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Biomedical subjects

J Vassallo

Publications and source records attributed to J Vassallo.

At least 19 recordsLinked to original sources

"In situ-like" mantle cell lymphoma: a report of two cases.

Mantle cell lymphoma (MCL) is a B cell neoplasm that most often shows a diffuse growth pattern. Two cases of MCL are reported here, both with a previous diagnosis of lymphoid hyperplasia. Morphologically, germinal centres are hyperplasic with a normal or discretely enlarged mantle zone, where foci of irregularly shaped small lymphocytes are seen. These are positive for CD20, CD5 and cyclin D1, confirming a diagnosis of in situ-like MCL. This type differs from the mantle zone pattern in that the neoplastic mantle zone is very thin and there is very little or no spread of tumour cells into interfollicular areas. To the best of our knowledge, this is the first report on such a pattern of MCL, which is important to recognise, as it can be confused with lymphoid hyperplasia.

Aged↗

Immunoexpression of CD95 in chronic gastritis and gastric mucosa-associated lymphomas.

CD95 (Fas/APO-1)-mediated apoptosis plays an important role in immunological regulation and is related to the pathogenesis of autoimmune diseases. Immunoexpression of CD95 has been reported to frequently occur in low grade non-Hodgkin lymphomas, especially of post-germinal center histogenesis, among which those originating in mucosa-associated lymphoid tissue (MALT lymphomas). However, there is no report comparing in situ immunoexpression of this marker in lymphomas and the hyperplastic lymphoid reaction (chronic gastritis) related to Helicobacter pylori infection. The purpose of the present research was to compare the intensity of lymphoid CD95 immunoexpression in 15 cases of H. pylori-related chronic gastritis and 15 gastric MALT lymphomas. CD95 (anti-CD95) was detected by an immunoperoxidase technique in paraffin sections using the catalyzed amplification system. Graduation of reaction intensity (percentage of CD95-positive cells) was semiquantitative, from 1+ to 4+. Nine cases of chronic gastritis were 4+, five 2+ and one 1+. Three lymphomas were 4+, three 3+, four 2+, four 1+, and one was negative. Although 14 of 15 lymphomas were positive for CD95, the intensity of the reaction was significantly weaker compared to that obtained with gastric tissue for patients with gastritis (P = 0.03). The difference in CD95 immunoexpression does not seem to be useful as an isolated criterion in the differential diagnosis between chronic gastritis and MALT lymphomas since there was overlapping of immunostaining patterns. However, it suggests the possibility of a pathogenetic role of this apoptosis-regulating protein in MALT lymphomas.

Antigens, Neoplasm↗

Comparison of immunoexpression of 2 antibodies for estrogen receptors (1D5 and 6F11) in breast carcinomas using different antigen retrieval and detection methods.

The importance of in situ immunodetection of hormone receptors for therapy planning and prognostic evaluation in patients with breast carcinoma is well established. Sensitive detection methods are of utmost importance, especially in poorly fixed tissues, which are not uncommon in routine pathologic practice. The purpose of the present study is to compare immunoexpression of estrogen receptors in 20 cases of invasive ductal carcinoma using two antibodies, 1D5 and 6F11, and to verify the effect of different antigen retrieval solutions and detection systems. Immunoperoxidase was performed on paraffin sections using 1D5 and 6F11 as primary antibodies. Heat-induced antigen retrieval was performed using citrate buffer (pH 6.0) or Tris-EDTA buffer (pH 8.9). Detection was achieved using the following systems: EnVision, EnVision Plus, and labeled streptavidin-biotin peroxidase complex. Reaction was semiquantified from 0 to 4. There were no differences between the two markers, 1D5 and 6F11, except when 6F11 was used with EnVision and citrate buffer, in which case weaker reactivity was observed. Only in this combination (6F11/EnVision) was EDTA buffer significantly better than citrate. Labeled streptavidin-biotin peroxidase complex presented the best results, followed by EnVision Plus.

Antibodies, Monoclonal↗

Human papillomavirus infection and p53 protein expression in vulvar intraepithelial neoplasia and invasive squamous cell carcinoma.

The etiopathogenesis of vulvar intraepithelial neoplasia (VIN III) and invasive squamous cell carcinoma are largely unknown. Since there are few studies on Brazilian patients, our purpose was to determine the frequency of human papillomavirus (HPV) infection and the expression of p53 in these lesions, and associate them with other factors such as age, morphological subtypes, multicentric and multifocal disease. Thirty-eight cases of VIN III, nine of superficially invasive carcinoma, and 55 of invasive vulvar carcinoma were retrospectively evaluated from 1983 to 1995 for the presence of HPV by immunohistochemistry and in situ hybridization, and for p53 protein expression by immunohistochemistry on paraffin sections. All cases for whom material (slides and paraffin blocks) and clinical data were available were included. HPV and p53 were detected in 57.9 and 21.1% of the VIN III lesions, 33.3 and 66.7% of superficially invasive carcinomas, and 7.3 and 58.2% of invasive squamous cell carcinomas, respectively. HPV infection was associated with younger age in the VIN III and invasive carcinoma groups. In the latter, HPV infection was associated with the basaloid variant. p53 expression rate was higher in superficially invasive and invasive lesions and was not related to HPV infection. Our findings are similar to others and support the hypothesis that there are two separate entities of the disease, one associated with HPV and the other unrelated, with p53 inactivation possibly being implicated in some of the cases.

Adult↗

Immunohistochemical study of the pancreatic basement membrane in non obese diabetic mice (NOD) with spontaneous autoimmune insulitis.

The role of the basement membrane as an antigenic structure in autoimmune diseases is controversial. To determine possible structural changes in the endocrine pancreatic basement membrane (PBM) in autoimmune diabetes, we studied the expression of laminin in the islets of 42 NOD mice, aged between 4 to 42 weeks, as an animal model of spontaneous diabetes. Insular lymphocytic inflammatory infiltration of variable intensity was present in 24 of these mice. An immunohistochemical staining using the streptavidin-biotin-peroxidase technique was performed on paraffin-embedded tissue sections, with a polyclonal antilaminin antibody. Staining for laminin was restricted to the basement membrane. In islets with no inflammatory infiltration, laminin was observed as a thin, continuous and uniform brown layer, covering the pericapsular basement membrane of the islets and their capillaries. The continuity of the PBM was lost in the islets with insulitis and the immunostaining showed clearcut interruption and destruction, particularly when the islets were in contact with inflammatory infiltrate. Our findings suggest that the loss of integrity of the PBM in islets with inflammatory infiltrate could facilitate antigenic exposure contributing towards the start o f autoimmune DM in NODmice.

Animals↗

Apoptosis-regulating proteins and prognosis in diffuse large B cell non-Hodgkin's lymphomas.

We evaluated the expression of apoptosis-regulating proteins (p53, Bcl-2, Bax, Bak and Mcl-1) in paraffin-embedded tissues of 33 patients with diffuse large B cell non-Hodgkin's lymphoma, and assessed the relationship of these proteins to clinical outcome and response to chemotherapy. Our results showed that p53 expression was an independent immunohistochemical parameter related to a poor prognosis in these lymphomas. Bcl-2, Bax, Bak and Mcl-1 proteins, though highly expressed in almost all cases were not associated with prognosis or response to treatment.

Adult↗

Characteristics of nasal T/NK-cell lymphoma among Brazilians.

Nasal T/NK-cell lymphomas are highly associated with Epstein-Barr virus (EBV). They are more frequent in Asia than in Western countries. In Central and South America there are few studies about nasal T/NK-cell lymphoma and they have shown a strong predominance of this phenotype in Native American descents, supporting the hypothesis of a racial predisposition for the disease. We studied the lymphomas involving midline facial region at a Brazilian institution. T/NK cell lymphomas (16/25) were more frequently found compared to B lymphomas (9 cases, all B large cell). T/NK cell lymphomas involved predominantly the nasal region. Histologically they showed angioinvasion and necrosis. All of them were positive for CD3 and CD56 and showed numerous tumor cells labeled by EBER-1. Although disease was localized in 61% at diagnosis, there was no tendency to cure. The racial distribution of patients with T/NK-cell phenotype was similar to that found in B-cell lymphomas. EBV was more frequently found in adenoids than in palatine tonsils. In inflammatory lesions of the nasal and palatal regions EBV was not found. In the present study the relative frequency of T/NK versus B cell sinonasal lymphomas was high and similar to that observed in other Latin American countries. However, there was not any racial association with T/NK-cell phenotype and the tumor showed an agressive behavior similar to that reported in Asia. The high frequency of EBV-positive lymphocytes in nasopharyngeal lymphoid tissue (adenoids) suggests that they could serve as a reservoir for the virus.

Adult↗

Detection of Epstein-Barr virus in tonsillar tissue of children and the relationship with recurrent tonsillitis.

Recurrent tonsillitis has been the subject of much investigation. Events considered to predispose to or cause recurrent tonsillitis (RT) include the misuse of antibiotic therapy in acute bouts, alterations in the microflora, structural changes in crypt epithelium and certain viral infections. Epstein-Barr Virus (EBV) infection usually occurs in early childhood and can persist in palatine tonsil lymphocytes to induce tonsillitis at a later date. We have examined the presence of EBV in palatine tonsils in order to assess the relationship between this virus and recurrent acute tonsillitis. Tonsils were obtained from 85 patients, 2--14 years old (mean 5.6 years old) who underwent tonsils and adenoid (T&A) removal because of recurrent tonsillitis (RT) or T&A hypertrophy (TH). Tissues specimens were processed for non-isotopic in situ hybridization (ISH) using EBER 1/2 oligonucleotides (EBER RNA). The indications for surgery were RT in 42 patients and TH in 43 patients. In 25 out of 85 cases (29.4%) a positive EBER RNA reaction (15 RT and 33 TH) was found. The chi(2)-test showed no statistically significant difference in frequency of positive results between RT and TH group. We conclude that tonsils of children can be colonized by EBV and that the virus may be implicated in RT and TH.

Adolescent↗

p53, Mdm2, and c-Myc overexpression is associated with a poor prognosis in aggressive non-Hodgkin's lymphomas.

The expression of p53, p21/WAF-1, Mdm2, c-Myc, and proliferating cell nuclear antigen (PCNA) proteins was examined by the immunohistochemistry of paraffin-embedded tissues of 62 patients with aggressive non-Hodgkin's lymphomas (NHL) and correlated to clinical data. Expression of p53, p21/WAF-1, Mdm2, and c-Myc protein was observed in 17 out of 62 cases (30%), 25 out of 60 (42%), 13 out of 44 (30%), and 39 out of 51 (76.5%), respectively. The p53+/p21WAF-1 phenotype, which is more frequently found in p53 mutations, was associated with a worse overall survival (P = 0.04) and with a lower rate of complete response (CR) (PF = 0.01). p53 and c-Myc negative expression was related to a better response to chemotherapy (PF = 0.005 and 0.035, respectively). The expression of p53, c-Myc, and Mdm2 was related to a shortened overall survival (P < 0.001, 0.05, and 0.037, respectively), suggesting that the expression of these proteins could be associated with a poor outcome in these patients.

Actuarial Analysis↗

Antithyroid drugs inhibit in vivo HLA-DR expression in thyroid follicular cells in Graves' disease.

Antithyroid drugs have been reported to reduce the expression of HLA-DR in thyrocytes in Graves' disease, but only circumstantial evidence has been provided about their in vivo immunologic effects. This present study was designed to examine the in vivo immunologic effect of antithyroid drugs on thyroid follicular cells. The study was conducted on 25 patients who had Graves' disease in remission or in activity and who were or were not receiving treatment (7 in overt thyrotoxicosis, 6 patients in remission, and 12 patients under medication). HLA-DR expression in thyroid biopsies was verified by immunohistochemistry. The follicular cells of all patients in overt thyrotoxicosis expressed HLA-DR whereas those of patients in remission were negative for HLA-DR. HLA-DR was also not expressed in all patients under medication, but this did not correlate with the clinical evolution after thyroid drug withdrawal. In conclusion, antithyroid drugs inhibit follicular cell HLA-DR expression in Graves' disease, when thyrotoxicosis is controlled. This suggests that additional mechanisms not involving HLA-DR play a role in thyroid autoimmune disease.

Adult↗

CLO vs histology: optimal numbers and site of gastric biopsies to diagnose Helicobacter pylori.

OBJECTIVE: To determine the optimal numbers and sites of biopsies required for diagnosis of Helicobacter pylori by using the CLOtest and comparing the results with those of a routine histological assessment in a district general hospital (DGH) setting. METHODS: A prospective study comparing the sensitivity of the CLOtest containing one antral (CLO 1), two antral (CLO 2) and two antral and one body biopsy (CLO 3), and with histological examination for H. pylori. Consecutive patients undergoing upper gastrointestinal endoscopy (UGIE) at Stepping Hill Hospital, Stockport, UK, who had evidence of gastritis, gastric ulcer, duodenitis or duodenal ulcer were included in the study. RESULTS: Ninety-six patients were biopsied. Forty were positive on at least one of the CLOtests; of these, nine were negative on histological assessment. Of these nine, two were positive on all CLOtests and seven were positive only on CLO 3. One was positive on histology but negative on all CLOtests. This study showed that CLO 3 was more sensitive than CLO 1 (P = 0.004), CLO 2 (P = 0.016) and histology (P = 0.022). There was no significant difference between CLO 1 and CLO 2 (P = 0.500), CLO 1 and histology (P = 1.000), CLO 2 and histology (P = 1.00). CONCLUSION: We feel that in a busy clinical setting, taking two antral and one body biopsy in a single CLOtest is superior to routine histological assessment for the detection of H. pylori, with resulting cost saving.

Adult↗

High risk HPV and p53 protein expression in cervical intraepithelial neoplasia.

INTRODUCTION: Cervical intraepithelial lesions due to HPV infection are common in Brazil. An understanding of the mechanisms of the interaction between HPV and host factors is still incomplete. In spite of the high incidence of cervical cancer in Brazil, such studies with Brazilian patients are scarce. The purpose of this study was to correlate the presence of high-risk types of HPV and expression of p53 protein, grade of cervical lesion, age, high-risk sexual behaviors and smoking. It was also intended to establish whether p53 expression might be useful as a marker for CIN progression. METHODS: HPV detection was performed on paraffin sections using biotin-labeled probes by in situ hybridization. p53 protein expression was evaluated by immunohistochemistry. RESULTS: Seventy-eight patients with cervical dysplasia were included in the study. CIN 1 was diagnosed in 38 cases, and CIN 2+3 in 40 cases. High-risk HPV was detected in 42 patients. No correlation was found between the grade of cervical lesion or the presence of HPV and smoking, and high-risk sexual behavior. Expression of p53 was significantly higher in CIN 1, as compared with CIN 2+3, but did not correlate with HPV status. CONCLUSION: Higher expression of p53 protein in early lesions supports the hypothesis of a partially protective role of the wild-type p53 in early stages of cervical lesions.

Adolescent↗

Detection of human papillomavirus in laryngeal squamous dysplasia and carcinoma. An in situ hybridization and signal amplification study.

We examined the presence of human papillomavirus (HPV) DNA in 65 cases of laryngeal squamous dysplasia and carcinomas using in situ hybridization with signal amplification in paraffin sections. Hybridization was performed with biotinylated DNA probes for HPV 6/11, 16/18, 31/33 and wide-spectrum HPV (6, 11, 16, 30, 31, 45, 51 and 52). HPV DNA was found in 7 cases of the total sample (10.7%); it was also found in 4 out of 45 (8.8%) cases of invasive carcinoma and in 5 out of 33 (15.5%) cases of squamous dysplasia. Morphological signs suggestive of HPV infection were observed in 35.5% of our sample but they were not related to HPV DNA positivity. In conclusion, HPV probably plays little, if any, role in laryngeal carcinogenesis among the population studied.

Adult↗

Osteolytic lesions as a presenting sign of acute myeloid leukemia.

Osteolytic lesions rarely occur in acute myeloid leukemia (AML). We reported an atypical form of the disease, with marrow fibrosis and osteolytic lesions, in a 17-year-old patient, whose main symptom was lumbar pain. Diagnosis of AML was established by bone marrow and lymph node histological analysis. Computed tomography (CT) scan and 99mTc-MDP bone scintyscan revealed osteolytic lesions. After remission-induction, bone marrow aspirate and biopsy showed no evidence of leukemic infiltration, nevertheless bone abnormalities persisted on 99mTc-MDP bone scintyscan, suggesting residual disease. Suspect bone areas were irradiated with symptomatic improvement and 99mTc-MDP bone scintyscan showed the appearance of more condensed bone compared with the pre-radiotherapy pattern. Twelve months later he was readmitted to the hospital due to relapse of AML and died of sepsis within a few weeks. This report illustrates the usefulness of histological studies to establish diagnosis of AML in atypical cases, as well as the importance of CT scan and bone scintigraphy scan for the identification of osteolytic lesions. It also provides additional data as evidence that although osteolytic lesions indicate an adverse prognosis in AML, local irradiation results symptomatic relief.

Acute Disease↗

Autoimmune and non-autoimmune thyroid diseases have different patterns of cellular HLA class II expression.

CONTEXT: Surface HLA-DR antigen is usually only expressed by antigen-presenting cells (APC). In autoimmune thyroid disease, follicle cells function as APC, thus expressing HLA-DR. However, non-autoimmune thyroid diseases may also express surface class II antigens. OBJECTIVE: To evaluate the presence and pattern of HLA class II expression in autoimmune and non-autoimmune thyroid disorders. DESIGN: Retrospective: histopathological and immunohistochemical analysis. LOCATION: Referral center, university hospital. SAMPLE: Ten histologically normal thyroids, 11 Graves' disease, 7 Hashimoto's thyroiditis, 10 atoxic multinodular goiter and 3 toxic adenomas were analyzed by immunohistochemistry, using a monoclonal antibody anti-HLA-DR. MAIN MEASUREMENTS: The presence of these antigens in thyroid follicular cells and their relation to inflammatory infiltrate was evaluated. The pattern of HLA-DR expression in thyroid follicular cells was analyzed: membrane, cytoplasmic or both. RESULTS: Although HLA-DR antigens were sparsely present in one of the 8 normal thyroids, in 6 of the 9 atoxic multinodular goiter and in 2 of the 3 toxic adenomas a net positivity could be seen in large areas. In all 5 Hashimoto's thyroiditis and in 7 of the 10 Graves' disease cases. This expression occurred in follicle cells either in contact with inflammatory cells or not. In non-autoimmune thyroid disease, HLA-DR positivity was essentially cytoplasmic, whereas in Graves' disease and Hashimoto thyroiditis it was mainly in cell membranes. CONCLUSIONS: It is suggested that the HLA class II expression on the surface of follicle cells could be related to auto-antigen presentation to the immune system by these cells, leading to inflammation.

Antibodies, Monoclonal↗

Evidence of integrity of the follicular basement membrane in Hashimoto's thyroiditis.

The basement membrane as an antigenic structure in autoimmune diseases has been a matter of controversy. The purpose of our study was to determine possible structural changes in the follicular basement membrane (FBM) in thyroid autoimmune and non-autoimmune diseases. Immunohistochemical staining for collagen IV and laminin showed that the continuity of the FBM was preserved in toxic adenoma (three cases), atoxic multinodular goiter (nine cases) as well as in autoimmune disease. Integrity of the FBM was observed in all 11 cases of Graves' disease and Hashimoto's thyroiditis (seven cases) studied. In some instances, the FBM was thinned in areas of contact with inflammatory infiltrate. We conclude that the auto-antibodies, and possibly other factors present in autoimmune thyroid diseases, do not significantly alter the integrity of the FBM.

Adenoma↗