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Esophageal adenoid cystic carcinoma (EACC) is an exceedingly rare malignant tumor constituting only 0.2% of all esophageal tumors. The tumor exhibits aggressive behavior, composed histologically of ductal and modified myoepithelial cells. We report a case of a 69-year-old female with a diagnosis of an EACC by preoperative endoscopic biopsy. Thoracoscopy esophagectomy was carried out. However, pleural metastasis was found. Therefore, surgical resection of the esophageal tumor was not carried out. The patient underwent an uneventful recovery, followed by palliative treatment and ongoing chemoradiotherapy. EACC is uncommon but exhibits a more aggressive nature compared to its counterparts in the head and neck region. Dysphagia associated with gastroesophageal reflux disease is a common symptom. The duration from symptom onset to diagnosis is typically short. Treatment options include surgical resection, chemotherapy, and radiotherapy, with surgery being the preferred initial approach despite high operative mortality. Prognosis remains inconclusive, with some studies associating poor outcomes with lymph node metastasis and vascular invasion, while others report better survival rates. EACC presents diagnostic and therapeutic challenges due to its rarity and aggressive nature. Prognostic considerations remain unclear, emphasizing the need for further research and accumulated cases to delineate optimal treatment. The presented case demonstrates a 1-year survival with systemic palliative care, contributing to the evolving knowledge surrounding EACC.
El carcinoma adenoide quístico primario de esófago (EACC) es un tumor maligno excepcionalmente raro que constituye solo el 0.2% de todos los tumores esofágicos. El tumor exhibe un comportamiento agresivo, compuesto histológicamente por células ductales y mioepiteliales modificadas. Presentamos el caso de una mujer de 69 años con diagnóstico de un EACC mediante biopsia endoscópica preoperatoria. Se realizó una esofagectomía por toracoscopia. Sin embargo, se encontró metástasis pleural. Por lo tanto, no se llevó a cabo la resección quirúrgica del tumor esofágico. La paciente tuvo una recuperación sin complicaciones, seguida de tratamiento paliativo y radioquimioterapia continua. El EACC es poco común, pero exhibe una naturaleza más agresiva en comparación con sus contrapartes en la región de la cabeza y el cuello. La disfagia asociada con la enfermedad por reflujo gastroesofágico es un síntoma común. La duración desde el inicio de los síntomas hasta el diagnóstico suele ser corta. Las opciones de tratamiento incluyen la cirugía, quimio y radioterapia, siendo la cirugía la preferida a pesar de la alta mortalidad operatoria. El pronóstico es inconcluso, algunos estudios asocian resultados pobres con metástasis e invasión vascular, mientras que otros informan mejores tasas de supervivencia. El EACC presenta desafíos diagnósticos y terapéuticos debido a su rareza y naturaleza agresiva. El pronóstico sigue siendo poco claro, lo que enfatiza la necesidad de más investigación para delinear el tratamiento óptimo. El caso presentado demuestra una supervivencia de un año con cuidados paliativos sistémicos, contribuyendo al conocimiento en evolución sobre el EACC.
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Carcinoma Adenoide Quístico , Neoplasias Esofágicas , Humanos , Carcinoma Adenoide Quístico/patología , Carcinoma Adenoide Quístico/terapia , Femenino , Anciano , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/terapia , Esofagectomía , BiopsiaRESUMEN
OBJECTIVE: To evaluate and compare the expression of E-cadherin, Snail1 and Twist1 in pleomorphic adenomas (PAs), adenoid cystic carcinomas (AdCCa) and carcinoma ex-pleomorphic adenomas (CaexPA) of salivary glands, as well as investigate possible associations with clinicopathological parameters. STUDY DESIGN: E-cadherin, Snail1 and Twist1 antibody immunostaining were analyzed semiquantitatively in 20 PAs, 20 AdCCas and 10 CaexPAs. Cases were classified as low and high expression for analysis of the association with clinicopathological parameters. RESULTS: Compared to PAs, AdCCas and CaexPAs exhibited higher nuclear expression of Snail1 (p = 0.021 and p = 0.028, respectively) and Twist1 (p = 0.009 and p = 0.001). Membranous and cytoplasmic expression of E-cadherin were positively correlated in PAs, AdCCas and CaexPAs (r = 0.645, p = 0.002; r = 0.824, p < 0.001; r = 0.677, p = 0.031). In PAs, positive correlation was found between nuclear expression of Snail1 and membrane expression of E-cadherin (r = 0.634; p = 0.003), as well as between nuclear expression of Snail1 and Twist1 (r = 0.580; p = 0.007). Negative correlations were detected between membrane expression of E-cadherin and cytoplasmic expression of Snail1 in AdCCas (r = - 0.489; p = 0.029). CONCLUSIONS: E-cadherin, Twist1, and Snail1 may participate in modulating events related to cell differentiation and adhesion in PAs and to biological behavior in AdCCas and CaexPAs, which indicates the involvement of EMT in these processes. Furthermore, the expression of these proteins in these carcinomas may reflect the plasticity feature of EMT.
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Adenoma Pleomórfico , Cadherinas , Carcinoma Adenoide Quístico , Transición Epitelial-Mesenquimal , Proteínas Nucleares , Neoplasias de las Glándulas Salivales , Factores de Transcripción de la Familia Snail , Proteína 1 Relacionada con Twist , Humanos , Neoplasias de las Glándulas Salivales/patología , Neoplasias de las Glándulas Salivales/metabolismo , Factores de Transcripción de la Familia Snail/metabolismo , Cadherinas/metabolismo , Femenino , Masculino , Proteína 1 Relacionada con Twist/metabolismo , Persona de Mediana Edad , Carcinoma Adenoide Quístico/patología , Carcinoma Adenoide Quístico/metabolismo , Proteínas Nucleares/metabolismo , Adulto , Adenoma Pleomórfico/metabolismo , Adenoma Pleomórfico/patología , Anciano , Factores de Transcripción Twist/metabolismo , Inmunohistoquímica , Factores de Transcripción/metabolismo , Biomarcadores de Tumor/metabolismoRESUMEN
BACKGROUND: Salivary gland tumors (SGTs) are rare and highly heterogeneous lesions, making diagnosis a challenging activity. In addition, the small number of studies and samples evaluated difficults the determination of prognosis and diagnosis. Despite the solid advances achieved by research, there is still an intense need to investigate biomarkers for diagnosis, prognosis and that explain the evolution and progression of SGTs. METHODS: We performed a comprehensive literature review of the molecular alterations focusing on the most frequent malignant SGTs: mucoepidermoid carcinoma and adenoid cystic carcinoma. RESULTS: Due to the importance of biomarkers in the tumorigenenic process, this review aimed to address the mechanisms involved and to describe molecular and biomarker pathways to better understand some aspects of the pathophysiology of salivary gland tumorigenesis. CONCLUSIONS: Molecular analysis is essential not only to improve the diagnosis and prognosis of the tumors but also to identify novel driver pathways in the precision medicine scenario.
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Biomarcadores de Tumor , Carcinoma Adenoide Quístico , Carcinoma Mucoepidermoide , Neoplasias de las Glándulas Salivales , Carcinoma Mucoepidermoide/patología , Carcinoma Mucoepidermoide/diagnóstico , Humanos , Carcinoma Adenoide Quístico/patología , Carcinoma Adenoide Quístico/diagnóstico , Neoplasias de las Glándulas Salivales/patología , Neoplasias de las Glándulas Salivales/diagnóstico , Biomarcadores de Tumor/análisisRESUMEN
Adenoid cystic carcinoma (ACC) is a rare tumor, with a documented annual incidence ranging from 3 to 4.5 cases per million. It constitutes approximately 1% of all head and neck malignancies and around 10% of salivary gland tumors. It is imperative to adopt a multidisciplinary approach to ensure the most appropriate therapeutic outcome. Treatment strategies usually involve a multidisciplinary approach and may include surgery, radiotherapy, chemotherapy, or various combinations of these. In this context, we present a clinical case of ACC originating in the palate of a woman. Throughout this article, we will detail the diagnostic challenges and multidisciplinary treatment strategies implemented, emphasizing the importance of a comprehensive approach in cases of palatal ACC. In addition, we will discuss the rehabilitation process and the outcomes observed during the follow-up of this case.
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OBJECTIVE: Pleomorphic adenoma (PA), mucoepidermoid carcinoma (MEC), and adenoid cystic carcinoma (ACC) are the most prevalent salivary gland tumors. Their pathogenesis has been recently associated with complex molecular cascades, including the TGFß signaling pathway. The aim of this study was to evaluate the expression of genes associated with the TGFß signaling pathway (TGFB1, ITGB6, SMAD2, SMAD4, FBN1, LTBP1, and c-MYC) to map possible downstream alterations in the TGFß cascade. DESIGN: Thirteen PA, 17 MEC, 13 ACC, and 10 non-neoplastic salivary gland samples were analyzed by real-time RT-PCR. RESULTS: Cases of PA presented increased TGFB1, LTPB1, c-MYC, and FBN1 expressions, whereas SMAD2 expression was decreased when compared to non-neoplastic tissue. MEC patients displayed increased expressions of TGFB1, ITGB6, FBN1, and c-MYC and decreased expressions of SMAD2 and SMAD4. ACC cases exhibited elevated expressions of the investigated genes except TGFB1. The present results suggest that decreased expression of SMAD2 and SMAD4 does not impede the transcriptional regulation of c-MYC, especially in PA and MEC. Increased expressions of ITGB6, TGFB1, LTBP1, and FBN1 appear to be related to the regulation of the TGFß signaling pathway in these tumors. Additionally, we observed a higher expression of SMAD4 in ACC and a raised expression of ITGB6 and lowered expression of SMAD2 in MEC. CONCLUSIONS: Our study demonstrated the differential expression of TGFß cascade members in salivary gland tumors such as SMAD2/SMAD4 and c-MYC as well as the participation of ITGB6, TGFB1, LTBP1, and FBN1, contributing to the understanding of the mechanisms involved in tumor progression.
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Adenoma Pleomórfico , Carcinoma Adenoide Quístico , Carcinoma Mucoepidermoide , Neoplasias de las Glándulas Salivales , Factor de Crecimiento Transformador beta , Humanos , Adenoma Pleomórfico/genética , Adenoma Pleomórfico/metabolismo , Adenoma Pleomórfico/patología , Biomarcadores de Tumor/metabolismo , Carcinoma Adenoide Quístico/genética , Carcinoma Adenoide Quístico/metabolismo , Carcinoma Mucoepidermoide/metabolismo , Neoplasias de las Glándulas Salivales/genética , Neoplasias de las Glándulas Salivales/metabolismo , Transducción de Señal , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
RESUMEN El carcinoma adenoide quístico (CAQ) es una neoplasia maligna de glándula salival, de evolución lenta pero de agresivo comportamiento, que se presenta frecuentemente en el paladar; sin embargo, en el labio superior, donde suelen encontrarse más neoplasias benignas, su presencia es escasamente relatada. Se expone un relato de una mujer de 63 años, derivada por presentar un nódulo en el labio superior derecho, de aspecto benigno, consistencia firme, circunscrito, móvil, doloroso a la palpación, sin tiempo de evolución determinado y cuyo estudio histopatológico exhibió una proliferación de células anguladas e hipercromáticas de escaso citoplasma, organizadas en patrón cribiforme y predominantemente tubular. Se realiza un estudio inmunohistoquímico, el cual mostró positividad para SMA, p63 y CD117 con un Ki-67 del 10 % aproximadamente. Estos resultados confirman diagnóstico de CAQ con patrón tubular, destacando el rol del CD117 para el diagnóstico diferencial con adenocarcinoma polimorfo. Se deriva a la paciente para tratamiento quirúrgico y radioterapia, y luego de un año de seguimiento mantiene un buen comportamiento clínico.
ABSTRACT Adenoid cystic carcinoma (ACCC) is a malignant neoplasm of the salivary gland, of slow evolution but aggressive behavior, which frequently occurs in the palate; however, in the upper lip, where more benign neoplasms are usually found, its presence is scarcely reported. We report the case of a 63-year-old woman, referred for presenting a nodule in the right upper lip, with benign appearance, firm consistency, circumscribed, mobile, painful to palpation, with no determined time of evolution and whose histopathological study showed a proliferation of angular and hyperchromatic cells with scarce cytoplasm, organized in a cribriform pattern and predominantly tubular. An immunohistochemical study was performed, which showed positivity for SMA, p63 and CD117 with a Ki-67 of approximately 10%. These results confirm the diagnosis of CAC with tubular pattern, highlighting the role of CD117 for the differential diagnosis with polymorphous adenocarcinoma. The patient was referred for surgical treatment and radiotherapy, and after one year of follow-up she maintained a good clinical behavior.
RESUMO O carcinoma adenoide cístico (CACC) é uma neoplasia maligna da glândula salivar, de evolução lenta, mas de comportamento agressivo, que ocorre frequentemente no palato; no entanto, a sua presença é raramente relatada no lábio superior, onde normalmente se encontram neoplasias mais benignas. Relatamos o caso de uma mulher de 63 anos que foi encaminhada por apresentar um nódulo benigno no lábio superior direito, de aspeto firme, circunscrito, móvel, doloroso à palpação, sem tempo de evolução definido. O exame histopatológico revelou uma proliferação de células angulosas e hipercromáticas com citoplasma escasso, organizadas em padrão cribriforme e predominantemente tubulares. Foi efetuado um estudo imuno-histoquímico que mostrou positividade para SMA, p63 e CD117 com um Ki-67 de aproximadamente 10 %. Estes resultados confirmam o diagnóstico de CAC com padrão tubular, realçando o papel do CD117 no diagnóstico diferencial com adenocarcinoma polimorfo. A paciente foi encaminhada para tratamento cirúrgico e radioterapia e, após um ano de seguimento, manteve bom comportamento clínico.
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B7-H4 (VTCN1), a member of the B7 family, is overexpressed in several types of cancer. Here we investigated the pattern of expression of B7-H4 in salivary gland carcinomas (SGC) and assessed its potential as a prognostic marker and therapeutic target. Immunohistochemistry (IHC) analyses were performed in a cohort of 340 patient tumors, composed of 124 adenoid cystic carcinomas (ACC), 107 salivary duct carcinomas (SDC), 64 acinic cell carcinomas, 36 mucoepidermoid carcinomas (MEC), 9 secretory carcinomas (SC), as well as 20 normal salivary glands (controls). B7-H4 expression was scored and categorized into negative (<5% expression of any intensity), low (5%-70% expression of any intensity or >70% with weak intensity), or high (>70% moderate or strong diffuse intensity). The associations between B7-H4 expression and clinicopathologic characteristics, as well as overall survival, were assessed. Among all tumors, B7-H4 expression was more prevalent in ACC (94%) compared with those of SC (67%), MEC (44%), SDC (32%), and acinic cell carcinomas (0%). Normal salivary gland tissue did not express B7-H4. High expression of B7-H4 was found exclusively in ACC (27%), SDC (11%), and MEC (8%). In SDC, B7-H4 expression was associated with female gender (P = .002) and lack of androgen receptor expression (P = .012). In ACC, B7-H4 expression was significantly associated with solid histology (P < .0001) and minor salivary gland primary (P = .02). High B7-H4 expression was associated with a poorer prognosis in ACC, regardless of clinical stage and histologic subtype. B7-H4 expression was not prognostic in the non-ACC SGC evaluated. Our comparative study revealed distinct patterns of B7-H4 expression according to SGC histology, which has potential therapeutic implications. B7-H4 expression was particularly high in solid ACC and was an independent prognostic marker in this disease but not in the other SGC assessed.
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Neoplasias de la Mama , Carcinoma de Células Acinares , Carcinoma Adenoide Quístico , Carcinoma Mucoepidermoide , Carcinoma , Neoplasias de las Glándulas Salivales , Humanos , Femenino , Carcinoma Adenoide Quístico/patología , Pronóstico , Carcinoma de Células Acinares/patología , Neoplasias de las Glándulas Salivales/patología , Carcinoma Mucoepidermoide/patología , Carcinoma/patología , Glándulas Salivales/química , Glándulas Salivales/metabolismo , Glándulas Salivales/patología , Biomarcadores de Tumor/análisisRESUMEN
PURPOSE: Amidst the rarity of High-grade transformation (HGT) in adenoid cystic carcinoma (ACC), this study offers unprecedented insights into its aggressive nature and clinical implications. METHODS: A 1:1 match comparison between 23 HGT patients and non-HGT counterparts was extracted from 412 ACC cases, focusing on dissecting distinctive clinicopathological features and prognostic outcomes. RESULTS: The predominant sites of HGT were the sinonasal and lacrimal glands (30.4% each). Notably, the solid subtype was the most prevalent pattern within HGT, accounting for 69.6% of cases. Compared to non-HGT, the HGT cohort exhibited significantly higher rates of lymph node metastasis (39.1% vs. 8.7%; P < 0.05), perineural invasion (60.9% vs. 26.1%; P < 0.05), and increased Ki-67 proliferation index (35.0% vs. 10.0%; P < 0.05). Moreover, HGT regions typically showed reduced or absent p63 expression, along with high-grade pathomorphology. HGT was associated with increased recurrence (55.0%) and distant metastasis (78.3%), leading to an average survival of 35.9 months and a 3-years mortality rate of 35.0%. Overall and progression-free survival rates were significantly decreased in the HGT group. CONCLUSION: This study represents the largest single-center cohort of HGT cases to our knowledge, highlighting its frequent occurrence in the sinonasal and lacrimal glands and association with poorer outcomes. The findings support classifying HGT in ACC as Grade 4, reflecting its severity.
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Carcinoma Adenoide Quístico , Humanos , Carcinoma Adenoide Quístico/patología , Carcinoma Adenoide Quístico/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , China/epidemiología , Estudios de Casos y Controles , Adulto , Anciano , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/mortalidad , Clasificación del Tumor , Transformación Celular Neoplásica/patología , Metástasis Linfática , Tasa de Supervivencia , Invasividad Neoplásica , Adulto JovenRESUMEN
Introducción: El carcinoma adenoide quístico de la vía aérea es un tumor poco común, que se origina de las glándulas submucosas del árbol traqueobronquial. Por el usual retraso entre los síntomas y el diagnóstico, y por la propensión de este tumor para expandirse a través de los haces perineurales y submucosa, el tratamiento recomen dado es la resección quirúrgica con radioterapia posoperatoria. La supervivencia está determinada por la presencia de metástasis a distancia. Caso clínico: Paciente de sexo femenino de 70 años de edad con antecedentes de hipertensión arterial, EPOC (extabaquista 34 paquetes/año) que acude a servicio de urgencias con episodios de hemoptisis y disnea mMRC 3-4 previa. Discusión: Las neoplasias malignas de la tráquea son muy raras y los datos relacionados con ellos son limitados. Los más importantes factores pronósticos en las enfermedades primarias malignas de la tráquea constituyen el diagnóstico temprano, estadiaje del tumor, histología y opciones de tratamiento. Conclusiones: La detección temprana puede estar asociada con el incremento de las tasas de resecabilidad e, incluso, supervivencia prolongada.
Introduction: Adenoid cystic carcinoma of the airway is a strange tumor that arises from the submucosal glands of the tracheobronchial tree. For the usual delay between symptoms and diagnosis, and for the propensity of this tumor to expand through the perineural fibers and submucosa, the recommended treatment is surgical resection with postoperative radiation therapy. Survival is determined by the presence of distance metastases. Clinical case: 70 year-old female patient with a history of hypertension, COPD (former smoker 34 pack/year) who came to the emergency room with episodes of hemoptysis and previous dyspnea mMRC 3-4. Discussion: Malignant neoplasms of the trachea are very strange and data related to them is limited. The most important prognostic factors in primary malignant diseases of the trachea are early diagnosis, tumor stating, histology, and treatment options. Conclusions: Early detection may be associated with increased resectability rates and even prolonged survival.
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FemeninoRESUMEN
Adenoid cystic carcinoma (ACC) is an aggressive tumor with a high propensity for distant metastasis and perineural invasion. This tumor is more commonly found in regions of the head and neck, mainly the salivary glands. In general, the primary treatment modality for ACC is surgical resection and, in some cases, postoperative radiotherapy. However, no effective systemic treatment is available for patients with advanced disease. Furthermore, this tumor type is characterized by recurrent molecular alterations, especially rearrangements involving the MYB, MYBL1, and NFIB genes. In addition, they also reported copy number alterations (CNAs) that impact genes. One of them is C-KIT, mutations that affect signaling pathways such as NOTCH, PI3KCA, and PTEN, as well as alterations in chromatin remodeling genes. The identification of new molecular targets enables the development of specific therapies. Despite ongoing investigations into immunotherapy, tyrosine kinase inhibitors, and anti-angiogenics, no systemic therapy is approved by the FDA for ACC. In this review, we report the genetic and cytogenetic findings on head and neck ACC, highlighting possible targets for therapeutic interventions.
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OBJECTIVE: Local recurrence, distant metastasis, and perineural invasion (PNI) viciously occur in salivary adenoid cystic carcinoma (SACC), resulting in a poor prognosis. This study aimed to explore the mechanism by which circular RNA RNF111 (circ-RNF111) regulates PNI in SACC by targeting the miR-361-5p/high mobility group box 2 (HMGB2) axis. METHOD: Circ-RNF111 and HMGB2 were highly expressed in SACC specimens, while miR-361-5p was underexpressed. Functional experiments showed that ablating circ-RNF111 or promoting miR-361-5p hindered the biological functions and PNI of SACC-LM cells. RESULTS: HMGB2 overexpression induced the reversal of SACC-LM cell biological functions and PNI caused by circ-RNF111 knockout. Furthermore, reduction of circ-RNF111 suppressed PNI in a SACC xenograft model. Circ-RNF111 regulated HMGB2 expression through targeted modulation of miR-361-5p. CONCLUSION: Taken together, circ-RNF111 stimulates PNI in SACC by miR-361-5p/HMGB2 axis and may serve as a potential therapeutic target for SACC.
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Carcinoma Adenoide Quístico , MicroARNs , Neoplasias de las Glándulas Salivales , Humanos , Carcinoma Adenoide Quístico/genética , Carcinoma Adenoide Quístico/metabolismo , Carcinoma Adenoide Quístico/patología , ARN Circular/genética , Proteína HMGB2/genética , Proteína HMGB2/metabolismo , Neoplasias de las Glándulas Salivales/genética , Neoplasias de las Glándulas Salivales/metabolismo , Neoplasias de las Glándulas Salivales/patología , Factores de Transcripción/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Línea Celular Tumoral , Invasividad Neoplásica/genética , Regulación Neoplásica de la Expresión Génica , Movimiento Celular/genética , Proliferación Celular , Proteínas Nucleares/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
Breast cancer is a heterogeneous disease with various histological and molecular subtypes. Among them, salivary gland tumors are rare and can be divided into three groups: pure myoepithelial differentiation, pure epithelial differentiation and myoepithelial with mixed epithelial differentiation. In the last group, adenoid cystic carcinoma stands out, a rare entity with low malignant potential. It represents less than 0.13% of breast cancer cases and has the most frequent clinical presentation as a palpable mass. The diagnosis is confirmed by histology and immunohistochemistry. Classically, they are low-aggressive triple-negative tumors, with overall survival and specific cancer survival at five and ten years greater than 95%. However, there are rare reports of aggressive variants with a risk of distant metastasis and death. Treatment is based on surgical resection with margins. Lymphatic dissemination is rare, and there is no consensus regarding the indication of an axillary approach. Adjuvant radiotherapy is indicated in cases of conservative surgery and should be discussed in other cases. The benefit of chemotherapy remains uncertain, as most tumors are indolent. We report a case that required individualized decisions based on its peculiarities of presentation, diagnosed in an asymptomatic elderly patient during screening, in which mammography showed heterogeneous gross calcifications clustered covering 1.6 cm. Stereotacticguided vacuum-assisted biopsy was performed, and the area was marked with a clip. The anatomopathological examination led to a diagnosis of salivary gland-type carcinoma, triple-negative. The patient underwent segmental resection of the right breast and sentinel lymph node biopsy. The final anatomopathological result was similar to that of the biopsy, with an immunohistochemicalprofile of the adenoid cystic type and two sentinel lymph nodes free of neoplasia. Considering age and histological subtype, adjuvant therapy was not indicated. Follow-up for three years showed no evidence of disease
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Humanos , Femenino , Anciano , Glándulas Salivales/patología , Carcinoma/diagnóstico , Neoplasias de la Mama Triple Negativas/diagnóstico , Carcinoma/cirugía , Neoplasias de la Mama Triple Negativas/cirugíaRESUMEN
Adenoid cystic carcinoma (ACC) is an uncommon malignant tumor that accounts for less than 5% of head and neck cancers. ACC is characteristic for its indolent nature and its propensity for late distant metastases. Late diagnosis, tendency to perineural invasion, periosteal infiltration and local recurrence are factors of poor prognosis. Although studies still discuss the ideal treatment, the initial therapy consists of surgical resection, followed by postoperative radiotherapy.
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Salivary gland neoplasms are a heterogeneous neoplasm group, including mucoepidermoid carcinoma (MECa), adenoid cystic carcinoma (AdCC), and many others. OBJECTIVE: We aimed to identify new critical genes of MECa and AdCC using bioinformatics analysis. METHODS: Gene expression profile of GSE153283 was analyzed by the GEO2R online tool to use the DAVID software for their subsequent enrichment. Protein-protein interactions (PPI) were visualized using String. Cytoscape with MCODE plugin followed by Kaplan-Meier online for overall survival analysis were performed. RESULTS: 97 upregulated genes were identified for MECa and 86 for AdCC. PPI analysis revealed 22 genes for MECa and 63 for AdCC that were validated by Kaplan-Meier that showed FN1 and SPP1 for MECa, and EGF and ERBB2 for AdCC as more significant candidate genes for each neoplasm. CONCLUSION: With bioinformatics methods, we identify upregulated genes in MECa and AdCC. The resulting candidate genes as possible therapeutic targets were FN1, SPP1, EGF, and ERBB2, and all those genes had been tested as a target in other neoplasm kinds but not salivary gland neoplasm. The bioinformatic evidence is a solid strategy to select them for more extensive research with clinical impact.
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BACKGROUND: Mitochondrial fission and fusion processes are known as mitochondrial dynamics and the occurrence of imbalances in the mitochondrial activity is related to the pathogenesis of many human cancers. However, the importance of mitochondrial dynamics in malignant salivary gland tumours remains unknown. Therefore, we aimed to investigate its prognostic significance in adenoid cystic carcinoma. METHODS: Fifty-seven formalin-fixed paraffin-embedded cases were retrieved and disposed in tissue microarray. Histological sections were submitted to immunohistochemical reactions against AMT, DRP1, FIS1, MFN1, MFN2 and OPA1 proteins. Clinical data were retrieved from the patients' medical files, including specific and disease-free survival data. RESULTS: It was observed that 50.9% of the cases were strongly positive for AMT and DRP1, and 49.1%, 21.1%, 22.8% and 24.6% strongly positive for FIS1, MFN1, MFN2 and OPA1, respectively. Reactions were observed in both epithelial and myoepithelial components of the tumour. The higher expression of MFN2 was associated with solid microscopic pattern (p = 0.016). DRP1 overexpression showed a trend towards a shorter overall survival (p = 0.054), while negative/weak OPA1 showed a trend towards a lower disease-free survival (p = 0.051) in the univariate analysis, but no mitochondrial marker represented an independent prognostic determinant under multivariate analysis. CONCLUSION: In conclusion, mitochondrial dynamics markers do not seem to carry a prognostic significance for adenoid cystic carcinoma patients, but these proteins may play an important role in its pathogenesis.
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Carcinoma Adenoide Quístico , Dinámicas Mitocondriales , Carcinoma Adenoide Quístico/metabolismo , Humanos , MitocondriasRESUMEN
Introducción: El carcinoma adenoide quístico es una neoplasia maligna poco común y a menudo agresiva, que puede surgir en una variedad de órganos portadores de glándulas. Objetivo: Caracterizar la presentación de una neoplasia maligna agresiva infrecuente, el carcinoma adenoide quístico. Caso clínico: Paciente de 56 años que acudió a cuerpo de guardia con lesión en cuero cabelludo correspondiente con cilindroma maligno. Se estudia posteriormente y se constataron además lesiones a nivel de mamas, colon y recidiva en el cuero cabelludo, que dieron como resultado carcinoma adenoide quístico. Conclusiones: Es infrecuente; realizar su diagnóstico conlleva un alto índice de sospecha y su diagnóstico es histopatológico. Su pronóstico depende de la localización primaria y tiende a ser muy agresivo cuando se localiza fuera de la mama(AU)
Introduction: Adenoid cystic carcinoma is an uncommon and often aggressive malignant neoplasm that can arise in a variety of gland-bearing organs. Objective: To characterize the presentation of an uncommon aggressive malignancy, adenoid cystic carcinoma. Clinical case: 56-year-old patient who presented to the on-call department with a lesion on the scalp corresponding to malignant cylindroma. She was subsequently studied and lesions were also found in the breast, colon and recurrence in the scalp, which resulted in adenoid cystic carcinoma. Conclusions: It is infrequent; making its diagnosis involves a high index of suspicion and its diagnosis is histopathological. Its prognosis depends on the primary location and it tends to be very aggressive when located outside the breast(AU)
Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Neoplasias de la Mama/diagnóstico , Carcinoma Adenoide Quístico/diagnósticoRESUMEN
Os tumores de glândula salivar (TGS) representam cerca de 3% a 6% das neoplasias da região de cabeça e pescoço e são caracterizados por sua diversidade morfológica e de comportamentos biológicos. Sabe-se que algumas das características de tumores malignos, como a invasão tumoral e metástases à distância, possuem envolvimento da transição epitélio-mesênquima (TEM), evento no qual proteínas como a E-caderina, Snail1 e Vimentina estão diretamente envolvidas. Esta pesquisa se propôs a analisar e relacionar a expressão imuno-histoquímica dessas proteínas com as características clínico-patológicas em adenomas pleomórficos (APs), carcinomas adenoides císticos (CACs) e carcinomas ex-adenomas pleomórficos (CaExAPs) de glândulas salivares maiores e menores. A análise da imunoexpressão dessas proteínas foi feita de forma semiquantitativa em 20 casos de APs, 20 de CACs e 10 de CaExAPs. Na avaliação de E-caderina, considerou-se a expressão em membrana e/ou citoplasma das células do parênquima tumoral. Para a Snail1, foi considerada a expressão nos compartimentos nuclear e/ou citoplasmático dessas células. A Vimentina foi analisada no citoplasma de células fusiformes presentes no estroma dos TGS. Os dados obtidos foram comparados e correlacionados utilizando o nível de significância de 5% (p ≤ 0,05). Observou-se imunopositividade para E-caderina principalmente em citoplasma das células neoplásicas nãoluminais; a marcação membranar, perceptível em células luminais, estava mais presente nas neoplasias malignas (p = 0,041). A expressão de Snail1 foi mais frequente no compartimento nuclear, sendo mais evidenciada em células não-luminais dos TGS e apresentou maior reatividade nuclear em tumores malignos (p = 0,012). A expressão nuclear dessa proteína também foi maior para CACs e CaExAPs ao compará-los, de forma separada, com os APs (p = 0,037 e p = 0,025, respectivamente). Não foram observadas diferenças estatisticamente significativas entre a expressão de E-caderina e Snail1 e outros parâmetros clinico-patológicos e os subtipos histopatológicos das lesões (p > 0,05). A positividade para Vimentina foi vista no estroma de todos os casos de TGS, sendo mais difusa e intensa em CACs. Não foram verificadas diferenças estatisticamente significativas entre a expressão desse biomarcador e os parâmetros clínico-patológicos e subtipos histopatológicos das lesões (p > 0,05). Houve correlações positivas entre as expressões membranar e citoplasmática de E-caderina em APs, CACs e CaExAPs (r = 0,645, p = 0,002; r = 0,781, p < 0,001; r = 0,677 p = 0,031), bem como entre a expressão nuclear e citoplasmática de Snail1 e a expressão citoplasmática de E-caderina e nuclear de Snail1 em APs (r = 0,569, p = 0,009; r = 0,481, p = 0,032). Foram verificadas correlações negativas entre a expressão membranar de E-caderina e citoplasmática de Snail1, bem como entre Snail1 nuclear e Vimentina em CACs (r = -0,471, p = 0,036; r = -0,514; p = 0,021). Essa última correlação, bem como correlação positiva entre a expressão membranar e citoplasmática de E-caderina, também foi vista entre os casos de CACs e CaExAPs quando agrupados (r = -0,457; p = 0,0011; r = 0,746, p < 0,001). Os resultados do presente estudo sugerem que a participação de E-caderina e Snail1 no processo da TEM pode estar relacionada ao estágio de diferenciação celular em APs e à progressão tumoral nas neoplasias malignas bem como é possível que a expressão dessas proteínas em neoplasias malignas seja indicativa da plasticidade presente na TEM. Ressalta-se, também, a expressão de Vimentina em células fusiformes presentes no estroma tumoral, provavelmente refletindo estágios tardios da TEM (AU).
Salivary gland tumors (SGTs) comprise about 2% to 10% of head and neck tumors and are known for their morphologic diversity and biologic behavior. Some features of malignant neoplasms, such as tumor invasion and distant metastasis, might have the participation of epithelial-mesenchymal transition (EMT), event in which proteins like E-cadherin, Vimentin and Snail1 are directly involved. This study aimed to analyze, by means of immunohistochemistry, the expression of these proteins, as well as to relate their expressions to clinical-pathological features of pleomorphic adenomas (PAs), adenoid cystic carcinomas (ACCs) and carcinomas ex-pleomorphic adenomas (CXPAs) located in minor and major salivary glands. This was a semi-quantitatively analysis which comprised 20 PAs, 20 ACCs and 10 CXPAs. Analysis of E-cadherin was made considering membranar and/or cytoplasmatic expression in parenchymal cells. For Snail1, it was considered the positivity in nucleus and/or cytoplasm of parenchymal cells. Vimentin was evaluated in the cytoplasm of fusiform stromal cells. Data were compared and correlated adopting a level of significance of 5% (p ≤ 0,05). Marked immunoexpression for E-cadherin was mostly found in the cytoplasm of non-luminal neoplastic cells in SGTs; membrane reaction for the protein, seen in luminal cells, was higher in malignant tumors (p = 0,041). Snail1 was more expressed in the nucleus, mostly of nonluminal cells of SGTs, with this reactivity being higher in malignant tumors(p = 0,012). Nuclear positivity for this marker was also higher for ACCs and CXPAs when compared with PAs separately (p = 0,037 e p = 0,025, respectively). No significant differences between E-cadherin and Snail1 and other clinical-pathological parameters were found (p > 0,05). Vimentin was seen in the stroma of all cases, being more diffuse and intense in ACCs. No significant differences between this marker and clinical-pathological parameters were found (p > 0,05). Positive correlations between membranar and cytoplasmatic E-cadherin in PAs, ACCs and CXPAs were observed (r = 0,645, p = 0,002; r = 0,781, p < 0,001; r = 0,677 p = 0,031), as well as between nuclear and cytoplasmatic Snail1 and between cytoplasmatic E-cadherin and nuclear Snail1 in PAs APs (r = 0,569, p = 0,009; r = 0,481, p = 0,032). Negative correlations between membranar E-cadherin and cytoplasmatic Snail1 were observed, as well as between nuclear Snail1 and Vimentin in ACCs (r = -0,471, p = 0,036; r = -0,514; p = 0,021). This last correlation and a positive correlation between membranar and cytoplasmatic E-cadherin were also seen when ACCs and CXPAs were grouped (r = -0,457; p = 0,0011; r = 0,746, p < 0,001). These results suggest that the participation of these proteins in EMT might be related to cellular differentiation in PAs and to tumoral progression in malignant tumors. In addition, it can be infered that the expression of E-cadherin and Snail1 in malignant tumors might reflect the plasticity seen in EMT process. Furthermore, the expression of Vimentin in fusiform stromal cells, probably in later stages of EMT, in the stroma of SGTs, is highlighted (AU).
Asunto(s)
Vimentina/metabolismo , Neoplasias de las Glándulas Salivales/patología , Cadherinas/metabolismo , Transición Epitelial-Mesenquimal/fisiología , Estudios Transversales/métodos , Carcinoma Adenoide Quístico/patología , Adenoma Pleomórfico/patología , Estadísticas no Paramétricas , Estudio Observacional , Factores de Transcripción de la Familia Snail/metabolismoRESUMEN
As neoplasias de glândulas salivares apresentam comportamentos diferenciados, que não seguem os padrões clássicos das neoplasias benignas e malignas. A raridade de algumas destas lesões dificulta ainda mais o entendimento dos mecanismos envolvidos na etiopatogenia. Marcadores moleculares como a proteína EZH2 têm sido utilizados na investigação de alterações epigenéticas em diferentes neoplasias, auxiliando na definição do diagnóstico e prognóstico das lesões. O objetivo do presente trabalho é avaliar a expressão da proteína EZH2 e descrever as características clínicas e microscópicas de amostras de carcinoma adenoide cístico (CAC) e adenoma pleomórfico (AP) com ênfase na importância da definição da malignidade da lesão. A análise dos cortes microscópicos corados em Hematoxilina e Eosina dos casos de Adenoma pleomórfico mostraram células epiteliais e mioepiteliais glandulares dispostas em lençóis e estruturas ductiformes em meio a estroma variável. Os casos de Carcinoma adenoide cístico mostraram três padrões distintos de crescimento incluindo formações tubulares, cribriformes e sólidas. Todos os casos de AP e CAC foram positivos para reação imuno-histoquímica para EZH2. As amostras de CAC apresentaram expressão de EZH2 significativamente maior comparado ao AP. As covariáveis metástase em linfonodos, recorrência, padrão histológico, presença de áreas sólidas e invasão perineural foram descritas em relação à marcação de EZH2 em amostras de CAC. Dessa forma, os resultados do estudo melhoram o entendimento das características clínicas e histológicas do CAC, assim como sobre o comportamento das lesões. Além disso, a análise mostra que o EZH2 é um potencial marcador de malignidade e ressalta a importância da validação de marcadores moleculares de alterações epigenéticas.
Salivary gland neoplasms present different behaviors, which do not follow the classic patterns of benign and malignant neoplasms. The rarity of some of these lesions makes it even more difficult to understand the mechanisms involved in the etiopathogenesis. Molecular markers such as the EZH2 protein have been used to investigate epigenetic changes in different neoplasms, helping to define the diagnosis and prognosis of the lesions. The aim of the study was to evaluate the expression of the EZH2 protein and to describe the clinical and microscopic characteristics of adenoid cystic carcinoma (ACC) and pleomorphic adenoma (PA) which emphasizes the importance of defining the malignancy of the neoplasm. Histopathological analysis of PA cases showed myoepithelial and glandular epithelial cells arranged as duct-like structures and sheets intermingled in the variable stroma and ACC cases showed the three growth patterns, tubular, cribriform and solid forms. All ACC and PA cases were positive for EZH2, with diffuse nuclear staining in neoplastic cells. The ACC samples showed significantly higher EZH2 expression compared to the PA. The covariables nodal metastasis, recurrence, growth pattern, presence of solid areas and perineural invasion have been described in relation to EZH2 staining in ACC samples. The results of the study improve the understanding of the clinical and histological characteristics of ACC, as well as on the behavior of lesions. In addition, the analysis showed that EZH2 is a potential marker of malignancy and highlights the importance of validating molecular markers of epigenetic alterations.
Asunto(s)
Neoplasias de las Glándulas Salivales , Inmunohistoquímica , Carcinoma Adenoide Quístico , Adenoma Pleomórfico , Epigenómica , Proteína Potenciadora del Homólogo Zeste 2RESUMEN
Abstract Introduction In the present study, we report a case of primary adenoid cystic carcinoma (ACC) of the Bartholin gland with high-grade transformation (HGT). Adenoid cystic carcinoma of the Bartholin gland is a rare tumor and HGT has only been reported in head and neck tumors. Case Report A 77-year-old woman with a non-ulcerated vulvar lesion on the topography of the right Bartholin gland. The patient was submitted to tumor resection followed by V-Y island flap and adjuvant radiotherapy. The histopathological examination revealed primary ACC of the Bartholin gland, with areas of HGT and extensive perineural invasion. The immunohistochemical study with p53 showed a diffuse and strong positive reaction in areas with HGT. After 24 months of follow-up, the patient presented distant metastases and died, despite having undergone to chemotherapy. Conclusion As far as we know, this case is the first description in the literature of HGT in ACC of the Bartholin gland, and HGT appears to be associated with tumor aggressiveness.
Resumo Introdução Este estudo relata o caso de um carcinoma adenoide cístico (CAC) de glândula de Bartholin com transformação de alto grau. O CAC de glândula de Bartholin é um tumor raro, e sua transformação de alto grau é relatada somente em tumores de cabeça e pescoço. Relato de caso Paciente de 77 anos de idade, do sexo feminino, com lesão vulvar não ulcerada na topografia da glândula de Bartholin direita. A paciente foi submetida a ressecção do tumor e realização de retalho em V-Y, seguidas de radioterapia adjuvante. O exame histopatológico revelou CAC primário de glândula de Bartholin, com áreas de transformação de alto grau e invasão perineural. O estudo imunohistoquímico com p53 mostrou reação positiva difusa e intensa em áreas com transformação de alto grau. Após 24 meses de seguimento, a paciente apresentou metástases à distância e faleceu, apesar de ter sido submetida a quimioterapia. Conclusão Pelo que sabemos, este caso é a primeira descrição na literatura de transformação de alto grau em CAC de glândula de Bartholin, e a transformação de alto grau parece estar associada à agressividade do tumor.
Asunto(s)
Humanos , Femenino , Anciano , Glándulas Vestibulares Mayores , Neoplasias de la Vulva , Carcinoma Adenoide Quístico/terapia , Radioterapia AdyuvanteRESUMEN
A prótese obturadora constitui o principal método para a reabilitação de grandes defeitos maxilares. Tem como objetivo fechar o defeito, separar a cavidade oral da cavidade nasal, prevenir a fala anasalada e a regurgitação nasal de alimentos e líquidos e dar sustentação ao perfil facial. Este artigo visa relatar um caso de reabilitação com prótese obturadora maxilar após maxilectomia parcial. Paciente do gênero feminino, 72 anos, diagnosticada com carcinoma adenoide cístico na região de palato, foi submetida a maxilectomia parcial que resultou em extenso defeito maxilar e comunicação bucosinusal. Após anamnese, exames extra, intraorais e radiográfico, foi planejado para o período cicatricial e de uso da sonda nasogástrica, a confecção de uma placa obturadora para melhorar a deglutição e fala. Em seguida, confecção de uma prótese total obturadora superior e prótese parcial removível inferior. A placa obturadora foi confeccionada e utilizada até a remoção da sonda e instalação das próteses. Após moldagem das duas arcadas, foram obtidos modelos funcionais que foram montados em articulador após os ajustes dos planos de orientação e registro das relações intermaxilares. Foram realizadas provas estéticas e funcionais dos dentes artificiais e ajustes necessários. Posteriormente à acrilização, as próteses foram instaladas e o ajuste oclusal executado. Para obter retenção e estabilidade satisfatórias durante a utilização da prótese obturadora superior foi sugerido o uso de adesivo para dentadura. Três proservações foram realizadas. A prótese obturadora reabilitou a estética, fonética, função mastigatória e deglutição restabelecendo a autoestima e a ressocialização da paciente(AU)
The obturator prosthesis is the main method for the rehabilitation of large maxillary defects. With the purpose to closethe defect, separate the oral cavity from the nasal cavity, prevent hypernasal speech, nasal regurgitation of food and liquids and provide support for the facial profile. This article aims to report a case of rehabilitation with maxillary obturator prosthesis after partial maxillectomy. A 72-year-old female patient, diagnosed with adenoid cystic carcinoma in the palate region, underwent partial maxillectomy that resulted in extensive maxillary defect and bucco-sinus communication. After anamnesis, extra, intraoral and radiographic exams, the construction of a palatal plate was planned to be used with the nasogastric tube and during the healing process, to improve swallowing and speech. Then, the manufacture of a maxillary obturator prosthesis and a lower removable partial prosthesis. The palatal plate was made and used until the tube was removed and the insertion of the prostheses. After the impressions, master casts were made and mounted on an articulator after adjustment of wax occlusion rims and registration of the maxillo-mandibular relations. Functional elements of speech, occlusion, and appearance were evaluated during the try-in of the provisional set-up and adjusts were made.After the acrylization, the prostheses were inserted and the occlusal adjustment performed. To obtain satisfactory retention and stability when using the maxillary obturator prosthesis, it was suggested to use denture adhesive. Three post-insertions visits were carried out. The obturator prosthesis rehabilitated aesthetics, phonetics, masticatory function and swallowing, restoring the patient's self-esteem and improving social life(AU)
La prótesis obturadora es el método principal para la rehabilitación de grandes defectos maxilares. Tiene por objetivo cerrarel defecto, separar la cavidad bucal de la cavidad nasal, prevenir el habla nasal, la regurgitación nasal de alimentos y líquidos,dando apoyo al perfil facial. Este artículo tiene objetivo de reportar un caso de rehabilitación con prótesis obturadora maxilar tras maxilectomía parcial. Una paciente de 72 años, diagnosticada de carcinoma adenoide quístico en región del palato, fué sometida a maxilectomía parcial que resultó en extenso defecto maxilar y comunicación bucosinusal. Después de anamnesis, exámenes extra, intraorales y radiográficos, se planificó para el período de cicatrización y el uso de la sonda nasogástrica,la construcción de una placa obturadora para mejorar la deglución y el habla. Luego, la fabricación de una prótesis obturadora total superior y una prótesis parcial inferior removible. La placa obturadora se hizo y se utilizó hasta que se retiró la sonda y se instalaron las prótesis. Se realizón la impresión de ambos arcos, obtuvieron modelos funcionales que se montaron en articulador, tras ajustes de los planos de orientación y registro de relaciones intermaxilares. Se realizaron pruebas estéticas y funcionales en dientes artificiales y ajustes necesarios. Después de la acrilización se instalaron las prótesis y se realizó ajuste oclusal. Para obtener una retención y estabilidad satisfactoria al utilizar la prótesis obturadora superior, fue sugirió utilizar un adesivo para prótesis. Se realizaron tres proservaciones. La prótesis obturatriz rehabilitó estética, fonética, función masticatoria y deglución, devolviendo autoestima y resocialización al paciente(AU)