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BACKGROUND: Salivary gland tumors are assumed to be predominantly malignant in the Greenlandic Inuit population, but there is limited literature on the subject. We conducted a retrospective cohort study using national registers to describe the histological tumor types, location, incidence, and survival of benign and malignant salivary gland tumors. METHODS: We analyzed data on all Greenlandic Inuit with an epithelial-derived salivary gland tumor from 1990 to 2019. We extracted data from the Central Personal Registry and crossmatched it with the Danish Pathology Data Bank. All specimens were reviewed by a specialized pathologist. We noted patient and histological characteristics, calculated crude and age-adjusted incidence rates, overall survival, and excess mortality. RESULTS: Our study found that 76% of salivary gland tumors in the Greenlandic Inuit population were benign, with pleomorphic adenoma being the most common. Malignant tumors accounted for 24% of cases, with lymphoepithelial carcinoma being the most common type. The most common place of origin for malignant tumors was the parotid gland (71%) and the submandibular gland (15%). The median age of onset for malignant tumors was 47 years. Age-adjusted incidence rates of malignant tumors for men and women were 3.00 and 4.12 per 100,000 person-years, respectively. CONCLUSION: Our findings suggest that the proportion of malignant salivary gland tumors in the Greenlandic Inuit population is similar to other nonendemic populations. Our incidence rates are higher than previously reported, likely due to differences in methodology and definitions of the Inuit population. This study provides valuable insights into the epidemiology of salivary gland tumors in the Greenlandic Inuit population and may have implications for other Inuit populations as well.
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Adenoma Pleomorfo , Carcinoma de Células Escamosas , Neoplasias das Glândulas Salivares , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Inuíte , Neoplasias das Glândulas Salivares/epidemiologia , Neoplasias das Glândulas Salivares/patologia , Adenoma Pleomorfo/epidemiologia , Adenoma Pleomorfo/patologiaRESUMO
Adenoid cystic carcinoma (ACC) is an aggressive malignancy that most often arises in salivary or lacrimal glands but can also occur in other tissues. We used optimized RNA-sequencing to analyze the transcriptomes of 113 ACC tumor samples from salivary gland, lacrimal gland, breast or skin. ACC tumors from different organs displayed remarkedly similar transcription profiles, and most harbored translocations in the MYB or MYBL1 genes, which encode oncogenic transcription factors that may induce dramatic genetic and epigenetic changes leading to a dominant 'ACC phenotype'. Further analysis of the 56 salivary gland ACC tumors led to the identification of three distinct groups of patients, based on gene expression profiles, including one group with worse survival. We tested whether this new cohort could be used to validate a biomarker developed previously with a different set of 68 ACC tumor samples. Indeed, a 49-gene classifier developed with the earlier cohort correctly identified 98% of the poor survival patients from the new set, and a 14-gene classifier was almost as accurate. These validated biomarkers form a platform to identify and stratify high-risk ACC patients into clinical trials of targeted therapies for sustained clinical response.
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Background: In the head and neck region the uvula is a rare site for extranodal lymphomas to develop. In this national study, we present six cases and provide an overview of the current literature, characterizing the clinical and histopathological features of lymphomas involving this location. Materials and Methods: Clinical information was obtained retrospectively from patient records in a nationwide Danish study covering from 1980 through 2019. In order to validate the diagnoses, uvular tissue specimens were examined histologically and immunohistochemically and if relevant for subtyping, cytogenetic rearrangements were investigated. Results: We present six cases of lymphomas involving the uvula, of which four of the cases were diagnosed with a B-cell lymphoma (two diffuse large B-cell lymphomas, one extranodal marginal zone B-cell lymphoma and one Mantle cell lymphoma), while two were diagnosed with a T-cell lymphoma (one peripheral T-cell lymphoma and one natural killer/T-cell lymphoma). Presenting symptoms included swelling, pain and ulceration of the uvula. Treatment was comprised of radiotherapy and/or chemotherapy, with T-cell lymphomas showing a poorer outcome than B-cell lymphomas. Conclusion: Lymphoma of the uvula is rare, with few case reports being reported in the literature. The most frequent histological subtypes reported are extranodal marginal zone B-cell lymphoma and peripheral T-cell lymphoma. When encountering a swollen, painful and/or ulcerated uvula, the clinician should always consider malignancy as a possible cause. Lymphoma of the uvula is a possible diagnosis and if this is the case, there is a high risk of disseminated disease at the time of diagnosis.
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The aim of this review is to analyze the latest trends in the management of non-vestibular skull base and intracranial schwannomas in order to optimize tumor control and quality of life. Non-vestibular cranial nerve schwannomas are rare lesions, representing 5-10% of cranial nerve schwannomas. Management decisions should be individualized depending on tumor size, location and associated functional deficits. Generally, large sized schwannomas exerting significant mass effect with increased intracranial pressure are treated surgically. In some cases, even after optimal skull base resection, it is not possible to achieve a gross total resection because tumor location and extent and/or to reduce morbidity. Thus, subtotal resection followed by stereotactic radiosurgery or fractioned radiotherapy offers an alternative approach. In certain cases, stereotactic radiosurgery or radiotherapy alone achieves good tumor control rates and less morbidity to gross total resection. Finally, given the slow growth rate of most of these tumors, observation with periodic radiographic follow-up approach is also a reasonable alternative for small tumors with few, if any, symptoms.
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PURPOSE: Salivary gland carcinoma is a rare disease and studies on epidemiology and outcome require data collection over many years. The aim of this study is to present an update of incidence rates, anatomical sites, histological subtypes, and survival rates based on the Danish national cohort of salivary gland carcinoma patients. METHODS: Data from all Danish patients with salivary gland carcinoma diagnosed from 1990 to 2015 (n = 1601) were included and analyzed following histological reevaluation and reclassification. Overall, disease-specific, and recurrence-free survival were evaluated. Prognostic factors were analyzed with multivariate Cox Hazard Regression. RESULTS: The study population consisted of 769 men and 832 women, median age 62 years (range 6-102). The most frequent anatomic site was the parotid gland (51.8%). Adenoid cystic carcinoma was the most common subtype (24.7%). The majority had tumor classification T1/T2 (65.3%). The mean crude incidence was 1.2/100.000/year with an increase of 1.5% per year. There was no increase in age-adjusted incidence. The 5-, 10-, and 20-year survival rates were for overall survival 68, 52, and 35%, for disease-specific survival, 77, 69, and 64%, and for recurrence-free survival, 75, 64, and 51%, respectively. Age, high-grade histological subtype, advanced T-classification, cervical lymph node metastases, vascular invasion, and involved surgical margins had significantly negative impact on survival rates. CONCLUSION: The age-adjusted incidence has been stable for a period of 26 years. Multivariate analysis confirmed that histological grade, advanced stage, involved surgical margins and vascular invasion are independent negative prognostic factors. Survival rates were stationary compared to earlier reports.
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Carcinoma Adenoide Cístico , Neoplasias das Glândulas Salivares , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Adenoide Cístico/epidemiologia , Carcinoma Adenoide Cístico/patologia , Criança , Dinamarca/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/epidemiologia , Neoplasias das Glândulas Salivares/patologia , Taxa de Sobrevida , Adulto JovemRESUMO
Salivary gland carcinomas represent a heterogeneous group of poorly characterized head and neck tumors. The purpose of this study was to evaluate ALK gene and protein aberrations in a large, well-characterized cohort of these tumors. A total of 182 salivary gland carcinomas were tested for anaplastic lymphoma kinase (ALK) positivity by immunohistochemistry (IHC) using the cut-off of 10% positive cells. ALK positive tumors were subjected to FISH analysis and followed by hybrid capture-based next generation sequencing (NGS). Of the 182 tumors, 8 were ALK positive by IHC. Further analysis using hybrid capture NGS analysis revealed a novel MYO18A (Exon1-40)-ALK (exon 20-29) gene fusion in one case of intraductal carcinoma. Additional genomic analyses resulted in the detection of inactivating mutations in BRAF and TP53, as well as amplifications of ERBB2 and ALK. ALK rearrangements are a rare entity in salivary gland carcinomas. We identified a potentially targetable novel ALK fusion in an intraductal carcinoma of minor salivary glands.
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Quinase do Linfoma Anaplásico/genética , Biomarcadores Tumorais/genética , Carcinoma/genética , Neoplasias das Glândulas Salivares/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/enzimologia , Carcinoma/patologia , Carcinoma Intraductal não Infiltrante/enzimologia , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/patologia , Criança , Feminino , Amplificação de Genes , Fusão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Neoplasias das Glândulas Salivares/enzimologia , Neoplasias das Glândulas Salivares/patologia , Adulto JovemRESUMO
Background: Lymphoma of the sublingual gland is rare, representing 1% of all salivary gland lymphomas. In this case report, we present three new cases and compare them to previously published cases, with the aim of characterizing the clinical, morphological, histopathological, and genetic features of this type of malignancy. Materials and Methods: We provide a clinical description of three cases along with a characterization of the microscopic features, including morphology, and immunohistochemistry. In addition, we analysed possible cytogenetic rearrangements with the use of fluorescence in situ hybridization (FISH). Results: Case 1: A 61-year-old male presenting with a painless swelling of the floor of the mouth diagnosed as extranodal marginal zone lymphoma (EMZL) of the left sublingual gland. The patient is alive with no evidence of disease after his fourth treatment regimen following several relapses. Case 2: A 68-year-old female with a prior history of mantle cell lymphoma (MCL) presenting with a tender swelling of the left sublingual gland as well as the right submandibular gland. The lesions were diagnosed as relapsing MCL. The patient died of unrelated causes after 18 months of treatment. Case 3: A 75-year-old female presenting with a swelling of the floor of the mouth diagnosed as follicular lymphoma (FL) of the left sublingual gland. The patient received chemotherapy along with radiotherapy and was still alive 10 years after the diagnosis. Conclusion: The three cases of sublingual gland lymphomas presented in this case report resemble lymphomas of other major salivary glands. The clinician should be aware of this type of malignancy and that the clinical presentation may not differ from benign lesions or other more common malignancies in this location.
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AIM: PD-L1 expression and high levels of microsatellite instability (MSI-H) may predict response to checkpoint inhibitors, but their prevalence and prognostic value are unknown in many cancers. METHODS: We retrospectively evaluated PD-L1 combined positive score (CPS) and MSI-H and their association with clinical outcomes among patients with ten advanced uncommon cancers. RESULTS: 398 of 426 patients (93%) had a valid PD-L1 result; most (242; 61%) had CPS ≥1. Prevalence of MSI-H tumors was 8/360. Median overall survival was shorter among patients with PD-L1 CPS ≥1 tumors after first-line treatment (23.0 vs 39.7 months, p = 0.014). CONCLUSION: PD-L1 was commonly expressed in solid tumors, and CPS ≥1 was associated with shorter overall survival. Prevalence of MSI-H was low.
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INTRODUCTION: Gamma knife radiosurgery (GKR) has shown promising results in the treatment of intraocular uveal melanoma (UM) in terms of local tumor control. However, GKR is not free from potentially sight-threatening side effects, including cataract, dry eye disease, vitreous hemorrhage, radiation retinopathy (RR), radiation maculopathy (RM), optic neuropathy, and neovascular glaucoma. The aim of this paper is to report our 20-year experience in UM management with GKR focusing on the rate of clinical treatment-induced complications. METHODS: Single-center, retrospective, observational study, including all patients with UM treated at the Ocular Oncology and Uveitis Service, in the Department of Ophthalmology of the San Raffaele Scientific Institute, Milan from September 1993 to September 2018. Clinical charts comprised complete ophthalmological examination with measurement of best-corrected visual acuity, slit-lamp biomicroscopy, intraocular pressure measurement, gonioscopy, and indirect ophthalmoscopy at each visit. B-scan ultrasound (Aviso S, 10 MHz probe; Paris, France), optical coherence tomography (Heidelberg Spectralis; Heidelberg Engineering, Heidelberg, Germany), retinography, and fundus fluorescein angiography (standard or ultra-widefield [UWF; California, Optos, Dunfermline, Scotland, UK]) were performed aiding in the diagnosis of complications. RESULTS: Overall, 194 patients (100 males, 51.6%) were reviewed. The median age at the time of the treatment was 65 years (range 27-89) and all participants were Caucasian. In 185 eyes (95.4%), the tumor was primarily located at the choroid. The median follow-up was 57.6 months; radiation-induced complications were found in 145 eyes (74.7%). Radiation-induced cataract and RR were the most frequent events, with a relative incidence of 41.2 and 34.5%, respectively, followed by neovascular glaucoma (27.3%), optic neuropathy (18.6%), RM (11.4%), vitreous hemorrhage (14.4%), phthisis bulbi (7.7%), hyphema (0.5%), and corneal melting (0.5%). The shorter onset of side effects involved the optic nerve (median 14.9 months) and the macula (median 13.7 months). CONCLUSION: Despite modern and advanced strategies introduced to limit GKR side effects, cataract and RR still represent a serious limitation of this treatment. Incidence of RR was higher in our cohort compared to other reports, probably due to increased diagnosis rate permitted by UWF retinal imaging.
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BACKGROUND: Treating recurrent pleomorphic adenoma (RPA) aims to reduce risk of malignant transformation (MT) while avoiding facial nerve injury. Our objective was to systematically investigate this natural history of RPA and address the current rational for its treatment. METHODS: The follow-up data of two nationwide series of PA was pooled with a focus on risk of MT and analyzed against the literature. RESULTS: The combined nationwide data (n = 9003 PA patients) showed 3.1% with first recurrence of which 6.2% were malignant. In the literature first RPA rate was >7% at 20 years follow-up. MT occurred in 0% to 7%, and facial nerve damage increased from with each surgery 3% to 16% at first RPA to 18% to 30% at second RPA. CONCLUSIONS: RPA showed a characteristic course with surgery being unreliable and damage to the facial nerve. The risk of MT was low. This might give flexibility towards a more conservative approach of management.
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Adenoma Pleomorfo , Traumatismos do Nervo Facial , Neoplasias Parotídeas , Adenoma Pleomorfo/cirurgia , Nervo Facial , Humanos , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Parotídeas/terapiaRESUMO
Since the first description of sinonasal undifferentiated carcinoma (SNUC) as a distinctive highly aggressive sinonasal neoplasm with probable origin from the sinonasal mucosa (Schneiderian epithelium), SNUC has been the subject of ongoing study and controversy. In particular, the SNUC category gradually became a "wastebasket" for any undifferentiated or unclassifiable sinonasal malignancy of definite or probable epithelial origin. However, with the availability of more specific and sensitive immunohistochemical antibodies and increasing implementation of novel genetic tools, the historical SNUC category became the subject of progressive subdivision leading to recognition of specific genetically defined, reproducible subtypes. These recently recognized entities are characterized by distinctive genetic aberrations including NUTM1-rearranged carcinoma (NUT carcinoma) and carcinomas associated with inactivation of different members of the SWI/SNF chromatin-remodeling gene complex such as SMARCB1-deficient and less frequently SMARCA4-deficient carcinoma. The ring became almost closed, with recent studies highlighting frequent oncogenic IDH2 mutations in the vast majority of histologically defined SNUCs, with a frequency of 82%. A review of these cases suggests the possibility that "true SNUC" probably represents a distinctive neoplastic disease entity, morphologically, phenotypically, and genetically. This review addresses this topic from a historical perspective, with a focus on recently recognized genetically defined subsets within the SNUC spectrum.
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Biomarcadores Tumorais/genética , Carcinoma/diagnóstico , Carcinoma/epidemiologia , Carcinoma/genética , DNA Helicases/genética , Humanos , Neoplasias do Seio Maxilar/diagnóstico , Neoplasias do Seio Maxilar/epidemiologia , Neoplasias do Seio Maxilar/genética , Proteínas Nucleares/genética , Proteína SMARCB1/genética , Fatores de Transcrição/genéticaRESUMO
Introduction: Management of clinically negative neck (cN0) in patients with parotid gland cancer is controversial. Treatment options can include observation, elective neck dissection or elective radiotherapy. Areas covered: We addressed the treatment options for cN0 patients with parotid gland cancer. A literature review was undertaken to determine the optimal management of this group of patients. Expert opinion: Patients with parotid carcinoma and clinically negative neck have various options for their management. The analysis of tumor stage, histology and grade is essential to better define patients at risk for occult lymph node metastasis. These patients can be managed by surgery, radiotherapy or their combination, depending on the presence of risk factors, the moment at which such risk factors are detected, patient-related clinical conditions, medical provider expertise and institutional facilities.
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Esvaziamento Cervical/métodos , Neoplasias Parotídeas/terapia , Medicina Baseada em Evidências , Humanos , Metástase Linfática , Estadiamento de Neoplasias , Neoplasias Parotídeas/patologia , Fatores de RiscoRESUMO
INTRODUCTION: A vast increase in knowledge of numerous aspects of malignant salivary gland tumours has emerged during the last decade and, for several reasons, this has not been the case in benign epithelial salivary gland tumours. We have performed a literature review to investigate whether an accurate histological diagnosis of the 11 different types of benign epithelial salivary gland tumours is correlated to any differences in their clinical behaviour. METHODS: A search was performed for histological classifications, recurrence rates and risks for malignant transformation, treatment modalities, and prognosis of these tumours. The search was performed primarily through PubMed, Google Scholar, and all versions of WHO classifications since 1972, as well as numerous textbooks on salivary gland tumours/head and neck/pathology/oncology. A large number of archival salivary tumours were also reviewed histologically. RESULTS: Pleomorphic adenomas carry a considerable risk (5-15%) for malignant transformation but, albeit to a much lesser degree, so do basal cell adenomas and Warthin tumours, while the other eight types virtually never develop into malignancy. Pleomorphic adenoma has a rather high risk for recurrence while recurrence occurs only occasionally in sialadenoma papilliferum, oncocytoma, canalicular adenoma, myoepithelioma and the membranous type of basal cell adenoma. Papillomas, lymphadenoma, sebaceous adenoma, cystadenoma, basal cell adenoma (solid, trabecular and tubular subtypes) very rarely, if ever, recur. CONCLUSIONS: A correct histopathological diagnosis of these tumours is necessary due to (1) preventing confusion with malignant salivary gland tumours; (2) only one (pleomorphic adenoma) has a considerable risk for malignant transformation, but all four histological types of basal cell adenoma can occasionally develop into malignancy, as does Warthin tumour; (3) sialadenoma papilliferum, oncocytoma, canalicular adenoma, myoepithelioma and Warthin tumour only occasionally recur; while (4) intraductal and inverted papilloma, lymphadenoma, sebaceous adenoma, cystadenoma, basal cell adenoma (apart from the membranous type) virtually never recur. No biomarker was found to be relevant for predicting recurrence or potential malignant development. Guidelines for appropriate treatment strategies are given.
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Adenoma Pleomorfo/classificação , Adenoma Pleomorfo/diagnóstico por imagem , Adenoma/classificação , Adenoma/diagnóstico por imagem , Glândulas Salivares/citologia , Glândulas Salivares/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
This study aimed to investigate the microRNA (miRNA) profile in primary tumors from conjunctival melanoma with and without subsequent metastatic spread along with their coupled distant metastases to identify miRNAs likely to be involved in metastatic progression. This observational study included 13 patients with metastatic conjunctival melanoma (follow-up: 1-39 years) treated at a Danish referral center. Twenty-five patients with nonmetastatic conjunctival melanoma (follow-up: 5-17 years) were included for comparison. Global miRNA profiling was performed with the Affymetrix GeneChip 4.1 microarray. Taqman qPCR arrays were used for validation. Significant differentially expressed miRNAs were defined as having a false discovery rate of less than 0.05. Primary conjunctival melanoma with and without subsequent metastatic spread clustered separately according to miRNA expression, and 15 miRNAs were found to have significant differential expression. Six miRNAs (hsa-miR-4528, hsa-miR-1270, hsa-miR-1290, hsa-mir-548f-4, hsa-mir-4278, and hsa-miR-34a-3p) were downregulated and nine miRNAs were upregulated (hsa-mir-575, hsa-miR-527, hsa-miR-518a-5p, hsa-miR-6759-5p, hsa-miR-8078, hsa-mir-4501, hsa-mir-622, hsa-mir-4698, and hsa-mir-4654) in primary conjunctival melanoma with subsequent metastatic spread. A comparison of primary conjunctival melanoma with their pair-matched metastases identified six significant differentially expressed miRNAs (hsa-miR-1246 and hsa-miR-302d-5p, hsa-mir-6084, hsa-miR-184, hsa-mir-658, and hsa-mir-4427). qPCR confirmed downregulation of hsa-miR-184 in the distant metastases when compared with the corresponding primary tumor. Primary conjunctival melanoma with and without subsequent metastatic spread separated clearly on the miRNA level when profiled with microarray-based methods. qPCR was able to replicate expression levels of one miRNA (hsa-miR-184) that was downregulated in metastases when compared with corresponding primary tumors.
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Neoplasias da Túnica Conjuntiva/genética , Melanoma/genética , MicroRNAs/genética , Idoso , Neoplasias Encefálicas/secundário , Neoplasias da Túnica Conjuntiva/patologia , Dinamarca , Progressão da Doença , Regulação para Baixo , Reações Falso-Positivas , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Metástase Neoplásica , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias Parotídeas/secundário , Reação em Cadeia da Polimerase , Manejo de Espécimes , Neoplasias da Glândula Submandibular/secundárioRESUMO
The field of haematopathology is rapidly evolving and for the non-specialized pathologist receiving a specimen with the possibility of a lymphoid malignancy may be a daunting experience. The coincidence of the publication, in 2017, of the WHO monographies on head and neck and haematopoietic and lymphoid tumours prompted us to write this review. Although not substantially different from lymphomas elsewhere, lymphomas presenting in this region pose some specific problems and these are central to the review. In addition, differences in subtype frequency and morphological variations within the same entity are discussed. The difficulty in diagnosis related to some specimens led us to briefly mention common subtypes of systemic lymphomas presenting in the head and neck region.
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Neoplasias de Cabeça e Pescoço/patologia , Linfoma/patologia , Gradação de Tumores , Glândulas Salivares/patologia , Humanos , Fatores Reguladores de Interferon/metabolismo , Linfoma/diagnóstico , Plasmócitos/patologiaRESUMO
The head and neck region harbor numerous specialized tissues of all lineages giving rise to a plethora of different malignancies. In recent years, new types and subtypes of cancer has been described here due to the recognition of their histological and molecular characteristics. Some have been formally accepted in the most recent classifications from the World Health Organization (WHO) and American Joint Committee on Cancer (AJCC) as distinct diseases due to characteristics in clinical presentation, outcome, and treatment. In particular, this applies to malignancies of the salivary gland, sinonasal tract, and oropharynx. In this overview, we present the most recent developments in the classification, histopathological characteristics, and molecular features of head and neck cancer. The clinical and radiological characteristics, outcome, and treatment options including perspectives for targeted therapies, are discussed.
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Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Eletroquimioterapia , Neoplasias de Cabeça e Pescoço/classificação , Humanos , Melanoma/patologia , Melanoma/terapia , Terapia de Alvo Molecular , Neoplasias Bucais/patologia , Neoplasias Bucais/terapia , Neoplasias Nasais/patologia , Neoplasias Nasais/terapia , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/terapia , Prognóstico , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/terapiaRESUMO
The spectrum of tumors arising in the salivary glands is wide and has recently been shown to harbor a network of tumor-specific fusion genes. Acinic cell carcinoma (AciCC) is one of the more frequently encountered types of salivary gland carcinoma, but it has remained a genetic orphan until recently when a fusion between the HTN3 and MSANTD3 genes was described in one case. Neither of these 2 genes is known to be implicated in any other malignancy. This study was undertaken to investigate whether the HTN3-MSANTD3 fusion is a recurrent genetic event in AciCC and whether it is a characteristic of one of its histological variants. Of the 273 AciCCs screened, 9 cases showed rearrangement of MSANTD3 by break-apart fluorescence in situ hybridization, 2 had 1 to 2 extra signals, and 1 had gain, giving a total of 4.4% with MSANTD3 aberrations. In 6 of 7 available cases with MSANTD3 rearrangement, the HTN3-MSANTD3 fusion transcript was demonstrated with real-time polymerase chain reaction. Histologically, all fusion-positive cases were predominantly composed of serous tumor cells growing in solid sheets, with serous tumor cells expressing DOG-1 and the intercalated duct-like cell component being CK7 positive and S-100 positive in 6/9 cases. All but one case arose in the parotid gland, and none of the patients experienced a recurrence during follow-up. In contrast, the case with MSANTD3 gain metastasized to the cervical lymph nodes and lungs. In conclusion, we find the HTN3-MSANTD3 gene fusion to be a recurrent event in AciCC with prominent serous differentiation and an indolent clinical course.
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Carcinoma de Células Acinares/genética , Carcinoma de Células Acinares/patologia , Proteínas de Ligação a DNA/genética , Histatinas/genética , Fusão Oncogênica , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Endolymphatic sac tumors (ELSTs) are rare, slowly growing temporal bone neoplasms which show a high association with von Hippel-Lindau (VHL) syndrome. The immunohistochemistry evaluation of these papillary-cystic neoplasms frequently raises the differential diagnosis with renal cell carcinoma, among other metastatic neoplasms, whether in VHL patients or not. A cohort of 26 patients with ELSTs were evaluated for histologic features, immunohistochemistry findings, and association with VHL. Standard immunohistochemistry evaluation was performed. Sixteen females and 10 males ranging in age from 10 to 69 years (mean 44; VHL mean: 32) at initial presentation, comprised the cohort of patients. Most (86%) experienced hearing changes or inner ear symptoms (vertigo, dizziness), with an average duration of symptoms for 39 months (range 2-240 months). The tumors were an average of 2.9 cm (range 0.4-8 cm), with 14 left, 11 right sided and one bilateral tumor. Nine patients had documented VHL, with 3 patients having a concurrent or subsequent clear cell renal cell carcinoma. Patients were followed an average of 6.2 years (available in 24 patients): 19 alive without disease, 7.5 years; 2 dead without disease, 1.2 years; and 3 alive with disease, 3.1 years. The neoplastic cells show the following immunohistochemistry findings: AE1/AE3, EMA, CK7, CAIX, GLUT1, VEGF: 100% of cases tested were positive; pax-8: 85% of cases positive; CD10 and RCC: 0% of cases reactive. Based on this cohort of 26 patients with ELST, 9 of whom had VHL, the strong pax-8 and CAIX should be used in conjunction with negative CD10 and RCC to help exclude a metastatic renal cell carcinoma. As CAIX is an enzyme overexpressed in hypoxia and hypoxia inducible factor is what VHL protein regulates, this is an expected, although previously unreported finding. Whether part of VHL or not, VHL mutations may be a somatic rather than germline finding in the tumors, a possible further explanation for the CAIX reaction.
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Biomarcadores Tumorais/análise , Carcinoma de Células Renais/diagnóstico , Neoplasias da Orelha/diagnóstico , Saco Endolinfático/patologia , Neoplasias Renais/diagnóstico , Adolescente , Adulto , Idoso , Anidrase Carbônica IX/análise , Carcinoma de Células Renais/etiologia , Criança , Diagnóstico Diferencial , Neoplasias da Orelha/etiologia , Feminino , Humanos , Neoplasias Renais/etiologia , Masculino , Pessoa de Meia-Idade , Fator de Transcrição PAX8/análise , Adulto Jovem , Doença de von Hippel-Lindau/complicaçõesRESUMO
Salivary myoepithelial cells bear particular appendages and are involved in processes that have received incomplete attention in previous reviews. Here, cilia on myoepithelial cells are reviewed as regards substructure, occurrence, detection (electron microscopy, double immunofluorescence together with confocal microscopy), and roles (sensory reception, evolutionary homology, paracrine interaction). Attention is drawn to regressive changes affecting those cells (e.g. accumulation of lipofuscin), possible alterations of their cytoskeleton, internalization of apoptotic bodies and haemosiderin, and role in salivary microcalcification. The ability of differentiated salivary myoepithelial cells to divide is re-examined, particularly its increase in chronic inflammation and under experimental conditions. Caution with regard to histogenetic models of salivary neoplasia is re-emphasized; methodological deficiencies and areas of controversy are outlined; and lines of future research are suggested.