with submitted slides subjected to an independent review by two pathologists (R.J.Z. and S.W.). The histologic parameters examined included the presence and amount of keratinization, nuclear pleomorphism, mitotic rate, gestalt grading, pattern of invasion at the stromal interface, and inflammatory cell infiltrate. The depth of invasion and presence or absence of vascular invasion also were assessed. The probability of pelvic lymph node metastasis and the progression-free interval were determined for each parameter. Surprisingly, none of the grading methods was effective in predicting nodal spread or progression-free interval. However, an increasing depth of invasion strongly correlated with nodal spread and a diminished progression-free interval (P less than 0.0001). Vascular invasion was less effective in these predictions (0.05 less than P less than 0.10). Both measurements were reasonable reproducible. It was concluded that histologic grading of surgically treated cervical carcinoma is not useful but that the depth of invasion and vascular invasion are important predictors of behavior that should be reported routinely.
Carcinoma, Squamous Cell↗
Apparent resistance in human endometrial carcinoma during combination treatment with tamoxifen and progestin may result from desensitization following downregulation of tumor progesterone receptor.
Combined treatment with tamoxifen and progestin effectively controlled human endometrial tumor growth in the nude mouse model. However, after an initial response the tumors became 'resistant' to continuous progestin administration. Tumors excised during the growth arrest or regrowth phases, showed return of the typical growth characteristics of EnCa-101, upon serial transplantation. The characteristic progesterone receptor proteins were observed by Western blot analysis in tamoxifen treated tumors, while tumors treated with both tamoxifen and progestin were devoid of receptor, beginning at 7 days after initiation of progestin therapy. Thus, downregulation of endometrial tumor PR resulting from continuous progestin administration presumably leads to desensitization to progestin, after an initial growth inhibitory response.
Animals↗
Endometrial carcinoma: the need to pursue a new path(ology)
Explore the source record for details and available documents.
Female↗
The significance of squamous differentiation in endometrial carcinoma. Data from a Gynecologic Oncology Group study.
Squamous differentiation is identified in about 25% of endometrial adenocarcinomas (AC). Its significance has been the subject of debate for decades, and it has been reported that the prognosis of adenoacanthoma (AA) is better than, the same as, and worse than that of AC. Part of this confusion has resulted from semantic differences relating to the use of AA and adenosquamous carcinoma (AS). To investigate the prognostic importance of squamous differentiation in endometrial carcinomas and compare the prognostic utility of two classification systems, 456 women were studied who had typical AC and 175 women who had typical AC containing areas of squamous differentiation (AC + SQ) and who had been entered in a Gynecologic Oncology Group protocol of Stage I and II endometrial adenocarcinoma. Assessment of histologic grade and depth of invasion was done both by the pathologist at the member institution and at a second highly structured review. Differentiation of the squamous component of endometrial carcinomas was found to parallel that of the glandular component in most tumors. The biologic behavior of endometrial carcinomas with squamous elements was similar, but not identical, to that of typical AC. Although the frequency of nodal metastasis was similar for both AC and AC + SQ, the presence of squamous elements was associated with an increased probability of survival. Division of AC + SQ by depth of myometrial invasion and by architectural grade of the glandular component provided useful prognostic information that was superior to that resulting simply from division of AC + SQ into AA or AS. The authors recommend that these terms be replaced by "adenocarcinoma with squamous differentiation" and that the pathologist provide information on the architectural grade and depth of myometrial invasion to guide the gynecologist in determining appropriate therapy.
Adenocarcinoma↗
Designing a schedule of progestin administration in the control of endometrial carcinoma growth in the nude mouse model.
We previously showed that combined treatment with tamoxifen and progestin was effective in arresting the growth of human endometrial carcinomas in the nude mouse model. After a 15- to 20-week tumoristatic period, the tumors began to regrow, reminiscent of the clinical situation. Lack of progestin sensitivity during the regrowth period appeared to reflect the absence of progesterone receptor. To test the prediction that intermittent progestin administration may circumvent the regrowth phenomenon, the effect of various doses of progestin on blood progestin levels, EnCa 101 tumor progesterone receptor profiles, and rate of tumor growth were examined. Whereas 1 mg progestin was ineffective in totally down-regulating tumor progesterone receptor, 2 and 5 mg doses resulted in the total disappearance of tumor progesterone receptor by 1 week followed by its reappearance at 5 to 6 weeks and 9 to 10 weeks, respectively. On the basis of these results we predict that intermittent progestin administration may result in better control of endometrial cancer growth in the nude mouse system.
Animals↗
Rhabdomyosarcoma of the uterus in a postmenopausal patient.
Pure rhabdomyosarcomas of the female genital tract most commonly occur in infancy or childhood as sarcoma botryoides (embryonal rhabdomyosarcoma) and involve the vagina and cervix. Such tumors rarely occur in adults. A pure rhabdomyosarcoma of the uterus that arose in a postmenopausal patient is described. The pertinent literature is discussed.
Aged↗
Hepatic granulomata. Presenting with prolonged fever. Resolution with anti-inflammatory treatment.
A patient is described who presented with a 1-month history of daily fever to 38.8 degrees C. There was no sign of joint pain or swelling and no skin rash. The patient had impressive hepatomegaly without splenomegaly. The only abnormal laboratory test was a sedimentation rate of 120 mm/hr. Ultrasound examination showed hypoechoic foci throughout the liver. These foci were confirmed by CT scan, which showed multiple well-marginated lesions of decreased attenuation and variable size throughout the right and left lobes of the liver. A liver biopsy specimen showed large nodules that were yellow and gritty in texture. Microscopic examination of biopsy specimens of these nodules showed extensive areas of necrotizing granulomatous inflammation with palisading histiocytes and occasional giant cells surrounded by necrotic foci. There was an associated fibroinflammatory infiltrate. The patient was treated with a nonsteroidal anti-inflammatory agent with prompt cessation of fever. A repeat CT examination of the liver after 14 months of treatment showed only mild hepatomegaly and a normal liver parenchyma. The focal lesions had disappeared. This is a case of hepatic granulomata in a child showing features of necrotizing inflammation.
Child↗
Clomiphene citrate stimulation as an adjunct in locating ovarian tissue in ovarian remnant syndrome.
Ovarian remnant syndrome results from residual ovarian tissue after bilateral oophorectomy. The syndrome is associated with chronic pelvic pain and is suspected when premenopausal levels of FSH and LH are present in a patient with documented bilateral oophorectomy. Histologic demonstration of ovarian tissue at operation confirms the diagnosis. We treated a patient with ovarian remnant syndrome with a 10-day course of clomiphene citrate, 100 mg daily, to stimulate the residual ovarian tissue and facilitate localization. Preoperative ultrasound revealed a 5.0 x 3.5 x 6.2-cm cystic mass in the right adnexal region. Exploratory laparotomy easily localized the mass, and it was removed intact. Histologic slides demonstrated normal ovarian tissue with multiple follicles in various stages of development and a corpus luteum cyst. Clomiphene citrate is capable of stimulating an ovarian remnant, producing an enlarged, cystic structure easily localized by ultrasound. The increased size and preoperative knowledge of the location facilitated surgical removal.
Adult↗
The core curriculum and the future of pathology. Another opinion.
Explore the source record for details and available documents.
Curriculum↗
A polyclonal antiserum against the rabbit progesterone receptor recognizes the human receptor: immunohistochemical localization in rabbit and human uterus.
A polyclonal antiserum, raised in guinea pigs immunized with the 116,000 Mr rabbit uterine progesterone receptor (PR), was used to demonstrate immunoreactive PR in frozen fixed sections of rabbit and human uterus. In both species, PR localization was exclusively nuclear. For the rabbit uterus, staining intensity was greatest in the myometrium, followed by endometrial stroma, glands, and luminal epithelium. In premenopausal human endometrium and myometrium there was intense staining of nuclei from proliferative phase glands and myometrium. In the secretory phase the glands failed to stain, yet immunostaining persisted in the myometrium.
Animals↗
Carcinoma of the endometrium and hormonal receptors.
Explore the source record for details and available documents.
Animals↗
Therapeutic effect of recombinant human tumor necrosis factor in ovarian carcinoma xenograft in nude mice.
Tumor necrosis factor (TNF) has been found to have in vitro and in vivo cytotoxicity against a variety of mouse and human experimental tumors. Synergistic effect with interferon-gamma (IFN) has also been reported. We examined the therapeutic effect of TNF and IFN using the human ovarian carcinoma cell line NIH:OVCAR-3 intraperitoneally transplanted in nude mice. Approximately 10 to 15 million cells were injected intraperitoneally in 80 nude mice. One week later the animals were divided into four treatment groups of 20 animals each: (1) untreated controls, (2) daily ip injections of 5 micrograms TNF, (3) daily ip injections of 5 x 10(4) U of IFN, and (4) daily ip injections of 5 micrograms TNF and 5 x 10(4) U of IFN. After 13 weeks of treatment, when 50% of the control animals were dead of disease, a survival analysis was performed. The remaining animals underwent laparotomies (comparable to second-look in humans) at Weeks 15, 18, 20, and 22 to determine the presence of tumor in various tissues by histologic examination. A statistically significant survival difference was found between the untreated control group and the groups that received TNF or TNF plus IFN (P less than 0.0001). The TNF effect was further reflected in decreased serum CA-125 levels compared with controls (P less than 0.001). Only one out of 20 animals receiving TNF or TNF in combination with IFN was found to have intraperitoneal tumor at the time of laparotomy, whereas all the untreated controls had gross intraabdominal carcinomatosis. These results, in addition to existing preclinical data, may form the basis for clinical protocols employing intraperitoneal TNF in selected ovarian carcinoma patients.
Animals↗
Serial renal function in an ovine model of unilateral fetal urinary tract obstruction.
Renal tubular and glomerular function following ovine fetal urinary tract obstruction has been studied predominantly in anesthetized, exteriorized fetuses immediately after relief of obstruction. Since surgery and anesthesia may alter fetal cardiovascular and renal physiology, we developed a chronically catheterized, ovine model of unilateral fetal urinary tract obstruction to compare function of the unobstructed and obstructed kidneys repeatedly after relief of obstruction. Split renal function of the previously obstructed kidneys and unobstructed kidneys was measured serially in 7 fetal sheep after obstruction at 55 to 85 days per 147 days of gestation for 30 to 49 days. Seventy-five split clearances were determined on days 1, 2, 3 to 4 and 5 to 6 postoperatively. Not every fetus was studied each day. By 2-way ANOVA, renal function was stable on day 1 after surgery and did not change with time. Previously obstructed kidneys had lower creatinine clearance (0.16 versus 0.71 ml. per minute, p equals 0.0001), higher fractional sodium excretion (33.04 versus 6.02 per cent, p equals 0.0001) and higher urine sodium/creatinine ratio (4.80 versus 0.90 mEq. per mg., p equals 0.0001). Urine flow in the unobstructed kidneys did not differ significantly from that of the obstructed kidneys (0.122 versus 0.083 ml. per minute, p equals 0.35). Obstruction reduced kidney weight (4.7 versus 9.7 gm., p equals 0.0006), cortical thickness (-39 per cent) and nephrogenic zone (-59 per cent), and it increased collecting duct dilatation and medullary fibrosis. No cysts or dysplasia was noted. Fetal urinary tract obstruction for 39.7 days alters renal histology, glomerular function and tubular function. Renal function is stable by 1 day after catheterization and does not change from days 1 to 6 following relief of obstruction.
Animals↗
Management of malignant, mixed mesodermal tumors of the uterus.
Forty-two patients with malignant, mixed mesodermal tumors of the uterus were identified by retrospective chart review. Only 2 patients were premenopausal at the time of diagnosis. Six of the patients had previously received pelvic radiotherapy. Surgical/pathologic findings were inconsistent with clinical staging in 17 of the patients. Patients with stage I tumors were found to have extrauterine extension of tumor in 39% of the cases. Overall, 2- and 5-year actuarial survival rates were 40 and 18%, respectively. The surgical extent of disease was a major prognostic factor in patient survival (P = 0.006). Patients with tumors showing no invasion or invasion limited to the inner two-thirds of the myometrium also demonstrated a significant survival advantage as compared to those with deeper myometrial invasion (P = 0.02). However, no statistically significant relationship was demonstrated between survival and patient age, the nature of the sarcomatous element (homologous or heterologous), or the presence of cervical involvement. Patients with recurrent or persistent disease did poorly; only 4 patients have survived more than 1 year after documentation of recurrent disease. Two patients had prolonged disease stabilization with radiotherapy and cisplatin. Another patient with pulmonary metastases had a 6-month, complete response to cisplatin.
Adult↗
Differential distribution of estrogen and progesterone receptors in rabbit uterus detected by dual immunofluorescence.
The action of sex steroids on the growth and differentiation of target tissues requires the presence of specific intracellular receptors. We compared the distribution of cells containing estrogen receptor (ER) and/or progesterone receptor (PR) in rabbit uterus by immunohistochemistry using monoclonal antibodies directed against these receptors. Initial experiments using serial cryostat sections surprisingly revealed the intensity of staining for ER to be inversely proportional to that of PR, as follows: ER, luminal and glandular epithelium greater than myometrium greater than stroma; PR, stroma greater than myometrium greater than glands greater than luminal epithelium. Localization was strictly confined to the nuclei of target cells. Single and dual immunofluorescent labeling of ER and PR in cryostat sections was accomplished using fluorochromes with differing emission spectra. Individual fields of dual labeled sections were examined for red [phycoerythrin (ER)] and green [fluorescein (PR)] fluorescence, with the same distribution as noted by single antibody immunohistochemistry. Myometrial nuclei displayed fluorescence of equivalent relative intensity for both antibodies. Further, sequential exposure photomicrography (exposure first in the spectrum of phycoerythrin emission, followed by exposure in the spectrum of fluorescein emission) revealed the presence of occasional stromal cells staining only for PR and some luminal cells staining only for ER. This differential distribution of ER and PR within various cell populations of rabbit is a novel observation and challenges current concepts of receptor regulation. Dual immunofluorescent localization of both ER and PR within individual cells provides a unique perspective from which to investigate the interactive influences of these sex steroid receptors at the cellular level.
Animals↗
Heterogeneity of progesterone receptor distribution in human endometrial adenocarcinoma.
The clinical response of advanced endometrial adenocarcinoma to progestin therapy does not correlate perfectly with biochemically assayed progesterone receptor status of the tumor. We have previously suggested that heterogeneity of progesterone receptor at the cellular, tumor, and tissue levels, not detectable by the biochemical assay, might contribute to this discrepancy. A monoclonal antibody, hPRa-1, generated against human progesterone receptor, was used in the present study to immunohistologically define the heterogeneity of progesterone receptor distribution in primary endometrial carcinomas. Twenty-four hysterectomy specimens removed for the treatment of endometrial adenocarcinoma were examined by biochemical assay of progesterone receptor and immunohistochemistry. In two cases, in which tumor occupied almost all of the endometrial lining, more extensive sampling was performed with removal of four noncontiguous sites. Each site was subdivided for immunohistochemistry and biochemical assay of progesterone receptor. When present, progesterone receptor localization was confined to the nuclei of target cells. Variability in the distribution and intensity of staining was consistently observed within the tumors. Of 24 tumors 15 were determined to be progesterone receptor positive by biochemical assay, while 12 of 24 tumors displayed immunolocalization for progesterone receptor. The correlation of the results by the two methods was high (20 of 24 cases, 83%), and the discrepancies in three cases appeared to reflect tissue and tumor heterogeneity. Immunolocalization has demonstrated that heterogeneity is present at the tumor, tissue, and cellular level within endometrial carcinomas, and the failure of some progesterone receptor-positive (by biochemical assay) tumors to respond to progestin therapy may reflect false positive results due to contamination of progesterone receptor-negative tumors by adjacent benign endometrium or myometrium.
Adenocarcinoma↗
Squamous differentiation in carcinoma of the endometrium: a critical appraisal of adenoacanthoma and adenosquamous carcinoma.
Although squamous differentiation within endometrial carcinomas has long been recognized by pathologists, its biologic significance has been the subject of continued debate. While some authors have found a worsened prognosis for women who have tumors with squamous elements, others have reported the prognosis to be better than conventional endometrial adenocarcinomas. Persisting confusion and disagreement about the use of the terms adenoacanthoma and adenosquamous carcinoma have complicated the issue. In this article we review the literature on the pathogenesis of squamous differentiation in the endometrium and discuss the histologic features, prevalence, and biologic behavior of adenocarcinoma with squamous differentiation. We conclude that keratin is a constituent of normal and neoplastic endometrial epithelial cells, and that overt squamous differentiation occurs by a mechanism that is currently unknown. Squamous differentiation is present in about 25% of endometrial adenocarcinomas, a frequency that appears to have been constant for the past 50 years. The squamous component of endometrial carcinomas may histologically appear benign, malignant, or indeterminant, and in the majority of instances closely parallels the differentiation of the glandular component. Endometrial adenocarcinomas with malignant-appearing squamous elements usually have poorly differentiated glandular components and have a prognosis identical to that of poorly differentiated adenocarcinoma without squamous differentiation. Endometrial adenocarcinomas with benign-appearing squamous elements are usually associated with well-differentiated glandular components and have a prognosis identical to that of typical well-differentiated adenocarcinoma. Some endometrial adenocarcinomas contain foci of squamous differentiation that appear neither clearly benign nor malignant. These often are associated with moderately differentiated glandular components; the prognosis for these women is not yet clearly defined. At the present time we are unable to attribute any prognostic significance to the presence of squamous differentiation in endometrial carcinomas. Because of the confusion and semantic arguments that revolve about the use of the terms adenoacanthoma and adenosquamous carcinomas, we recommend that those terms be abandoned and be replaced by the single term adenocarcinoma with squamous differentiation. As for any other endometrial tumor, the pathologist should provide information on histological grade, depth of myometrial invasion, and presence of vascular involvement or spread to the cervix in order to guide the gynecologist in determining appropriate therapy.
Adenocarcinoma↗