Identification of Growth Hormone Receptor in Plexiform Neurofibromas of Patients with Neurofibromatosis Type 1

OBJECTIVE: The aim of this study was to investigate the presence of growth hormone receptor in plexiform neurofibromas of neurofibromatosis type 1 patients. INTRODUCTION: The development of multiple neurofibromas is one of the major features of neurofibromatosis type 1. Since neurofibromas commonly grow during periods of hormonal change, especially during puberty and pregnancy, it has been suggested that hormones may influence neurofibromatosis type 1 neurofibromas. A recent study showed that the majority of localized neurofibromas from neurofibromatosis type 1 patients have growth hormone receptor. METHODS: Growth hormone receptor expression was investigated in 5 plexiform neurofibromas using immunohistochemistry. RESULTS: Four of the 5 plexiform neurofibromas were immunopositive for growth hormone receptor. CONCLUSION: This study suggests that growth hormone may influence the development of plexiform neurofibromas in patients with neurofibromatosis type 1

Oral hairy leukoplakia: histopathologic features of the subclinical stage

A leucoplasia pilosa oral (LPO) é uma das manifestações orais mais comuns na AIDS, com valor diagnóstico e prognóstico. A LPO está relacionada ao Epstein-Barr vírus (EBV), com características clínicas e histopatológicas definidas. Já existem relatos de uma fase subclínica da LPO, porém sem caracterização histopatológica. O presente trabalho teve por objetivo descrever os aspectos histopatológicos desta fase, bem como realizar uma análise comparativa entre a LPO subclínica e clínica, com a finalidade de verificar a suficiência diagnóstica dos critérios histopatológicos. Trata-se de um estudo retrospectivo de 11 casos, obtidos a partir de cinco biópsias realizadas em pacientes com lesão e da borda de seis línguas sem lesão macroscopicamente detectável, provenientes de necropsias. Foram utilizados os seguintes métodos: histopatologia, imuno-histoquímica e hibridização in situ. Os aspectos histopatológicos que caracterizaram a fase subclínica da LPO foram: ausência de paraceratose e papilomatose, acantose leve, presença de células claras e alterações nucleares (inclusão tipo Cowdry A, núcleo em "vidro fosco" e núcleo "em colar"). Houve identificação do EBV através da hibridização in situ e da imuno-histoquímica nas alterações nucleares observadas na histopatologia. Concluiu-se, com fundamentos na identificação do EBV nas alterações nucleares, que a LPO em sua fase subclínica, da mesma forma que na lesão clínica, apresenta características histopatológicas específicas e suficientes para um diagnóstico definitivo, independentemente da identificação do EBV.Oral hairy leukoplakia (OHL) is one of the most common oral manifestations of AIDS, with diagnostic and prognostic value. OHL is associated to the Epstein-Barr virus and presents clinical and histological defined characteristics. There have already been reports about a subclinical stage of OHL, although they lacked histopathologic characterization. The present study had the aim to describe the histopathological characteristics of subclinical hairy leukoplakia, as well as to carry out a comparative analysis between clinical and subclinical OHL. For that, 11 cases were analyzed - 5 biopsies from patients who presented with the lesion and 6 samples from the borders of tongues obtained in necropsies. The histopathological findings in subclinical OHL were: absence of parakeratosis and papillomatosis, mild acanthosis, ballooning cells and nuclear alterations. In situ hybridization and immunostaining were positive for EBV in the nuclear alterations identified in the histophatological analysis. Based on the identification of EBV in the nuclear alterations, it was possible to conclude that subclinical OHL, similarly to the clinical lesion, presents histopathological features that are specific and sufficient to establish the definitive diagnosis, regardless of the identification of the virus

Immunoexpression of cleaved caspase-3 shows lower apoptotic area indices in lip carcinomas than in intraoral cancer

Objective This study aimed to evaluate apoptosis by assessing cleaved caspase-3 immunoexpression in hyperplastic, potentially malignant disorder (PMD), and malignant tumors in intraoral and lower lip sites. Material and Methods A retrospective study using paraffin blocks with tissues from patients with inflammatory fibrous hyperplasia (IFH), actinic cheilitis, oral leukoplakia, lower lip and intraoral squamous cell carcinoma (SCC) was performed. The tissues were evaluated by immunohistochemical analysis with anti-cleaved caspase-3 antibody. Apoptotic area index was then correlated with lesion type. Results From 120 lesions assessed, 55 (46%) were cleaved caspase-3-positive. The SCC samples (n=40) had the highest apoptotic area indices (n=35; 87.5%). Significant differences were detected between SCCs and PMDs (p=0.0003), as well as SCCs and IFHs (p=0.001), regarding caspase-3 immunopositivity. Carcinomas of the lower lip had lower apoptotic area indices than intraoral cancer (p=0.0015). Conclusions Cleaved caspase-3 immunoexpression showed differences in oral SCCs and PMDs and demonstrated a distinct role of apoptosis in carcinogenesis of intraoral and lower lip cancer. In future, the expression of cleaved caspase-3 with other target molecules in oral cancer may be helpful in delineating the prognosis and treatment of these tumors

Análise histopatológica comparativa entre líquen plano oral e cutâneo Comparative histopathological analysis between oral and cutaneous lichen planus

INTRODUÇÃO: Líquen plano é uma doença inflamatória crônica relativamente comum que acomete pele e membranas mucosas, separadamente ou em combinação. Freqüentemente envolve a cavidade oral, com ou sem comprometimento cutâneo concomitante. Microscopicamente, enquanto a pele apresenta aspectos bastantes característicos, a mucosa oral pode apresentar variações relacionadas às características locais da mucosa na cavidade oral. OBJETIVOS: Comparar as alterações histopatológicas do líquen plano oral (LPO) com as do líquen plano cutâneo (LPC), estudando os componentes do infiltrado inflamatório. MATERIAL E MÉTODOS: 59 biópsias (29 de LPO e 30 de LPC ) fixadas em formol e incluídas em blocos de parafina. Foi realizada análise semiquantitativa das alterações epidérmicas e dérmicas utilizando-se as colorações de hematoxilina-eosina e ácido periódico Schiff. RESULTADOS: No LPC foram observados os aspectos clássicos de ortoceratose, hipergranulose em cunha e acantose em dente de serra. Tais aspectos diferem do LPO, no qual ortoceratose e camada granulosa espessada ocorrem com menos freqüência, observando-se aquisição destas camadas nos locais onde estão normalmente ausentes. Vacuolização e apagamento do limite epitélio-conjuntivo predominaram nas duas localizações (pele e mucosa oral), e linfócitos e histiócitos foram as células inflamatórias presentes em todos os casos. CONCLUSÕES: O conjunto de alterações clássicas como ortoceratose compacta, hipergranulose em cunha, acantose em dente de serra e vacuolização da basal, associadas a linfócitos em faixa superficial é diagnóstico de LPC. Para o LPO, no entanto, devem ser consideradas as características próprias da mucosa no local biopsiado, devendo ser valorizadas alterações mais sutis da camada córnea - leve ortoceratose - e aparecimento da camada granulosa em locais onde normalmente é ausente. Aspecto em cunha da hipergranulose é de ocorrência rara no LPO. Acantose em dente de serra é achado pouco freqüente no LPO, porém vacuolização basal está sempre presente associada a infiltrado linfocitário em faixa; plasmócitos podem acompanhar linfócitos no LPO, mas estão ausentes do LPC.<br>BACKGROUND: Lichen planus is a relatively common chronic inflammatory disease affecting skin and mucous membranes, separately or together. It frequently involves the oral cavity, with or without concomitant cutaneous compromise. Microscopically, while skin presents well characteristic aspects, oral mucosa can present variations related to local characteristics of the mucosa in the oral cavity. OBJECTIVES: To compare histopathological alterations of oral lichen planus and cutaneous lichen planus with the study of the inflammatory infiltrate components. METHODS: 59 biopsies (29 of OLP and 30 of CLP), formalin-fixed, paraffin-embedded were studied. Semi-quantitative analysis of both epidermal and dermal alterations was performed using the hematoxylin-eosin and periodic acid-Schiff stains. RESULTS: For CLP the classic aspects of orthokeratosis, wedge shaped hypergranulosis and saw tooth rete ridges were observed. Such aspects differ from those of OLP in which orthokeratosis and thickened granular layer happen less frequently; instead, acquisition of those layers is observed in places where they are usually absent. Basal cell vacuolar alteration and effacement of the epithelium-conjunctive limit prevailed in both locations (skin and oral mucosa) and lymphocytes and histiocytes were the inflammatory cells present in all cases. CONCLUSIONS: Classic alterations as compact orthokeratosis, wedge shaped hypergranulosis, saw tooth rete ridges acanthosis and basal cell vacuolar alteration associates to lymphocytes in superficial band-like pattern are diagnostic of CLP. However, for OLP, the particular own characteristics of oral mucosa in the biopsied place should be considered; also, subtler alterations of horny (light orthokeratosis) and granular (presence where it is usually absent) layers should be valued . Wedge shape pattern of hypergranulosis is rarely seen in OLP. Saw tooth rete ridges acanthosis is not frequently seen in OLP, however, basal cell vacuolar alteration is always present and associated to band-like lymphocitic infiltrate. Plasma cells can accompany lymphocytes in OLP, however, they are absent in CLP

Investigação da LMP1 do EBV e a coinfeçcão do HPV em lesões genitais de pacientes infectados ou não pelo HIV Investigation of the LMP1 EBV and co-infection by HPV in genital lesions of patients infected or not by HIV

INTRODUÇÃO: Vários estudos têm demonstrado associação do vírus Epstein-Barr (EBV) com neoplasias malignas, inclusive genitais, em que o papilomavírus humano (HPV) é o principal vírus associado às neoplasias epiteliais benignas e malignas. OBJETIVO: Investigar a presença do EBV e do HPV em lesões genitais de ambos os sexos, em pacientes soropositivos (grupo A) ou não (grupo B) para o vírus da imunodeficiência humana (HIV). MATERIAL E MÉTODO: Selecionados 126 pacientes e 135 lesões anogenitais, sendo 67 pacientes (53%) e 75 lesões (56%) no grupo A e 59 pacientes (47%) e 60 lesões (44%) no grupo B, para análise imuno-histoquímica (IHQ) por meio dos anticorpos monoclonais antiproteína latente de membrana 1 (LMP1) e HPV (DAKO®). RESULTADOS: A análise mostrou que o número total de lesões com imunopositividade para o HPV e para a LMP1 foi maior no grupo A (32 e 35, respectivamente) quando comparado ao B (16 e seis, respectivamente). A análise estatística (nível de significância de 5%) mostrou que as proporções para o HPV não são estatisticamente significativas (z = 1,93; valor p = 0,053). Entretanto, para a LMP1, a diferença (47% no grupo A e 10% no B) é significativa (z = 4,60; valor p = 4,2×10-6). Do mesmo modo, a associação HPV-LMP1 (21% no grupo A e 7% no B) também mostrou diferença estatisticamente significativa (z = 2,38; valor p = 0,017). CONCLUSÃO: Esses resultados indicam a possibilidade de sinergismo da infecção pelo EBV e a coinfecção EBV-HPV em lesões epiteliais genitais, particularmente em pacientes soropositivos para o HIV. Entretanto, investigações com metodologia de maior especificidade e sensibilidade são necessárias para a verificação da real participação do EBV na patogênese de lesões epiteliais genitais.<br>INTRODUCTION: Several studies have demonstrated the association between Epstein-Barr virus (EBV) and malignant neoplasias, including genital lesions, in which the human papillomavirus (HPV) is the main virus associated with both benign and malignant epithelial neoplasias. OBJECTIVE: Investigate the presence of EBV and HPV in genital lesions in HIV-infected patients (group A) or HIV non-infected patients (group B) from both genders. MATERIAL AND METHOD: We selected 126 patients and 135 anogenital lesions, comprising 67 patients (53%) and 75 lesions (56%) from group A and 59 patients (47%) and 60 lesions (44%) from group B, to histopathological and immunohistochemical analyses through latent membrane protein 1 (LMP1) monoclonal antibodies and HPV (DAKO®). RESULTS: The analysis showed that the total number of lesions with immunopositivity for HPV and for LMP1 was higher in group A (32 and 35 respectively) in comparison with B (16 and six respectively). Statistical analysis (significance level of 5%) showed that the proportions for HPV are not statistically significant (z = 1.93; value p = 0.053). However, the difference (47% in group A and 10% in B) is significant for LMP1 (z = 4.60; value p = 4.2×10-6). Similarly, the association of HPV and LMP1 (21% in group A and 7% in B) also showed a significant statistical difference (z = 2.38; value p = 0.017). CONCLUSION: The results demonstrated the possibility of synergism between EBV infection and EBV-HPV co-infection in genital epithelial lesions, mainly among HIV-infected patients. However, further investigations with a more specific and sensitive methodology are required in order to assess the real influence of EBV on the pathogenesis of genital epithelial lesions

Is the thymus a target organ in infectious diseases?

The thymus is a central lymphoid organ, in wich T cell precursors differentiale and generate most of the so-called T cell reprtoire. Along with a variety of acute infectious diseases, we and others determined important changes in both microenvironmental and lymphoid compartments of the organ. For example, one major and common feature observed in acute viral, bacterial and parasitic diseases, is a depletion of cortical thymocytes, mostly those bearing the CD4-CD8 double positive phenotype. This occurs simmultaneously to the relative enrichment in medullary CD4 or CD8 single positive cells, expressing high densities of the CD3 complex. Additionally we noticed a variety of changes in the thymic microenvironment (and particularly is epithelial component), comprising abnormal location of thymic epithelial cell subsets as well has a denser Ia-bearing cellular network. Moreover, the extracellular matrix network was altered with an intralobular increase of basement membrane proteins that positively correlated with the degree of thymocyte death. Lastly, anti-thymic cell antibodies were detected in both human and animal models of infectious diseases, and in some of them a phenomenon of molecular mimicry could be evidenced. Taken together, the data receiwed herein clearly show that the thymus should be regarded as a target in infectious diseases

Immunoexpression of cleaved caspase-3 shows lower apoptotic area indices in lip carcinomas than in intraoral cancer

ABSTRACT Objective This study aimed to evaluate apoptosis by assessing cleaved caspase-3 immunoexpression in hyperplastic, potentially malignant disorder (PMD), and malignant tumors in intraoral and lower lip sites. Material and Methods A retrospective study using paraffin blocks with tissues from patients with inflammatory fibrous hyperplasia (IFH), actinic cheilitis, oral leukoplakia, lower lip and intraoral squamous cell carcinoma (SCC) was performed. The tissues were evaluated by immunohistochemical analysis with anti-cleaved caspase-3 antibody. Apoptotic area index was then correlated with lesion type. Results From 120 lesions assessed, 55 (46%) were cleaved caspase-3-positive. The SCC samples (n=40) had the highest apoptotic area indices (n=35; 87.5%). Significant differences were detected between SCCs and PMDs (p=0.0003), as well as SCCs and IFHs (p=0.001), regarding caspase-3 immunopositivity. Carcinomas of the lower lip had lower apoptotic area indices than intraoral cancer (p=0.0015). Conclusions Cleaved caspase-3 immunoexpression showed differences in oral SCCs and PMDs and demonstrated a distinct role of apoptosis in carcinogenesis of intraoral and lower lip cancer. In future, the expression of cleaved caspase-3 with other target molecules in oral cancer may be helpful in delineating the prognosis and treatment of these tumors