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Objective To carry out a systematic review to address the prevalence and the prognostic potential of translocation (6;9) (MYB-NFIB genes) mutation in head and neck adenoid cystic carcinoma (AdCC). Study Design Articles published were retrieved from multiple databases using specific search strategies. They were screened and articles included had their data extracted by 2 authors who latter assessed the risk of bias of each study. Quantitative analysis was done to determine the incidence of the translocation. Results A total of 1107 articles were initially retrieved with 36 remaining for data extraction. The presence of t(6;9)(MYB-NFIB) translocation varied significantly, especially due to methodologic heterogeneity among studies. The meta-analysis revealed a range from 16% to 100% in the prevalence of the translocation. A total of 11 studies attempted to determine the prognostic importance of the mutation, but no study found any significant association with survival rates and only 3 studies observed a significant association with age, sex, tumor location, and the presence of recurrences and metastases. Conclusions The prevalence of t(6;9)(MYB-NFIB) translocation in head and neck AdCC varies according to the laboratory methods used and the best evidence available demonstrate that t(6;9)(MYB-NFIB) is not a prognostic determinant. Support: CNPq and FAPEMIG.

Carcinoma ex-pleomorphic adenoma (CXPA) arises in pleomorphic adenoma (PA) and with an increase in lipogenesis during its malignant transformation. The increase in lipogenesis is a feature of the cancer cells and it is characterized by the increase of fatty acid (FA) synthesis. This way, the overexpression of the enzyme fatty acid synthase (fasn) has been correlated. In the same way, the increase of glycolytic metabolism in neoplastic cells is due to the high expression of glycolytic enzymes and glucose transporters (gluts). Objective: Compare the fasn and glut-1 expression between CXPAs and PAs samples. Study Design: Forty PA and 40 CXPA were analyzed by immunohistochemistry with fasn and glut-1 antibodies. The proportion of positive neoplastic cells was assessed according to a 2-tiered scale: >10% to 50%, and >50% positive cells. Results: Fifteen PA (37.5%) and 30 CXPA (75%) were fasn positive. Twenty PA (20%) and 29 CXPA (70%) were glut-1 positive. Conclusions: The present results suggest that fasn and glut-1 enzyme overexpression are associated with the malignant transformation of the PA. This way, the increase of the lipogenesis and glycolytic metabolism should be collaborative factors for carcinogenesis since cancer requires a highest demand of energy for survival and progression.

A 2-year-old male patient came to our service with the complaint of swelling located in the left side of the lower jaw. There was a history of trauma 3 months prior to the lesion formation. The swelling was initially noticed as a small nodule, which increased in size gradually. On palpation, the swelling was well localized, firm, nonmobile, 3 × 3 cm in diameter, nontender, fixed to the underlying bone, and nonadherent to the superficial skin. No submandibular lymphadenopathy was noted. Computed tomography scan of the jaws with a 3-dimensional reconstruction image showed the presence of a soft tissue lesion with bone erosion of the inferior aspect of the left side of the body of the mandible. Histologically, a typical biphasic cellular arrangement was noted. Immunohistochemical markers have been useful for the definitive diagnosis of this uncommon neoplasm. The clinical, radiologic, histologic and immunohistochemical aspects corroborate the diagnosis of infantile myofibroma.

Introduction Villitis is characterized by the presence of inflammatory infiltrate (CD8 lymphocyte) in the placental villous and is classified as to the etiology in known and unknown. In most cases, villitis is idiopathic (villitis of unknown etiology [VUE]) because no microorganisms are evident and there are no maternal symptoms or signs. It has recently been proposed that pregnancy is, in fact, an active and highly regulated immune process in which macrophages play an important role. Macrophages may present with M1 phenotype, important effector cells, or M2 phenotype, capable of suppressing the function of M1 macrophages and influencing immunoregulation and tissue repair. CD68 antibody recognizes macrophages M1 and M2, whereas CD11c and CD163 antibodies are specific for the identification only of M1 and M2 macrophages, respectively. The objective of our study is to characterize in human placentas in the subpopulation of M1 and M2 macrophages in VUE. Methods Sixteen cases of chronic villitis (all without an identifiable etiologic agent) and three control placentas were examined using immunohistochemistry with antibodies for CD68, CD11c, CD163, and CD3. Results CD68 and CD163 were present in all cases in the normal areas. CD68, CD163, and CD11c were present in the villous stroma and in the intervillous space in the inflamed areas. The percentage of CD68-positive macrophages was higher than CD163- and CD11c-positive macrophages in all specimens studied. A total increase of CD68, CD163, and CD11c with the predominance of CD11c over CD163 in the inflamed areas was observed. Conclusion The predominance of M1 macrophages (CD11c) in the inflamed areas suggests the influence of these cells in the pathogenesis VUE. The higher amount of M2 (CD163) in the inflamed villous compared to normal areas suggests a possible immunoregulatory mechanism of the inflammatory process in VUE.

Introduction Pleomorphic adenoma (PA) is a benign lesion of the salivary glands that can suffer malignant transformation to carcinoma ex adenoma pleomorphic (CXPA). The pathogenesis of CXPA has been attributed to the accumulation of genetic disorders in preexisting PAs. However, there is no confirmation whether there is a common target gene involved in all histopathological subtypes or the decisive factors for malignant transformation in a histopathological subtype are specific. Objectives To further analyze genes found in PA and CXPA using the CGH-array technique. The genes found were analyzed using the InteractiVenn virtual tool (http://www.interactivenn.net/) and grouped into a Microsoft Excel worksheet. Results: Of the 460 genes amplified in the studied samples, 287 (62.4%) were related only to CXPA, whereas 144 (31.3%) were related to residual PA. Twenty-nine (6.3%) of these genes were common between residual PA and CXPA. Regarding the degree of invasion of CXPA, there was an increase in the number of genes amplified as the degree of invasion and aggression increased: 8 genes related to intracapsular CXPA, 65 to minimally invasive CXPA, and 373 to weakly invasive. Moreover, when comparing residual AP and intracapsular CXPA, two genes were common to these groups: ERRB2 and GRB7. As for the histological subtype, the high-grade samples had more amplifications (320 amplified genes) than the low-grade ones (129 genes). Three of these genes were common among residual PAs and CXPA: HMGA2, RPSAP52, and LOC100129940. As for the replicates, MYNC, ERBB2, BRIP1, and HMGA2 were the most repeated amplified genes in the residual PAs. HMGA2, ERRBB2, CDK12, RPSAP52, LOC100129940, and LOC100507250 were the genes with the most replicates in CXPA. Conclusion HMGA2, ERRB2, and RPSAP52 may play a key role in PA carcinogenesis, whereas GRB7, CDK12, MYNC, and BRIP1 appear to act as coadjutants.

Aims The morphological criteria for identification of intercalated duct lesions (IDLs) of salivary glands have been defined recently. It has been hypothesised that IDL could be a precursor of basal cell adenoma (BCA). BCAs show a variety of histological patterns, and the tubular variant is the one that presents the strongest resemblance with IDLs. The aim of this study was to analyse the morphological and immunohistochemical profiles of IDLs and BCAs classified into tubular and non-tubular subtypes, to determine whether or not IDL and tubular BCA represent distinct entities. Methods and results Eight IDLs, nine tubular BCAs and 19 non-tubular BCAs were studied. All tubular BCAs contained IDL-like areas, which represented 20–70% of the tumour. In non-tubular BCA, IDL-like areas were occasional and small (

Introduction: A key step of cancer development is the progressive accumulation of genomic changes resulting in disruption of several biological mechanisms. Carcinoma ex-pleomorphic adenoma (CXPA) is an aggressive neoplasm that arises from a pleomorphic adenoma. CXPA derived from a recurrent PA (RPA) has been rarely reported, and the genomic changes associated with these tumors have not yet been studied. Objective: We analyzed CXPA from RPAs and RPAs without malignant transformation using array-comparative genomic hybridization (array-CGH) to identify somatic copy number alterations and affected genes. Methods: DNA samples extracted from FFPE tumors were submitted to array-CGH investigation, and data was analyzed by Nexus Copy Number Discovery Edition v.7. Results: No somatic copy number alterations were found in RPAs without malignant transformation. As for CXPA from RPA, although genomic profiles were unique for each case, we detected some chromosomal regions that appear to be preferentially affected by copy number alterations. The first case of CXPA-RPA (frankly invasive myoepithelial carcinoma) showed copy number alterations affecting 1p36.33p13, 5p and chromosomes 3 and 8. The second case of CXPA-RPA (frankly invasive epithelial-myoepithelial carcinoma) showed several alterations at chromosomes 3, 8, and 16, with two amplifications at 8p12p11.21 and 12q14.3q21.2. The third case of CXPA-RPA (minimally invasive epithelial-myoepithelial carcinoma) exhibited amplifications at 12q13.3q14.1, 12q14.3, and 12q15. Conclusion: The occurrence of gains at chromosomes 3 and 8 and genomic amplifications at 8p and 12q, mainly those encompassing the HMGA2, MDM2, WIF1, WHSC1L1, LIRG3, CDK4 in CXAP from RPA can be a significant promotional factor in malignant transformation. Resumo Introdução: Uma etapa fundamental do desenvolvimento do câncer é o acúmulo progressivo de alterações genômicas, resultando na ruptura de vários mecanismos biológicos. Carcinoma ex-adenoma pleomórfico (CXAP) é uma neoplasia agressiva que surge a partir de um adenoma pleomórfico. O CXAP derivado de um AP recorrente (APR) foi raramente relatado e, até o momento, as alterações genômicas associadas a esses tumores não foram estudados. Objetivo: Avaliar as diferenças entre os CXAPs decorrentes de APRs e os APRs sem transformações malignas usando hibridização genômica comparativa em microarrays (array Comparative Genomic Hibridization - aCGH) a fim de identificar alterações no número de cópias somáticas e os genes afetados. Método: Amostras de DNA extraídas de tumores provenientes de tecido emblocado em parafina foram submetidos à investigação com a técnica aCGH, e os dados foram analisados com o Nexus Copy Number Discovery Edition v.7. Resultados: Não observamos alterações no numero de cópias somáticas nos APRs sem transformação maligna. Quanto ao CXAP de APR, embora os perfis genômicos sejam exclusivos para cada caso, detectamos algumas regiões cromossômicas que pareciam ser preferencialmente afetadas por alterações no número de cópias. O primeiro caso de CXAP-APR (carcinoma mioepitelial francamente invasivo) apresentou alterações no numero de cópias afetando 1p36.33p13, 5p e cromossomos 3 e 8. O segundo caso de CXAP-APR (carcinoma epitelialmioepitelial francamente invasivo) apresentou várias alterações nos cromossomos 3, 8 e 16, com duas amplificações em 8p12p11.21 e 12q14.3q21.2. O terceiro caso de CXAP-APR (carcinoma epitelial-mioepitelial minimamente invasivo) apresentou amplificações em 12q13.3q14.1, 12q14.3, e 12q15. Conclusão: A ocorrência de ganhos de cromossomos 3 e 8, e as amplificações genômicas em 8p e 12q, principalmente aquelas que englobam os HMGA2, MDM2, WIF1, WHSC1L1, RG3, CDK4 no CXAP decorrente de APR podem ser fatores promocionais significativos para a transformação maligna.

Introduction Cribriform adenocarcinoma of the tongue and minor salivary glands (CATMSG) is a recently described entity, with most cases previously published as polymorphous low-grade adenocarcinoma (PLGA). Typical cases share some main characteristics, such as oral sites (mainly tongue), regional lymph node metastasis, and morphology resembling solid and follicular variants of papillary thyroid carcinoma. Objective To present a CATMSG and emphasize the importance of reclassifying PLGAs with unusual behavior. Case report A 78-year-old male presented with an ulcerated mass in the soft palate treated as PLGA. The patient developed 5 regional metastases over 11 years of follow-up, all diagnosed as PLGA. He died due to the disease, and because of the very aggressive behavior of PLGA, all histopathologic slides were revised and the tumor was reclassified as CATMSG. Conclusion This report emphasizes the importance of reevaluating aggressive PLGA and contributes to a better understanding of CATMSG.

The diagnosis of pleomorphic adenoma (PA) of salivary glands is usually straightforward posing few diagnostic problems for the general surgical histopathologist. The purpose of our investigation was to present a series of 22 cases of PA of major salivary glands, each of which contained small foci of tumor within vascular spaces. This feature has previously been described very rarely in PA and may represent a significant diagnostic pitfall. The patients included 12 women and 10 men, ranging in age at diagnosis from 17 to 82 years. Histopathologically, all 22 tumors displayed the features of PA with mixed epithelial and myoepithelial growth patterns and chondromyxoid areas. None of these neoplasms showed any cytologic evidence of malignancy. In all cases, there were multiple dilated thin-walled and/or muscular thick-walled blood vessels containing small intraluminal collections of neoplastic cells with or without myxoid stromal components. The intravascular tumor cells expressed cytokeratins, and in some cases they were also immunoreactive for S-100 protein, GFAP, D2-40, and p63 protein. The intravascular location of the neoplastic cells was confirmed by CD31, CD34, and factor VIII-related antigen immunostains. Reaction for D2-40 was negative in the endothelium of the involved vessel in all cases, confirming that they were vascular rather than lymphatic channels. Seven patients (36%) underwent fine-needle aspiration biopsy 25 days to several years before excision of the tumor. Follow-up of the patients in our series revealed no cases of recurrence or metastasis (range, 6 mo to 9.5 y; mean 3.8 y; median 3.5 y). The biological significance of intravascular tumor in PA is not clear, but there is growing evidence that it is an innocuous phenomenon that might be related to artifactual spillage caused by tumor injury presumably by either fine-needle aspiration or intraoperative trauma.

Primary nasal melanoma is a rare tumor of unknown etiopathogenesis that occurs in adult and elderly patients usually diagnosed at advanced stages. The aim of this study was to analyze the clinicopathologic and immunohistochemical characteristics of 12 cases of primary nasal melanomas in Brazil. Twelve cases of primary nasal melanoma were analyzed histologically and by immunohistochemistry using the antibodies S-100 protein, HMB-45, Melan-A, CD63 (NKI/C3), CD68/KP1, fatty acid synthase (FASN), and Ki-67. The mean age of the patients was 60 years, and 7 of 12 patients were men. Microscopically, 10 cases presented level III of invasion; 4 were amelanotic; and in 7, cells were epithelioid. S-100 protein and FASN were positive in all cases, whereas 9, 8, 7, and 6 cases were positive for HMB-45, Melan-A, CD63 (NKI/C3), and CD68/KP1, respectively. Ki-67 labeling index ranged from 11.45% to 28.5% of positive cells. S-100 protein is more frequently expressed in nasal melanomas than in HMB-45, Melan-A, CD63 (NKI/C3), and CD68/KP1. FASN seems to be involved in the pathogenesis of nasal melanomas, and also, it can be helpful to confirm the diagnosis.

To determine the sensitivity, specificity, negative predictive value (NPV) and accuracy of hematoxylin-eosin (HE) staining compared to immunohistochemistry (IHC) in sentinel lymph node (SLN) histological analyses of head and neck squamous cell carcinoma. The Clinical prospective study was carried out at Tertiary referral university hospital. Patients with oral, lip and oropharyngeal squamous cell carcinoma undergoing elective neck dissection with clinically and radiologically negative necks were included. All patients were submitted to computer tomography scan for the evaluation of lymphatic metastases. The surgical procedure consisted of tumor resection, SLN sampling and elective neck dissection. Negative SLNs via HE were then submitted for IHC analysis of cytokeratin AE1/AE3 and step serial section (SSS). The main outcome measures were the negative predictive value of conventional HE staining techniques in the diagnosis of lymphatic metastases with the SSS/IHC analysis. Of 46 patients undergoing 63 neck procedures, 53 were SLN negative and 10 were positive on HE analysis. Using SSS/IHC analysis of these 53 negative SLNs on HE, two (3.8 %) were found to be positive. For HE, the sensitivity, specificity, NPV and accuracy were 77, 100, 94, and 95 %, respectively. With subsequent analysis with SSS/IHC, these values increased to 92, 100, 98 and 98 %, respectively. SSS/IHC is important in SLN analysis as the false negative rate decreased significantly while increasing the inherent sensitivity of the analyses.

Costa A F, Tasso M G, Mariano F V, Soares A B, Chone C T, Crespo A N, Fresno M F, Llorente J L, Suarez C, de Araujo V C, Hermsen M & Altemani A (2012) Histopathology 60, 816–837 Levels and patterns of expression of hypoxia-inducible factor-1α, vascular endothelial growth factor, glucose transporter-1 and CD105 in adenoid cystic carcinomas with high-grade transformation Aims: To compare the expression of proteins regulated by hypoxia between adenoid cystic carcinoma (ACC) with and without high-grade transformation (HGT). Methods and results: In eight ACC–HGT and 18 ACC without HGT, expression of hypoxia-inducible factor-1 (HIF-1α), vascular endothelial growth factor (VEGF), glucose transporter-1 (GLUT-1) and microvascular density (MVD) by CD105 (a hypoxia-inducible protein expressed in angiogenic endothelial cells) was determined. Expression levels of HIF-1α and VEGF as well as CD105-MVD did not differ significantly between: (i) transformed and conventional areas (TA and CA, respectively) of ACC–HGT, (ii) CA and ordinary ACC. HIF-1α was detected in 100% of cases and presented a diffuse expression pattern. No significant association was found between levels of HIF-1α expression and tumour size, metastasis and recurrence. GLUT-1 showed a prostromal expression pattern and was observed exclusively in TA (three of six cases) and in only three of 14 ACC. Conclusions: Both the absence of significant alterations in levels of expression of HIF-1α, VEGF and CD105 and the patterns of expression of HIF-1α and GLUT-1 suggest that hypoxia may not play a key role in the process of high-grade transformation of ACC. Although HIF-1α expression is a common finding in ACC, it cannot be used as a marker of tumour aggressiveness.

Nodal metastasis is an important prognostic indicator in head and neck cancers, including salivary carcinomas. In these, the risk for lymph node metastasis is variable and strongly associated with the tumor histologic type. The aim of the current study was to evaluate the lymphatic vessel density (LVD) and expressions of lymphangiogenic growth factors by tumor cells in different histologic types of salivary carcinomas subdivided according to the risk for nodal metastasis. In 15 high-risk (undifferentiated, high-grade mucoepidermoid and salivary duct carcinomas) and 60 low/moderate-risk tumors (adenoid cystic, low/intermediate-grade mucoepidermoid, acinic cell, myoepithelial, epithelial-myoepithelial and polymorphic low-grade carcinomas) the expressions of vascular endothelial growth factor-C (VEGF-C), hepatocyte growth factor (HGF) and D2-40 (for assessing LVD) were examined. No significant differences were encountered between high- and low/moderate/-risk carcinomas regarding LVD and VEGF-C or HGF expressions. Furthermore, the expression of these proteins did not correlate with LVD. Lymphatic vascular invasion was found mainly in high-risk carcinomas. Intratumoral LVD was significantly lower than peritumoral, regardless of the risk for metastasis and primary site of the lesion. The histologic types of salivary carcinomas which are associated with high-risk for nodal metastasis do not present increased LVD or VEGF-C and HGF expressions. The greater tendency for metastasis in these carcinomas seems to be related to their capacity to invade lymph vessels. Further studies on tumor cell interactions with lymphatic endothelial cells are needed to improve our understanding of the metastatic potential of salivary carcinomas.

Soares A B, Demasi A P D, Altemani A & de Araujo V C (2011) Histopathology58, 377–382 Increased mucin 1 expression in recurrence and malignant transformation of salivary gland pleomorphic adenoma Aims: Pleomorphic adenoma (PA) is the most common salivary gland tumour with a tendency to recur (RPA) and a risk of malignant transformation. Mucin 1 (MUC-1) plays a role in the progression of many tumours and may be a marker to predict RPA. The aim of this study was to evaluate MUC-1 expression in different phases of the adenoma to carcinoma sequence. Methods and results: Twenty-one cases of PA, 18 cases of RPA, three cases of RPA with focal transformation (TRPA) and 11 cases of carcinoma ex-pleomorphic adenoma (CXPA) were analysed immunohistochemically for MUC1 expression using an antibody to MUC1/DF3. MUC1 reactivity in RPA was stronger than that observed in PA and, in all the different carcinoma groups, MUC-1 expression was significantly higher in carcinoma than in RPA and PA. Conclusion: This study has confirmed that MUC-1 is related to the recurrence of PA and that this molecule is associated with malignant transformation of PA with carcinoma cells overexpressing MUC-1.

To gain further knowledge on the subject we evaluated Epstein-Barr virus (EBV) gene expression and TCD4+, TCD8+, and B lymphocyte counts in lung tissue samples from 20 human immunodeficiency virus (HIV)-infected children with chronic lung disease. Twenty HIV-1 infected children with chronic pulmonary disease underwent open lung biopsy to define the diagnosis. Histological section of this material was submitted to nonisotopic in situ hybridization (ISH) using EBV-encoded RNA (EBER) 1/2 probes and TCD4+, TCD8+, and CD20+ B-cell counts by immunohistochemistry. The histology of 16 out of the 20 children (median age 53.5 months) proved to be examples of pulmonary lymphoid hyperplasia/lymphoid interstitial pneumonitis (PLH/LIP) complex, 13 of which were EBER positive, but no significant association was found (Fisher exact test P = 0.439). Four patients had non-LIP diseases (3, nonspecific interstitial pneumonia; 1, diffuse advanced alveolar damage), two being EBER negative. Nineteen children showed a predominant T-CD8+ cell response (CD4+/CD8+

Carcinoma ex pleomorphic adenoma is a rare salivary gland malignancy. It constitutes an important model for the study of carcinogenesis, as it can display the tumor in different stages of progression, from benign pleomorphic adenoma to frankly invasive carcinoma. Growth signaling pathways undergo continuous activation in human tumors, commonly as a consequence of the overexpression of ligands and receptors such as platelet-derived growth factor and platelet-derived growth factor receptor. Hydrogen peroxide is produced after platelet-derived growth factor receptor activation, and it is essential for the sequential phosphorylation cascade that drives cell proliferation and migration. By their ability to degrade hydrogen peroxide, peroxiredoxins are involved in growth factor signaling regulation and in the oxidative stress response. To verify the potential association of peroxiredoxin I, platelet-derived growth factor-A, and platelet-derived growth factor receptor-alpha with carcinoma ex pleomorphic adenoma progression, we investigated the expression of these molecules in carcinoma ex pleomorphic adenoma showing different degrees of invasion. The peroxiredoxin I, platelet-derived growth factor-A, and platelet-derived growth factor receptor-alpha proteins were present in remnant pleomorphic adenoma to only a small extent, but, collectively, they were highly expressed as soon as the malignant phenotype was achieved and remained at elevated concentrations during progression to the advanced stages of carcinoma ex pleomorphic adenoma. In addition, their locations overlapped significantly, strengthening their connection to this growth-signaling pathway. Our results indicate that carcinoma ex pleomorphic adenoma cells acquire at least 2 significant advantages relative to their normal counterparts: resistance to oxidative stress-induced apoptosis, conferred by high peroxiredoxin I concentrations, and sustained growth, reflecting platelet-derived growth factor-A and platelet-derived growth factor receptor-alpha overexpression.

Sebaceous carcinoma (SC) is a rare malignancy, affecting mainly the periocular glands. To the best of the authors' knowledge, this is the first English-language report of parotid SC affecting children; two cases are presented. Immunohistochemical studies included 29 different antibodies (15 of these were cytokeratins, CKs). For each case, DNA ploidy status was determined using isolated nuclei stained with Feulgen and analysed using a DNA image cytometry system. Most of the tumour cells were positive for CKs AE1/AE3, 34B12, 5 and 7. The CK14 pattern depicted the monolayer of basal cells surrounding the islands of malignant tissue, while the more central sebaceous differentiated cells were negative. Epithelial membrane antigen was strongly positive in the well differentiated cells, while most of the basaloid peripheral cells were negative, and only a few cells were positive for carcinoembryonic antigen. beta catenin, E cadherin and C-erb B2 were expressed by most of the cells including the more differentiated sebaceous cells. Tumour cells were negative for muscle or myoepithelial markers, androgen, oestrogen and progesterone receptors. Both SCs were uniformly diploid, and showed low proliferative indices for p53, Ki-67 and Mcm-2, which is consistent with the good clinical course presented by these patients so far.

The aim of the present study was to evaluate the signal transducer and activator of transcription (STAT3) expression, which is constitutively active in different types of malignant tumours, in salivary gland tumours. Fifty biopsies of salivary gland tumours (9 pleomorphic adenomas, 12 adenoid cystic carcinomas, 7 epithelial-myoepithelial carcinomas, 10 polymorphous low-grade adenocarcinomas and 12 mucoepidermoid carcinomas) and 10 normal salivary glands were immunohistochemically labeled for STAT3 and Phospho-STAT3 (STAT3P). The labeled sections were qualitatively and quantitatively evaluated. The results showed that, in normal salivary gland, STAT3 was expressed in cytoplasm and STAT3P in nuclei of all tissue cells, except in large mucous acinar cells for which both antibodies were negative. In pleomorphic adenoma, the expression was the same as in normal glands. In malignant tumours, there were variations in the expression of these antibodies. The most important one was the presence of STAT3 in the nuclei of the malignant tumour cells, most evident in the cribriform-type of adenoid cystic carcinoma. Both loss and variation of STAT3P expression were also observed. The presence of STAT3 in the nuclei of malignant salivary gland tumours may represent an important event in oncogenesis probably contributing to tumour cell proliferation while blocking apoptosis. However, further investigation will be necessary to support this hypothesis.

Introduction. Polymorphous low-grade adenocarcinoma (PLGA) occurs more frequently in minor salivary glands. The diagnosis of PLGA, in general, is not difficult but in occasional tumors showing limited invasion or in small biopsy specimens, PLGA may be confused with cellular pleomorphic adenoma (PA). Plasmacytoid cells, a usual component of PAs, have been considered helpful for correct tumor identification. Objective. The aim of this study was to verify the frequency (if any) of plasmacytoid-type cellular differentiation (PD) in PLGA. Materials and Methods. Thirty-two cases of PLGA were reviewed. PD was recognized in 2 cases (6.25%), in which immunohistochemical expression of AE1/AE3, CK7, CK14, vimentin, α-SMA, p63, S-100, calponin, GFAP, and Ki-67 was evaluated. Results. The 2 cases presented conventional areas of PLGA and variable quantities of cells with PD forming aggregates in the stroma and lining ductal structures. Cells with PD showed positivity for AE1/AE3, CK7, S-100, and vimentin and were negative for CK14, calponin, and GFAP in both cases. In case 1, cells with PD did not present α-SMA and p63 positivity whereas in case 2 they were positive, but for α-SMA such reactivity was restricted to cells forming solid aggregates. Conclusion. Although PD in PLGA is rare, it is necessary to be aware of this possibility, particularly in small incisional biopsies and in PLGA with limited invasion, to avoid confusion with cellular PA.

Eosinophilic angiocentric fibrosis (EAF) and granuloma faciale (GF) share several histopathologic features, including eosinophil-rich inflammation, microangiitis, and progressive fibrosis. Concurrent presentation of EAF and GF suggests a pathogenetic link between them.To identify histologic findings that tell them apart and construe the pathogenetic mechanisms behind each morphologic variable, 14 immunohistochemical markers were used to study the cells subpopulations in 14 cases of GF and 3 cases of EAF.The lesions were classified according to their stage of development. The antibodies studied were: CD4, Foxp3, CD8, granzymes A and B, perforin, granulysin, CD20, CD56, CD68, ICAM-1, CD34, CD105, and 1A4.The intensity of the sclerotic response and the density of 1A4-immunostained cells were significantly higher in EAF. In both diseases, CD68 cells were the most numerous, followed by CD20, CD8, and CD4 cells. About 30% of cells expressed ICAM-1. Among cells with cytotoxic granules, granulysin-positive cells were the most frequent.Differences between GF and EAF were found to be mostly like due to anatomic site (usually skin of the face vs. sinonasal cavity) and stage of the disease development (usually earlier in cutaneous lesions because of their visibility). Innate and adaptive immunity, including B cells, T cells, and cytotoxic granules have a role in their pathogenesis.

Lysozyme is an enzymatic marker of acinar and intercalated duct cells of normal salivary glands. The aim of this study was to verify whether lysozyme expression could be useful to distinguish acinic cell carcinoma (ACC) from its main mimic, mammary analog secretory carcinoma (MASC). For comparison, DOG1 expression was analyzed as well. Seventeen cases of ACC, 15 MASC, and 125 other salivary tumors were studied. Lysozyme expression was found in tumor cells as well as in secreted material of MASC (86.6 % of cases) and in ductal cells of epithelial–myoepithelial carcinoma (EMC-53.8 %), pleomorphic adenoma (PA-29.1 %) and polymorphous low-grade adenocarcinoma (PLGA-23.8 %). However, in ACC, lysozyme was not expressed. Three patterns of DOG1 staining were seen: apical–luminal, cytoplasmic, and mixed cytoplasmic/membranous. The apical–luminal pattern was detected in ductal cells of ACC (58.8 % of cases), EMC (38.4 %), adenoid-cystic carcinoma (AdCC-35.3 %), PA (8.3 %), and PLGA (4.8 %). These tumors also showed mixed membranous/cytoplasmic staining for DOG1. MASC, mucoepidermoid, and salivary duct carcinomas exhibited only DOG1 cytoplasmic staining. In conclusion, lysozyme cannot be used as a marker of acinar differentiation in salivary tumors. However, lysozyme expression can be helpful to distinguish MASC from ACC due to its high frequency in the former and absence in ACC. It is likely that in MASC, lysozyme expression may reflect a lactational-like secretory differentiation since lysozyme belongs to breast milk proteins. Regarding DOG1 expression, the apical–luminal pattern is related to acinar and intercalated duct differentiation whereas the cytoplasmic staining does not seem to be associated with a specific cellular phenotype.

We analyzed the tumor vascularization in carcinomas ex-pleomorphic adenoma (CXPA) to investigate the angiogenic switch during the malignant transformation of pleomorphic adenoma (PA) to carcinoma and during tumor progression. In eight cases of early CXPA (intracapsular and minimally invasive tumors), eight of advanced CXPA (widely invasive tumors), and ten of PA without malignant transformation, tumor vascularization was assessed in histological samples by measuring total microvascular area (TVA) and microvessel density (MVD) using CD34 and CD105 antibodies. MVD for CD105 increased significantly during tumor progression, whereas this was not the case for CD34 MVD. Comparing widely invasive CXPA with and without myoepithelial differentiation, CXPA with myoepithelial differentiation showed a significantly lower number of CD105 positive vessels but revealed higher TVA values. In these tumors, the neoplastic cells usually formed larger hypovascularized aggregates that were often surrounded by large-sized vessels. In conclusion, the antibody CD105 reveals an angiogenic switch during the progression from adenoma to carcinoma in salivary glands. The degree of angiogenesis and the total vascular area have distinctive patterns in CXPA with and without myoepithelial differentiation. Low angiogenesis associated with high TVA value is more characteristic of CXPA with myoepithelial differentiation.

Tonsillar lymphoid polyps are uncommon lesions that have rarely been studied. The authors describe the clinical, histopathologic, and immunohistochemical features of 6 tonsillar polyps in which lymphoid tissue represented more than 80% of the lesion. Presenting symptoms were tonsillar mass and/or dysphagia. No predisposing factor was detected. Microscopically, all polyps contained follicles with germinal centers, crypts lined by lymphoepithelium, and a small amount of fibrous tissue in the center of the lesion. B cells (CD20+), T cells (CD45RO+), plasma cells (κ+ and λ+) and vessels (lymphatic, D2-40+; blood, CD34+) presented distribution and architectural patterns as expected for lymphoid tissue of a palatine tonsil. Tonsillar lymphoid polyps are possibly hamartomas characterized by overgrowth of lymphoid elements, which maintain an architectural pattern and cellular composition similar to those of the palatine tonsil.

Background Data on prevalence of lung diseases due to inhalation of carbonaceous materials other than mineral coal is very limited. Methods We present three cases of wood charcoal pneumoconiosis, two due to activated carbon, and one from wood charcoal artisan handling. To our knowledge, no clinical cases of wood charcoal pneumoconiosis, from artisan handling has been published so far. Clinical Cases The three cases had their X rays classified by two B-readers as p/q round opacities with profusion ranging from 2/2 to 3/3. HRCT of two of them showed a diffuse centrilobular ground glass nodular pattern with subpleural small areas of consolidations. Transbronchial biopsies showed deposition of black pigment in the bronchiolar interstice similar to the histological appearance of simple coal workers pneumoconiosis, with no signs of fibrosis. Spirometry showed no abnormalities in the three cases. Conclusions The authors point out to a probably underestimated respiratory occupational risk related to wood charcoal manipulation, which must be addressed mostly in developing countries, where deficient workplace conditions can lead to exposure above limit levels. Am. J. Ind. Med. 50: 191–196 2007. © 2007 Wiley-Liss, Inc.

Objective The progression of pleomorphic adenoma (PA) to carcinoma ex-pleomorphic adenoma (CXPA) encompasses several genomic alterations involving complex pathways. Tumor suppressor genes seem to play important roles in the tumorigenesis of both tumors. The aim of this study was to evaluate copy number and methylation of tumor suppressor genes' status in PA and CXPA samples. Study Design Eight cases of PA, 2 cases of residual PA in CXPA, and 5 cases of CXPA were studied; the latter were classified according to invasiveness and histopathological subtype. Changes in 41 tumor suppressor genes were evaluated by multiplex ligation-probe dependent amplification analysis. Results Copy number losses of CASP8, MLH1, and RARB genes were associated with PA and CXPA, while KLK3 and AI69125 copy number losses were exclusive to CXPA. The sarcomatoid carcinoma showed more copy number alterations compared with other subtypes. Hypermethylation of RASSF1 was found mainly in PA and less frequently in malignant tumors. Conclusions CASP8, MLH1, and RARB tumor suppressor genes were altered by copy number losses during PA progression to CXPA. Lastly, RASSF1 inactivation by methylation was also detected in both tumors.

// Leisa Lopes-Aguiar 1 , Ericka Francislaine Dias Costa 1 , Guilherme Augusto Silva Nogueira 1 , Tathiane Regine Penna Lima 1 , Marilia Berlofa Visacri 2 , Eder Carvalho Pincinato 1 , Luciane Calonga 3 , Fernanda Viviane Mariano 4 , Albina Messias de Almeida Milani Altemani 4 , Joao Mauricio Carrasco Altemani 5 , Claudia Malheiros Coutinho-Camillo 6 , Maria Almerinda Vieira Fernandes Ribeiro Alves 1 , Patricia Moriel 2 , Celso Dario Ramos 5 , Carlos Takahiro Chone 3 , Carmen Silvia Passos Lima 1 1 Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Campinas, Sao Paulo, Brazil 2 Department of Clinical Pathology, Faculty of Medical Sciences, University of Campinas, Campinas, Sao Paulo, Brazil 3 Department of Ophthalmology and Otorhinolaryngology, Faculty of Medical Sciences, University of Campinas, Campinas, Sao Paulo, Brazil 4 Department of Pathology, Faculty of Medical Sciences, University of Campinas, Campinas, Sao Paulo, Brazil 5 Department of Radiology, Faculty of Medical Sciences, University of Campinas, Campinas, Sao Paulo, Brazil 6 Department of Pathology, A.C. Camargo Cancer Center, Sao Paulo, Sao Paulo, Brazil Correspondence to: Carmen Silvia Passos Lima, e-mail: carmenl@fcm.unicamp.br Keywords: head and neck squamous cell carcinoma, cisplatin, nucleotide excision repair pathway, single nucleotide polymorphisms, outcome Received: October 30, 2015 Accepted: February 16, 2016 Published: February 24, 2016 ABSTRACT This study aimed to investigate the associations of XPC c.2815A>C, XPD c.934G>A and c.2251A>C, XPF c.2505T>C and ERCC1 c.354C>T single nucleotide polymorphisms (SNPs) of nucleotide excision repair pathway in outcome of head and neck squamous cell carcinoma (HNSCC) patients treated with cisplatin (CDDP) chemoradiation. Patients with XPC c.2815AC or CC and XPD c.934GA or AA genotypes had 0.20 and 0.38 less chances of presenting moderate/severe ototoxicity and nausea, respectively. Patients with XPD c.934AA and c.2251AC or CC genotypes had 8.64, 12.29 and 3.55 more chances of achieving complete response (CR), consistent ototoxicity and nephrotoxicity, respectively. AA haplotype of XPD and ACT haplotype of XPD and ERCC1 SNPs were associated with 9.30 and 3.41 more chances of achieving CR and consistent nephrotoxicity, respectively. At 24 months of follow-up, patients with XPD c.934AA genotype presented lower progression-free survival and overall survival in Kaplan-Meier estimates, and differences between groups remained the same in univariate Cox analysis. Patients with XPD c.934AA genotype had 2.13 and 2.04 more risks of presenting tumor progression and death than others in multivariate Cox analysis. Our data present preliminary evidence that XPC c.2815A>C, XPD c.934G>A and c.2251A>C, and ERCC1 c.354C>T SNPs alter outcome of HNSCC patients treated with CDDP chemoradiation.

Objectives A subgroup of tonsillar squamous cell carcinoma (SCC) is associated with human papillomavirus (HPV). Nevertheless, the prevalence of HPV seems to be variable in different regions and ethnic groups. There are no reports of HPV in tonsillar carcinomas in Guatemala, and data from Brazil are scarce. The aim of this study is to analyze and compare HPV presence in samples of tonsillar SCC from these countries. Study Design This study describes the histologic features, expression of p16 by immunohistochemistry (IHC), and HPV by in situ hybridization (ISH) in 13 Guatemalan and 13 Brazilian patients. Results All cases of tonsillar SCC from Guatemala were positive for p16, 92% expressed HPV by ISH, and 75% corresponded to the high-risk genotype 16/18. From the Brazilian patients, only four expressed p16, and all were negative for HPV. Conclusions Cases from Guatemala, which were mostly nonkeratinizing SCC and originated from the crypt/reticular epithelium of the tonsil, had high-risk integrated HPV, whereas in Brazilian cases, which were mostly keratinizing SCC that originated from the surface epithelium, there was no association with HPV.

In the present study, we evaluated and described the sensitivity of the stem cell marker B cell-specific moloney murine leukemia virus integration site 1 (Bmi-1) in identifying early lesions of carcinoma ex pleomorphic adenoma (CXPA). While invasive CXPAs are tumors with a prominent and easily recognizable malignant component, the identification of early carcinomatous changes in PA remains a diagnostic challenge due to the lack of objective morphological criteria. The immunohistochemical expression of Bmi-1 was assessed in both adenomatous and carcinomatous components of 9 CXPA cases at an early phase of histological progression (6 intracapsular and 3 minimally invasive) grouped according to the cellular differentiation as luminal (7 cases) or myoepithelial (2 cases). A selective nuclear expression of Bmi-1 was found exclusively in the malignant component of 8 cases (6 luminal type and 2 myoepithelial type), including intraductal carcinoma areas, except for 1 case in which scarce cells of the remnant PA were positive. Thus, Bmi-1 is expressed from the earliest morphologically detectable stages of PA malignant transformation. When faced with atypical features in PA, evaluation of Bmi-1 expression can provide more objective criteria for identification and diagnosis of early lesions of CXPA. This is applied to carcinomas with luminal or myoepithelial differentiation.

Salivary gland tumors are a highly heterogeneous group of lesions with diverse microscopic appearances and variable clinical behavior. The use of clinical and histological parameters to predict patient prognosis and survival rates has been of limited utility, and the search for new biomarkers that could not only aid in a better understanding of their pathogenesis but also be reliable auxiliaries for prognostic determination and useful diagnostic tools has been performed in the last decades with very exciting results. Hence, gene rearrangements such as CRTC1-MAML2 in mucoepidermoid carcinomas have shown excellent specificity, and more than that, it has been strongly correlated with low-grade tumors and consequently with an increased survival rate and better prognosis of patients affected by neoplasms carrying this translocation. Moreover, MYB-NFIB and EWSR1-ATF1 gene fusions were shown to be specifically found in cases of adenoid cystic carcinomas and hyalinizing clear cell carcinomas, respectively, in the context of salivary gland tumors, becoming reliable diagnostic tools for these entities and potential therapeutic targets for future therapeutic protocols. Finally, the identification of ETV6-NTRK3 in cases previously diagnosed as uncommon acinic cell carcinomas, cystadenocarcinomas, and adenocarcinomas not otherwise specified led to the characterization of a completely new and now widely accepted entity, including, therefore, mammary analogue secretory carcinoma in the list of well-recognized salivary gland carcinomas. Thus, further molecular investigations of salivary gland tumors are warranted, and the recognition of other genetic abnormalities can lead to the acknowledgment of new entities and the acquirement of reliable biomarkers.

Pleomorphic adenoma (PA) is the most common salivary gland neoplasm, and while mostly benign, recurrences (RPA) and malignant transformation to carcinoma ex-PA (CXPA) do occur. Cell cycle proteins important in its tumorigenesis have been studied as markers for PA with a high risk of RPA or CXPA. The aim of the present study was to investigate cell cycle markers p-16, cyclin D1, CDK4, E2F, and retinoblastoma (Rb) in this context. Expression of p16, cyclin D1, E2F, CDK4, and Rb was studied by immunohistochemistry in 24 cases of PA, 21 of RPA, and 2 of CXPA. The presence of HPV was assessed by in situ hybridization. Immunostaining for p16 and cyclin D1 was negative or weakly positive in most cases of PA while strongly positive in the majority of RPA and both CXPA cases. Staining for Rb and CDK4 was either negative or weakly positive in PA, RPA, and CXPA. Expression of E2F was stronger in RPA and CXPA than in PA. Nuclear reactivity for HPV was not observed in any case. In conclusion, the strong staining for p16, cyclinD1, and E2F in RPA and CXPA, while weak or negative in PA, suggests that these proteins might be involved in recurrence and malignant transformation of PA.

Aims: To assess lymphatic vascular density (LVD) and lymph vessel endothelial proliferation in a series of carcinoma ex pleomorphic adenoma (CXPA) that represents the tumour in the different carcinogenesis phases and tumour progression. Methods: In 8 cases of early CXPA (intracapsular and minimally invasive tumours), 8 of advanced CXPA (widely invasive tumours) and 10 of pleomorphic adenoma (PA) without malignant transformation, lymphatic vessels and proliferating cells were detected using the antibodies D2-40 and Ki-67 respectively. Results: Comparing early tumours with advanced ones, LVD was not significantly different at the tumour margin. In contrast, regarding intratumoural lymphatics, PA without malignant transformation and early CXPA contained rare, if any, lymph vessels, whereas in widely invasive carcinomas they were more numerous. However, neither intratumoural nor peritumoural LVD were increased in comparison to adjacent normal salivary gland tissue. In no case did dual immunohistochemistry using D2-40 and the cell proliferation marker Ki-67 reveal the existence of proliferating lymphatics. Carcinomatous emboli were found in peritumoural as well as in intratumoural lymphatics only in advanced CXPA without myoepithelial differentiation. Conclusion: In CXPA, the lymphatic network is mainly composed of pre-existing lymphatics which are rare in tumours that have not infiltrated outside the confines of the original PA. In the widely invasive CXPA, intratumoural as well as peritumoural lymphatics are a conduit for carcinoma cells, but in carcinomas with myoepithelial differentiation, the neoplastic cells seem to have a lower invasion capacity.

The myoepithelial cell (MC) is a component of various secretory glands, including salivary glands. Besides its function, a tumor suppressor and a tumor facilitating functions have been attributed to this cell. We investigated the immunoprofile of benign MC in intraductal areas of carcinoma ex-pleomorphic adenoma (CXPA), comparing them with the MC in duct-like areas of pleomorphic adenoma, origin of the malignant tumor. Antibodies against myoepithelial markers-CK14, alpha-SMA, calponin, P63, CD10, and D2-40-plus laminin and maspin was applied in four selected cases of intracapsular and minimal invasive CXPA with only luminal differentiation presenting areas of intraductal carcinoma. The immunohistochemical reactions of all the antibodies showed stronger staining in benign MC surrounding the malignant epithelial cells than in benign MC in duct-like areas of pleomorphic adenoma, thus revealing that in the malignization process the benign MC become differentiated and produce important proteins related to the tumor suppressor function.

This study evaluated the expression of E-cadherin and β-catenin in salivary gland tumors. Twelve biopsy specimens from cases diagnosed as pleomorphic adenoma, 17 adenoid cystic carcinomas, 10 epithelial-myoepithelial carcinomas, and 4 polymorphous low-grade adenocarcinomas were immunohistochemically labeled for E-cadherin and β-catenin antibodies. Healthy salivary glands were used as controls. Membrane-associated E-cadherin and β-catenin expression was present in all the tumor types studied. E-cadherin and β-catenin showed a similar distribution; however, β-catenin labeling was weaker than that for E-cadherin. In the epithelial-myoepithelial carcinomas, myoepithelial cells exhibited diffuse nuclear staining, although occasional cells presented only focal labeling. Epithelial-myoepithelial carcinomas present changes in [.beta]-catenin expression but the other salivary tumors studied do not, which may reflect divergence in tumorigenesis of this extensive subset of salivary gland tumors.

Although an in vitro study has hypothesized that expression of ICAM-1 by villous trophoblasts could be important for the influx of maternal immune cells in villitis, it remains to be shown whether the same phenomenon occurs in human villitis. To investigate the expression of ICAM-1 by villous trophoblasts, its relationship with rupture of the trophoblastic barrier and influx of immune cells into the villi, we analysed 18 paraffin-embedded placentas with placentitis (5 by Toxoplasma gondii , 3 by Trypanosoma cruzi , 2 by Paracoccidioides brasiliensis and 8 of unknown aetiology – VUE) and 8 control placentas for detection of ICAM-1 by immunohistochemistry. All cases but one of placentitis showed trophoblast overexpression of ICAM-1 in the inflamed villi, located almost exclusively next to the areas of trophoblastic rupture. The villitis cases (caused by T. cruzi , T. gondii and VUE) presented leukocyte adherence in the areas of trophoblastic rupture. When the inflammatory reaction was situated in the intervillous space (placentitis by P. brasiliensis ), in spite of the trophoblastic rupture and ICAM-1 overexpression there was no leukocyte influx into villi. None of the control placentas showed ICAM-1 expression by the trophoblast. We concluded that overexpression of ICAM-1 by villous trophoblasts occurs during placentitis characterized by accumulation of leukocytes in the villous or intervillous space and probably plays an important role in the rupture of the trophoblastic barrier. The influx of immune cells into the villi appears to be mediated by ICAM-1 but the location of the antigen within villous stroma is certainly a crucial factor for its occurrence.

Polymorphous low-grade adenocarcinoma (PLGA) is a malignant neoplasm of low aggressiveness that occurs almost exclusively in the minor salivary glands, primarily those in the palate. We report a case of PLGA that arose in the base of the tongue and subsequently metastasized to the neck. The tumor was resected through the oral cavity with wide margins and dissection. The neck metastasis was treated with radical neck dissection and radiotherapy. The patient recovered and remained disease-free at follow-up 30 months later. This case shows that PLGA, which has a variable morphologic appearance, can occur at sites other than the salivary glands.

To perform histopathological evaluation in biopsies of palatine tonsils in a group of patients, with symptoms of chronic caseous tonsillitis, treated with an innovative and conservative method, using CO(2) laser.In general, the treatment of chronic caseous tonsillitis with CO(2) laser, as described in the literature, refers to the clinical experience of the authors and, the technique used for criptolysis encourages tissue vaporization, which leads to the consequent reduction of the tonsillar parenchyma.The individuals were submitted to cryptolysis coagulation with only 6 W of CW, CO(2) laser power, in scanned and unfocused mode, over a mean area of 2.2 mm diameter, leading to energy doses from 18 to 54.5 joules/cm(2). Biopsies were performed at the beginning and end of each treatment. A comparative analysis was performed between the initial and final biopsies taking into consideration possible alterations in the following: germinal centers, lymphoid tissue, sub-epithelial fibrosis, and parenchyma fibrosis.The histopathological analysis of these biopsies showed that the laser, used at a specific energy density, could relieve the symptoms of the disease causing neither increase of the fibrotic content nor decrease of the lymphoid structure. The action of the laser, following the proposed technique, is superficial, causing only epithelial coagulation, which enables a weakening of the tension forces in the crypt borders, causing them to open. This effect results in the reduction and even disappearance of caseous retention.We, therefore, conclude that the proposed method of treatment with CO(2) laser, called laser cryptolysis by coagulation (LCC) is an effective and conservative method, causing no significant morphological alterations to the tonsils.

BACKGROUND: The objectives of this study are to analyze the frequency and the histopathological features of the villitis of unknown etiology (VUE) in placentas of pregnancies with hypertensive disorders and of small-for-gestational-age infants (SGA). METHODS: Two hundred and thirteen placentas from pregnancies without clinical or laboratorial evidence of infection were studied. These cases were subdivided according to: a) maternal condition in: non-complicated pregnancy (NCP)- 151 cases, pregnancy-induced hypertension (PIH)- 37 and sustained chronic hypertension (SCH)- 25 and b) newborn weight in: small for gestational age (SGA)- 38 cases and adequate for gestational age (AGA)- 175. Of these placentas, 81 belong to the random sample, which was used to determine the frequency of VUE in the population studied. Eight blocks were taken from placental parenchyma and the histological sections were stained with hematoxylin and eosin. Frequency tables of categorical data were analyzed using the chi- square test and Fisher test; statistical significance was considered for p< 0.05. RESULTS: The frequency of VUE in the placentas was 30.8% in the random sample, 39% in NCP, 29.7% in PIH, 32% in SCH, 34.2% in SGA infants and 37.1% in AGA infants. Placentas of pregnancies with hypertensive disorders were more affected by villitis with parenchymatous component (PIH - 27.0%, SCH - 28.0%). This lesion was also the predominant villitis in the placentas of the SGA infants (31.5%). In contrast, in placentas of NCP and AGA infants, the principal kind of villitis was basal, not associated to a parenchymatous component (16.5% and 14.8% respectively). In the majority of the cases the villitis was mild. CONCLUSION: In the population studied, the frequency of VUE is high (around 30%). The lesion occurs in a similar frequency in placentas from NCP, PIH, SCH, SGA and AGA infants, but basal villitis not associated to a parenchymatous component affects mainly the placentas of NCP and AGA infants. It is possible that this kind of villitis could be an expression of an antigenic stimulation diverse from villitis with a parenchymatous component.

Linear epidermal nevus is an uncommon diagnosis of benign lesions of the oral cavity. It is characterized by a congenital malformation arising from the ectoderm cells, which are arranged according to a typical linear configuration known as Blaschko’s lines. We report a case of linear epidermal nevus of oral cavity in a 51-year-old lady or woman. The linear epidermal nevus of the oral cavity, although rare, can be considered a differential diagnosis of oral papillomatosis (OP). The histopathological studies and detailed description are the center of the diagnostic and clinical evolution.

During tumor invasion, benign myoepithelial cells of carcinoma ex-pleomorphic adenoma (CXPA) surround malignant epithelial cells and disappear. The mechanisms involved in the death and disappearance of these myoepithelial cells were investigated via analysis of the expression of regulatory proteins for apoptosis, autophagy and cellular senescence in an in situ in vitro model. Protein expression relating to apoptosis (Bax, Bcl-2, Survivin), autophagy (Beclin-1, LC3B) and cellular senescence (p21, p16) was evaluated using indirect immunofluorescence. β-galactosidase expression was assessed via histochemistry. Biopsies of CXPA (ex vivo) allowed immunhistochemical evaluation of p21 and p16, whilst LC3B, p21 and p16 protein expression was analyzed by western blotting. In the in vitro model, the myoepithelial cells were positive for LC3B (cytoplasm) and p21 (nucleus), whilst in vivo positivity for p21 and p16 was observed. In vitro, β-galactosidase activity increased in the myoepithelial cells over time. Western blotting analysis revealed an increased LC3B, p16 and p21 expression in the myoepithelial cells with previous contact with the malignant cells when compared with those without contact. The investigation of behavior of benign myoepithelial cells in ductal areas of CXAP revealed that the myoepithelial cells are involved in the autophagy-senescence phenotype that subsequently leads to their disappearance.