Study of MDM2 and SUMO-1 expression in actinic cheilitis and lip cancer

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Immunocytochemistry associated with oral exfoliative cytology methodological analysis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Evaluation of dentists' knowledge of the use of oral exfoliative cytology in clinical practice

Oral exfoliative cytology (EC) is a rapid and practical complementary test that can be used in the diagnosis of various diseases. The objectives of this study were to assess dentists'knowledge of EC and to disseminate information on the technique. The study included 240 dentists from the city of Anapolis (Goias, Brazil) who answered a questionnaire regarding demographic data and data relating to EC and who then received information on the technique. The data revealed that 26.92% of the dentists did not know about EC. Among those who reported knowledge of EC, 33.91% did not know the procedures for performing the technique, and 85.38% had no experience with EC. In addition, 54.09% of the answers regarding the instrument used to collect the material and 56.82% of the answers concerning suitable fixatives were inappropriate. Although 73.02% of the dentists adequately identified the pathologies for which EC is recommended, it was concluded that the respondents had poor knowledge of EC. There is a need to increase dentists'awareness of this subject and of EC's use in diagnostic practices.

Crystal structure of Staphylococcus aureus exfoliative toxin D-like protein: structural basis for the high specificity of exfoliative toxins

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Actinic Cheilitis: epidemiological study in a riverine population of northern Brazil

AIM: The aim of this survey was to assess the prevalence of AC in riverine population in countryside of Amazonas, northern Brazil. MATERIAL AND METHODS: Patients answered a questionnaire and were examined between January and December of 2008. Data were gathered on the following participant’s characteristics: 1) age group; 2) gender; 3) ethnicity 4) outdoor activities (sunlight exposure); 5) smoking habits; 6) drinking habits; and 7) access to oral health services (the last dental visit). Clinical observation of the lips for determination of AC presence was used. Patients who presented clinical manifestation of moderate and severe AC were submitted to incisional biopsy to confirm the diagnosis. In case of a positive result after histopathological examination, patients were advised and appropriate treatment was offered. All patients received information about AC and its'prevention. RESULTS: Among the 200 participants that were examined, the prevalence of AC was 2% (4 cases). Of all patients surveyed, women were the majority totalizing 124 patients (72.0%). According to age, 48 (24.0%) people were 20g34 yeargold; 42 (21.0%) were 35g44gyeargold; 50 (25.0%) were 45g60gyeargold; and 60 (30.0%) were 61 or older. CONCLUSION: Even though AC was present in a low prevalence rate, an epidemiological variety is expected, once geographic and ethnic differences should be considered.

Photodynamic therapy in actinic cheilitis: clinical and anatomopathological evaluation of 19 patients

BACKGROUND: Actinic cheilitis, a common disease caused by chronic solar exposure and tobacco use, is considered a premalignant lesion with potential to develop into squamous cell carcinoma. Some of the available treatments are invasive, have unaesthetic results and require multiple sessions. OBJECTIVE: To assess the efficacy of a therapy and its cosmetic results. METHODS: In this uncontrolled clinical trial a single photodynamic therapy (PDT) session using 16% methyl-aminolevulinate was performed on actinic cheilitis of the lower lip. A standardized questionnaire was applied in order to assess the clinical improvement from the patients' point of view and the satisfaction with the treatment. Anatomopathological evaluation was performed before the treatment and two months afterwards. RESULTS: The sample was composed of 19 patients (10 males and 9 females), phototypes I to III, with average age of 62 years. Main adverse effects were: sudden pain, scabs, herpes flare-up, and edema. The average score of pain during the procedure was 5,8+2,9. At the final assessment the patients reported improvement of 80% and satisfaction of 85% (p<0.01). Anatomopathological analysis showed a significant decrease of dysplasia (p=0.03) in spite of its presence in 84% of cases. There was no significant correlation between the level of dysplasia with either the subjective impression of clinical improvement (p=0.82) or with the patients' final satisfaction (p=0.96). CONCLUSION: PDT is effective in the treatment of actinic cheilitis, but it is associated with a significant level of pain. Due to the persistence of dysplasia, more research needs to be done in order to define the ideal number of sessions for the effective treatment of these lesions.

Expression of laminin-5 and integrins in actinic cheilitis and superficially invasive squamous cell carcinomas of the lip

The progression of carcinogenesis entails the detachment of cells, invasion and migration of neoplastic cells. Alterations in epithelial adhesion and basement membrane proteins might mediate the early stages of carcinogenesis. This study investigated the expression of adhesion molecules and the basement membrane protein laminin-5 in actinic cheilitis (AC) and incipient squamous cell carcinoma of the lower lip to understand early photocarcinogenesis. Ln-5 gamma 2 chain as well as alpha 3, beta 1 subunits of alpha 3 beta 1 heterodimer and beta 4 subunit of integrin alpha 6 beta 4 were evaluated by immunohistochemistry in 16 cases of AC and 16 cases of superficially invasive squamous cell carcinoma (SISCC). Most AC cases showed reduced expression of beta 1, beta 4 and alpha 3 integrins, and SISCCs lacked beta 1, beta 4 and alpha 3 integrins in the invasive front. AC cases were negative for the Ln-5 gamma 2 chain. Five cases of SISCC (31%) showed heterogeneous Ln-5 gamma 2 chain expression in the invasive front of the tumor. Integrin beta 1, beta 4 and alpha 3 expression is lost during the early stages of lip carcinogenesis. Expression of Ln-5 gamma 2 in the invasive front in cases and its correlation with tumor progression suggest that it mediates the acquisition of the migrating and invading epithelial cell phenotype. (C) 2012 Elsevier GmbH. All rights reserved.

Nonthymoma-associated exfoliative dermatitis in 18 cats.

BACKGROUND Exfoliative dermatitis has been described in cats as a paraneoplastic skin disease associated with thymoma. There are anecdotal reports of cases without thymoma, with various suspected aetiologies. HYPOTHESIS/OBJECTIVES To identify common features, underlying causes, response to therapy and outcome of nonthymoma-associated exfoliative dermatitis in cats. METHODS Retrospective analysis was carried out of cases presented to dermatology referral centres or cases submitted for histopathological examination. Detailed historical and clinical data were obtained and evaluated statistically. Histopathology was reviewed in a blinded fashion by three dermatopathologists, and PCR for herpesvirus was performed. RESULTS Eighteen cats fulfilled all inclusion criteria. There was no sex, age or breed predisposition. All cats presented with severe generalized (77%) or multifocal exfoliation (23%); 12 cats were severely depressed. In all cats, thymoma was excluded radiographically and feline leukaemia virus tests were negative. Additional imaging procedures in 14 cats and postmortem examination in two cats did not detect neoplasia. Histopathology revealed interface dermatitis, mural interface folliculitis and sebaceous adenitis indistinguishable from findings in thymoma-associated cases. PCR for herpes DNA was negative. No aetiology was identified. Treatment in 12 cases consisted of immunosuppressive doses of corticosteroids and/or ciclosporin; one responded to antibiotics, one to shampoo, two went into spontaneous remission, and two did not receive any therapy and were euthanized. CONCLUSIONS AND CLINICAL IMPORTANCE Nonthymoma-associated exfoliative dermatitis in cats is clinically and histopathologically indistinguishable from thymoma-associated cases. Most cases benefit from immunosuppressive therapy; therefore, an immunopathological response to an undefined trigger is suspected.

Peripheral facial palsy : Grading, Etiology, and Melkersson-Rosenthal Syndrome

The objective of this study was to assess the utility of two subjective facial grading systems, to evaluate the etiologic role of human herpesviruses in peripheral facial palsy (FP), and to explore characteristics of Melkersson-Rosenthal syndrome (MRS). Intrarater repeatability and interrater agreement were assessed for Sunnybrook (SFGS) and House-Brackmann facial grading systems (H-B FGS). Eight video-recorded FP patients were graded in two sittings by 26 doctors. Repeatability for SFGS was from good to excellent and agreement between doctors from moderate to excellent by intraclass correlation coefficient and coefficient of repeatability. For H-B FGS, repeatability was from fair to good and agreement from poor to fair by agreement percentage and kappa coefficients. Because SFGS was at least as good in repeatability as H-B FGS and showed more reliable results in agreement between doctors, we encourage the use of SFGS over H-B FGS. Etiologic role of human herpesviruses in peripheral FP was studied by searching DNA of herpes simplex virus (HSV) -1 and -2, varicella-zoster virus (VZV), human herpesvirus (HHV) -6A, -6B, and -7, Epstein-Barr virus (EBV), and cytomegalovirus (CMV) by PCR/microarray methods in cerebrospinal fluid (CSF) of 33 peripheral FP patients and 36 controls. Three patients and five controls had HHV-6 or -7 DNA in CSF. No DNA of HSV-1 or -2, VZV, EBV, or CMV was found. Detecting HHV-7 and dual HHV-6A and -6B DNA in CSF of FP patients is intriguing, but does not allow etiologic conclusions as such. These DNA findings in association with FP and the other diseases that they accompanied require further exploration. MRS is classically defined as a triad of recurrent labial or oro-facial edema, recurrent peripheral FP, and plicated tongue. All three signs are present in the minority of patients. Edema-dominated forms are more common in the literature, while MRS with FP has received little attention. The etiology and true incidence of MRS are unknown. Characteristics of MRS were evaluated at the Departments of Otorhinolaryngology and Dermatology focusing on patients with FP. There were 35 MRS patients, 20 with FP and they were mailed a questionnaire (17 answered) and were clinically examined (14 patients). At the Department of Otorhinolaryngology, every MRS patient had FP and half had the triad form of MRS. Two patients, whose tissue biopsies were taken during an acute edema episode, revealed nonnecrotizing granulomatous findings typical for MRS, the other without persisting edema and with symptoms for less than a year. A peripheral blood DNA was searched for gene mutations leading to UNC-93B protein deficiency predisposing to HSV-1 infections; no gene mutations were found. Edema in most MRS FP patients did not dominate the clinical picture, and no progression of the disease was observed, contrary to existing knowledge. At the Department of Dermatology, two patients had triad MRS and 15 had monosymptomatic granulomatous cheilitis with frequent or persistent edema and typical MRS tissue histology. The clinical picture of MRS varied according to the department where the patient was treated. More studies from otorhinolaryngology departments and on patients with FP would clarify the actual incidence and clinical picture of the syndrome.

Lesões orais com potencial de malignização: análise clínica e morfológica de 205 casos

Silveira , E. J. D. et al. Lesões orais com potencial de malignização: análise clínica e morfológica de 205 casos. J. Bras. Patol. Med. Lab., v. 45, n. 3, p. 233-238, jun 2009. ISBN 1676-2444.

Prevalência e fatores associados a lesões labiais e periorais decorrentes da exposição solar em trabalhadores de praia

This study aimed to verify the prevalence of lip and perioral lesions in worker who were under sunshine on the beaches of Natal/RN and to investigate possible associations of these with sociodemographic, occupational and general health variables. For this, 362 individuals who had one of the urban beaches (Ponta Negra / Environment / Redinha) in the city of Natal/RN as a working environment in the study. We excluded people under 18 years old. Data collection was done through epidemiological analysis and extra-oral validated questionnaire with questions that characterize socioeconomic and demographic factors, occupational exposure and general health. The male subjects (72.6%) were the majority in the sample. The people who worked directly exposed to high peaks of ultraviolet radiation, as well as informal workers predominated. Considering the total sample of individuals, ephelides in the perioral region (33.7%) and labial region (24.0%), solar lentigo perioral (15.2%) and actinic cheilitis (13.8%) stood out as the most prevalent lesions. Indoor workers and those who had a habit occurrence of injuries by 19% and 21% respectively higher when compared to outdoor workers and people without habits. The variable use of cap / hat was associated with the presence of cold sores (Qui2 = 1,328, p = 0,058). On the threshold of significance, the type of work was also associated with lesions in lip occurrence (p = 0,042). Men showed a lower incidence of perioral lesions when compared to female workers (PR=0,716, p valor = 0,002). The present study showed high prevalence of lip and perioral lesions. The premalignant lesions were the most identified, both as in lip skin. It is important therefore to be encouraged to adopt protective measures against excessive sun exposure, fairly and consistently

Análise comparativa da imunoexpressão das proteínas hmlh1 e hmsh2 em carcinomas epidermóides de lábio inferior e queilites actínicas com graus variados de displasia

Lip squamous cell carcinoma (SCC) may develop from a premalignant condition, actinic cheilitis (AC) in 95% of the cases. Both premalignant and neoplastic lip diseases are caused mainly by chronic exposure to the ultraviolet component of solar radiation, especially UVB. This exposure causes disruption of the cell cycle and damage to DNA repair systems, like mismatch repair, altering proteins repair as hMLH1 and hMSH2. This research aimed to investigate the immunohistochemical expression of hMLH1 and hMSH2 proteins in lower lip SCCs and ACs, providing additional information about carcinogenesis of the lower lip. The sample consisted 40 cases of ACs and 40 cases of lower lip SCCs. Histological sections of 3 μm were submitted to immunoperoxidase method, for immunohistochemical analysis of lesions were counted in 1000 cells (positive and negative), data were evaluated both in absolute numbers and percentage of immunostained cells, the latter by assigning scores. Associations of the variables and comparative analysis of biomarker expression were performed by Fisher s exact and Pearson s chi-square, "t" student, one-way ANOVA, Mann- Whitney e Kruskal-Wallis tests. The level of significance was 5%. It was found that, in lower lip SCC, the mean of the proteins was higher in female patients (hMLH1= 369,80 + 223,98; hMHS2 = 534,80 + 343,62), less than 50 years old (hMLH1 = 285,50 + 190,65; hMHS2 = 540,00 + 274,79) and classified as low-grade malignancy (hMLH1 = 264,59 + 179,21; hMHS2 = 519,32 + 302,58), in these data only to sex, for hMLH1 protein, was statistically significant (p=0.034). Comparing the different lesions, we observed that for both hMLH1 and hMSH2 protein, the average of positive epithelial cells decreased as the lesion was graded at later stages. The ACs classified without dysplasia or mild dysplasia had the highest average of immunostained cells (hMLH1 = 721.23 + 88.116; hMHS2 = 781.50 + 156.93). The ACs classified as moderate or severe dysplasia had intermediate values (hMLH1 = 532,86 + 197,72; hMHS2 = 611,14 + 172,48) and SSCs of the lower lip had the lowest averages (hMLH1 = 255,03 + 199,47; hMHS2 = 518,38 + 265,68). There was a statistically significant difference between groups (p<0.001). In conclusion, our data support the hypothesis that changes in immunoexpression of these proteins is related to the process of carcinogenesis of the lower lip

Mycobacterium DNA detection in liver and skin of a horse with generalized sarcoidosis

Sarcoidosis is a rare equine skin disease characterized primarily by an exfoliative and granulomatous dermatitis but also presenting granulomatous inflammation of multiple systems. The current report presents the clinical and histopathological findings of sarcoidosis in a 16-year-old American Quarter Horse gelding with nested polymerase chain reaction Mycobacterium spp. DNA detection within hepatic and skin samples. Mycobacterium spp. may play a role in the pathogenesis of equine sarcoidosis as has been proposed for human sarcoidosis.

Imunomarcação de células CD3+ e CD79a+ nas lesões descamativas e ulcerativas de cães com leishmaniose

Canine visceral leishmaniasis is an endemic infectious disease in some regions from São Paulo state and even though it is a systemic disease, in the dog, the main clinical sign is dermatological. Thirty dogs with positive results in serology (IFI) and parasitological exams (fine needle aspiration) for leishmaniasis from Aracatuba city were evaluated. They only showed dermatological signs and were divided in two groups, one with exfoliative (n=15) and other with ulcerative (n=15) lesions. There was significant statistical difference between CD3 and CD79a population in the same dermatological pattern, and with CD79a population between exfoliative and ulcerative patterns (p<0,05).

Padrões histopatológicos das lesões descamativas e ulcerativas da pele em cães com leishmaniose

Canine visceral leishmaniasis is an endemic infectious disease in some São Paulo state regions and even though it is a systemic disease, in the dog, the main clinical sign is dermatological. Thirty dogs with positive results in serology and parasitological exams for leishmaniasis from Aracatuba city were evaluated. They just showed dermatological signs and were divided in two groups, one with exfoliative(n = 15) and other with ulcerative (n = 15) lesions. Histopathological. patterns in the group of exfoliative lesions were: periadnexial dermatitis (5115, 33,3%), superficial perivascular dermatitis (1/5, 6,6%), nodular dermatitis (1115, 6,6%) and mixed dermatitis (8/15, 53,3%), including intersticial/periadnexial dermatitis (1/8, 12,5%). lichenoid/perivascular superficial and deep dermatitis (1/8, 12,5%), perivascular superficial and deep/periadnexial dermatitis (1/8, 12,5%) and superficial perivascular/perianexial dermatitis (5/8, 62,5%). In the group of ulcerative lesions, the histopathological patterns were: perivascular superficial and deep dermatitis (5115, 33,3%), diffuse dermatitis (3/15. 20%), periadnexial dermatitis (2/15, 13,3%), nodular dermatitis (1/15, 6,6%) and mixed dermatitis (4/15, 26,6%), including intersticial/perivascular superficial and deep dermatitis (1/4, 25%), nodular/periadnexial dermatitis (1/4, 25%), fibrosing/perianexial dermatitis (1/4. 25%) and perivascular superficial and deep/periadnexial dermatitis(1/4, 25%). Parasites were found in eight dogs (8/15, 53,3%) with exfoliative dematitis and seven (7/15, 46,6%) with ulcerative dermatitis.