Extra-tongue oral granular cell tumor : histological and immunohistochemical aspect

Granular cell tumor (GCT) is an uncommon benign tumor founded in any part of the body but mainly in the tongue. Extra-tongue oral granular cell tumor (ETOGCT) is rare with few cases reported. Here we describe seven cases of oral GCT located in sites other then the tongue and discuss histopathological and immunohistochemical differences between differential diagnoses. We retrieved all cases diagnosed with oral granular cell tumor, from the Oral Pathology Service at the School of Dentistry/ University of São Paulo, and excluded the ones sited in the tongue. Immunohistochemical staining anti-S100 was also performed. The presented cases of Extra-tongue Oral Granular Cell Tumor (ETOGT) are composed by granular cells with intimately association with the adjacent tissue. Atypia and mitoses were not seen, and in most cases, the typical pseudoepitheliomatous hyperplasia was not observed. The importance of an adequate attention is to avoid misdiagnoses, since ETOGT is rare and the tricking histopathological findings could induce to it. All the cases can be differentiated from the tumors that has a granular cell proliferation through a morphological analysis and when needed, immunohistochemistry stain

The stem cell marker BMI-1 is sensitive in identifying early lesions of carcinoma ex pleomorphic adenoma

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)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.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 CXPAs9427FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [process 2012/00786-1]2012/00786-

Adenocarcinoma polimorfo de baixo grau: relato de caso clínico

O adenocarcinoma polimorfo de baixo grau (APBG) é uma neoplasia maligna incomum em região de cabeça e pescoço e que ocorre quase exclusivamente em glândulas salivares menores. Esta lesão apresenta baixo potencial biológico de malignidade e tem como principais diagnósticos diferenciais tanto clínico quanto histológico o adenoma pleomórfico e o carcinoma adenoide cístico. Descrevemos um caso de APBG em um paciente do sexo masculino com 59 anos de idade, leucoderma e que apresentava um nódulo assintomático de aproximadamente 10 dias de evolução em palato mole. Foi realizada uma biópsia incisional e o exame microscópico confirmou o diagnóstico de APBG. O tratamento dessas lesões envolve a completa excisão cirúrgica e raramente há recorrência ou desenvolvimento de doença metastática. Após três meses da excisão cirúrgica, o paciente não apresentou recorrências

Expression of stem cell-related pluripotency transcription factors in carcinoma ex pleomorphic adenoma progression

O adenoma pleomórfico (AP) é a neoplasia mais frequente das glândulas salivares e a sua transformação maligna em um carcinoma ex-adenoma pleomórfico (CXAP) é um evento incomum que ocorre em menos de 10% dos casos. O CXAP é tipicamente uma neoplasia infiltrativa, de alto grau e associada com metástase linfonodal no momento do diagnóstico. Acredita-se que a patogênese do CXAP tenha como base o acúmulo de alterações genéticas em APs de longa duração. Evidências recentes têm demonstrado que neoplasias podem conter subpopulações de células raras, com capacidade de auto-renovação e potencial proliferativo indefinido, as chamadas células-tronco neoplásicas (CTN). As CTN parecem estar envolvidas nos processos de iniciação e progressão neoplásicas, assim como metástases e resistência terapêutica. O objetivo deste trabalho foi avaliar a expressão imuno-histoquímica, tanto nas áreas benignas quanto nas malignas, dos fatores de transcrição relacionados à pluripotência de células-tronco Bmi-1, SOX2 e Nanog em CXAPs em fases precoces (7 intracapsulares e 3 minimamente invasivos) e avançada (14 francamente invasivos) de progressão histológica. A análise dos resultados de imuno-histoquímica foi realizada de maneira semi-quantitativa de acordo com o escore 0 (ausência de células positivas), 1 (60% de células positivas). Correlacionou-se, ainda, esses resultados com parâmetros anatomopatológicos de agressividade neoplásica através do teste Exato de Fisher. A parótida foi a glândula mais acometida em ambos os grupos (62,5%), e homens e mulheres foram igualmente acometidos. A média de idade foi 61,1 anos. No grupo de CXAPs precoces, Bmi-1 foi expresso no componente carcinomatoso de todos os casos e em escassas células das áreas benignas de 1 caso. O fator SOX2 foi expresso pelas células carcinomatosas em 90% desses casos e em escassas células do AP residual de 1 caso. Já Nanog foi expresso apenas no componente maligno de 60% dos casos. Por outro lado, Bmi-1 foi expresso nas áreas malignas de 71,4% dos CXAPs avançados e em ocasionais células da área benigna de 1 caso. O AP residual de nenhum caso desse grupo foi positivo para SOX2 e Nanog, que foram expressos pelas áreas malignas em 92,8% e 35,7% dos casos, respectivamente. Assim, notou-se queda na expressão de Bmi-1 e Nanog na progressão do CXAP. Ainda, a expressão de SOX2 parece correlacionar-se com necrose neoplásica (p=0,06) e metástase linfonodal ao diagnóstico (p=0,08), entretanto a amostra estudada parece pequena para evidenciar esse dado estatístico. Concluiu-se que Bmi-1, SOX2 e Nanog são superexpressos na transformação maligna do AP. Entretanto, Bmi-1 e Nanog aparentemente não exercem função determinante no processo de progressão neoplásica, ao passo que SOX2 parece contribuir com o processo de metástase em CXAP.Pleomorphic adenoma (PA) is the most common salivary gland tumor and its malignant transformation into a carcinoma ex pleomorphic adenoma (CXPA) is an unusual event occuring in less than 10% of the cases. The CXPA is typically an infiltrative and high-grade neoplasm at diagnosis associated with lymph node metastases. It is believed that the pathogenesis of CXPA is based on the accumulation of genetic changes in long-standing PAs. Recent evidences have shown that tumors may contain subpopulations of rare cells, capable of self-renewal, and with indefinite proliferative potential, the so-called neoplastic stem cells (NSC). The NSC appears to be involved in neoplastic initiation and progression, as well as metastasis and treatment resistance. The objective of this study was to evaluate the immunohistochemical expression of stem cell-related pluripotency transcription factors Bmi-1, SOX2, and Nanog in benign and malignant areas of CXPA at early (7 intracapsular and 3 minimally invasive) and advanced (14 frankly invasive) stages of histological progression. Immunohistochemical analysis was performed semiquantitatively according to the scores 0 (no positive cell), 1 (60% positive cells). These results were also correlated with pathological parameters of neoplastic aggressiveness using the Fisher\'s Exact test. The parotid gland was the most affected site in both groups (62.5%), and men and women were equally affected. The mean age was 61.1 years. In the early CXPA group, Bmi-1 was expressed in carcinomatous component of all cases and in occasional cells of benign areas of 1 case. The SOX2 factor was expressed by the carcinomatous cells in 90% of cases and scant cells in residual PA of 1 case. Nanog was expressed in 60% of cases, only in the malignant component. On the other hand, Bmi-1 was expressed in malignant areas of 71.4% of advanced CXPAs and in occasional cells of benign area of 1 case. The residual PA of none of the cases in this group was positive to SOX2 and Nanog, which were expressed by carcinomatous areas in 92.8% and 35.7% of cases, respectively. Thus, it was noted that Bmi-1 and Nanog expression decreases in CXPA progression. Yet, SOX2 expression seems to be correlated with neoplastic necrosis (p= 0.06) and lymph node metastasis at diagnosis (p=0.08), but the current sample seems to be small to evidence this statistic data. It was concluded that Bmi-1, Nanog, and SOX2 are overexpressed in malignant transformation of PA. However, Bmi-1 and Nanog apparently do not exert a decisive role in the process of neoplastic progression, while SOX2 seems to contribute to the process of metastasis in CXPA

Carcinoma ex pleomorphic adenoma of minor salivary glands with major epithelial-myoepithelial component: clinicopathologic and immunohistochemical study of 3 cases

In the present study, 3 cases of very rare intraoral carcinomas ex pleomorphic adenomas showing a striking differentiation of the malignant component towards epithelial-myoepithelial carcinoma were described. The tumors occurred in 2 men and 1 woman with median age of 56 years. Involved sites included palate and buccal mucosa. Two patients experienced local recurrences, of which one died of disease complications. In all cases, residual pleomorphic adenoma was present The malignant component in all cases shared morphological aspects with epithelial-myoepithelial carcinoma. Those areas were characterized by eosinophilic duct-forming cells surrounded by layers of clear cells. The studied immunohistochemical markers highlighted a biphasic cell population. Duct-forming cells expressed pan-cytokeratin, cytokeratin 7, and focally cytokeratin 14, whereas the clear cell component strongly stained to cytokeratin 14, vimentin, and p63 but weakly stained to pancytokeratin and focally to a-smooth muscle actin, an immunophenotype compatible with both epithelial and myoepithelial differentiation. The Ki-67 proliferation index was up to 40% in malignant areas. Carcinoma ex pleomorphic adenomas of minor salivary glands with major epithelial-myoepithelial component are rare, locally aggressive, and potentially lethal tumors. The peculiar morphological and immunohistochemical aspects described may raise problems in diagnosis and classification of such cases, particularly in incisional biopsies. (C) 2015 Elsevier Inc. All rights reserved.In the present study, 3 cases of very rare intraoral carcinomas ex pleomorphic adenomas showing a striking differentiation of the malignant component towards epithelial-myoepithelial carcinoma were described. The tumors occurred in 2 men and 1 woman with193164168sem informaçãosem informaçã

ORAL HIV-ASSOCIATED KAPOSI SARCOMA: A COMPARISON BETWEEN IMMUNOHISTOCHEMISTRY AND qPCR TECHNIQUES FOR DETECTION OF HHV8

Objective: To compare the diagnostic accuracy of immunohistochemistry compared to real-time PCR (using a simple phenol-chloroform DNA extraction protocol) in the detection of HHV8 in small oral biopsies of Kaposi sarcoma. Also to validate the use of this DNA extraction protocol to extract HHV8 DNA.Material and methods: Seventeen cases of oral KS were examined. Data including gender, age, and anatomic location were obtained from patient´s records and histological sections stained with hematoxylin and eosin (H&E) were reviewed. Immunohistochemistry was used to detect HHV8 in lesions of interest, as well as real-time PCR.Results: All the patients were HIV positive, the mean age was 35.5 years old, and the affected oral sites were palate (47%), gingiva (29.4%), tongue (11.8%), lip (5.9%), and oral floor (5.9%). Fifteen samples showed positive staining for HHV8 and only two samples were negative. The same results were observed using real-time PCR HHV8-DNA detection.Relevance: Our findings suggest that immunohistochemistry is faster and cheaper to perform than real-time PCR and was shown to have similar levels of sensitivity and accuracy for detection of HHV8 even in small biopsies. Additionally DNA extraction using a non-commercial kit, as done in this study can further reduce the costs to a pathology service

ORAL HIV-ASSOCIATED KAPOSI SARCOMA: A COMPARISON BETWEEN IMMUNOHISTOCHEMISTRY AND qPCR TECHNIQUES FOR DETECTION OF HHV8

Objective: To compare the diagnostic accuracy of immunohistochemistry compared to real-time PCR (using a simple phenol-chloroform DNA extraction protocol) in the detection of HHV8 in small oral biopsies of Kaposi sarcoma. Also to validate the use of this DNA extraction protocol to extract HHV8 DNA.Material and methods: Seventeen cases of oral KS were examined. Data including gender, age, and anatomic location were obtained from patient´s records and histological sections stained with hematoxylin and eosin (H&E) were reviewed. Immunohistochemistry was used to detect HHV8 in lesions of interest, as well as real-time PCR.Results: All the patients were HIV positive, the mean age was 35.5 years old, and the affected oral sites were palate (47%), gingiva (29.4%), tongue (11.8%), lip (5.9%), and oral floor (5.9%). Fifteen samples showed positive staining for HHV8 and only two samples were negative. The same results were observed using real-time PCR HHV8-DNA detection.Relevance: Our findings suggest that immunohistochemistry is faster and cheaper to perform than real-time PCR and was shown to have similar levels of sensitivity and accuracy for detection of HHV8 even in small biopsies. Additionally DNA extraction using a non-commercial kit, as done in this study can further reduce the costs to a pathology service