Synchronous metastatic cutaneous squamous cell carcinoma and chronic lymphocytic leukaemia/small lymphocytic lymphoma in a cervical lymph node: case report of an unusual event

The synchronous occurrence of two different neoplasias is an uncommon event, which may arise between tumors originating in the same organ or in cancer-to-cancer metastasis. We report a rare case of chronic lymphocytic leukaemia / small lymphocytic lymphoma associated with a cutaneous metastatic squamous cell carcinoma in a cervical lymph node. In the affected lymph node, it was observed an effacement of the normal architecture by neoplastic lymphocytes and it was noted the presence of neoplastic invasive epithelial islands. Immunohistochemical analysis demonstrated that lymphocytic proliferation was positive for CD20, CD5, CD23 and Kappa, and negative for CD3, CD10, Cyclin D1 and Lambda. The morphological and immunohistochemical profile lead to a phenotype of B-cell chronic lymphocytic leukaemia / small lymphocytic lymphoma. The epithelial cells were positive for CK5, thus rendering the diagnosis of synchronous metastatic cutaneous squamous cell carcinoma and chronic lymphocytic leukaemia/small lymphocytic lymphoma. Literature supports the poor prognosis in cases that present coexistence of squamous cell carcinoma and chronic lymphocytic leukaemia / small lymphocytic lymphoma. Thus, it is necessary to be aware about this unusual finding in order to provide specific treatment

Plasma cell cheilitis: the diagnosis of a disorder mimicking lip cancer

Plasma cell cheilitis (PCC) is an inflammatory disorder of unknown etiology that affects the lip. It is characterized histologically by a dense infiltrate of plasma cells with a variety of clinical features. The response to different therapeutic modalities is controversial, especially regarding the effectiveness of corticosteroids. We present a case of a 56-year-old Caucasian man with a painful ulcerated and crusted area in the lower lip, resembling a squamous cell carcinoma or actinic cheilitis. Topical corticosteroid was used for one week, which resulted in partial regression and motivated a biopsy. The histological examination provided the diagnosis of PCC. The patient has been disease-free for six months. We also provide a discussion on the criteria of differential diagnosis and management of this rare condition. See ERRATUM&nbsp

Intracytoplasmic lipid droplets in salivary gland carcinomas : immunohistochemical study

Orientadores: Albina Messias de Almeida Milani Altemani, Fernanda Viviane MarianoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de PiracicabaResumo: Introdução: Gotas lipídicas (GL) são organelas altamente reguladas envolvidas na ativação e metabolismo celular assim como em processos inflamatórios e neoplásicos. O aumento da lipogênese levando a um aumento no número de GL é um fenótipo comum a numerosos carcinomas humanos e tem sido associado com: diferenciação, proliferação e agressividade tumoral. Objetivo: Avaliarem carcinomas salivares: a) a frequência e quantidade das GLs citoplasmáticas, correlacionando-as com a morfologia tumoral, grau de diferenciação e proliferação celular e b) a expressão de proteínas relacionadas ao processo secretório celular (STAT5a e mamoglobina). Material e métodos:em 79 casos de carcinomas de glândulas salivares foram utilizados os anticorpos Ki-67, adipophilin, STAT 5a e mamoglobina. A quantificação da imunoreatividade ao adipophilin, STAT 5a e mamoglobina foi através de uma escala semi-quantitativa. A intensidade de marcação do STAT 5a e mamoglobina foi subjetivamente avaliada como fraca/moderada ou intensa. A positividade ao Ki-67 foi calculada através da relação entre o número de células positivas e o número total de células tumorais em três áreas selecionadas da amostra. Resultados:os subtipos histopatológicos que apresentaram positividade ao adipophilin em 50% ou mais das células, foram os casos: MASC (100%), CCA (85,64%), CM (83%), CDS (75%) e CSeb (50%). Índice de proliferação maior que 10% das células tumorais foi observado no CSeb (Ki-67 = 29%), seguido do CDS (Ki-67 = 23,11%) e do CM (Ki-67 = 12,15%). Nos casos de CAC com transformação para alto grau a área transformadaapresentou maior proliferação e lipogênese quando comparada à área convencional. Somente os casos de MASC apresentaram imunorreatividade acentuada para STAT5a e mamoglobina. Conclusões: Embora exista correlação entre o acúmulo de gotas lipídicas e o índice proliferativo do tumor, em alguns tipos de carcinomas salivares tal depósito está possivelmente relacionado à diferenciação celular (CSeb e MASC) ou alteração metabólica (CCA). O acúmulo de Gl refletindo diferenciação celular se apresenta como gotas maiores em contraste com as microgotas frequentemente detectadas nos carcinomas com alto índice proliferativo. No MASC a forte expressão de STAT5a e mamoglobina sugere que a que o acúmulo de GL possivelmente reflete diferenciação do tipo lactacional.Mais estudos são necessários para entender o papel das gotas lipídicas citoplasmáticas em carcinomas de glândulas salivares. (Apoio FAPESP: 2012/18104-4 e 2012/18086-6)Abstract: Introduction: Lipid droplets (LD) are highly regulated organelles involved in cell activation and metabolism as well as in inflammatory and neoplastic processes Upregulated lipogenesis leading to an increased number of cytoplasmic LD is a common phenotype to numerous human carcinomas and has been associated with: differentiation, proliferation and aggressiveness of the tumor. Objective: to evaluate in salivary carcinomas: a) the frequency and quantity of cytoplasmics LDs, correlating it with tumoral morphology, differentiation grade e cellular proliferation and b) the expression of proteins associated with cellular secretor process (STAT5a and mammaglobin). Material and Methods:in 79 cases of salivary gland carcinomas, an immunohistochemical study was performed with the antibodies Ki-67, adipophilin, STAT 5a and mammaglobin. The positive neoplastic cells were assessed regarding quantity using a semi-quantitative scale. The intensity of expression for each antibody was subjectively evaluated as weak/ moderate or intense.The positivity for Ki-67 was calculated based on the relation between the number of positive cells and the total number of the tumoral cells in three selected areas. Results: the histopatologic subtypes that presented positivity for adipophilin in 50% or more of cells were: AciCC (85,64%), MASC (100%), MC (83%), SDC (75%), SebC (50%). Proliferation index higher than 10% of tumoral cells was observed in SebC (Ki-67 = 29%), SDC (Ki-67 = 23,11%) and MC (Ki-67 = 12,15%). In ACC with high grade transformation the, the transformed area presented both higher proliferation and lipogenesis when compared to the convencional area. Only the cases of MASC presented accentuated immunoreactivity for STAT5a and mammaglobin. Conclusions: Although in salivary carcinomas there is correlation between the accumulation of lipid droplets and the proliferative index of the tumor, in some types of carcinomas such deposit is possibly related to cellular differentiation (SebC and MASC) or metabolic alteration (AciCC). The accumulation of LD that reflects cellular differentiationpresents features of macro droplets in contrast to micro-droplets frequently detected in carcinomas with high proliferative index. In MASC, the strong expression of STAT5a and mammaglobin suggests that LD accumulation is probably due to lactational-like differentiation. More studies are necessary to understand the role of cytoplasmic lipid droplets in salivary gland carcinomas (Supported by FAPESP: 2012/18104-4and2012/18086-6)MestradoPatologiaMestre em Estomatopatologi

Evaluation of cell cycle proteins in sinonasal melanomas and FASN gene polymorphisms in cutaneous melanomas

Orientadores: Albina Messias de Almeida Milani Altemani, Fernanda Viviane MarianoTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de PiracicabaResumo: O melanoma é considerado um tumor de baixa incidência, porém de alta letalidade, devido ao seu potencial metastático e à refratariedade medicamentosa. O incremento da proliferação celular é uma característica comum às neoplasias malignas, porém em relação ao melanoma sinonasal (MS), são escassos os estudos que delineiam possíveis alterações do aparato coordenador do ciclo celular. Ainda, a patogênese das neoplasias malignas caracteriza-se por uma mistura complexa de alterações genéticas e metabólicas. Neste cenário, a hiperatividade e superexpressão da enzima responsável pela fase catalítica terminal na síntese do ácido graxo (fatty acid synthase ¿ FASN) nas células cancerosas tem despertado muito interesse. A FASN- associada a tumor, além de funcionar como uma via para estoque de energia anabólica, confere vantagens de crescimento e sobrevida tumoral levando a um aumento do risco de recidiva, metástases e consequentemente pior prognóstico.O objetivo desse estudo foi verificar numa série de MSs a expressão de proteínas do ciclo celular e em melanomas cutâneos (MC) avaliar se os polimorfismos da FASN afetam o comportamento do MC. Para tanto foi avaliada a expressão de proteínas do ciclo celular nos MSs e os polimorfismos do gene FASN em MCs. Nos MSs, a expressão nuclear do p27 foi detectada em 37,5% dos casos e apenas 2 casos mostraram imunoreatividade citoplasmática. A expressão nuclear e citoplasmática de Skp2 ocorreu em 81,2%. A expressão aumentada de Skp2 concomitante com um nível reduzido ou ausente de p27 foi detectada em 11 casos (68,7%)e a média de expressão da proteína Ki-67 foi semelhante nas lesões com e sem expressão nuclear de p27 (15,4 e 16,2, respectivamente). Neste estudo, observamos que alguns dos polimorfismos do gene FASN mostraram várias associações com o risco e características clínicas do MC, o que em conjunto indica que a FASN pode desempenhar um importante papel na tumorigênese do MC. Concluímos que os MSs apresentam aspectos morfológicos compatíveis com neoplasias agressivas, expressão aumentada de Skp2 e baixa ou ausente de p27. É possível que esse padrão de expressão possa contribuir para o comportamento agressivo do MS. Porém, devido à ausência de associação entre expressão de p27 e proliferação celular, é provável que outras vias de atuação destas proteínas possam influenciar a agressividade tumoral. Em relação aos polimorfismos do gene FASN, acreditamos que os nossos resultados possam contribuir para identificar indivíduos com alto risco para a ocorrência do MC que mereçam receber atenção especial na prevenção, diagnóstico precoce e terapêutica diferenciadaAbstract: Melanoma is a low incidence tumor, although with high lethality, due to its metastatic potential and drug refractoriness. The increment of cellular proliferation is a common characteristic to malignant neoplasias, but in relation do sinonasal melanoma (SM), the studies that outline possible alterations in the coordinator apparatus of cell cycle are scarce. Yet, the pathogenesis of malignant neoplasias is characterized by a mixture of complex genetic and metabolic alterations. In this scenario, the hyperactivity and superexpression of the enzyme responsible for the final catalytic phase in synthesis of fatty acid (fatty acid synthase - FASN) in cancerous cells aroused much interest. The tumor associated FASN, besides its function as a way of anabolic energy storage, confers advantages to the tumor growth and survival leading to an increased risk of recurrence, metastasis, and consequently, worse prognosis. The aim of this study was to verify in a series SMs the expression of cell cycle proteins and in cutaneous melanomas (CM) evaluate if FASN polymorphisms affect the behavior of CM. Therefore, it was evaluated the immunohistochemical expression of Skp2, p27 and Ki-67 in SMs and the polymorphisms of FASN gene in CMs. In SMs, the nuclear expression of p27 was detected in 37.5% of the cases and only 2 cases showed cytoplasmic immunoreactivity. Nuclear and cytoplasmic expression of Skp2 occurred in 81.2% of the cases. The increased expression of Skp2 concomitant to a decreased or absent level of p27 was detected in 11 cases (68.7%) and the average of the expression of Ki-67 protein was similar in lesions with or without nuclear expression of p27 (15.4% and 16.2%, respectively). In this study, it was observed that some FASN gene polymorphisms showed several associations with the risk and clinical features of CM, which indicates that FASN may play an important role in the tumorigenesis of CM. It was concluded that SMs present morphological aspects compatible with aggressive neoplasias, increased expression of Skp2 and low or absent expression of p27. It is possible that this pattern of expression may contribute to the aggressive behavior of SM. However, due to the lack of association between the expression of p27 and cellular proliferation, it is probable that other pathways of these proteins may influence tumoral aggressiveness. In regard to the FASN gene polymorphisms, we believe that our results may contribute to the identification of people at high risk of CM that deserve special attention in prevention, early diagnosis and differentiated therapyDoutoradoPatologiaDoutor em Estomatopatologia2015/10240-4FAPES

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

Chronic paracoccidioidmycosis in a woman with Crohn Disease

We report a rare case of chronic paracoccidioidomycosis(PCM) in a woman with Crohn disease in the setting oftreatment with azathioprine and mesalazine. Serumtests for antigens to Paracoccidioides brasiliensis,Histoplasma capsulatum, and Aspergillus fumigatuswere negative. An incisional biopsy of an oral lesionwith periodic acid-schiff and Grocott-methenaminesilverstains revealed chronic granulomatousinflammation with multinucleated giant cells withParacoccidioides brasiliensis within the cytoplasm,confirming the diagnosis of PCM

Copper chelation reduces early collagen deposition and preserves saliva secretion in irradiated salivary glands

Radiation therapy is a first-line treatment for head and neck cancer; however, it typically leads to hyposalivation stemming from fibrosis of the salivary gland. Current strategies to restore glandular function are dependent on the presence of residual functional salivary gland tissue, a condition commonly not met in patients with extensive fibrotic coverage of the salivary gland resulting from radiation therapy. Fibrosis is defined by the pathological accumulation of connective tissue (i.e., extracellular matrix) and excessive deposition of crosslinked (fibrillar) collagen that can impact a range of tissues and given that collagen crosslinking is necessary for fibrosis formation, inhibiting this process is a reasonable focus for developing anti-fibrotic therapies. Collagen crosslinking is catalyzed by the lysyl oxidase family of secreted copper-dependent metalloenzymes, and since that copper is an essential cofactor in all lysyl oxidase family members, we tested whether localized delivery of a copper chelator into the submandibular gland of irradiated mice could suppress collagen deposition and preserve the structure and function of this organ. Our results demonstrate that transdermal injection of tetrathiomolybdate into salivary glands significantly reduced the early deposition of fibrillar collagen in irradiated mice and preserved the integrity and function of submandibular gland epithelial tissue. Together, these studies identify copper metabolism as a novel therapeutic target to control radiation induced damage to the salivary gland and the current findings further indicate the therapeutic potential of repurposing clinically approved copper chelators as neoadjuvant treatments for radiation therapy

Lipid Droplets Are Involved In The Process Of High-grade Transformation Of Adenoid Cystic Carcinoma

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