The outcome of transnasal endoscopic total maxillectomy in the treatment of sinonasal adenoid cystic carcinoma / 临床耳鼻咽喉头颈外科杂志

Objective:To assess the prognosis of sinonasal adenoid cystic carcinoma with hard palatine invasion treated by transnasal endoscopic total maxillectomy. Methods:Clinical data of twenty-six patients with sinonasal adenoid cystic carcinoma invading hard palatine treated by transnasal endoscopic total maxillectomy between May 2014 and December 2020 was analyzed retrospectively. Survival rate, local recurrence and distant metastasis were analyzed using Kaplan-Meier method. Cox regression was used to investigate the prognosis factors. Masticatory function after maxillectomy has also been assessed using the questionnaire of patients' satisfaction about masticatory function. Results:Margins in 8 patients（30%） were positive. The median time of follow-up was 38 months（6 to 85 months）. Twenty-five patients recurred. Four patients died of distant metastasis. The 5-year overall survival rate and relapse-free survival rate was 79.5% and 89.1%, respectively. Independent predictors of outcome on multivariate analysis were positive margin（P=0.018）, recurrence（P=0.006） and distant metastasis（P=0.04）. Conclusion:Transnasal endoscopic total maxillectomy could be performed for the treatment of the sinonasal adenoid cystic carcinoma with hard palatine invasion. Positive margin, local recurrence and distant metastasis were important predictors for patients' prognosis.

TRPS1 expression in salivary gland-type breast carcinoma and its clinical application / 中华病理学杂志

Objective: To investigate the expression of TRPS1 in salivary gland-type breast carcinoma and its clinical application. Methods: A total of 30 cases of salivary gland-type breast carcinoma diagnosed from May 2015 to November 2022 at the Department of Pathology of the First Affiliated Hospital of Nanjing Medical University were collected. The expression of TRPS1 was detected by immunohistochemistry and compared with that of GATA3. TRPS1 and GATA3 expression in 24 cases of primary salivary gland carcinoma. Results: There were 10 cases of breast secretory carcinoma, aged 21-61 years (median 53.5 years), with the size ranging from 0.9-2.2 cm (median 1.6 cm), 2 of which were accompanied by axillary nodal macrometastasis. All patients were alive after 2-55 months of follow-up (median 29.5 months, mean 29.7 months). There were 20 cases of breast adenoid cystic carcinoma, aged 36-77 years (median 53.5 years), with the size ranging from 1.2-5.5 cm (median 2.5 cm), 3 of which were accompanied by axillary nodal macrometastasis. All patients were alive after 3-92 months of follow-up (median 22.5 months, mean 31.7 months), and 1 patient had lung metastasis 15 months after surgery. The medium/high expression ratio of TRPS1 in breast secretory carcinoma was 10/10, which was higher than that of GATA3 (7/10). TRPS1 was also positive in the 2 cases with lymph node metastases. The medium/high expression rate of TRPS1 in breast adenoid cystic carcinoma was 20/20, which was significantly higher than that of GATA3 (2/20). TRPS1 was highly expressed in both classic and solid subtypes, while GATA3 was only expressed in a few cases of the classic subtype. TRPS1 was also positive in 3 cases with lymph node metastases and 1 case of the pulmonary metastases. The expression level of TRPS1 was the same in 1 case before and after neoadjuvant chemotherapy. In addition, TRPS1 was positive in parotid secretory carcinoma and adenoid cystic carcinoma. The medium/high expression rate of TRPS1 in parotid secretory carcinoma (6/6) was higher than that of GATA3 (2/6), and the medium/high expression rate of TRPS1 in parotid adenoid cystic carcinoma (17/18) was higher than that of GATA3 (2/18). Conclusions: The expression of TRPS1 is highly sensitive to salivary gland-type breast carcinoma, especially in GATA3-negative solid subtype of adenoid cystic carcinoma, which plays an important role in clinical practice.

Misdiagnosis of adenoid cystic carcinoma of oropharynx: a case report / 临床耳鼻咽喉头颈外科杂志

Adenoid cystic carcinoma usually occurs in the salivary glands of the head and neck. It is a malignant tumor with a high degree of malignancy, resistance to radiotherapy and chemotherapy and poor prognosis. The clinical course of adenoid cystic carcinoma is slow and easy to be misdiagnosed. The main diagnosis and treatment means are individualized and precise treatment under the multi-disciplinary consultation mode, that is, surgical treatment and radiotherapy and chemotherapy. Adenoid cystic carcinoma is prone to relapse and hematologic metastasis, and the traditional radiotherapy and chemotherapy based therapies have not achieved satisfactory efficacy in the past three decades. How to detect, diagnose and treat early is an urgent task faced by clinicians.

Treatment and prognosis analysis of perineural invasion on sinonasal adenoid cystic carcinoma / 中华肿瘤杂志

Objective: To analyze the efficacy of sinonasal adenoid cystic carcinoma (ACC) with perineural invasion (PNI), and explore the prognostic value of PNI on sinonasal adenoid cystic carcinoma. Methods: The clinical data of 105 patients with sinonasal ACC admitted to Cancer Hospital, Chinese Academy of Medical Sciences from January 2000 to December 2016 were retrospectively reviewed. All patients were restaged according to American Joint Committee on Cancer 8th edition. Follow-up visits were conducted to obtain information of treatment failure and survival outcome. The Log rank test was used for univariate analysis of prognostic factors, and Cox regression model was used for multivariate prognostic analysis. Results: The maxillary sinus (n=59) was the most common primary site, followed by the nasal cavity (n=38). There were 93 patients with stage Ⅲ-Ⅳ. The treatment modalities included surgery alone (n=14), radiotherapy alone (n=13), preoperative radiotherapy plus surgery (n=10), and surgery plus postoperative radiotherapy (n=68). The median follow-up time was 91.8 months, the 5-year local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were 72.6%, 73.0%, 52.9% and 78.0%, respectively. There were 33 patients (31.4%) with PNI-positive. The 5-year DMFS, PFS, and OS rates of PNI-positive group were 53.7%, 29.4% and 56.5%, respectively, which were significantly inferior to those of PNI-negative group (80.8%, 63.0% and 86.8%, respectively, P<0.05), while there was no significant difference in the 5-year LC rate between both groups (64.5% vs 76.5%, P=0.273). The multivariate Cox regression analysis showed PNI was one of the poor prognostic factors of DMFS (HR=3.514, 95%CI: 1.557-7.932), PFS (HR=2.562, 95%CI: 1.349-4.866) and OS (HR=2.605, 95%CI: 1.169-5.806). Among patients with PNI-positive, the 5-year LC, PFS and OS rates of patients received surgery combined with radiotherapy were 84.9%, 41.3% and 72.7%, respectively, which were significantly higher than 23.3%, 10.0% and 26.7% of patients receiving surgery or radiotherapy alone (P<0.05). Conclusion: The presence of PNI increases the risk of distant metastasis in patients with sinonasal ACC. Compared with patients with PNI-negative, the prognosis of patients with PNI-positive is relatively poor, and surgery combined with radiotherapy for PNI-positive sinonasal ACC results in good clinical outcomes.

Overexpression of CDC7 in malignant salivary gland tumors correlates with tumor differentiation / Superexpressão de CDC7 em tumores malignos de glândulas salivares correlaciona-se com a diferenciação dos tumores

Abstract Introduction: Cell division cycle-7 protein is a serine/threonine kinase that has a basic role in cell cycle regulation and is a potential prognostic or therapeutic target in some human cancers. Objectives: This study investigated the expression of cell division cycle-7 protein in benign and malignant salivary gland tumors and also its correlation with clinicopathologic factors. Methods: Immunohistochemical expression of cell division cycle-7 was evaluated in 46 cases, including 15 adenoid cystic carcinoma, 12 mucoepidermoid carcinoma, 14 pleomorphic adenoma, and 5 normal salivary glands. Cell division cycle-7 expression rate and intensity were compared statistically. Results: The protein was expressed in almost all tumors. The intensity and mean of cell division cycle-7 expression were higher in malignant tumors in comparison with pleomorphic adenomas (p = 0.000). The protein expression was correlated with tumor grades (p = 0.000). Conclusions: The present study demonstrated cell division cycle-7 overexpression in malignant salivary gland tumors in comparison with pleomorphic adenomas, and also a correlation with tumor differentiation. Therefore, this protein might be a potential prognostic and therapeutic target for salivary gland tumors.

Resumo Introdução: A cell division cycle-7 é uma serina/treonina quinase que tem um papel básico na regulação do ciclo celular e é um potencial marcador prognóstico ou terapêutico em alguns tipos de câncer humano. Objetivos: Este estudo investigou a expressão de cell division cycle-7 em tumores de glândulas salivares benignos e malignos e também sua correlação com fatores clínico-patológicos. Método: A expressão imuno-histoquímica de cell division cycle-7 foi avaliada em 46 casos, incluindo 15 carcinomas adenoide císticos, 12 carcinomas mucoepidermoides, 14 adenomas pleomórficos e 5 glândulas salivares normais. A taxa de expressão e a intensidade da proteína cell division cycle-7 foram comparadas estatisticamente. Resultados: A proteína foi expressa em quase todos os tumores. A intensidade e a média da expressão de cell division cycle-7 foram maiores em tumores malignos em comparação com adenoma pleomórfico (p = 0,000). A expressão da proteína foi correlacionada com os graus do tumor (p = 0,000). Conclusões: O presente estudo demonstrou a superexpressão de cell division cycle-7 em tumores malignos de glândulas salivares quando comparada com o adenoma pleomórfico, além de uma correlação com a diferenciação de tumores. Portanto, essa proteína pode ser um potencial marcador prognóstico e terapêutico para tumores de glândulas salivares.

Análise da relação entre a expressão de marcadores de células tronco tumorais (ALDH-1 e SOX-2) e as características clinico patológicas de neoplasias de glândulas salivares / Analysis of the relationship between the expression of tumor stem cell markers (ALDH-1 and SOX-2) and the clinicopathological characteristics of salivary gland neoplasms

Os mecanismos moleculares e celulares que estão associados a patogênese, baixa resposta ao tratamento, recidiva e óbito em tumores de glândula salivar não são totalmente conhecidos. Nesse sentido, é importante ressaltar que as células-tronco (CT) dentro de um tumor (CTT) estão relacionadas com a tumorigenicidade e progressão em neoplasias humanas. Diante do exposto, o objetivo desse trabalho foi avaliar a expressão de marcadores relacionados às CT (ALDH-1 e SOX-2) em neoplasias de glândula salivar e verificar se suas expressões apresentam associação com dados clinicopatológicos e desfecho dos pacientes. Foram selecionados 103 casos de neoplasias malignas (25 CME; 15 CCA; 13 CAC; 10 ACP; 13 ACSOE; 8 CEME; 7 CAEXAP; 5 CDS; 4 ACCB; 3 CCC) e 51 casos de neoplasias benignas (25 AP; 9 MIO; 7 TW; 5 ACA; 5 ACB). Os dados obtidos foram analisados no software Statistical Package for Social Science, GraphPad Prism e STATA. O nível de significância de 5% foi adotado para os testes estatísticos (p<0.05). Os pacientes do estudo foram principalmente do sexo masculino, com média de idade de 52 anos; a parótida foi o sítio anatômico mais afetado. A maioria das neoplasias malignas, foi classificada como T1-T2, N0 e M0. A expressão das proteínas foi avaliada através de imuno-histoquímica e confirmadas por meio de Western-blot, verificando-se que os resultados foram semelhantes entre as técnicas e que estavam correlacionados estatisticamente, tanto para SOX-2 (p<0.001) quanto para ALDH-1 (p=0.039). Em relação a expressão da SOX-2, a maioria dos tumores benignos foi negativa (n=39; 76.5%), sendo constatada expressão apenas nos tumores sem diferenciação mioepitelial (ACA e TW) (p<0.0001). Em contraparte a maioria dos tumores malignos estudados foi positiva para SOX-2 (n=54; 52.4%) sendo esse resultado estatisticamente significativo (p=0.002). Também foi evidenciada que essa expressão ocorreu em casos sem diferenciação mioepitelial (p=0.006) principalmente em CME e CCC. Não foram evidenciadas associações estatisticamente significativas entre a expressão de SOX-2 e parâmetros clínicos. A proteína ALDH-1 esteve frequentemente expressa no parênquima de neoplasias malignas (n=88; 85.6%) e benignas (100%). De maneira geral, a expressão da ALDH-1 no parênquima não se associou com parâmetros clínicos das neoplasias malignas, entretanto, os casos de CME com alta expressão no parênquima estavam associados com tumores de estadiamento clínico avançado (p=0.047). Foi constatada expressão da ALDH-1 em células do estroma tumoral, principalmente de neoplasias malignas (n=67; 65.0%), estando associada com metástase em linfonodos (p=0.032), estadiamento clínico avançado (p=0.008), recorrência tumoral (p=0.006) e óbito (p=0.013). A sobrevida global e livre de doença em 5 e 10 anos foi menor em pacientes diagnosticados com CAC, estadiamento clínico avançado, que apresentaram recorrência e com expressão estromal de ALDH-1. Destaca-se que na análise multivariada, o estadiamento clínico avançado e expressão estromal da ALDH-1 representaram fatores prognósticos independentes na sobrevida livre de doença. Com base nos resultados apresentados pode-se concluir que o perfil que caracteriza as CTT apresenta variações nos diferentes tumores de glândula salivar. A expressão diferencial da SOX-2 e ALDH-1 nessas neoplasias sugere que existem subtipos diferentes de CTT que podem ser ativadas por vias moleculares distintas. Conclui-se também que a presença de marcação estromal para ALDH-1 caracteriza células com perfil de CT mesenquimais que podem estar diretamente relacionada com o comportamento biológico e progressão de tumores malignos em glândula salivar (AU).

The molecular and cellular mechanisms that are associated with pathogenesis, poor treatment response, recurrence, and death in salivary gland tumors are not fully known. In this matter, stem cells (SC) within a tumor (TSC) are related to tumorigenicity and progress in human neoplasms. As such, the aim of this study was to evaluate the expression of SC-related markers (ALDH-1 and SOX-2) in salivary gland neoplasms and their possible association with clinicopathological data and patient outcomes. We selected 103 cases of malignant neoplasms (25 mucoepidermoid carcinoma; 15 acinic cell carcinoma; 13 adenoid cystic carcinoma; 10 polymorphous adenocarcinoma; 13 adenocarcinoma NOS; 8 epithelial-myoepithelial carcinoma; 7 carcinoma ex pleomorphic adenoma; 5 salivary duct carcinoma; 4 basal cell adenocarcinoma; 3 clear cell carcinoma) and 51 cases of benign neoplasms (25 pleomorphic adenoma; 9 myoepithelioma; 7 Warthin tumor; 5 canalicular adenoma; 5 basal cell adenoma). Data were analyzed in Statistical Package for Social Science, GraphPad Prism and STATA softwares. A significance level of 5% was adopted for the statistical tests (p<0.05). Most patients were male, with a mean age of 52 years, and the parotid was the most common anatomical site. Most malignant neoplasms were classified as T1-T2, N0 and M0. Protein expression assessed by immunohistochemistry and confirmed by western blot showed similar results that were statistically correlated for both SOX-2 (p<0.001) and ALDH-1 (p=0.039). Regarding the expression of SOX-2, most benign tumors were negative (n=39; 76.5%), and expression was only observed in tumors without myoepithelial differentiation (p<0.0001). In the other hand, most of the malignant tumors were positive for SOX-2 (n=54; 52.4%), being statistically significant (p=0.002). The expression occurred in cases without myoepithelial differentiation (p=0.006) mainly in mucoepidermoid carcinoma and clear cell carcinoma. No association was found between SOX-2 expression and clinical parameters. ALDH-1 was frequently expressed in the parenchyma of malignant (n=88; 85.6%) and benign (100%) neoplasms. Overall, the presence of ALDH-1 in the parenchyma was not associated with clinical data of malignant neoplasms; nevertheless, the cases of mucoepidermoid carcinoma with high expression in the parenchyma were associated with advanced clinical stage (p=0.047). The expression of ALDH-1 in tumor stroma cells occurred mainly in malignant neoplasms (n=67; 65.0%), being associated with lymph node metastasis (p=0.032), advanced clinical stage (p=0.008), recurrence (p=0.006) and death (p=0.013). Overall survival and Diseasefree survival at 5 and 10 years were lower in patients diagnosed with adenoid cystic carcinoma, advanced clinical stage, recurrence and stromal expression of ALDH-1. Multivariate analysis showed advanced clinical stage and stromal expression of ALDH1 were independent prognostic factors for disease-free survival. Based on the results, the profile of TSC presents variations in different salivary gland tumors. The differential expression of SOX-2 and ALDH-1 in these neoplasms suggests that there are different subtypes of TSC that can be activated by distinct molecular pathways. Also, the presence of ALDH-1 stromal expression characterizes cells with mesenchymal CT profile that may be directly related to the biological behavior and progress of malignant tumors in the salivary gland (AU).

BRD4 inhibition suppresses cell growth, migration and invasion of salivary adenoid cystic carcinoma

BACKGROUND: Bromodomain-containing protein 4 (BRD4) inhibition is a new therapeutic strategy for many malignancies. In this study, we aimed to explore the effect of BRD4 inhibition by JQ1 on in vitro cell growth, migration and invasion of salivary adenoid cystic carcinoma (SACC). METHODS: The human normal epithelial cells and SACC cells (ACC-LM and ACC-83) were treated with JQ1 at concentrations of 0, 0.1, 0.5 or 1 µM. Cell Counting Kit-8 (CCK-8) assay was performed to evaluate cell proliferation. Cell apoptosis and cell cycle distribution was evaluated by Flow cytometry. Immunofluorescence staining was used to examine the expression of BRD4 in SACC cells. The quantitative real-time polymerase chain reaction (qRT-PCR) assay and western blot assay were performed to examine messenger RNA (mRNA) and protein levels in SACC cells. Wound- healing assay and transwell assay were used to evaluate the activities of migration and invasion of SACC cells. RESULTS: JQ1 exhibits no adverse effects on proliferation, cell cycle and cell apoptosis of the normal human epithelial cells, while suppressed proliferation and cell cycle, and induced apoptosis of SACC cells, down-regulated the mRNA and protein levels of BRD4 in SACC cells, meanwhile reduced protein expressions of c-myc and BCL-2, two known target genes of BRD4. Moreover, JQ1 inhibited SACC cell migration and invasion by regulating key epithelial-mesenchymal transition (EMT) characteristics including E-cadherin, Vimentin and Twist. CONCLUSIONS: BRD4 is an important transcription factor in SACC and BRD4 inhibition by JQ1 may be a new strategy for SACC treatment.

Adenoid cystic carcinoma of the lacrimal sac: case report / Carcinoma adenóide cístico do saco lacrimal: relato de caso

ABSTRACT Lacrimal sac tumors are rare with a clinical presentation that typically includes obstruction of the lacrimal drainage system and epiphora as the most frequent symptom. Cribriform adenoid cystic carcinoma (ACC) is the most common malignant epithelial tumor of the lacrimal gland and minor salivary glands; however, its occurrence in the lacrimal drainage apparatus is extremely rare. Given the rarity of ACC, definitive diagnosis is almost invariably late conferring a poor prognosis. Herein we report the case of a 41-year-old woman with primary ACC of the lacrimal sac and describe the ophthalmological examination, diagnosis, and multidisciplinary treatment of this rare type of tumor.

RESUMO Tumores do saco lacrimal são raros. A apresentação clínica muitas vezes mostra uma obstrução no sistema de drenagem lacrimal sendo a epífora o sinal mais frequente. Carcinoma adenóide cístico cribriforme (ACC) é o tumor epitelial maligno mais comum da glândula lacrimal e glândulas salivares menores, mas a sua ocorrência no aparelho de drenagem lacrimal é extremamente rara. Infelizmente, devido a raridade destes tumores, o diagnóstico preciso é quase sempre atrasado, o que por sua vez leva a um pior prognóstico. Nós relatamos o caso de uma mulher de 41 anos de idade, com ACC primário do saco lacrimal e analisamos o exame oftalmológico, diagnóstico e tratamento multidisciplinar deste tipo de tumor.

Carcinoma adenoideo quístico de mama: serie de casos / Adenoid cystic carcinoma of the breast: case series

El carcinoma adenoideo quístico (CAQ) de mama es un cáncer poco frecuente y representa entre el 0,1% y el 0,4% de todos los carcinomas de mama. A continuación se presentan dos casos con el objetivo de describir un tipo de carcinoma de mama de presentación poco frecuente con evolución clínica no común. El primero de una mujer de 34 años y el segundo de una mujer de 44 años, ambas con diagnóstico confirmado de CAQ de mama. El CAQ de mama es de predominio en el sexo femenino en la etapa postmenopáusica. Sin embargo, ambas pacientes presentaron el CAQ en edad fértil. Generalmente posee un pronóstico favorable con rara diseminación, a diferencia de estos dos casos presentados donde se observa varias metástasis a distancia y un curso muy agresivo de la enfermedad.

Adenoid cystic carcinoma (ACC) of the breast is a rare neoplasm and accounts for 0.1% to 0.4% of all breast carcinomas. This is a description of two clinical cases that describe a rare presentation with an uncommon clinical course. The patients are 34 and 44 year old women, both with a confirmed diagnosis of ACC of the breast. The ACC of the breast predominantly grows in postmenopausal women. However, both patients are still fertile. Commonly it has a favorable prognosis and a rare presentation of metastasis. Nevertheless, in both cases, distant dissemination and an aggressive course of the disease was observed.

Expressão de VEGF-C, VEGF-D, mensuração da densidade linfática e da proliferação endotelial linfática em neoplasias de glândulas salivar / Expression of VEGF-C, VEGF-D density measurement of lymphatic and lymphatic endothelial proliferation in salivary gland neoplasms

As neoplasias de glândulas salivares exibem uma grande diversidade morfológica e comportamentos biológicos variados o que suscita o interesse na pesquisa destas lesões. A disseminação das células tumorais é um passo inicial para a progressão de neoplasias malignas e, dentro deste contexto, os vasos linfáticos neoformados são considerados essenciais para que ocorra essa disseminação. O papel do VEGF (fator de crescimento endotelial vascular) na formação dos vasos é fato conhecido mas, pouco se sabe a respeito de sua participação em tumores de glândula salivar. Desta forma, o objetivo deste estudo foi avaliar a expressão do VEGF-C e VEGF-D, a densidade linfática tumoral (D2-40) e a proliferação endotelial linfática (dupla marcação D2-40/Ki-67) em uma série de neoplasias de glândulas salivares. A amostra foi composta por 20 adenomas pleomórficos, 20 carcinomas adenóides císticos, 20 carcinomas mucoepidermóides e 10 casos de tecido glandular salivar com características de normalidade para efeito comparativo. Todos os casos estudados exibiram expressão positiva para VEGF-C em região peritumoral e intratumoral, não sendo encontrada diferenças de imunoexpressão entre os grupos. No entanto, o grupo dos carcinomas adenóides císticos demonstrou diferença significativa da imunoexpressão do VEGF-C segundo o padrão cribriforme e sólido (p = 0,004). A maioria dos casos constantes do presente estudo, apresentou fraca marcação para VEGF-D em região peritumoral e intratumoral...

Salivary gland neoplasms exhibit a great morphological diversity and varied biological behavior which raises the interest in the study of these lesions. The spread of tumor cells is an early step in the progression of malignancies and the neoformed lymphatic vessels are considered essential in tumor dissemination. Vascular endotelial growth fator (VEGF) is a family of proteins involved in angiogenesis e lymphangiogenesis. However, in salivar tumors we have limited information on the expression. The aim of this study was to assess the expression of VEGF-C and VEGF-D, lymphatic vessel density (single-staining D2-40) and lymphatic endothelial proliferation (double labeling D2-40/Ki-67) in a series of salivary glands neoplasms. We selected 20 cases of pleomorphic adenoma, 20 of mucoepidermoide carcinoma, 20 of adenoid cystic carcinoma and 10 tissue sample of normal salivary gland. All cases studied showed positive expression of VEGF-C in intratumoral and peritumoral region, no differences in immunoreactivity was found between the groups. However, the group of adenoid cystic carcinoma showed a significant difference in immunoreactivity of VEGF-C by the cribriform and solid pattern (p = 0.004). Most of the cases included in this study showed weak immunoreactivity for VEGF-D in intratumoral and peritumoral region. In the assessment of lymphatic endotelial density peritumoral, intratumoral and total, the groups showed an increasing gradient, with lower values for the group of pleomorphic adenomas followed by mucoepidermoid carcinoma and adenoid cystic carcinoma. Lymphatic endothelial cell density was higher in malignant than benign tumors. No correlation was observed between the immunoreactivity of VEGF-C and VEGF-D in relation to tumor lymphatic density and lymphatic endothelial proliferation.

Avaliação da via do c-kit no adenoma pleomórfico e carcinoma adenoide cístico das glândulas salivares: estudo da expressão das proteínas da via, das mutações e da regulação pós-transcricional do gene kit / c-Kit signaling cascade in pleomorphic adenoma and adenoid cystic carcinoma of salivary glands: evaluation of cascade proteins, mutations and post-transcriptional regulation of gene Kit

Introdução: As neoplasias das glândulas salivares têm amplo espectro histológico resultante da múltipla diferenciação celular tumoral. O adenoma pleomórfico (AP) e o carcinoma adenoide cístico (CAC) são as mais comuns neoplasias benignas e malignas provenientes do ducto intercalado, respectivamente, além de serem compostas por estruturas luminais e células mioepiteliais. Em estudo realizado previamente pelo nosso grupo, detectamos que a proteína c-kit está envolvida nos processos da morfogênese das glândulas salivares e no adenoma pleomórfico. A proteína c-Kit tem papel importante no desenvolvimento de muitos processos embrionários, incluindo a gametogênese, melanogênese e hematopoiese, e também na biologia de tumores. Sua ativação induz diversas respostas intracelulares através de cascatas de sinalização de vias como PI3K/AKT e MAPK. Em tumores da glândula salivar ainda há poucos estudos sobre as alterações do gene KIT e das proteínas relacionadas a sua via de sinalização, assim como sua regulação pós-transcricional, realizada principalmente por meio dos microRNAs. O presente estudo avaliou, em APs e CACs (a) a localização das proteínas das vias PI3K/AKT/mTOR e MAPK por meio da técnica de imunoistoquímica; (b) a expressão dos microRNAs 221 e 222, relacionados ao gene KIT (c) a associação dos achados laboratoriais com variáveis clínicas, patológicas e sobrevida. Resultados: Nos casos de AP a proteína c-Kit foi identificada em formações luminais e em raras células isoladas no parênquima tumoral. Já nos CAC, observou-se positividade na membrana das células ductais. Para a via de PI3K/AKT/mTOR, no AP, a proteína PI3K beta mostrou-se parcialmente positiva no citoplasma das células próximas à capsula tumoral, e as proteínas AKT e mTOR fosforiladas, foram expressas especialmente nas células epiteliais e em poucas células mioepiteliais. Já no CAC, a proteína PI3K beta e AKT fosforilada mostraram-se negativas na maioria dos casos, e a proteína mTOR fosforilada foi expressa no citoplasma das células epiteliais e em algumas células mioepiteliais. Para a via MAPK, as proteínas RAS, MEK-1 fosforilada e ERK 1/2 foram negativas na maioria dos AP e CAC; B-Raf e MEK-2 fosforilada foram observadas nas células luminais dos AP. Nos CAC, estruturas luminais neoplásicas foram positivas para a proteína MEK-2 fosforilada; B-Raf foi positivo nas células luminais e mioepiteliais. Além disso, os pacientes que expressaram as proteínas mTOR e MEK-2 fosforilada apresentaram sobrevida câncer-específica significativamente aumentada (p=0,040 e p=0,005, respectivamente). Na análise do microRNAs, a expressão do miR-221 foi variável nas 13 amostras analisadas, tendo baixa expressão em 30,77% dos casos, expressão normal em 38,46 e expressão aumentada em 30,77% dos casos. Já nos APs o miR-221 foi detectado em 19 amostras, sendo 36,84% com baixa expressão, 52,63% com expressão normal e expressão aumentada foi vista em 10,53% dos casos. A expressão do miR-222 foi detectada em 14 CACs, sendo que a maioria dos casos (8 casos ­ 57,1%) a expressão do miR-222 foi semelhante ao observado nas amostras não neoplásicas. Nos APs, o miR-222 foi detectado em 22 amostras, sendo 31,8% com baixa expressão, 31,8% com expressão normal e 36,4% com expressão aumentada. Conclusão: Apesar de a proteína c-Kit ser expressa em ambas as neoplasias ­ AP e CAC, sua influência sobre as vias de sinalização MAPK e PI3K/AKT/mTOR ainda permanece por ser estabelecida. Ainda, os microRNAs 221 e 222 não mostram correlação consistente com a expressão de c-Kit nos tipos tumorais estudados.

Introduction: Salivary gland tumors present broad histological spectrum resulting from multiple tumor cell differentiation. Pleomorphic adenoma (PA) and adenoid cystic carcinoma (ACC) are the commonest benign and malignant salivary gland neoplasms originated from the intercalated duct region, respectively, and are composed by luminal structures and myoepithelial cells. In a previous study we detected that protein c-kit is involved in the process of salivary gland morphogenesis and PA. c-Kit protein is important during embryogenesis, including gametogenesis, melanogeneis and hematopoiesis as well as in tumorigenesis. Its activation induces various intracellular responses through pathways such as MAPK and PI3K/AKT/mTOR signaling cascades. In salivary gland neoplasms, only a few reports have shown that alterations in KIT gene are present and proteins related to its signaling pathway as well as its post-transcriptional regulation. This study has aimed at evaluating in PA and ACC: (a) the proteins location of PI3K/AKT/mTOR and MAPK pathways using immunohistochemistry (IHC); (b) expression of miR-221 and miR-222, related to KIT gene; and (c) the association of these findings with clinical, pathological and survival data of patients. Results: In PA c-kit was positive in isolated luminal cells; in ACC, neoplastic luminal structures were positive for c-Kit. In PA, PI3K beta protein was shown to be partially positive in the cytoplasm of cells near the tumor capsule and phosphor AKT and phospho mTOR, are specifically expressed in epithelial cells and in a few myoepithelial. In ACC, PI3K and phosphor AKT protein showed to be negative in most of cases. Phospho mTOR protein was expressed in the cytoplasm of epithelial cells and some myoepithelial cells. In MAPK pathway, Ras, ERK1/2 and phosphor MEK-1 proteins were negative in most PAs and CACs; B-Raf and phospho MEK-2 were detected in luminal cells of PA. In ACC neoplastic luminal structures were positive for phospho MEK-2; B-Raf was also positive in myoepithelial and epithelial cells. In addition, cases with expressed phospho-mTOR and phosphor MEK-2 proteins were significantly associated with higher cancer-specific survival (p = 0.040 and p = 0.005, respectively). Moreover, expression of miR-221 was detected in 13 CAC samples and 19 PA samples. In CAC, expression of miR-221 was downregulated in 30,77% of the samples, upregulated in 30,77% samples, and normal in 38,46% samples. In PA, miR-221 expression was downregulated in 36,84% samples, upregulated in 10,53% samples, and normal in 52,63% samples. Expression of miR-222 was detected in 14 CAC samples and 22 PA samples. In the majority of CAC samples, the expression of miR-222 was similar to that observed in non-neoplastic samples. In PA samples, expression of miR-222 was downregulated in 31,8% samples, upregulated in 36,4% samples, and normal in 31,8% samples. Conclusion: Although c-Kit expression is detected in PA and ACC, its influence on the MAPK e PI3K/AKT/mTOR signaling cascades remains to be established. miR-221 e -222 did not show a robust correlation with c-Kit expression in the tumors studied.

Primary cutaneous adenoid cystic carcinoma of the eyelid and literature review / Carcinoma adenóide cístico cutâneo primário de pálpebra e revisão da literatura

ABSTRACTPrimary cutaneous adenoid cystic carcinoma (PCACC) is a rare malignant epithelial tumor most commonly observed in the scalp and skin of the chest and originating from the palpebral portion of the lacrimal gland in the orbit. Here we describe the diagnosis and treatment of a rare case of PCACC in an eye of a 52-year-old male. The patient presented with a mass lesion of the right lower eyelid. During incisional biopsy, lack of encapsulation and a secretion pattern different to that of chalazion was observed, which differentiated the lesion from chalazion. Pathological analysis revealed the diagnosis of PCACC. This case highlights the importance of careful inspection for macroscopic differentiation of PCACC from chalazion after initial surgery and pathological evaluation of all surgically removed mass lesions for accurate diagnosis and treatment.

RESUMOO carcinoma adenóide cístico cutâneo primário (PCACC) é um tumor maligno epitelial raro, mais comumente observado no couro cabeludo e na pele do peito sendo originário da porção palpebral da glândula lacrimal na órbita. Apresentamos o diagnóstico e tratamento de um caso raro de carcinoma adenóide cístico cutâneo primário do olho em um paciente do sexo masculino de 52 anos de idade, com uma lesão maciça da pálpebra inferior direita. A observação da falta de encapsulamento e um padrão de secreção diferente do calázio durante biópsia incisional permitiu a diferenciação da lesão de um calázio. A avaliação dos resultados do exame patológico resultou no diagnóstico de carcinoma adenóide cístico cutâneo primário. A análise do caso indica a importância de uma inspeção cuidadosa para a diferenciação macroscópica da carcinoma adenóide cístico cutâneo primário do calázio após a cirurgia inicial e avaliação patológica de todas as lesões de massa removidas cirurgicamente para o diagnóstico e tratamento corretos.

Metástasis en el carcinoma adenoquístico de glándula salival / Metastatic salivary adenoid cystic carcinoma

El carcinoma adenoide quístico (CAQ) es un tumor difícil de tratar en el que actualmente no hay consenso sobre el tratamiento óptimo. La tendencia a realizar cirugías radicales con intención curativa se ha ido modificando ante la evidencia que ni la supervivencia (en cantidad o calidad) ni la tasa de recidiva local mejora, comparado con cirugías más conservadoras que asocian radioterapia posquirúrgica. La diseminación metastásica ganglionar es poco habitual, pero las metástasis a distancia pulmonar y ósea son frecuentes. La supervivencia a 5 años es elevada, pero disminuye notablemente a los 10-20 años, habiéndose descrito metástasis muy tardías en la literatura. Presentamos cuatro pacientes con carcinoma adenoquístico de glándula salivar con múltiples metástasis a distancia valorados en nuestro servicio en los últimos 10 años. Revisamos los principales aspectos de esta entidad.

It is recognized that adenoid cystic carcinoma (ACC) remains an extremely difficult disease to treat, the optimal therapy for ACC of the head and neck has not been established. In the past, radical surgery was advocated for curative intent, but it gradually became apparent that this may not improve survival (in quantity o quality) and it may not even reduces local recurrence rates compared with a more conservative surgical approach and postoperative radiotherapy. Metastatic spread to regional lymph nodes is uncommon, but distant spread to the lungs and bones is frequent. Five-year survival rates are high, but 10 to 20 year survival rates are low, with very late metastasis described in literature. We report 4 patients with salivary ACC that were evaluated during the last ten years in our department. We review the main aspects of this entity.

Clinicopathological characteristics and perineural invasion in adenoid cystic carcinoma: a systematic review / Características clinicopatológicas e invasão perineural do carcinoma adenoide cístico

INTRODUCTION: Adenoid cystic carcinoma is the most frequent malignant tumor of the submandibular gland and the minor salivary glands. It is a malignant neoplasm that, despite its slow growth, shows an unfavorable prognosis. OBJECTIVES: The aim of this study was to perform a systematic review of the literature on Adenoid cystic carcinoma in the head and neck region and its clinicopathological characteristics, with emphasis on the perineural invasion capacity of the tumor. METHODS: A systematic search of articles published between January 2000 and January 2014 was performed in the PubMed/MEDLINE, SciELO, Science Direct, and Scopus databases. RESULTS: Nine articles were selected for this systematic review. These demonstrated that the female gender was more often affected and that malignant tumors showed a high rate of distant metastasis, recurrence, and a low survival rate. The presence of perineural invasion ranged from 29.4% to 62.5% and was associated with local tumor recurrence. CONCLUSION: Adenoid cystic carcinoma is commonly characterized by the presence of pain, high rate of recurrence, metastasis, and a low survival rate. Reporting studies with patient follow-up is of utmost importance for a better clinical-pathological understanding and to improve the prognosis of this pathology. .

INTRODUÇÃO: O carcinoma adenoide cístico (CAC) é o tumor maligno mais frequente da glândula Submandibular e das glândulas salivares menores. Sendo uma neoplasia maligna, apesar de ter crescimento lento, apresenta um prognóstico desfavorável. Objetivos: O objetivo deste trabalho foi realizar uma revisão sistemática de literatura sobreo carcinoma adenóide cístico na região de cabeça e pescoço e suas características clínico-patológicas com ênfase na capacidade de infiltração perineural do tumor. MÉTODO: Uma busca sistemática de artigos publicados entre janeiro de 2000 a janeiro de 2014 foi executada nas bases de dados PubMed/MEDLINE, SciELO, Science Direct e Scopus. RESULTADOS: Nove artigos foram selecionados para realização da revisão sistemática. Nestes, o sexo feminino foi o mais afetado e o tumor maligno apresentou uma alta taxa de metástase a distância, recidiva e baixa taxa de sobrevida. A presença de invasão perineural variou entre 29,4% a 62,5% e foi relacionada à recidiva local do tumor. CONCLUSÃO: O CAC é comumente caracterizado pela presença de dor, alta taxa de recidiva, metástase e baixa sobrevida. A realização de estudos com acompanhamento dos pacientes é de extrema importância para uma melhor avaliação clinico-patológica visando melhorar o prognóstico da doença. .

A rare case of primary adenoid cystic carcinoma of lung.

A 33-year-old male presented with repeated episodes of blood-streaked sputum for last one-and half-year. Chest radiograph showed consolidation in the right lower zone. Fibreoptic bronchoscopy revealed an endoluminal growth in the right lower lobe bronchus. Histopathological examination of bronchoscopic biopsy specimen confirmed adenoid cystic carcinoma.

Syndrome In Question

Brooke-Spiegler syndrome is an autosomal dominant disorder with variable penetrance and expression. It is characterized by a genetic predisposition to develop multiple adnexal neoplasias: cylindromas, trichoepitheliomas, and trichoblastomas. We describe a 54-year-old male patient with cylindromas, trichoepitheliomas, and trichoblastoma.

Tumor híbrido parotídeo / Parotid hybrid tumor

Los tumores de glándulas salivales representan el 3%-10% de las neoplasias de cabeza y cuello. La localización más común es en la glándula parótida, representando el 50%-85% de los casos, siendo 20%-30% de ellos malignos. Los siguientes son indicadores de malignidad: Crecimiento acelerado, masa dolorosa, parálisis facial asociada y linfoadenopatía. La mayoría de las neoplasias de parótida derivan de un único tipo histológico, pero eventualmente puede ocurrir el desarrollo de más de un tipo en la misma glándula. Este trabajo presenta un caso de una neoplasia en parótida con dos tipos histológicos diferentes, con una presentación clínica atípica. El paciente se presentó inicialmente con otalgia y otorrea, al examen destacaba un tumor en el canal auditorio externo. El estudio complementario evidenció una neoplasia de parótida y se realizó resección total de la glándula. La biopsia informó un carcinoma adenoideo-quístico con áreas basaloideas diferenciadas. Se administró radioquimioterapia adyuvante, y el control imagenológico con PET-TC mostró la ausencia de recurrencias o diseminación del tumor.

Tumors of the salivary glands represent 33%-10% of head and neck neoplasms. The most common location is the parotid gland, accounting for 50%-85% of the cases, with 20%-30% of them being malignant. The following are known to be indicative of a malignant tumor: fast growing, painless mass, associated facial paralysis and lymphadenopathy. Most parotid neoplasm derive from a single histological type but eventually the development of more than one type on the same gland can occur. This paper presents a case of a parotid neoplasm with two different histological tumors, with uncharacteristic clinical presentation. The patient presented initially with ear pain and otorrhoea, in the clinical examination highlighted an external auditory canal tumor. The complementary study revealed a parotid neoplasm and a total resection of the gland was performed. The biopsy revealed an adenoid-cystic carcinoma with differentiated basaloid areas. Adjuvant radio-chemotherapy was administered, and the imaging control with PET-CT showed no evidence of recurrence or dissemination of the tumor.

Sinonasal adenoid cystic carcinoma: clinical case report and literature Review / Carcinoma adenoide quístico nasosinusal: caso clínico y revisión de la literatura

We present the case of a patient, a 59 year-old man, with Sinonasal Adenoid Cystic Carcinoma. Magnetic resonance exam revealed invasion of the right orbit and brain at the level of the anterior cranial fossa floor. Due to the large volume, we decided to perform radio-chemotherapy treatment to diminish the size of the lesion. On conclusion of the first stage of treatment, reduction in tumor size was confirmed by computerized tomography exam and we decided to perform surgical resection with right ocular globe preservation. At present the patient is under periodic control and without major complications...

Se presenta el caso de un paciente de sexo masculino de 59 años con carcinoma adenoide quístico nasosinusal. El examen de resonancia magnética reveló la invasión de la órbita derecha y el cerebro a nivel del suelo de la fosa craneal anterior. Debido al gran volumen, se decidió realizar el tratamiento de radio-quimioterapia para disminuir el tamaño de la lesión. Al término de la primera etapa del tratamiento, la reducción del tamaño del tumor fue confirmada por el examen de tomografía computarizada y se decidió realizar una resección quirúrgica con preservación del globo ocular derecho. En la actualidad el paciente se encuentra bajo el control periódico y sin mayores complicaciones...