ATYPICAL STROMAL GIANT-CELLS OF CERVIX UTERI - EVIDENCE OF SCHWANN-CELL ORIGIN

The report describes atypical multinucleated giant cells adjacent to proliferated nerve fascicles in a circumscribed subepithelial area of the cervix uteri of a 44-year-old multipara. Ultrastructural examination revealed cytoplasmatic processes, basal lamina, intracytoplasmic microfibrils, bizarre nuclear shapes with pseudoinclusions and nuclear fragments connected by small chromatin bridges (nucleotesimals). Immunohistochemical examination showed positive staining for vimentin and S-100 protein. Quantitative topography exhibited an isotropic distribution of the giant cells in an anisotropic architecture of mononuclear cells. A Schwann cell origin of the atypical giant cells is postulated. Aetiopathogenetically the lesion is regarded to be due to a trauma during delivery followed by regenerative proliferation of nerve fascicles and degenerative alterations of proliferating Schwann cells. The knowledge of this lesion is considered important, because the atypical cells could be confounded with malignant neoplastic cells.18781031103

Endometrial polyp with sex cord-like pattern

We report on an unusual endometrial polyp in a postmenopausal woman taking tamoxifen for 7 years after surgical resection of a breast carcinoma. A 63-year-old woman with endometrial thickening was submitted to hysteroscopy with biopsy, which revealed a polyp with a sex cord-like pattern. The hysterectomy specimen showed florid adenomyosis, and in the background, there were rare sex cord-like foci. Immunohistochemistry can be useful in differentiating sex cord-like elements from metastatic breast cancer to endometrium. This is, to our knowledge, the first observation in literature correlated to tamoxifen intake.25217017

Metastatic Mucinous Carcinomas in the Ovary: A Practical Approach to Diagnosis Related to Gross Aspects and to Immunohistochemical Evaluation

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Ovarian mucinous carcinomas are uncommon, and the differential diagnosis is metastatic carcinoma mainly from the gastrointestinal tract. The aim was to verify the importance of immunohistochemical reactions and the algorithm described in literature on the basis of laterality and tumor size. Twenty-five cases identified as metastatic mucinous adenocarcinomas were reviewed, along with clinical records; a tissue microarray was created, and immunohistochemical reactions for CK7, CK20, Ca125, hormonal receptors, WT1, DPC4, beta-catenin, and Cdx2 were determined. The median age was 51, and only 9 patients had a history of cancer. Sixteen patients (64%) had bilateral tumors, with sizes ranging from 5 to 36 cm (average, 20.5 cm); 9 (36%) had unilateral tumors varying from 5.5 to 38 cm (average, 21.8 cm). Algorithm agreement was 76%; most unilateral tumors were 413 cm. Common positive markers were Dpc4 (88%), Cdx2 (68%), CK20 (60%), and CK7 (44%). The useful markers were CK7, CK20, and Cdx2, although there were cases with overlapping results. The most common primary tumor was of colorectal origin (14 cases). The mean survival age was 32.6 mo. Although the proposed algorithm and immunohistochemical reactions are useful tools for diagnosis, some mucinous tumors cannot be definitively classified as primary or metastatic without further clinical evaluation, emphasizing the limits of this challenging diagnosis.314313318Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Forsikring mod Arbejdsløshed i Gent.

The treatment of cervical microinvasive carcinoma is controversial. Hysterectomy is performed in almost all cases, associated or not with more radical procedures. Currently, there is a tendency to adopt conservative management to treat patients with early invasion, as long as it can be assured that the whole lesion has been removed. The aim of this study was to establish which histological information should be obtained from the cones that would give the best possible assurance of absence of residual neoplasia in the patient. This was done by comparing cone and hysterectomy specimens from each patient. One hundred sixty-three cases, treated from 1967 to 1994, underwent simple or radical hysterectomy following tone biopsy. We evaluated the following histological features in the cones: (i) invasion depth, (ii) lateral extension of the lesion, (iii) unifocal or extensive lesion, (iv) vascular invasion, (v) morphological signs of HPV infection, and (vi) free or involved cone surgical margins. Residual neoplasia in the histerectomy was more frequent when the margins of the cone were involved by atypical epithelium, and in cases with signs of HPV infection. However, according to statistical analysis, these two variables were not mutually independent, and the only important parameter to predict residual neoplasia in the hysterectomy specimens was involved surgical margins in the cone. (C) 1997 Academic Press.65343744

Immunohistochemical patterns for alpha- and beta-catenin, E- and N-cadherin expression in ovarian epithelial tumors

Objectives. This study aims were to analyze and compare the E- and N-cadherin, beta- and alpha-catenin expression in benign and malignant epithelial neoplasms of the ovary, correlating with tumor staging, histological grade, and presence of metastases during evolution. Methods. Immunohistochemical reactions were performed on paraffin-embedded tissues and evaluated according to the number of positive, stained cellular structures and reaction intensity for each molecule. Information about histological type and grade, tumoral stage, and disease evolution was obtained from the patients' clinical records. Results. Most of the carcinomas showed more intense beta-catenin reaction (P = 0.02). More than 50% of the endometrioid carcinomas showed increased beta-catenin expression, with a large number of positive cells and more intense staining, being the same also observed for most of the serous benign tumors (P < 0.01). E-cadherin membrane expression was frequently observed in carcinomas without metastasis, whereas cases with metastases in evolution were negative or showing E-cadherin expression only in the cytoplasm (P = 0.04). N-cadherin expression differed according to histological type and grade and &alpha;-catenin was also related to histological type, but these findings were not conclusive. Conclusions. Increased &beta;-catenin expression was more frequent in ovarian carcinomas, especially, but not only, in the endometrioid ones. The maintenance of E-cadherin expression in cellular membrane may be an independent marker of good prognosis in ovarian cancer. New studies about N-cadherin and &alpha;-catenin and their importance during ovarian carcinogenesis will be required. (C) 2004 Elsevier Inc. All rights reserved.941162

HPV in situ hybridization signal patterns as a marker for cervical intraepithelial neoplasia progression

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Objective. HPV-DNA integration is one factor for malignant transformation and can be identified using in situ hybridization (ISH), where a diffuse signal represents episomal HPV and punctate, integrated. The aim is to verify if a punctate pattern could be a marker of CIN1 that progresses. Methods. 74 CIN1 biopsies were studied. In the follow up, a second biopsy was performed and 65% showed CIN1 or no lesion (group without progression) and 35% CIN2/3 (with progression). ISH was carried out with HR-HPV GenPoint (R) in the first biopsy looking for the positive distribution in epithelium regions (basal, intermediate, superficial) and reaction pattern (diffuse and punctate). The Mann-Whitney and Fisher tests were used to compare the groups (p <= 0.05). Results. The mean age of patients without progression was 26 and, with progression 31 (p = 0.02). ISH was positive in 22 cases, 8 with CIN2/3 in the second biopsy. The punctate signal was observed in all epithelial layers, and the mean coefficient between the number of cells with punctate and diffuse signals was 3.5 times more common in the progression group (p = 0.08). The average percentage of punctate nuclei patterns in the basal region in cases without progression was 0.5% and 11% in those with progression (p = 0.05). However, in superficial layer this was not correlated with progression. Conclusion. Progression was observed in 35% of CIN1 and associated with age; 30% of the cases were positive by ISH, but must be carefully interpreted. Punctate signals were related to progression only in basal cells, identifying CIN1 with potentially aggressive behavior. (c) 2008 Elsevier Inc. All rights reserved.1121114118Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Correlation between endometrial histology, microvascular density and calibre, matrix metalloproteinase-3 and bleeding pattern in women using a levonorgestrel-releasing intrauterine system

BACKGROUND: The main reason for discontinuation of the levonorgestrel-releasing intrauterine system (LNG-IUS) is unpredictable bleeding pattern. METHODS: The objective of the study was to evaluate the endometrial histology, microvascular density and calibre, and the quantification of matrix metalloproteinase (MMP-3) in long-term users of LNG-IUS, with and without bleeding. Endometrial biopsies were obtained from 58 healthy women, 29 who maintained some degree of endometrial bleeding and 29 who were amenorrhoeic. RESULTS: In the histological analysis, the majority of samples displayed a progestin-modified appearance. The major glandular diameter and the perimeter were significantly greater in the group of women with amenorrhoea. A significantly higher number of leukocytes was found in the group with bleeding (P=0.014). No significant correlation was observed between the microvascular density or calibre and the bleeding pattern. MMP-3 showed a significantly higher number of reactive cells (P=0.005) in the group who maintained some degree of bleeding. CONCLUSIONS: Women using LNG-IUS who maintained endometrial bleeding during its use presented a higher number of leukocytes and MMP-3 in the endometrium when compared to women using LNG-IUS who became amenorrhoeic. However, the results did not provide evidence for microvascular pattern changes.1981778178

Malignant mixed Mullerian tumor of the uterine cervix with neuroendocrine differentiation

Malignant mixed Mullerian tumors (MMMTs) are rare neoplasms. We report the clinical, pathologic, and immunohistochemical features of an MMMT primary of uterine cervix. This lesion was composed of a poorly differentiated epithelial component (cytokeratin positive) and a spindle cell component (vimentin positive) with heterologous (myoblastic) differentiation (focal 1A4 positive). There were also cells with neuroendocrine features that expressed S-100 and chromogranin A. Along with a brief review of this amazing neoplasm, some histogenetic concepts relevant to this case are discussed. To our knowledge this is the first report of a malignant mixed Mullerian tumor of the uterine cervix with neuroendocrine differentiation.12222322

Correlation between histological criteria and human papillomavirus presence based on PCR assay in cervical biopsies

The aim was to correlate histological findings in cervix lesions to human papillomavirus (HPV), as detected by polymerase chain reaction (PCR). One hundred and seven women with atypical Pap smear were submitted to colposcopic examination, and suspicious images were biopsied. The PCR assay was performed with the primers MY09/11 and GP05/06+ and, as control, the beta-globin gene was amplified. The morphological findings were correlated to HPV positivity: parakeratosis, acanthosis, koilocytotic atypia (KA), binucleation, dyskeratosis, and number of mitoses. From 107 patients, 61 biopsies were taken: 11 chronic cervicitis (CC), 36 cervical intraepithelial neoplasia (CIN) (13 CIN I; 10 CIN II; 13 CIN III), and 14 suggestive for HPV (SHPV). DNA extraction was not possible in eight cases. HPV was found in 35% CC, 77% CIN, and 64% SHPV. The analysis did not indicate any morphological criteria strongly related to HPV. The findings with highest sensitivity for HPV were KA (88.89%) and binucleation (75%), but with low specificity of 29.41 and 52.94%, respectively. The higher predictive positive values (PV+) for HPV were also KA (72.73%) and binucleation (77.14%). Considering KA, dyskeratosis and binucleation together, PV+ was 72.41%. Conclusion: Although indicative, none of the studied morphological criteria was always related to PCR virus detection, denoting some limitations for histological diagnosis.14112613

Ex vivo Expansion of CD56(+) NK and NKT-like Lymphocytes from Peripheral Blood Mononuclear Cells of Patients with Ovarian Neoplasia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Methods for ex vivo expansion of natural killer (NK) cells have allowed obtaining enough numbers of human NK cells for clinical trials. However, the evaluation of these methods has been mostly limited to haematological malignancies. This study aimed at evaluating a method for selective expansion of NK cells when applied in peripheral blood mononuclear cells (PBMC) of patients with ovarian neoplasia. PBMC from 13 volunteer patients with ovarian neoplasia, seven benign and six malignant tumours, were cultured in Cell-Gro medium supplemented with anti-CD3 (9-10 initial days), IL-2 and foetal bovine serum for 21 days. The resulting effector cells were evaluated for their phenotype, cytotoxicity and cytokine secretion. PBMC cultures resulted in multiple populations (NK, NKT and T) of effector cells, enriched with CD56(+) lymphocytes. NK cells from patients with benign and malignant ovarian neoplasia were expanded 139.6 +/- 63.4 and 82.7 +/- 25.3-fold, respectively, being the largest lymphocyte subtype among CD56(+) population. Effector cells expanded from patients with malignant ovarian neoplasia had higher proportion of T lymphocytes and altered cytokine production patterns, characterized by lower INF-gamma, TNF-alpha and higher IL-4, compared with patients with benign ovarian neoplasia. Effector cells were cytotoxic against K562 and OVCAR3 cell lines. Cytotoxicity was significantly higher (P < 0.05) using magnetically separated CD56(+) effector cell fractions compared with CD56-deprived ones. The present study demonstrates the feasibility of the culture system employed to generate effector cells, enriched with CD56(+) lymphocytes, from PBMC of patients with ovarian neoplasia. NK cells were the largest lymphocyte subtype among the CD56(+) population and the main variable among the final effector cell preparation affecting target cell killing.743244252Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [2006/04600-2