Role of Intracystic Cytokines and Nitric Oxide in Ovarian Neoplasms.

The development of new biomarkers for the diagnosis and prognosis of ovarian cancer may provide an opportunity for new therapies. In this study, we aimed to compare cytokines (interleukin [IL]-2, IL-5, IL-6, IL-8, IL-10 and tumour necrosis factor [TNF]-α) and nitric oxide (NO) metabolite levels in non-neoplastic tumours, benign primary ovarian tumours and malignant primary ovarian neoplasms. The secondary aim was to relate cytokine and intracystic NO metabolite levels to clinical, laboratory and pathologic characteristics for patients with primary ovarian malignancies. We evaluated 110 patients with adnexal masses. Cytokine concentrations were quantified by enzyme-linked immunosorbent assay and nitrate concentrations by enzymatic reduction of nitrite by nitrate reductase. Patients with malignant neoplasms had higher IL-6, IL-8 and NO levels compared to patients with benign neoplasms. Histologic grade 1 tumours were associated with elevated IL-2 levels, whereas anaemia was associated with elevated IL-6 levels. On average, those patients with elevated IL-8 levels also had a neutrophil/lymphocyte ratio (NLR) greater than 2.6 and less than 36 months of disease-free survival (DFS). Patients with normal CA 19-9 levels had elevated IL-10 levels. TNF-α was elevated in patients with two carcinogenesis and those with a platelet/lymphocyte ratio (PLR) less than 300. NO levels were higher in patients with an NLR less than 2.6 and CA 19-9 greater than 35 U/ml. Elevated intracystic cytokine levels, especially IL-6 and IL-8, are associated with worse prognosis in ovarian cancer.

An evaluation of immune system cell infiltrate in the cervical stroma of patients with grade III cervical intraepithelial neoplasia after treatment with intralesional alpha-2B interferon.

The aim of this study was to characterize infiltrating immune cells in cervical stroma biopsy samples from patients diagnosed with cervical intraepithelial neoplasias (CINs) who were treated with IFN-alpha 2b. The authors studied 13 volunteers who were diagnosed with Cervical intraepithelial neoplasia CIN II or III and who received intra-lesional treatment with IFN-alpha 2b. They collected pre- and post-treatment biopsies from each patient. They also examined the slides under a common optical microscope with a X400 lens for biopsy sample sections that were labeled with immunohistochemistry for T lymphocyte, B lymphocyte, natural killer cell, macrophage, iNOS, and perforin markers. The presence of immune response cells in the lesion was observed after treatment with intralesional IFN-alpha 2b in patients with CIN II/III changes, a reduction in CD4+ and CD8+ T lymphocyte infiltration in the women who responded well to treatment. However, there was a significant increase in these markers in samples from women who did not respond to treatment. Nonetheless, immunotherapy with IFN-alpha 2b administered intralesionally in patients with CIN II/III yields favorable results in patients who do not smoke.

Loss of heterozygosity in the fragile histidine triad (FHIT) locus and expression analysis of FHIT protein in patients with breast disorders.

PURPOSE OF INVESTIGATION: The fragile histidine triad (FHIT) gene is a tumor suppressor frequently inactivated in various types of tumors. The authors evaluated the occurrence of loss of heterozygosity (LOH) in the FHIT locus and FHIT protein changes in breast tissue. MATERIALS AND METHODS: Blood and breast tissue samples were obtained from 35 women with mammary disorders. The occurrence of LOH in FHIT locus was assayed by polymerase chain reaction (PCR), and the results obtained from blood and breast tissues from each patient were compared. FHIT protein expression was evaluated by immunohistochemistry. RESULTS: LOH in the FHIT gene occurred in 48.6% (17/35) of patients with mammary disorder. Among patients with malignant breast disorders, 59.1% (13/22) presented LOH in the FHIT gene in comparison with patients with benign breast lumps, in which the LOH was observed in 30.8% (4/13) of women, suggesting that changes in this gene occur prior to the process of mammary carcinogenesis. The changes in the locus of the FHIT gene occur with greater frequency in the coded region of the gene, principally near exons 5 and 8, where the FRA3B site and the histidine triad respectively are found. Changes in FHIT did not modify protein expression. The association between menopause and LOH in the FHIT gene was evident. CONCLUSIONS: LOH in the FHIT gene may be related to menopause in women with breast disorders.

Gynecological malignant neoplasias diagnosed after hysterectomy performed for leiomyoma in a university hospital.

PURPOSE: To analyze the findings of malignant neoplasms after hysterectomy for benign conditions. METHODS: A retrospective study from January 1987 to December 2008 was conducted. We analyzed all simple hysterectomies with or without salpingo-oophorectomy for benign conditions (leiomyoma). Incomplete dossiers of patients or cases with uncertain clinical diagnostics were excluded. We analyzed histopathological results, age, parity, indications for hysterectomies with or without salpingo-oophorectomy, stage (if malignant) and therapy. RESULTS: 2,016 hysterectomies with or without salpingo-oophorectomy were performed. Of 2,016, 652 (32.3%) had had a previous diagnosis of malignancy and 1,364 (67.7%) had had a clinical diagnosis of benignancy (leiomyoma). From the total of 1,364, three (0.22%) cases of cancer were diagnosed after anatomopathological study of the uterine specimen, two sarcomas and one endometrial cancer. No cases of incidental ovarian or uterine cervical cancer were diagnosed. CONCLUSIONS: Gynecological malignances in surgical specimens of patients submitted to surgery (hysterectomy and/or salpingo-oophorectomy) for benign conditions are rarely found.

T lymphocytes (CD3) may participate in the recurrence of cervical intraepithelial neoplasia grade III.

OBJECTIVE: Data from the literature demonstrate that the local and systemic immune responses seem to play an important role in the progression of cervical intraepithelial neoplasia (CIN). Our aim was to investigate whether recurrences among CIN III patients might be related to the presence of local lymphocytes, macrophage and enzyme iNOS. METHODS: We analyzed 35 patients with CIN III who underwent conization and followed up for a minimum of 4 years. Using immunohistochemistry, the presence of T lymphocytes (CD3, CD8 and CD45RO), B lymphocytes (CD20), macrophages (CD68) and the expression of the enzyme iNOS were investigated. The quantity of marked cells is graded as: 0, absence of cells; 1, rare cells; 2, moderate number of cells; 3, many cells. For statistical purposes, we took the scores 0 and 1 to indicate weak marking and the scores 2 and 3 to indicate strong marking. RESULTS: We found strong positive expression of CD3-positive T lymphocytes among CIN III patients with recurrence following conization (100 vs. 50% without recurrence, p=0.02). We did not find any statistical differences in the expression of CD20, CD68, CD45RO, CD8 or iNOS. CONCLUSIONS: It is concluded that strong positive findings of CD3 T lymphocytes were related to recurrence following conization due to CIN III.

Peri- and intratumoral T and B lymphocytic infiltration in breast cancer.

PURPOSE: To investigate peritumoral and intratumoral infiltrates in surgical specimens obtained from patients with invasive breast cancer, and of relating these to tumor size. METHODS: Twenty-six surgical specimens obtained from patients diagnosed with breast cancer underwent immunohistochemical preparation and CD3, CD8, CD20 and CD68 labeling. The positive cells were counted in the tissue samples and correlated with the tumor size determined by imaging methods (TIA < or = 2 or TIB > 2 cm). RESULTS: There was a significant reduction in intratumoral B lymphocytes (CD20+), although this reduction could only be observed in TIA. In relation to peritumoral T lymphocytes (CD3+), there was a significant reduction in TIB, in comparison with TIA. Peritumoral and intratumoral CD3+ and CD68+ presence in completely opposite ways in both sizes of tumors. CONCLUSION: Peritumoral and intratumoral infiltrates of T and B lymphocytes are different and depend on tumor size.

Neuron count reevaluation in the myenteric plexus of chagasic megacolon after morphometric neuron analysis.

This study was made with the objective of reevaluating the colon denervation in chronic Chagas' disease. The diameters of neuron perikaryons of the myenteric plexus were measured on paraffin sections in a ring from the sigmoid in Chagas' disease patients, 17 with and 10 without megacolon and in 10 non-chagasic controls. All neurons were counted in ten en-echelon sections. Neuron hypertrophy only occurred in the group with megacolon, and the average increase in diameter was 69.3%. This could generate an error factor in the neuron count by increasing the probability of neurons being seen in a greater number of histological sections. The original result of the neuron count gave medians of 1264, 1961, and 2665 in the groups of chagasic patients with megacolon, without megacolon, and in the control, respectively. The denervation was greater than 55% in only seven megacolon cases (41.2%). After applying a correction factor, the median in the group with megacolon was 746, and the denervation was greater than 55% in 13 cases (76.5%). This occurrence demonstrates the need to apply a correction factor when the neuron count in chagasic megacolon is being evaluated and in the other pathologies where neuron hypertrophy may be found.

Leiomyosarcoma of the esophagus in a patient with chagasic megaesophagus: case report and literature review.

Leiomyosarcoma constitutes approximately 0.5% of the malignant neoplasias of the esophagus and its association with megaesophagus has not been described. We report on a case of a woman with dysphagia that was slowly progressive from the age of 19 due to chagasic megaesophagus. The woman was subjected to cardiomyotomy at the age of 49. She presented a rapid worsening of the dysphagia due to leiomyosarcoma at the age of 61, and was subjected to subtotal esophagectomy with cervical esophagogastroplasty. She developed pulmonary and hepatic metastases 14 months after surgery and died six months later.

[Progressive multifocal leukoencephalopathy as initial manifestation of acquired immunodeficiency]. / Leucoencefalopatia multifocal progressiva como manifestação inicial da síndrome da imunodeficiência adquirida.

This is a report of a man with acquired immunodeficiency syndrome (AIDS) who presented acutely ill with severe progressive multifocal leukoencephalopathy (PML) as the first manifestation of AIDS. PML was diagnosed in the brain after gross and microscopical examination as well as by immunohistochemistry with an antibody against JC virus.

Cyto-histological correlation of 219 patients submitted to surgical treatment due to diagnosis of cervical intraepithelial neoplasia.

CONTEXT: Cervical cytology continues to be the most appropriate method for investigating cervical neoplasia and its precursors. Greater diagnostic acuity is obtained by combining cytology, colposcopy and guided biopsy methods. OBJECTIVE: To analyze the diagnostic acuity of cyto- and histopathological exams and causes of diagnostic error. DESIGN: Retrospective study. SETTING: A public tertiary referral center. SAMPLE: Reports on 219 patients submitted to cone biopsy and/or hysterectomy due to diagnosis of cervical intraepithelial neoplasia (CIN) in the period between January 1982 and March 1997 were reviewed, comparing. MAIN MEASUREMENTS: Cytological and histological exams (guided biopsy and surgically-removed tissue). In cases of discordance, the cyto- and histological preparations were reviewed to try to evaluate the causes of errors. RESULTS: In 193 cases (88.1%) there was cyto-histological agreement but none in 26 (11.9%). Review of the discordant cases showed that in 2 (0.9%) there was invasion of the stromata to a depth greater than 3 mm, and in 7 (3.2%) microinvasion, unsuspected via cytology; in 2 (0.9%) microinvasion was suspected via cytology but not confirmed by the final histological exam; and in 15 (6.8%) there was disagreement about the degree of CIN. CONCLUSION: The principal causes of error in the cytological exam were the lack of reliable morphological criteria for microinvasion, absence of sampling of the squamocolumnar junction, and scarcity of neoplastic cells in the sample. As for the histological exam, the errors were related to inadequate technical processing and underestimation of focal lesions.

Leucoencefalopatia multifocal progressiva como manifestação inicial da síndrome da imunodeficiência adquirida / Progressive multifocal leukoencephalopathy as initial manifestation of acquired immunodeficiency

This is a report of a man with acquired immunodeficiency syndrome (AIDS) who presented acutely ill with severe progressive multifocal leukoencephalopathy (PML) as the first manifestation of AIDS. PML was diagnosed in the brain after gross and microscopical examination as well as by immunohistochemistry with an antibody against JC virus.

Relata-se caso de homem portador da Síndrome da Imunodeficiência Adquirida que apresentou quadro agudo e grave de Leucoencefalopatia Multifocal Progressiva (LMP) como primeira manifestação da Síndrome. A LMP foi caracterizada macro e microscopicamente e através de estudo imuno-histoquímico utilizando o anticorpo antivírus JC.