Restoration of distorted colour microscopic images from transverse chromatic aberration of imperfect lenses.

An algorithm is presented for restoration of colour microscopic images with distortions from imperfect microscope lenses having transverse chromatic aberrations, resulting in a magnification that slightly varies with wavelengths or colours. The differential of each colour component image is computed as the difference between the component image and its slightly magnified version. The absolute values in the differential component images are generally higher at the edges where greater discontinuities occur. The two cross-correlation functions of the absolute differentials between red and green colours and between red and blue colours are then computed. The maximum in the two cross-correlation functions were sought, respectively, and the cross-correlation delays were then calculated. The two cross-correlation delays were used to determine dispersions and to realign the three colour components. Results of real microscopic images are provided. The restored image and the original are compared both visually and quantitatively in terms of the estimated entropies measured for the degree of concentrations using vector distributions.

Histological evaluation of in vitro responses of endometrial adenocarcinoma to progestins and their relation to progesterone receptor levels.

In vitro responsiveness of endometrial adenocarcinoma to progestins was evaluated histologically by incubation of tissue fragments in medium containing 10(-6) M medroxyprogesterone acetate. In a series of 19 experiments, formation of sub- and supranuclear vacuoles, which reflects accumulation of glycogen in response to medroxyprogesterone acetate added to the medium, was observed in well-preserved glandular epithelial cells only when the level of cytosolic progesterone receptor was above 300 fmol/mg protein. Previously, we have reported similar results obtained in in vivo experiments. The present findings suggest that simple organ culture and histological procedures can be used to identify specimens of endometrial cancer that have functional progesterone receptors and are capable of responding to progestins. They also indicate that levels of progesterone receptor required to obtain responses to progestins are considerably higher than those necessary for analytical detection and that therefore the quantity and not merely the detectability of progesterone receptors must be taken into consideration for the prediction of responses to progestins. In addition, in vitro responses to progestins may indicate the presence in endometrial cancer tissue of functional estrogen receptors and potential responsiveness to antiestrogens, since estrogen stimulation appears to be needed for the synthesis of progesterone receptors.

Histopathological effects of exogenously administered testosterone in 19 female to male transsexuals.

The effects of exogenously administered testosterone were evaluated in a group of 19 female to male transsexuals who underwent bilateral salpingo-oophorectomy after a variable period of androgen therapy. The findings were compared to those in an age-matched group of 12 patients who underwent pelvic surgery for nonendocrine reasons. The most significant findings in the 19 androgen-treated female transsexuals was the finding of enlarged or borderline enlarged ovaries in 5 subjects. In addition, we found multiple cystic follicles in 17 patients (89.5%), diffuse ovarian stromal hyperplasia in 16 patients (84.2%), collagenization of the outer cortex in 13 patients, and 4) luteinization of stromal cells in 5 patients (26.3%). Findings consistent with polycystic ovaries were thus present in 13 of the 19 patients based on the presence of 3 of the above 4 findings. The data suggest that increased blood levels and presumably increased ovarian concentrations of testosterone may produce the morphological features of polycystic ovarian disease.

Immunohistochemical localization of epidermal growth factor in human endometrium, decidua, and placenta.

Epidermal growth factor (EGF) was localized immunohistochemically in human endometrium throughout the menstrual cycle, in gestational decidua, and in first, second, and third trimester placenta using two polyclonal antihuman EGF antisera. In proliferative phase endometrium, moderate EGF immunostaining was localized to the cytoplasm of stromal cells, with absent to light staining of glandular epithelium. In the secretory phase, EGF immunostaining was intense and localized predominantly to stromal cells, particularly those surrounding spiral arterioles. There was absent to light EGF immunostaining within epithelial cells; however, there was no staining of subnuclear vacuoles. In addition, the luminal surface of exhausted secretory glands demonstrated moderate EGF immunostaining. In gestational decidua, EGF immunostaining was light to moderate in the stromal cells, but was intense in the surface epithelium. Intense EGF immunostaining was noted in the syncytiotrophoblast layer of first trimester placenta, with light to moderate staining of the cytotrophoblast. Immunostaining decreased in both layers of trophoblast as pregnancy progressed. Immunoreactive EGF is found in endometrium and trophoblast and may have a physiological role in endometrial and placental function.

Epidermal growth factor and its receptor in human implantation trophoblast: immunohistochemical evidence for autocrine/paracrine function.

Epidermal growth factor (EGF) and its receptor (EGF-R) were immunohistochemically localized in trophoblast during human implantation from intrauterine and ectopic pregnancies. EGF immunostaining was absent to light in the cytotrophoblast (CT), light to moderate in intermediate trophoblast (IT), and intense in the syncytiotrophoblast (ST). In ST, EGF immunostaining was found mostly in the cytoplasm; however, staining of the plasma membrane was also noted. Immunostaining for the EGF-R was absent to light in the CT and moderate to intense in the IT. Immunostaining for the EGF-R was intense in the ST, with moderate staining in the cytoplasm and intense staining in the plasma membrane. Staining was most intense on the microvilli of the ST. Additionally, EGF-R immunostaining could be demonstrated on nuclear membranes. The increase in the intensity of the immunostaining for both EGF and EGF-R noted in CT, IT, and ST suggests a differentiated expression of this receptor-ligand system in human trophoblast and provides evidence for an autocrine/paracrine role for EGF in trophoblast function. The presence of this receptor-ligand system during early human implantation strongly supports a role for EGF and the EGF-R in embryo-uterine signalling and the implantation process.

Interactive morphometry of normal and hyperplastic peritoneal mesothelial cells and dysplastic and malignant ovarian cells.

This study used computerized interactive morphometry to evaluate the differential characteristics of mesothelial normal cells, mesothelial hyperplastic cells, and carcinomatous cells, and also compared hyperplastic mesothelial cells with ovarian dysplastic cells from a previous study. The procedure included extraction of multiple descriptors of the nuclear profile: perimeter length, area, longest chord, circularity factors, standard deviations of these characteristics, and a 10-bin size distribution table of the nuclear area. The final classification is achieved by stepwise discriminant analysis of these variables. The analysis classified all cases correctly with high posterior probabilities.

Mycobacterium xenopi: infection in an immunocompromised host.

Mycobacterium xenopi was isolated from bronchoscopic and resected lung specimens from a patient who had diabetes mellitus and chronic myelogenous leukemia. While in remission, the patient developed spreading pulmonary infiltrates and died. At postmortem examination, acid fast bacilli were found in enormous numbers in histologic preparations of pulmonary hilar and mesenteric lymph nodes. Concomitant pulmonary infection with Aspergillus, Pneumocystis carinii, and cytomegalovirus was also evident. The probable dissemination of M. xenopi to pulmonary hilar and mesenteric lymph nodes attests to its invasive potential in the immunocompromised host and reinforces its role as an agent of nontuberculous mycobacterial disease.

Morphometric differentiation between responsive tumor cells and mesothelial hyperplasia in second-look operations for ovarian cancer.

We developed a procedure based on computerized image analysis to establish objective criteria for the differential diagnosis between mesothelial hyperplasia and cancer in peritoneal tissue samples obtained at second-look operations for ovarian cancer. The tumor tissue after chemotherapy was classified as "nonresponsive" if it was found by histologic criteria to be roughly similar to the tumor before chemotherapy and as "responsive" if it was found to be different (small clusters of bland-looking cells with no mitotic activity). Eighty-five samples of tissue had been classified previously by a pathologist into one of the four following groups: ovarian tumor prior to chemotherapy, "responsive" tumor, "nonresponsive" tumor, or mesothelial hyperplasia. Cell profiles of the tissue samples were studied by computerized image analysis using 21 morphometric descriptors derived from the manual tracings of tumor nuclei, including nuclear perimeter, nuclear area, maximal chord, circularity factor, and standard deviations of these descriptors. Size distribution curves of nuclear areas and maximal chords were included in the analysis. A multivariate discriminant analysis confirmed the separation into the four diagnostic groups, accomplished with consideration of the physical descriptors alone, except for some overlapping between groups 1 and 3. The separation between carcinoma and mesothelial hyperplasia was clear in all cases.

Dysgerminoma of the ovary associated with true hermaphroditism.

A dysgerminoma of the left gonad exhibiting malignant features was diagnosed at laparotomy in a 33-year-old virginal phenotypic female who had a normal menstrual history. Pathologic examination of the contralateral (right) gonad revealed an ovotestis. The nonaffected residual portion of the tumor-bearing left gonad exhibited only ovarian stroma. The ovotestis was characterized by a nodule of testicular parenchyma composed of partly hyalinized seminiferous tubules without evident spermatogenesis. The ovotestis was contiguous to normal ovarian elements, including a cystic corpus luteum and primordial follicles. Proliferative endometrium was found lining the small uterus. The findings are indicative of true hermaphroditism. The occurrence of dysgerminoma and other tumors in association with various forms of gonadl dysgenesis is discussed. To the authors' knowledge, this is the first reported case of dysgerminoma occurring in a phenotypic female hermaphrodite.

Metastatic uterine leiomyosarcoma presenting as a primary sarcoma of the parotid gland.

BACKGROUND: Leiomyosarcoma of the uterus has a high metastatic potential to distant sites due to its tendency for hematogenous spread. CASE: A 49-year-old woman presented with an enlarging parotid mass, diagnosed originally as a primary fibrosarcoma. Six years later, she developed pulmonary metastases and heavy, abnormal uterine bleeding. At hysterectomy, a uterine leiomyosarcoma, identical morphologically to the previous lesions, was identified. All tumors showed similar immunohistochemical staining, suggesting the metastatic nature of the original parotid tumor. CONCLUSION: This rare case of uterine leiomyosarcoma, presenting as a primary parotid sarcoma, underscores the importance of considering the possibility of a uterine primary tumor when a sarcoma arises in an organ in which these tumors are unusual.

Pathologic changes in gonadotropin releasing hormone agonist analogue treated uterine leiomyomata.

OBJECTIVE: To define the pathologic changes underlying the mechanism of shrinkage of uterine leiomyomata in patients treated with luprolide acetate. DESIGN: Retrospective study of pathologic changes seen in leiomyomata removed by hysterectomy or myomectomy in treated and untreated patients, matched by age and size of uteri and leiomyomata. PATIENT(S): Gross description and histologic slides of 30 treated and 30 untreated patients. INTERVENTION(S): Histologic examination performed blindly (without knowledge of treatment). Statistical work-up using chi 2 analysis with 1 df. MAIN OUTCOME MEASURE(S): Degree of hyaline and hydropic degeneration, cellularity, nuclear atypia, necrosis, and obliteration of interface. RESULT(S): Confluent nodular hyaline degeneration representing a scarlike retraction, geographic hydropic degeneration necrosis and obliteration of the interface between myoma and myometrium were found in higher proportions in the treated patients; differences in cellularity, nuclear atypia, and edema were not statistically significant. CONCLUSION(S): The decrease in size of the treated leiomyomata occurs as an accelerated postmenopausal shrinkage because of the antiestrogenic effect of the therapy. Obliterated cleavage planes may explain the difficult enucleation of myomatous nodules in some of the treated patients.

Tamoxifen and endometrial cancer.

Tamoxifen is a nonsteroidal antiestrogen employed frequently in the treatment of breast cancer. An association between this drug and endometrial neoplasia has been reported. We report on 11 postmenopausal women with breast cancer who developed endometrial cancer while undergoing tamoxifen therapy and recommend aggressive investigation of vaginal bleeding in all women being treated with this agent.

Interaction of ovarian hormones with normal endometrium and endometrial adenocarcinoma.

PIP: Steroid receptors (tissue specific proteins which bind with high affinity, low capacity and remarkable selectivity to compounds having similar biologic action) have provided the basis for developing tests to predict responsiveness of patients with breast cancer to surgical procedures (eg, ovariectomy, adrenalectomy or hypophysectomy) aiming to eliminate estrogens from circulation. Clinical studies have confirmed the claim that breast tumors without estrogen receptors do not benefit from these major procedures. Besides cytoplasmic and nuclear receptors, 2 types of high affinity, low capacity binders of E2 (estradiol) had been identified, this time in rat uterus cytosol, by resolving saturation curves with H 3 -E2 into 2 components. Heterogeneity in the cytosol receptors for E2 in the rat uterus was found. The specificity of receptors towards different classes of active sterioids has also been considered. A new finding is that some steroids, when their concentrations are sufficiently high, bind receptors that are primarily involved in the action of another group of hormones. The metabolism of E2 in the target cell is an important consideration in analyzing physiologic action of estrogens. Intracellular metabolism of the hormone is an important determinant of its action as is the amount of receptor found in the cell. The relation of estrogens in the development of endometrial cancer has been reported. Women exposed to prolonged estogen stimulation in the absence of progesterone are at higher risk to develop endometrial adenomatous hyperplasia, a precursor of adenocarcinoma.^ieng

Lichen planus and the vulvovaginal-gingival syndrome.

Lichen planus is a dermatologic disease that affects both skin and mucosa. Here we report five cases of lichen planus that presented as the oral component of the vulvovaginal-gingival syndrome. Four of the cases were associated with biopsy-proven oral lichen planus, and all five patients had oral lesions that clinically resembled lichen planus. Three patients were taking medications that are associated with lichenoid drug reactions; four patients were postmenopausal; and all five patients had desquamative vulvovaginitis. Clinicians may see these patients when they show persistent signs and symptoms of oral lichen planus. We report five case histories and review the 127 cases found in the literature to make the practicing clinician aware of this unusual clinical entity. The hepatitis C virus association and drug-induced lichenoid mucositis are topics that are addressed. In addition, clarification of the issues surrounding the premalignant potential of oral lichen planus is provided with evidence, rationale, and data from the literature to support the position that true oral lichen planus has no inherent predisposition to become malignant.

Interactive morphometric procedures and statistical analysis in the diagnosis of ovarian dysplasia and carcinoma.

We report on our continued experience with an interactive morphometric method recently introduced by us for the definition and diagnosis of ovarian dysplasia vs. normal or malignant epithelium. The main quantitative differences between these three diagnostic categories are based on 1) cytology of the nuclei (nuclear area, circularity factor, maximum chord) and 2) on stratification (distances of nuclear centers to the basement membrane and number of cells per unit length of basement membrane). We implemented our approach on live video images viewed on a monitor overlaid with a touch sensitive screen by one of two interactive procedures: 1) by tracing nuclear profiles (procedure DRAW) or 2) by tracing the basement membrane and touching the center of all nuclei (procedure NU-MEAS). In all cases statistical analysis was performed on a string of multiple variables by stepwise discriminant analysis. Now we have straightened our data basis and are able to obtain diagnosis of unknown samples with very high posterior probabilities. Both procedures are effective but NU-MEAS requires the least effort and seems to give the best statistics.

Two types of endometrial papillary neoplasm. A morphometric study.

Fourteen cases of Papillary Endometrial Carcinoma (EC) were analyzed by Interactive Computerized Morphometry. Seven cases were diagnosed as well differentiated adenocarcinomas with papillary features (PF) and belonged to a group of EC with associated adenomatous hyperplasia (AH). Seven cases were diagnosed as uterine papillary serous carcinomas (PA) and belonged to a group of EC without associated AH. Two morphometric procedures were used. DRAW for the characterization of individual nuclei (area, perimeter, chord) and NU-MEAS for tissue architectural features (crowding and stratification). Using a stepwise discriminant multifactorial analysis, both methods proved to be accurate for the two diagnostic categories, as shown by the 100% posterior probabilities and by the two diagnostic categories, as shown by the 100% posterior probabilities and by the distances between group means. A doubtful case was analyzed and classified using a K-nearest neighbor procedure, compared to the individual case in the database. The distinction between the two types of papillary EC is important for the differential diagnosis of the two lesions. Well differentiated adenocarcinoma with papillary features is seen usually in the context of a well-differentiated adenocarcinoma, in a group of patients known to have estrogen-related less aggressive tumors. Uterine papillary serous carcinoma was described to have a biological behavior similar to that of papillary ovarian carcinoma and is encountered in a group of patients with more invasive and less differentiated EC2. Computerized interactive morphometry is a valuable method to use for the accuracy of this differential diagnosis in doubtful cases.

Pituitary-containing benign cystic teratoma arising from the uterosacral ligament.

We report on the incidental finding of pituitary tissue in a mature teratoma on the uterosacral ligament of a 56-year-old woman who underwent exploratory laparotomy for ovarian masses. While the occurrence of pituitary tissue has been reported rarely in benign cystic teratoma of the ovary, and while pituitary adenomas can occur in ectopic sites, we have found only one report in the literature of benign cystic teratoma of extragonadal origin composed of mature adenohypophyseal and neurohypophyseal elements.

Morphometric and electron-microscopic analyses of the effects of gonadotropin-releasing hormone agonists on uterine leiomyomas.

OBJECTIVE: Reports on the histologic effects of gonadotropin-releasing hormone agonists on uterine leiomyomas provide conflicting results. Most previous studies used qualitative methods of analysis. Using quantitative and semiquantitative stereologic methods of analysis, we assessed volume density of hyalinized areas, cell density, nuclear volume, and cytoplasmic cross-sectional areas of smooth muscle cells in histologic sections and also measured diameters of collagen fibrils in electron micrographs of uterine leiomyomas. DESIGN: Thirty leiomyomas from patients treated with gonadotropin-releasing hormone agonists (10 different patient samples), age-matched control patients (10 different patient samples), and postmenopausal women (10 different patient samples) were used. Hyalinization was assessed using a microscope with a projection head and affixed morphometric grid. Cell size and density were evaluated using a video-based, computerized system attached to the microscope, for which morphometric ad hoc programs were written. Diameters of collagen fibrils were measured from electron micrographs. SETTING: The study was conducted in the Department of Pathology, Mount Sinai Medical Center, New York, NY. PATIENTS: A total of 30 patient samples were studied, with three groups comprising 10 samples each, including patients treated with gonadotropin-releasing hormone agonists, age-matched control patients, and postmenopausal women. RESULTS: Myomas from patients treated with gonadotropin-releasing hormone agonists exhibited more hyalinization, greater cell density, slightly smaller cell sizes, and larger collagen fibrils than those of age-matched control patients and postmenopausal women. CONCLUSIONS: Shrinkage after treatment with gonadotropin-releasing hormone agonists is attributed to smaller cell size and increased collagenization in myomas.

Uterine fibroleimoyomata with aortic lymph node metastases.

This is a report of extensive metastases of histologically benign uterine leiomyomas to para-aortic lymph nodes in a 32-year-old woman. The pathologic features and clinical characteristics are described, and the previously recorded experience with this rare entity is reviewed.

Postmenopausal endometriosis associated with hormone replacement therapy. A case report.

A postmenopausal woman on hormone replacement therapy presented with abdominal pain, a large pelvic mass and high-grade ureteral obstruction, with endometriosis found at exploration.