A rare case of mucoepidermoid carcinoma ex-pleomorphic adenoma of the hard palate

Carcinoma Ex-Pleomorphic Adenoma (CExPA) is a salivary gland carcinoma derived from a primary or recurrent benign pleomorphic adenoma (PA) extremely rare in minor salivary glands. In this paper, we report the case of a male afrodescendant patient, 37 years old, presenting a palatal irregular nodular lesion with approximately 3.5 cm diameter. The lesion had over two years of evolution, but started growing faster and presenting pain and ulceration in the last two months. The incisional biopsy revealed a typical pleomorphic adenoma with focal areas of nests of epidermoid and mucous cells, as well as microcyst formations, resembling the mucoepidermoid carcinoma (MEC). Immunohistochemical analysis revealed positivity for CK7, CK13, CK 14, p63 and Ki67 (about 30%), whereas alpha-SMA was restricted to the PA component. The diagnosis was CExPA (MEC-type). A discussion on the histopathological and immunohistochemical criteria for differential diagnosis of CExPA is provided in this work, hoping to contribute to a better knowledge and understanding of this rare malignant tumor. Key words:Salivary gland neoplasms, pleomorphic adenoma, adenocarcinoma, mucoepidermoid carcinoma, pathology, differential diagnosis

Mis casos clínicos de especialidades odontológicas

Libro que muestra la atención de casos clínicos particulares referente a las diferentes especialidades odontológicasLibro que muestra la atención de casos clínicos particulares referente a las diferentes especialidades odontológicasUniversidad Autónoma de Campeche Universidad Autónoma del Estado de Hidalgo Universidad Autónoma del Estado de Méxic

Odontogenic carcinoma with dentinoid in long-term follow-up with 2 recurrences

Dentinoid has been mentioned as a frequent component in several types of benign odontogenic tumors; however, there are some other very rare dentinoid-producing odontogenic tumors that have been described, which are not recognized in the current World Health Organization Histological Classification of Odontogenic Tumours. In this context, we report an unusual malignant odontogenic tumor containing dentinoid located in the left maxilla of a 41-year-old man. The lesion was initially diagnosed and treated as a cemento-ossifying fibroma. After 7 years, a tumor was noted at the same location and was diagnosed as pleomorphic adenoma. The patient developed a new lesion 2 years later. Histological features included an epithelial proliferation of basaloid and clear cells, some with peripheral palisading, which were scattered both in a fibrous stroma and within an amorphous eosinophilic dentinoid product. Because of doubts about the first 2 diagnoses and the current situation, all histopathological slides were reviewed in our service as a consultation case, and the findings were consistent with the diagnosis of an odontogenic carcinoma with dentinoid. Immunohistochemical analysis was performed and an ultrastructural study by scanning electronic microscopy and energy-dispersive X-ray microanalysis was made to characterize dentinoid material. After 1 year of follow-up, the patient is alive and free of the disease. This case highlights the wide variability regarding cytological evidence of malignancy, and adds a new case of odontogenic carcinoma with dentinoid, which represents a distinct entity with locally aggressive behavior and should be considered be included in a future World Health Organization Histological Classification of Tumours.282FAPESP – Fundação de Amparo à Pesquisa Do Estado De São Paulo2016/07399-4; 2017/00831-

Evaluation of a subset of tumor suppressor gene for copy number and epigenitic changes in pleomorphic adenoma and carcinoma ex-pleomorphic adenoma carcinogenesis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)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 RARE 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.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 of1223322331FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)2011/23366-5; 2011/23204-

Loss of expression of Plag1 in malignant transformation from pleomorphic adenoma to carcinoma ex pleomorphic adenoma

PLAG1 (pleomorphic adenoma gene 1) is frequently activated in pleomorphic adenoma (PA). Carcinoma ex pleomorphic adenoma (CXPA) arises in PA, and PLAG1 expression is believed to be maintained from PA to CXPA, as it can contribute to the carcinogenesis process. To evaluate if PLAG1 is a good marker of malignant transformation from PA to CXPA as well as to evaluate if PLAG1 expression is associated with progression and histopathologic subtype of CXPA. Forty PAs, 21 residual PAs (without malignant transformation), and 40 CXPAs were analyzed by immunohistochemistry with PLAG1 antibody. The proportion of positive neoplastic cells was assessed according to a 2-tiered scale: >10% to 50%, and >50% positive cells. The CXPA group was classified according to histopathologic subtype and invasiveness degree. Thirty-seven PAs (92.5%), 15 residual PAs (71%), and 14 CXPAs (35%) were positive for PLAG1. In relation to the CXPA group, among the intracapsular cases, myoepithelial carcinoma and epithelial-myoepithelial carcinoma showed the highest level of PLAG1 expression. PLAG1 expression is lost when PA undergoes malignant transformation, possibly due to other pathway activation and different clone cells. In addition, PLAG1 expression seems to be present mainly in low-grade carcinomas and in cases with early phase of invasion, due to its regulation of oncogene-induced cell senescence. In CXPA, PLAG1 expression was most associated with myoepithelial differentiation. This way, loss of PLAG1 expression can be considered a hallmark of CXPA carcinogenesis, mainly when there is only epithelial differentiation57152159FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2014/18312-1; 2011/23366-5; 2011/23204-