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.

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.

Endometrial cancer in elderly women: A histologic and steroid receptor study.

BACKGROUND: Information on steroid receptor content in endometrial tissue of aging women is limited and somewhat controversial. The high incidence of endometrial cancer (EC) and the implication of hormone replacement therapy (HRT) in this group prompted the investigation of steroid receptors and endometrial cancer histology in the elderly. OBJECTIVE: Review of histologic characteristics correlated with estrogen and progesterone receptors (ER and PR) status in EC in women over 75 years of age in order to determine the prevalence of a more aggressive endometrial neoplasm arising in late postmenopausal atrophic endometrium of elderly patients. METHODS: Histologic slides and deeper sections stained immunohistologically for ER/PR from 54 cases of EC in women aged 75-95 years were reviewed. The histologic characteristics and degree of differentiation were correlated with the steroid receptor status, evaluated on a scale of 0-3. Benign endometrial tissue from women of the same group was used as controls. RESULTS: The 57.4% endometrioid adenocarcinomas were mostly moderately and poorly differentiated. The nonendometrioid carcinomas were anaplastic, papillary, clear cell, squamous cell, mixed müllerian and nongestational choriocarcinoma. The staining intensity for ER/PR decreased with the degree of dedifferentiation being weak or absent in nonendometrioid tumors. CONCLUSION: Elderly patients have less differentiated EC displaying histologically nonendometrioid patterns ('alienation') with no differential loss of receptors in cancer. ER/PR are partly preserved in endometrioid tumors and controls. We conclude that differential loss of receptor capacity is not a factor in pathogenesis of this age-related cancer.

Endometrial histopathology in 700 patients treated with tamoxifen for breast cancer.

OBJECTIVE: The aim of this study was the evaluation of endometrial histopathologic findings from 700 patients treated with tamoxifen (Tx) for breast cancer from two medical centers (United States and France). METHODS: A retrospective review of data including histologic slides from 134 hysterectomies and 566 endometrial biopsies from Tx-treated patients who presented with abnormal vaginal bleeding and/or abnormal sonograms was performed. Analysis of histologic characteristics included inactive/atrophic and functional endometria, endometrial polyps, hyperplasia and metaplasia, and endometrial cancer. Duration of Tx therapy was recorded when available, and its correlation with endometrial pathology was assessed. RESULTS: The only statistically significant difference between the data from the United States and France was the number of hysterectomies, which was almost double in France (27% vs 13.7%). Nonpathologic endometria made up 61.14% (inactive/atrophic 46%, functional 15.14%). Pathologic changes were found in 39.86% cases, of which polyps were 23.14%, glandular hyperplasia 8%, and metaplasia 3%; endometrial cancer made up 4.71% (33 cases). Nine cancers were well-differentiated endometrioid adenocarcinomas, and 24 were moderately or poorly differentiated, of which 13 had nonendometrioid components (serous, clear cell, MMMT). Fifteen cancers were found in endometrial polyps; 12 were invasive to the myometrium and 4 to blood vessels. The weight of the uteri exceeded 300 g in 15 cases, with 4 exceeding 900 g. The average age of all patients was 60.91 years and of the cancer patients alone it was 69.26 years. The shortest average duration of Tx therapy (2.5 years) was found in patients with inactive/atrophic endometria and the longest (6.8 years) in patients with endometrial cancer. Patients with endometrial polyps and cancer presented more often with abnormal vaginal bleeding than those with inactive/atrophic endometrium. CONCLUSIONS: Most Tx-treated patients had no pathologic endometrial changes. Endometrial polyps, hyperplasia, and metaplasia, consistent with an estrogen-agonist effect of Tx, were found in roughly one-third of all patients. The endometrial cancers were often high-grade and invasive tumors. Patients with endometrial pathology were more often symptomatic than patients with inactive/atrophic endometria.

Hormonal pathology of the endometrium.

The endometrial tissue is a sensitive target for steroid sex hormones and is able to modify its structural characteristics with promptness and versatility. This article discusses briefly endogenous hormonal effects (cyclic changes, luteal phase defect, unopposed estrogen effect) and describes the histologic patterns encountered in the most commonly used hormone therapies: oral contraceptives, ovulation stimulation, hormone replacement therapy, and antitumoral hormone therapy. Oral contraceptives exert a predominant progestational effect on the endometrium, inducing an arrest of glandular proliferation, pseudosecretion, and stromal edema followed by decidualized stroma with granulocytes and thin sinusoidal blood vessels. Prolonged use results in progressive endometrial atrophy. Ovulation induction therapy accelerates the maturation of the stroma and is often associated with a discrepancy between early secretory glands and an edematous or decidualized stroma with spiral arterioles. Hormone replacement therapy with estrogen alone may result in continuous endometrial proliferation, hyperplasia, and neoplasia. The use of both estrogen and progesterone elicits a wide range of histologic patterns, seen in various combinations: proliferative and secretory changes, often mixed in the same tissue sample; glandular hyperplasia (in polyps or diffuse) ranging from simple to complex atypical; stromal hyperplasia and/or decidual transformation; epithelial metaplasia (eosinophilic, ciliated, mucinous); and inactive and atrophic endometrium. Progesterone therapy for endometrial hyperplasia and neoplasia induces glandular secretory changes, decidual reaction, and spiral arterioles. Glandular proliferation is usually arrested, but neoplastic changes may persist and coexist with secretory changes. Lupron therapy produces a shrinking of uterine leiomyomas by accelerating their hyaline degeneration, similar to that in postmenopausal involution. It generally produces endometrial atrophy. Tamoxifen for breast carcinoma has an estrogen agonist effect on the uterus in approximately 20% of patients, who develop endometrial polyps, glandular hyperplasia, adenomyosis, and/or leiomyomata. Both endometrioid and nonendometrioid carcinomas are seen, often in polyps. Their causal relationship to tamoxifen therapy is debatable.

Morphometric Characterization of HPV-Related Lesions of Uterine Cervix.

OBJECTIVES: This study addresses three issues related to human papillomavirus (HPV) cervical lesions: identification of HPV in histologic normal tissue, identification of HPV subtypes with risk for cervical cancer, and histologic differences between HPV not associated to cervical intraepithelial neoplasia (CIN1) lesions (condyloma) and HPV associated to CIN1 lesions. MATERIALS AND METHODS: The authors histologically classified 48 cervical biopsy slides into three groups: normal (n = 22), condyloma (n = 20), and CIN1 (n = 6). Morphometric analyses of nuclear and cytoplasmic ratio for area, length, and diameter of 25 cells per case were performed. Histologic reports and in situ hybridization for HPV subtype were compared to morphometric data to assess correlation among them. RESULTS: Using image analysis, the authors correctly classified all cases except two into histologic or in situ hybridization diagnosis. Morphometry helped identify viral changes in cells that appeared histologically normal, HPV subtype at risk in condyloma lesions, and condyloma from those combining HPV lesions and CIN1. CONCLUSIONS: There were enough data supporting morphometric distinction of HPV-related cervical lesions assessed by nuclear and cytoplasmic ratio.

Ovarian dysplasia in prophylactic oophorectomy specimens: cytogenetic and morphometric correlations.

BACKGROUND: Ovarian dysplasia, a potential precursor to ovarian carcinoma, has been described in ovarian tissue obtained by prophylactic oophorectomy and also adjacent to ovarian carcinoma. Women with a family history of ovarian carcinoma, especially those of Jewish Ashkenazi descent, often test positive for BRCA mutant genes. Prophylactically removed ovaries, generally described as normal on macroscopic examination, can exhibit a "preneoplastic phenotype" and unsuspected neoplasm. METHODS: Histologic slides of ovarian tissue from 54 Ashkenazi Jewish women were reviewed. All had a family history of ovarian carcinoma and all were tested for BRCA mutations. Forty-four women tested positive. Thirty-one women underwent prophylactic oophorectomy and 23 underwent oophorectomy for ovarian carcinoma. Normal, dysplastic, and ovarian carcinoma epithelial cells were analyzed morphometrically combining nuclear area measurements with chromatin texture assessment using a novel method based on the computation of autocorrelation coefficients and a derived parameter (Beta). Discriminant analysis between classificatory algorithms was used to obtain results. RESULTS: Ovarian dysplasia was identified in 77.6% of the prophylactic oophorectomy specimens. An unsuspected ovarian carcinoma was diagnosed in one prophylactic oophorectomy specimen. Of 10 women who underwent prophylactic oophorectomy and were negative for BRCA mutations, three had ovarian dysplasia. The average nuclear measurements of the dysplastic cells were similar to those published previously. The new autocorrelation-based method evaluating nuclear texture, as revealed by tridimensional surface plots, demonstrated high discriminatory potential. Discriminant analysis based on nuclear area and nuclear texture information resulted in the correct classification of nearly all the cases in the three diagnostic categories. CONCLUSIONS: Ovaries removed by prophylactic oophorectomy examined in their entirety often reveal ovarian dysplasia and occasionally ovarian carcinoma. The new morphometric method used was highly discriminatory in the evaluation of nuclear texture. Ovarian dysplasia in women with risk factors for ovarian carcinoma is significant in early ovarian carcinogenesis.

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.

Endometrial adenocarcinoma associated with intrauterine pregnancy. A report of five cases and a review of the literature.

Endometrial adenocarcinoma associated with pregnancy is a rare lesion; only 14 acceptable examples have been reported in the literature. This study describes five additional examples with a critical review of the previously published cases. Four of the five women were nulliparous and three had sought medical intervention for infertility. The tumors were all well-differentiated endometrioid adenocarcinomas; three had a focal to extensive papillary pattern and three had focal to extensive squamous differentiation. Four were diagnosed at the time of dilatation and curettage and one at the time of cesarean section for a 28-week, live infant. Follow-up was available for four of the five women. Two women underwent hysterectomy with bilateral oophorectomy and were alive and well 12 and 48 months after diagnosis. The woman who had the live birth and the remaining woman were treated by repeat curettage with or without progesterone therapy, and each woman has had two subsequent full-term pregnancies with live births. These women are alive and well 57 and 58 months after diagnosis. Women with focal, well-differentiated carcinomas can successfully maintain their fertility if followed by repeat curettage with or without progesterone therapy.

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.

Cytology of sex cord tumor with annular tubules: a case report.

The cytologic findings of a sex cord tumor with annular tubules (SCTAT) that ruptured during laparoscopy are described. Features useful in distinguishing SCTAT from other ovarian sex cord tumors include the presence of highly cellular tubular formations containing well-delimited glassy pink material and absence of single cells. To the best of our knowledge, the cytology of SCTAT has not been previously reported.

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.

Ovarian dysplasia in epithelial inclusion cysts. A morphometric approach using neural networks.

BACKGROUND: Ovarian dysplasia has been described in the ovarian surface epithelium by histologic and morphometric studies. This study evaluates ovarian dysplasia in epithelial inclusion cysts adjacent to overt carcinoma and also incidentally found in ovaries removed for nonneoplastic diseases, including oophorectomies for family history of ovarian cancer, using an artificial neural network. METHODS: Histologic sections from 37 ovaries of which 26 were diagnosed with dysplasia in epithelial inclusion cysts (10 adjacent to carcinoma and 16 incidental) and 11 with benign epithelial inclusion cysts were evaluated by tracing nuclear profiles and assessing measures of nuclear area, shape, and texture. These sections were analyzed using artificial neural networks and also statistically using the Kruskal-Wallis test with the Dunn procedure to compare the morphologic similarity of dysplasia found incidentally in inclusion cysts unrelated to carcinoma from that in inclusion cysts adjacent to carcinoma. RESULTS: Neither statistical nor artificial neural network analysis was able to distinguish between incidental and adjacent dysplasia. Both types differed significantly from the control cases. CONCLUSIONS: Neural networks are powerful classification tools when applied to multiple variables extracted from individual cases. In this study, they helped to substantiate the similarity between dysplasia found incidentally and that adjacent to ovarian carcinoma. Because dysplasia represents a potential precancerous lesion, its incidental finding may help identify patients at risk for developing ovarian carcinoma.

Endometrial carcinoma in elderly women.

Endometrial carcinoma remains the most common invasive gynecologic malignancy. Increased longevity is associated with an increased incidence of endometrial carcinoma (EC) in elderly women. While recent studies have looked at aging and its relation to ovarian, breast, and cervical cancer, few have focused on EC in the growing elderly population. This study analyzed 35 histologic specimens of EC in women 75-92 years of age. Findings revealed that only 23% of the tumors were Stage I, G1. The majority (77%) were deeply invasive or of advanced stage (IC-IV). These were G2, G3, or "virulent" types of nonendometrioid EC (undifferentiated, clear cell, uterine serous papillary, and squamous cell carcinoma). Fifty-seven percent of tumors were endometrioid, of which 9% were mixed, including a rare case of nongestational choriocarcinoma. The nonendometrioid tumors, compared to the endometrioid types, were more often high-stage tumors with vascular invasion. They were also more often associated with atrophic (vs hyperplastic) uninvolved endometrium. Clinical risk factors (nulliparity, obesity, estrogen replacement therapy) were assessed and correlated with the histologic findings. It was shown that tumors in the elderly were less likely to be estrogen-related. It was concluded that EC in this age group is more aggressive, histologically less differentiated, and often nonendometrioid compared with EC in the general population. The increased virulence of EC in the elderly may be related to the tumor's independence from hormonal factors, to the poorly understood but well-known diminished immunologic defense against cancer in general in elderly patients, and/or to the belated diagnosis of the disease in this population.

Endometrial adenocarcinoma with choriocarcinomatous differentiation in an elderly virginal woman.

A 70-year-old virginal woman underwent hysterectomy and bilateral salpingo-oophorectomy for endometrial carcinoma. Gross examination of the surgical specimen showed normal ovaries and fallopian tubes, an enlarged uterus with several intramural leiomyomata, an endometrium completely carpeted by cancer, and, additionally, a necrotic and hemorrhagic nodular mass that protruded into the endometrial cavity. Histologic examination showed a widespread and superficially invasive, moderately differentiated endometrial adenocarcinoma that merged with a choriocarcinoma. Immunohistochemical studies showed cytoplasmic staining for human chorionic gonadotrophin in syncytiotrophoblast cells, cytotrophoblast-like cells and rare adenocarcinoma cells. A discussion of previously reported similar cases and possible mechanisms of dual differentiation in tumors, as well as comments on histogenesis are included.

Immunohistochemical localization of urokinase-type plasminogen activator and the plasminogen activator inhibitors 1 and 2 in early human implantation sites.

OBJECTIVE: Our purpose was to immunolocalize urokinase-type plasminogen activator and the plasminogen activator inhibitors 1 and 2 in human implantation sites, with emphasis on the types of trophoblast expressing the plasminogen activator and the inhibitors. STUDY DESIGN: Urokinase and the plasminogen activator inhibitors 1 and 2 were localized immunohistochemically in early human implantation sites in unruptured ectopic pregnancies from patients in an in vitro fertilization program. RESULTS: Urokinase kinase and the plasminogen activator inhibitors 1 and 2 were localized in the cytoplasm of cytotrophoblasts and in the cytoplasm and plasma membranes of intermediate and syncytiotrophoblast. Greater staining was noted in nonvillous, relative to villous, cytotrophoblasts for urokinase and both inhibitors. CONCLUSIONS: Urokinase-type plasminogen activator and the plasminogen activator inhibitors 1 and 2 were localized in all three forms of trophoblast at the maternal-fetal interface in early human implantation sites, particularly the differentiated and invasive forms of trophoblast. These results support a role for the plasminogen activator or inhibitors in the controlled invasion of the maternal decidua by the trophoblast during human implantation.

Chemotherapy for angiosarcoma of the breast: case report of 30-year survival and analysis of the literature.

Angiosarcoma of the breast is a rare and highly malignant neoplasm with few long-term survivors. Little is known about the effects of chemotherapy for patients with disseminated disease or its role in the adjuvant setting. We report the case of a patient with metastatic angiosarcoma of the breast who achieved a long-term clinical and pathological remission after treatment with methotrexate. The 30-year course of her disease is the longest reported survival with documented metastatic angiosarcoma of the breast. Analysis of the role of chemotherapy in the adjuvant setting and its effects in relation to histological subtype is undertaken. Adjuvant chemotherapy for patients with poorly differentiated angiosarcoma of the breast results in a higher proportion of patients relapse-free (29.2%) compared to patients not receiving adjuvant chemotherapy (4.4%) (p < 0.05). Patients with well-differentiated tumors do not appear to derive benefit from adjuvant chemotherapy. The effects for patients with disseminated disease are reported.

Ovarian dysplasia: nuclear texture analysis.

BACKGROUND: Ovarian dysplasia has been defined by histologic and morphometric studies focusing on architectural and nuclear profile changes. A new technique is used to enhance the accuracy of this diagnosis by a quantitative evaluation of the nuclear texture that represents the nuclear chromatin pattern on which conventional diagnoses of malignancy are usually made. METHODS: Histologic sections from 35 ovaries classified as malignant (12), dysplastic (12), and normal (11) were evaluated by tracing boundaries of nuclear profiles and measuring "textons" (texture primitives) with a histogram analysis of three zones of gray level densities (called for simplification white, gray, and dark). The average combined area was tabulated for specimens with the same diagnosis, and linear regression plots compared the texton area with total nuclear area. RESULTS: The dimensions of textons originally hidden inside the chromatin and revealed by histograms were found to be closely clustered in normal epithelium, and increasingly dissociated from the containing nucleus as the lesion progressed from dysplastic to malignant. The statistical multivariate analysis including nine parameters correctly classified the three diagnostic categories as normal, dysplastic, and malignant. CONCLUSIONS: Computerized image analysis of nuclear texture adds accuracy to the recently elaborated morphometric methods to define ovarian dysplasia, a potential precursor of ovarian carcinoma.

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.