Focal melanocytic lesions of the oral mucosa: An epidemiological and morphological study.

OBJECTIVE: This study aimed to analyse the clinical and histopathological characteristics of focal oral melanocytic lesions in a Brazilian reference service in Oral and Maxillofacial Pathology. MATERIALS AND METHODS: A cross-sectional study was conducted over an 18-year period. Demographic data and clinical features were collected from the archives, and all biopsy specimens diagnosed as oral melanocytic lesions were retrieved and reviewed. RESULTS: We identified 339 melanocytic lesions. Of these, 191 were melanotic macules, 112 melanocytic nevi, 14 mucosal lentigo simplex, 12 melanomas, 9 solar lentigos, and 1 melanoacanthoma. Lesions occurred mostly in white-skinned (74.2%) women (65.2%). The main reported clinical aspect was the macule (67.4%), and the most affected site was the lip vermilion (25.4%), followed by the palate (22.9%). Melanomas were larger in size and were observed in older patients with an overall shorter time of onset. The most frequent subtypes of melanocytic nevi were intramucosal (44.6%), compound (24.1%), and blue nevus (20.5%). They showed a heterogeneous architectural pattern with the presence of the three cell types. CONCLUSION: The most frequent lesions are melanotic macule and nevus, especially the intramucosal subtype. Patients are usually white-skinned women presenting a small, long-lasting, macular lesion on the lip vermilion or palate.

Oral manifestations of autoimmune polyglandular syndrome type 1.

AIMS: Autoimmune polyglandular syndrome type I (APS-I) is a rare condition of autosomal recessive and monogenic inheritance, which is characterized clinically by at least two signs of the classic triad: mucocutaneous candidosis, hypoparathyroidism, and Addison's disease. This study aims to report the oral manifestations of APS-I in a 42-year-old woman, who attended the Special Care Dentistry Center. METHODS AND RESULTS: The patient presented with hypoparathyroidism, diabetes mellitus, and autoimmune hepatitis. Chronic hyperplastic candidosis (CHC) was the main oral manifestation and it was diagnosed based on clinical and cytologic characteristics. Microstomia, angular cheilitis, xerostomia, enamel hypoplasia, and microdontia were also present. CONCLUSIONS: CHC was treated with topical nystatin and oral fluconazole, resulting in a significant improvement of the lesions.

Acurácia da análise da discrepância de Bolton proposta por método manual e digital com softwares ortodônticos / ccuracy of Bolton discrepancy analysis proposed by manual and digital method with orthodontic software

objetivo desse estudo foi avaliar o desempenho diagnóstico da Análise da Discrepância de Bolton (DB) anterior e total proposta pelo programa ClinCheck®, bem como dos softwares ortodônticos Dolphin Imaging® e 3D Slicer, comparado com mensurações manuais realizados em modelos impressos tridimensionalmente. Cinquenta e cinco pares de modelos digitais da fase inicial de pacientes tratados com sistema Invisalign® (Align, San Jose, Califórnia, EUA) foram impressos tridimensionalmente por estereolitografia e usados para mensuração da DB por método manual, com paquímetro digital, por um operador previamente calibrado. Os valores da DB fornecidos pelo software de planejamento ClinCheck® foram tabulados e os arquivos da amostra em formato STL foram medidos utilizando os softwares Dolphin Imaging® e 3D Slicer. Para avaliar a confiabilidade das análises usadas como referência das comparações seguintes, o erro do método foi calculado utilizando vinte por cento da amostra, com intervalo de 2 semanas. A análise estatística foi executada no software Jamovi (versão 2.0) e um nível de significância de 5% foi adotado. Os dados em milímetros foram avaliados pelo coeficiente de correlação intraclasse (ICC), fórmula de Dahlberg, teste t pareado e método de Bland-Altman. Os resultados indicaram que os três métodos evidenciaram medidas confiáveis (ICC ≥ 0,7), sendo a DB anterior ligeiramente mais confiável. No entanto, apenas as medidas da DB anterior realizadas pelo ClinCheck e Dolphin Imaging® foram acuradas (p>0,5, sem viés de proporção). Para o DB total, todos os programas pesquisados apresentaram diferença estatisticamente significativa em relação ao método manual (p<0.001), embora essas diferenças não tenham implicação clínica relevante. Conclui-se que as ferramentas disponíveis apresentam validade para aplicação no diagnóstico e planejamento ortodôntico no que diz respeito a DB, especialmente as medidas indicadas pelo ClinCheck® e Dolphin Imaging® para região anterior do arco. (AU)

This study aimed to evaluate the diagnostic performance of the analysis of anterior and overall Bolton Discrepancy (BD) proposed by the ClinCheck® program, as well as the orthodontic software Dolphin Imaging® and 3D Slicer, compared with manual measurements performed on three-dimensionally printed models. Fifty-five pairs of early-stage digital models of patients treated with the Invisalign® system (Align, San Jose, California, USA) were three-dimensionally printed by stereolithography and used to measure BD by manual method with a digital caliper by a previously calibrated operator. DB values provided by ClinCheck® planning software were tabulated and sample files in STL format were measured using Dolphin Imaging® and 3D Slicer software. To assess the reliability of the analyzes used as a reference for the following comparisons, the method error was calculated using twenty percent of the sample, with an interval of 2 weeks. Statistical analysis was performed using the Jamovi software (version 2.0) and a significance level of 5% was adopted. Data in millimeters were evaluated using the intraclass correlation coefficient (ICC), Dahlberg formula, paired t-test, and the Bland-Altman method. The results indicated that the three methods showed reliable measurements (ICC ≥ 0.7), with the anterior BD slightly more reliable. However, only anterior BD measurements performed by ClinCheck® and Dolphin Imaging® were accurate (p>0.5, without proportion bias). For overall BD, all programs surveyed showed a statistically significant difference from the manual method (p<0.001), although these differences have no relevant clinical implications. The available tools studied are valid for application in the diagnosis and orthodontic planning concerning BD, especially the measures indicated by ClinCheck® and Dolphin Imaging® for the anterior region of the arch. (AU)

Therapeutic Group of The Elderly: Knowledge About Diabetes Mellitus and Arterial Hypertension / Grupo Terapêutico de Idosos: Conhecimento Sobre Diabetes Mellitus e Hipertensão Arterial

Control and the care are continuous challenges in the treatment of chronic diseases, and it is necessary to know the users' realities in order to seek intervention alternatives. The study aimed to identify the participants' knowledge in a therapeutic group of the elderly regarding diabetes mellitus and systemic arterial hypertension. Descriptive and exploratory study with a qualitative approach, conducted with 12 elderly in the therapeutic group. Semi-structured interviews were used as data collection technique. Data were transcribed and analyzed using the content analysis technique. In the results the category about the participants' knowledge on the diseases emerged, namely: etiological factors; main signs, symptoms and complications; drug therapy; use of herbal medicines; food control; lifestyle and regular follow up at the health unit. It was concluded that the participants have knowledge about the diseases; however, they cultivate habits that can trigger complications. Knowledge from experience should not be neglected, but should be directed towards achieving the goal of the therapeutic group, helping to improve the understanding of the elderly about their disease (s) and stimulating self-care. (AU)

O controle e o cuidado são desafios contínuos na terapêutica das doenças crônicas, sendo necessário conhecer as realidades dos usuários para buscar alternativas de intervenção. O estudo objetivou identificar o conhecimento dos participantes de um grupo terapêutico de idosos em relação ao diabetes mellitus e hipertensão arterial sistêmica. Estudo descritivo e exploratório, com abordagem qualitativa dos dados. A pesquisa foi realizada no munícipio de Itabuna na Bahia, na Unidade de Saúde da Família Simão Fitterman, no ano de 2014. Participaram do estudo 12 idosos do Sistema de Cadastramento e Acompanhamento de Hipertensos e Diabéticos (HIPERDIA), que participaram das reuniões do grupo terapêutico de idosos. A técnica utilizada para coleta de dados foi a entrevista com roteiro semiestruturado, realizadas nas reuniões do grupo terapêutico da unidade referida. O instrumento de coleta foi composto por dados sócio demográficos, conceitos e fatores desencadeantes das doenças estudadas, tratamento não farmacológico, complicações, prevenção e noções de autocuidado. Concluiu-se que os participantes possuem conhecimento sobre as doenças, entretanto cultivam hábitos que podem desencadear complicações. O conhecimento advindo da experiência, não deve ser negligenciado, mas direcionado ao alcance do objetivo do grupo terapêutico, contribuindo na melhoria do entendimento dos idosos sobre sua (s) doença (s), e estimulando o autocuidado. (AU)

Buschke-Lowenstein tumor in a patient with HIV and Psoriasis / Tumor de Buschke-Lowenstein em um paciente com HIV e psoríase

Abstract The Buschke-Lowenstein tumor, known as the giant condyloma acuminatum, is a rare lesion of the anorectal and PerianaL region; it is sexually transmitted and associated with human papilloma virus, types 6 and 11. Histologically, it is a benign tumor, but it can reach big proportions and may behave aggressively. The purpose of this study is to report the case of a patient diagnosed with HIV and psoriasis 14 years ago, associated with Buschke-Lowenstein tumor and other diffuse condylomatous lesions in the body.

Resumo O tumor de Buschke-Lowenstein, também conhecido como condiloma acuminado gigante, é uma lesão rara da região anorretal e perianal, sexualmente transmitida, associada ao papiloma vírus humano, Tipos 6 e 11. Histologicamente, trata-se de um tumor benigno, mas clinicamente atinge grandes proporções e pode se comportar de forma agressiva. O objetivo deste estudo é relatar o caso de um paciente com diagnóstico de HIV e psoríase há 14 anos, associado ao tumor de Buschke-Lowenstein e outras lesões condilomatosas difusas no corpo.

Expanding the Molecular Spectrum of Secretory Carcinoma of Salivary Glands With a Novel VIM-RET Fusion.

BACKGROUND: Secretory carcinoma (SC), originally described as mammary analogue SC, is a predominantly low-grade salivary gland neoplasm characterized by a recurrent t(12;15)(p13;q25) translocation, resulting in ETV6-NTRK3 gene fusion. Recently, alternative ETV6-RET, ETV6-MAML3, and ETV6-MET fusions have been found in a subset of SCs lacking the classic ETV6-NTRK3 fusion transcript, but still harboring ETV6 gene rearrangements. DESIGN: Forty-nine cases of SC revealing typical histomorphology and immunoprofile were analyzed by next-generation sequencing using the FusionPlex Solid Tumor kit (ArcherDX). All 49 cases of SC were also tested for ETV6, RET, and NTRK3 break by fluorescence in situ hybridization and for the common ETV6-NTRK3 fusions using reverse transcription polymerase chain reaction. RESULTS: Of the 49 cases studied, 37 (76%) occurred in the parotid gland, 7 (14%) in the submandibular gland, 2 (4%) in the minor salivary glands, and 1 (2%) each in the nasal mucosa, facial skin, and thyroid gland. SCs were diagnosed more frequently in males (27/49 cases; 55%). Patients' age at diagnosis varied from 15 to 80 years, with a mean age of 49.9 years. By molecular analysis, 40 cases (82%) presented the classic ETV6-NTRK3 fusion, whereas 9 cases (18%) revealed an alternate fusion. Of the 9 cases negative for the ETV6-NTRK3 fusion, 8 cases presented with ETV6-RET fusion. In the 1 remaining case in the parotid gland, next-generation sequencing analysis identified a novel VIM-RET fusion transcript. In addition, the analysis indicated that 1 recurrent high-grade case in the submandibular gland was positive for both ETV6-NTRK3 and MYB-SMR3B fusion transcripts. CONCLUSIONS: A novel finding in our study was the discovery of a VIM-RET fusion in 1 patient with SC of the parotid gland who could possibly benefit from RET-targeted therapy. In addition, 1 recurrent high-grade case was shown to harbor 2 different fusions, namely, ETV6-NTRK3 and MYB-SMR3B. The expanded molecular spectrum provides a novel insight into SC oncogenesis and carries important implications for molecular diagnostics, as this is the first SC-associated translocation with a non-ETV6 5' fusion partner. This finding further expands the definition of SC while carrying implications for selecting the appropriate targeted therapy.

Tumor de célula granular em cavidade oral: relato de caso / Granular cell tumor in oral cavity: case report

Introdução: O tumor de células granulares (TCG) é uma neoplasia benigna de tecido mole incomum que acomete principalmente mulheres na quarta e sexta década de vida. A lesão possui predileção pela região de cabeça e pescoço, sendo a superfície dorsal da língua o local de maior acometimento. Clinicamente, apresenta-se como um nódulo submucoso firme, de coloração semelhante a mucosa ou levemente amarelada, de crescimento lento e assintomático. O objetivo deste trabalho é relatar um caso de TCG apresentando suas características clínicas, histopatológicas bem como os possíveis diagnósticos diferenciais. Relato de caso: Paciente sexo feminino, 46 anos de idade, apresentando nódulo localizado no bordo lateral posterior da língua. Ao exame intraoral foi possível observar tumefação firme à palpação, com coloração amarelada, medindo aproximadamente 1cm no seu maior diâmetro. Baseado na hipótese diagnóstica de lipoma, foi realizada uma biópsia excisional. A análise histopatológica revelou características morfológicas compatíveis com o TCG. Considerações finais: O Cirurgião-Dentista deve conhecer os diagnósticos diferenciais clínicos e histopatológicos, uma vez que a conduta terapêutica pode ser distinta em alguns casos... (AU)

Introduction: Granular cell tumor (GCT) is a benign neoplasm of uncommon soft tissue that mainly affects women in the fourth and sixth of life. The lesion has a predilection for the head and neck region, and the dorsal surface of the tongue is the site of major involvement. Clinically, it presents as a firm, mucosal or slightly yellowish, slowly growing, asymptomatic submucosal nodule. The objective of this work is to report a case of GCT presenting its clinical, histopathological and possible differential diagnoses. Case report: A 46-year-old female patient with a nodule located on the posterior lateral border of the tongue. On intraoral examination, it was found on a table, with a yellowish color, measuring approximately 1cm in its largest diameter. Based on the diagnostic hypothesis of lipoma, an excisional biopsy was performed. A histopathological analysis revealed morphological characteristics compatible with GCT. Final considerations: The Dentist should know the differential clinical and histopathological diagnoses, since the therapeutic behavior may be different in some cases... (AU)

Histopathological features of photodamage and mast cell infiltrate in actinic cheilitis with different grades of epithelial dysplasia.

BACKGROUND: Actinic cheilitis is induced by chronic exposure to ultraviolet radiation and shows solar elastosis, a feature that has been associated with mast cell infiltrates. This study aimed to investigate the area of solar elastosis, collagen loss, and mast cell infiltrates in a series of actinic cheilitis. METHODS: We evaluated the epithelial dysplasia in 52 cases of actinic cheilitis and the solar elastosis with Weigert's resorcin-fuchsin. Collagen loss was evaluated with Picrosirius red, analyzed under polarized microscopy, and scored from 1 to 3. Elastosis proportionate area (EPA) was calculated with image software. Mast cells were highlighted with toluidine blue stain. RESULTS: EPA varied from 2% to 45%, with a mean of 17.1% in the cases, with no differences among epithelial dysplasia degrees. Most cases presented collagen loss scores of 2 or 3, and higher loss of type I collagen was associated with older age. Mast cell density was higher in severe epithelial dysplasia (P = 0.002) and in high-risk cases (P = 0.01). CONCLUSION: Actinic cheilitis presented variable EPA and marked loss of type I collagen; however, these features were not associated with the degrees of epithelial dysplasia. Besides, mast cell density increased with epithelial dysplasia worsening and this was not associated with elastosis area or collagen loss.

Can immunohistochemical biomarkers distinguish epithelial dysplasia degrees in actinic cheilitis? A systematic review and meta-analysis

BACKGROUND: Actinic cheilitis (AC) is a potentially malignant disorder of the lip, characterized by epithelial and connective tissue alterations caused by chronic exposure to ultraviolet radiation. In the past decades, diverse studies have been conducted in lip carcinogenesis and many biomarkers have been identified in lip lesions, yet there is no scientific evidence that determines its usefulness in the clinical setting or in histopathological routine. Therefore, we conducted the first systematic review in this field to summarize the results of published studies on immunohistochemical biomarkers in lip carcinogenesis, to evaluate if there is a marker than can distinguish the different histological grades of AC. MATERIAL AND METHODS: Retrospective studies that investigated immunohistochemical biomarkers in AC defined on standardised histological assessment were gathered from five databases and evaluated. Each study was quali-tatively evaluated using the Critical Appraisal Tools from SUMARI. RESULTS: The proliferation marker Ki-67 was the most studied biomarker and we observed, through meta-analysis, that it was differently expressed between AC and lip cancer, but not in AC subgroups. Most articles had a high risk of bias. CONCLUSIONS: In summary, the literature lacks quality follow up studies in actinic cheilitis. Multi-centre cohort studies, with patients stratified by treatment type and the use of image analysis software, could be the solution to further address the issues of investigating potentially malignant lesions and help change clinical practice, in terms of individualizing patients' treatment and prognosis prediction

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"Efficacy of photodynamic therapy on the treatment of herpes labialis: A systematic review".

OBJECTIVE: We conducted a systematic review to evaluate the efficacy of PDT in the management of recurrent herpes labialis (RHL). STUDY DESIGN: systematic review. METHODS: This study was reported according to the PRISMA checklist and we performed a literature search on five databases. RESULTS: The search revealed that there are no published clinical trials addressing PDT on RHL, therefore we conducted a review of case reports and five studies were included for qualitative review. The number of treated patients varied from 2 to 6 in each article. Most studies used methylene blue as a photosensitizer, while one used 5-aminolevulinic acid. For light irradiation, most studies used laser and one used a red light from halogen lamp. Patients' follow-up varied from 24 h to 12 months. All articles reported good outcomes with resolution of disease and no recurrences. Only one study reported adverse effects during treatment (burning and pain). CONCLUSION: The results of this review suggest that PDT could be an effective treatment for herpes labialis. However, due to very few case reports and heterogeneity among protocols, there is a call for well-designed randomized clinical trials to confirm the efficacy of this therapy and to establish standardized protocols. The review protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) under number CRD CRD42018108973.

Clear Cell Odontogenic Carcinoma Harboring the EWSR1-ATF1 Fusion Gene: Report of a Rare Case.

Clear cell odontogenic carcinoma (CCOC) is a rare and aggressive malignant epithelial neoplasm, which occurs most frequently in the mandible of elderly patients. Morphologically, CCOC shares similar characteristics with other clear cell tumors, especially hyalinizing clear cell carcinoma of the salivary glands (HCCC). Both CCOC and HCCC are known to harbor EWSR1 rearrangements, especially the EWSR1-ATF1 gene fusion, which indicates a possible link between the two lesions. So far, this fusion has been demonstrated in five cases of CCOC in the literature. Herein, we add another CCOC case to the literature, which arose in the mandible of an 82-year-old female patient and was proven to harbor the EWSR1-ATF1 gene fusion. Immunohistochemically, this case was focally positive for CK7, CK14, CK19 and p63. The patient was referred to surgical treatment; however, she died of disease 2 months after the diagnosis, thereby demonstrating the aggressive nature of this tumor.

Biomarker immunoprofile and molecular characteristics in salivary duct carcinoma: clinicopathological and prognostic implications.

Salivary duct carcinoma (SDC) is one of the most aggressive salivary gland tumors, and prognosis remains poor for most patients. The aim of this study was to investigate the prognostic implications of biomarker immunoprofile in a cohort of SDC and to identify molecular characteristics through next-generation sequencing (NGS) in a subset of cases. Clinicopathological and follow-up information of 25 cases diagnosed as SDC was collected. Immunoexpression of AR, HER-2/neu, GATA3, CK5/6, and MIB1 was analyzed, and ERBB2 (HER-2/Neu) gene amplification was investigated by fluorescence in situ hybridization. Cases were classified under the "SDC revised classification system." Eight SDC cases were analyzed by targeted NGS for detection of gene fusions and variants. Overall survival and disease-free survival were analyzed with Kaplan-Meier curves and Cox regression. Most cases expressed AR (100%), GATA3 (73%), and CK5/6 (76.5%), and 42% expressed HER-2/neu. ERBB2 gene amplification was proven by fluorescence in situ hybridization in 7 of 15 (46%) cases. Apocrine HER2 (AR+/HER2+) subtype was significantly associated with lower overall survival (P = .05). NGS analysis revealed 9 pathogenic mutations in 7 SDC cases, and the most frequently mutated gene was HRAS (4/9) followed by PIK3CA (2/9) and TP53 (2/9). One case (1/9) presented homozygous deletion of locus 9p21 (CDKN2A), and another case (1/9) showed MDM2 amplification. In conclusion, we demonstrated that Apocrine HER2 (AR+/HER2+) is a potential biomarker of poor outcome in SDC. Furthermore, NGS analysis revealed recurrent mutations in SDC.

NCOA4-RET and TRIM27-RET Are Characteristic Gene Fusions in Salivary Intraductal Carcinoma, Including Invasive and Metastatic Tumors: Is "Intraductal" Correct?

Intraductal carcinoma (IC) is the new WHO designation for tumors previously encompassed by "low-grade cribriform cystadenocarcinoma" and "low-grade salivary duct carcinoma." The relationship of IC to salivary duct carcinoma (SDC) is controversial, even though they are considered to be distinct entities. IC is a rare low-grade malignant salivary gland neoplasm with histopathological features reminiscent of atypical ductal hyperplasia or ductal carcinoma in situ of the breast, showing diffuse S100 protein and mammaglobin positivity, while it is partially defined genetically. Recently, RET rearrangements including NCOA4-RET and TRIM27-RET have been described in IC. Here, we genetically characterize the largest cohort of IC to date (33 cases) including 8 cases with focal or widespread invasive growth and 1 case with lymph node metastasis. Thirty-three cases of IC were analyzed by next-generation sequencing (NGS) using the FusionPlex Solid Tumor kit (ArcherDX). Identified gene fusions were confirmed using fluorescence in situ hybridization break-apart and fusion probes and an reverse transcription polymerase chain reaction designed specifically for the detected breakpoints. Ten cases of SDC were analyzed for comparison using NGS panels that detect mutations and fusion transcripts. NGS analysis detected an NCOA4-RET fusion transcript in 11 cases of intercalated duct-type IC joining exon 7 or 8 of NCOA4 gene and exon 12 of the RET gene. Eight cases of IC had an invasive growth pattern, including one with widespread invasion and lymph node metastasis. Three invasive ICs harbored an NCOA4-RET fusion transcript, while 1 case was negative, and 2 cases were not analyzable. In addition, a novel TRIM27-RET fusion transcript between exon 3 of TRIM27 and exon 12 of RET was identified in 2 cases of IC with apocrine features, and one of them displayed invasive growth. Two IC cases with invasive growth harbored novel fusions TUT1-ETV5 and KIAA1217-RET, respectively. A total of 42.4% of the cases in this series of IC harbored fusions involving RET. Such fusion transcripts were not detected in any of the 10 SDC cases. We have confirmed NCOA4-RET as a predominant fusion in intercalated duct-type IC, including 3 cases with invasive growth pattern. A novel finding in our series was a case of widely invasive intercalated duct-type IC, with a single lymph node metastasis that revealed an NCOA4-RET fusion transcript. We also demonstrated that a subset of apocrine ICs harbored a TRIM27-RET gene fusion, including one case with invasive growth. In contrast, neither NCOA4-RET nor TRIM27-RET fusions were detected in any tested SDCs. Thus, the distinct molecular findings in IC and SDC support that the tumors are separate malignant salivary tumor entities. The presence of tumor-type-specific NCOA4-RET or TRIM27-RET translocations in a subset of widely invasive carcinomas with intercalated duct-like immunoprofiles suggests that a recharacterization of IC including its redesignation as "intercalated duct carcinoma, invasive or noninvasive" may be appropriate.

Differential expression of cyclooxygenase-2 and cyclin D1 in salivary gland tumors.

PURPOSE: Salivary gland tumors are complex and have a great histomorphological diversity; more than 30 histological subtypes are currently described and the study of proteins that help understand and differentiate these tumors is essential. We aimed to analyze the immunoexpression of cyclooxygenase-2 (COX-2) and cyclin D1 proteins in pleomorphic adenomas (PA), mucoepidermoid carcinomas (MEC) and adenoid cystic carcinomas (AdCC) of salivary glands. METHODS: A total of 38 PA, 12 AdCC and 12 MEC underwent immunohistochemical study by the polymeric biotin-free technique. Immunopositive cells were analyzed semi-quantitatively. For statistical analysis, a significance level was set at p ≤ 0.05. RESULTS: Overall, these tumors were more prevalent in women (n = 37). The mean age of these patients was 58-year-old and the parotid gland was the most affected anatomic site (n = 33). All cases of AdCC and MEC showed immunopositivity to cyclin D1; however, 39.5% of the PAs were negative (p < 0.001). Regarding COX-2 immunoexpression, we observed that all cases of CME were positive, whereas 60.5% of the PA and 75% of the CAC analyzed were completely negative (p = 0.042). CONCLUSIONS: The overexpression of COX-2, observed only in MEC, emphasizes that salivary gland tumors have different profiles. Cyclin D1 is more immunoexpressed in malignant tumors. Together, these immunohistochemical findings may be useful in differentiating the studied tumors.

Evaluation of epithelial dysplasia adjacent to lip squamous cell carcinoma indicates that the degree of dysplasia is not associated with the occurrence of invasive carcinoma in this site.

BACKGROUND: We analyzed the different grades of dysplasia in the epithelium adjacent to lip squamous cell carcinoma (LSCC), as a parallel to actinic cheilitis (AC) that suffered malignant transformation. METHODS: Forty samples of epithelium adjacent to LSCC were histologically graded according to the World Health Organization (WHO) and the binary systems. The expression of mutated p53 was evaluated through immunohistochemistry. RESULTS: According to WHO system, 37.5% of the cases were graded as mild, 45% as moderate and 17.5% as severe dysplasia (P = 0.09). Considering the binary system, 90% of the cases were classified as low-risk and 10% as high-risk lesions. Mutated p53 was present in 73.3% of mild, 88.8% of moderate and 71.4% of severe dysplasia cases. Considering the binary system, 80.5% of the low-risk and 75% of high-risk lesions were immunopositive; 62.5% expressed the protein in both tumor cells and adjacent epithelium; 17.5% in adjacent epithelium only, and 7.5% in LSCC islands only (P = 0.03). CONCLUSIONS: We observed heterogeneous grades of epithelial dysplasia in the epithelium adjacent to LSCC, which indicates that the analysis of AC morphological features is insufficient to predict patient's prognosis and to determine a treatment decision. Positive expression of mutant p53 in mild dysplasia reinforces this idea.

Expression of cancer stem cell markers CD44, ALDH1 and p75NTR in actinic cheilitis and lip cancer.

PURPOSE: The aim of this work was to evaluate the expression of the cancer stem cell (CSC) markers CD44, ALDH1 and p75NTR in the ultraviolet-induced lesions actinic cheilitis (AC) and lip squamous cell carcinoma (LSCC), and to correlate it with p53 expression. METHODS: Immunohistochemistry was performed in 4 cases of normal lip (NL), 43 of AC and 20 of LSCC. RESULTS: All cases were positive for CD44, showing a membranous staining without differences between the groups. ALDH1 showed cytoplasmic staining and it was invariable amongst the grades of epithelial dysplasia and between AC and LSCC. p75NTR presented membranous/cytoplasmic staining in the basal and parabasal layer of NL and AC, while LSCC presented cytoplasmic staining in the peripheral layers of the tumor islands. p75NTR showed different expression amongst the dysplasia grades (p < 0.001) but no differences between AC and LSCC. p53 expression was similar amongst the dysplasia grades and between AC and LSCC. CD44, ALDH1 and p75NTR were unrelated amongst themselves and to p53 expression. CONCLUSIONS: CSC markers are expressed in potentially malignant and malignant lesions of the lip. Their expressions were invariable between AC and LSCC and unrelated to p53. p75NTR expression increased with the worsening of epithelial dysplasia grade.

Prognostic significance of 1p36 locus deletion in adenoid cystic carcinoma of the salivary glands.

Adenoid cystic carcinoma (AdCC) of the salivary glands is characterized by MYB-NFIB or MYBL1-NFIB fusion, prolonged but relentlessly progressive clinical course with frequent recurrences, and development of distant metastasis resulting in high long-term mortality. Currently, no effective therapy is available for patients with advanced non-resectable and/or metastatic disease. Complicating the clinical management of this patient group is the lack of prognostic markers. The purpose of this study is to investigate the prognostic value of 1p36 loss in patients with AdCC. The presence of 1p36 deletion and gene fusions involving the MYB, NFIB, and MYBL1 genes in a cohort of 93 salivary gland AdCCs was studied using fluorescence in situ hybridization. These results were statistically correlated with clinical data and outcome. Deletion of 1p36 in AdCC was identified in 13 of 85 analyzable cases (15.29%). MYB-NFIB fusion was detected in 57/85 (67.1%), MYBL1-NFIB fusion in 12/85 (14.1%), MYB-X fusion in 4/85 (4.7%), MYBL1-X in 4/85 (4.7%), and NFIB-X in 2/85 (2.4%) of AdCC cases. None of the 1p36-deleted samples showed MYBL1 rearrangement. Statistical analysis demonstrated a significant correlation between 1p36 deletion and advanced tumor stage and solid histology (p = 0.0061 and 0.0007, respectively). Kaplan-Meier survival curves showed statistically significant correlations between 1p36 deletion and decreased overall survival, disease-specific survival, recurrence-free interval, and recurrence-free survival, all of which were maintained in multivariate analysis. We demonstrate that 1p36 deletion can serve as an indicator of unfavorable outcome of patients with salivary gland AdCC.