Oral Gastric Heterotopia: First Reported Case in the Hard Palate.

Gastric heterotopia is characterized by the presence of mature gastric tissue outside the stomach, yet its occurrence in the palate has not been previously documented. We describe a case of gastric heterotopia in the hard palate of an elderly female patient, presenting as a swollen mass with associated secretion. Given the patient's age and clinical symptoms, a presumptive diagnosis of a malignant tumor originating from the minor salivary glands was made. An incisional biopsy of the mass revealed gastric heterotopia. Subsequently, the extended excision of the lesion was performed, leading to the full resolution of the patient's symptoms. After a two-year follow-up period, no evidence of recurrence was observed. The importance of this case, underscored by the unprecedented location of gastric heterotopia, emphasizes the critical need for thorough evaluation to avert misdiagnosis, as well as the complete surgical excision of the lesion to prevent recurrence.

A seven-gene signature to predict the prognosis of oral squamous cell carcinoma.

The prognosis of oral squamous cell carcinoma (OSCC) patients remains poor without implemented biomarkers in the clinical routine practice to help in the patient's management. With this study we aimed to identify specific prognostic biomarkers for OSCC using a whole genome technology as well as to verify the clinical utility of a head and neck cancer-specific multiplex ligation-dependent probe amplification (MLPA) panel. A genomic characterization of tumor samples from 62 OSCC patients was performed using array comparative genomic hybridization (aCGH) and a more straightforward and cost-effective molecular technology, MLPA. The identification of a genomic signature and prognosis biomarkers was carried out by applying several statistical methods. With aCGH we observed that the chromosomes most commonly altered were 3p, 3q, 5q, 6p, 7q, 8p, 8q, 11q, 15q, 17q, and 18q. The MLPA results showed that the chromosomes with a higher frequency of alterations were 3p, 3q, 8p, 8q, and 11q. We identified a genomic signature with seven genes OCLN (3p21.31), CLDN16 (3q29), SCRIB (3q29), IKBKB (3q22.3), PAK2 (8q22.3), PIK3CB (3q28), and YWHAZ (8q24.3) that together allow to differentiate the patients that developed metastases or relapses after primary tumor treatment, with an overall accuracy of 79%. Amplification of PIK3CB as a predictor of metastases or relapses development was validated using TCGA data. This amplified gene showed a reduction in more than 5 years in the median survival of the patients. The identified biomarkers might have a significant impact in the patients' management and could leverage the OSCC precision medicine.

Eagle Syndrome: an underdiagnosed cause of orofacial pain.

Eagle Syndrome (ES), also termed stylohyoid syndrome or styloid syndrome, is a rare condition characterised by a cluster of symptoms related to an elongation of the styloid process (SP) of the temporal bone. These may range from mild pharyngeal foreign body sensation and dysphagia to severe orofacial pain. High clinical suspicion is necessary owing to the unspecific clinical picture and limited diagnostic clues. Until a definitive diagnosis is achieved, these patients may develop symptoms which significantly impact their quality of life. The aim of this article is to report a case of ES in which a considerable length of SP was documented. Diagnosis was made years after the initial complaints and several medical workups by different specialties. Surgical resection of the elongated process by cervical approach was the adopted treatment modality. Patient recovery and follow-up was satisfactory, with remission of the afflicting symptoms.

Proteomics-based Predictive Model for the Early Detection of Metastasis and Recurrence in Head and Neck Cancer.

BACKGROUND/AIM: Head and neck squamous cell carcinoma (HNSCC) presents high morbidity, an overall poor prognosis and survival, and a compromised quality of life of the survivors. Early tumor detection, prediction of its behavior and prognosis as well as the development of novel therapeutic strategies are urgently needed for a more successful HNSCC management. MATERIALS AND METHODS: In this study, a proteomics analysis of HNSCC tumor and non-tumor samples was performed and a model to predict the risk of recurrence and metastasis development was built. RESULTS: This predictive model presented good accuracy (>80%) and comprises as variables the tumor staging along with DHB12, HMGB3 and COBA1 proteins. Differences at the intensity levels of these proteins were correlated with the development of metastasis and recurrence as well as with patient's survival. CONCLUSION: The translation of proteomic predictive models to routine clinical practice may contribute to a more precise and individualized clinical management of the HNSCC patients, reducing recurrences and improving patients' quality of life. The capability of generalization of this proteomic model to predict the recurrence and metastases development should be evaluated and validated in other HNSCC populations.

Bronchogenic cyst of the neck in an elder patient: A case report.

INTRODUCTION: Bronchogenic cysts are rare malformations, mostly diagnosed in children. We report the rare case of a neck bronchogenic cyst diagnosed in an elderly patient. PRESENTATION OF CASE: The patient complained of a long-standing submental mass. The diagnostic work-up resulted in a thyroglossal duct cyst diagnosis for which the patient underwent a Sistrunk procedure. However, the histological analysis of the lesion ultimately revealed a bronchogenic cyst. DISCUSSION: Neck bronchogenic cysts are rare and, in adults, normally asymptomatic. Imaging exams can suggest the diagnosis but they are most important for surgical planning. Surgery is the elected treatment for bronchogenic cysts and the histopathologic exam of the specimen provides definitive diagnosis. CONCLUSION: This case demonstrates than even though they are a rare diagnosis, bronchogenic cysts should be considered in the diagnostic work-up of neck cysts, even in elderly patients.

Genomic and epigenetic signatures associated with survival rate in oral squamous cell carcinoma patients.

Purpose: Although oral squamous cell carcinoma (OSCC) presents great mortality and morbidity worldwide, the mechanisms behind its clinical behavior remain unclear. Biomarkers are needed to forecast patients' survival and, among those patients undergoing curative therapy, which are more likely to develop tumor recurrence/metastasis. Demonstrating clinical relevance of these biomarkers could be crucial both for surveillance and in helping to establish adjuvant therapy strategies. We aimed to identify genomic and epigenetic biomarkers of OSCC prognosis as well as to explore a noninvasive strategy to perform its detection. Methods: OSCC tumor and non-tumor tissue samples and cells scrapped from the tumor surface were genomic and epigenetically evaluated by Methylation-Specific Multiplex Ligation-dependent Probe Amplification technique. Results: Copy number alterations in ATM, CASR, TP73, CADM1, RARB, CDH13, PAX5, RB1 genes and GATA5, PAX6, CADM1 and CHFR promoter methylation were shown to be associated with worse OSCC patients' survival. Copy number alterations in BRCA1, CDKN2A, CHFR, GATA5, PYCARD, STK11, TP53, VHL genes and GATA5, CADM1, KLLN, MSH6, PAX5, WT1 promoter methylation were shown to be associated with development of metastasis/relapses during or after OSCC patients' treatment. We also found a good agreement in the status of CDKN2A promoter methylation evaluated noninvasively or in the tumor tissue. Conclusions: Genomic and epigenetic signatures were validated in a larger and geographically separate cohort, from TCGA database, which reinforce their clinical applicability. Noninvasive methodologies for detection of these signatures require further studies before translation in to clinical practice.

Genomic predictive model for recurrence and metastasis development in head and neck squamous cell carcinoma patients.

The head and neck squamous cell carcinoma (HNSCC) population consists mainly of high-risk for recurrence and locally advanced stage patients. Increased knowledge of the HNSCC genomic profile can improve early diagnosis and treatment outcomes. The development of models to identify consistent genomic patterns that distinguish HNSCC patients that will recur and/or develop metastasis after treatment is of utmost importance to decrease mortality and improve survival rates. In this study, we used array comparative genomic hybridization data from HNSCC patients to implement a robust model to predict HNSCC recurrence/metastasis. This predictive model showed a good accuracy (>80%) and was validated in an independent population from TCGA data portal. This predictive genomic model comprises chromosomal regions from 5p, 6p, 8p, 9p, 11q, 12q, 15q and 17p, where several upstream and downstream members of signaling pathways that lead to an increase in cell proliferation and invasion are mapped. The introduction of genomic predictive models in clinical practice might contribute to a more individualized clinical management of the HNSCC patients, reducing recurrences and improving patients' quality of life. The power of this genomic model to predict the recurrence and metastases development should be evaluated in other HNSCC populations.

Genomic and epigenetic characterization for the comparison of synchronous bilateral tongue squamous cell carcinomas-A case report.

The tongue is the most common and aggressive site for tumors in the oral cavity. These tumors are usually located in the lateral border of the tongue and are often related to the use of tobacco and alcohol. Clinical management of these tumors is predominantly based on anatomic location and TNM classification. The identification of molecular signatures with ability to explain the different outcomes observed in these patients is of paramount importance to guide and help their management. CASE PRESENTATION: we herein describe an 88-year-old woman diagnosed with synchronous bilateral tongue carcinoma. This woman did not present the traditional risk factors related to oral cancer-alcohol, tobacco, or presence of human papiloma virus (HPV). Both tumors were classified by a pathologist as pT2. This patient was submitted to surgery, 6 months later was diagnosed with cervical metastasis and in the following 2 months died. Copy number alterations and methylation status of these 2 simultaneous tumors were analyzed using array comparative genomic hybridization, multiplex ligation-dependent probe amplification, and methylation specific multiplex ligation-dependent probe amplification. In conclusion, in both tumors we identified several molecular traits usually found among oral cavity tumors and some of those have been associated with clinical outcome, reinforcing their importance to accurately establish biomarkers with clinical applicability. Specific genomic and epigenetic signatures for each of these 2 tumors were also observed allowing their molecular discrimination. The tumor of the right side of the tongue exhibited more copy number gains than the tumor of the left side. In the left side tumor less and smaller copy number alterations and more methylated genes were observed, which could be indicative of an early phase of tumor development. This case shows the molecular heterogeneity of oral cavity tumors even in the same patient and anatomic site, which could be the key to explain the different outcomes of oral tumor patients.

Genomic profile of oral squamous cell carcinomas with an adjacent leukoplakia or with an erythroleukoplakia that evolved after the treatment of primary tumor: A report of two cases.

Oral leukoplakia and erythroleukoplakia are common oral potentially malignant disorders diagnosed in the oral cavity. The specific outcome of these lesions remains to be elucidated, as their malignant transformation rate exhibits great variation. The ability to predict which of those potentially malignant lesions are likely to progress to cancer would be vital to guide their future clinical management. The present study reported two patients with tongue squamous cell carcinoma: Case study 1 was diagnosed with a simultaneous leukoplakia and case study 2 developed an erythroleukoplakia following the primary tumor treatment. Whole genome copy number alterations were analyzed using array comparative genomic hybridization. The present study determined more genomic imbalances in the tissues from leukoplakia and erythroleukoplakia compared with their respective tumors. The present study also identified in tumor and potentially malignant lesions common alterations of chromosomal regions and genes, including FBXL5, UGT2B15, UGT2B28, KANSL1, GSTT1 and DUSP22, being some of these typical aberrations described in oral cancer and others are linked to chemoradioresistance. Several putative genes associated with hallmarks of malignancy that may have an important role in predicting the progression of leukoplakia and erythroleukoplakia to squamous cell carcinoma, namely gains in BNIPL, MCL1, STAG2, CSPP1 and ZNRF3 genes were also identified.

Genetic and epigenetic characterization of the tumors in a patient with a tongue primary tumor, a recurrence and a pharyngoesophageal second primary tumor.

BACKGROUND: The choice of therapeutic modality for oral carcinoma in recurrent or second primary tumors remains controversial, as the treatment modalities available might be reduced by the treatment of the first tumor, and the overall survival is lower when compared with patients with a single or first tumor. Identifying biomarkers that predict the risk of relapse and the response to treatment is an emerging clinical issue. CASE PRESENTATION: A Caucasian 49-years-old man was treated with chemotherapy followed by chemoradiotherapy for a primary left side tongue tumor, achieving a complete response. After 49-months of follow-up, a local recurrence was diagnosed. After 3 months, a second primary tumor at the pharyngoesophageal region was detected. Genomic and epigenetic characterization of these three tumors was performed using array Comparative Genomic Hybridization, Multiplex Ligation-dependent Probe Amplification (MLPA) and Methylation Specific MLPA. RESULTS: The three tumors of this patient shared several imbalances in all chromosomes excluding chromosomes 9, 20 and 22, where genes related to important functional mechanisms of tumorigenesis are mapped. The shared genomic imbalances, such as losses at 1p, 2p, 3p, 4q, 5q, 6q, 7q, 8p, 10p, 11q, 12p, 12q, 13q, 15q, 16p, 16q, 17p, 17q, 18q, 19p, 19q, 21q and Xp and gains at 3q, 7q, 14q and 15q showed a common clonal origin for the diagnosed relapses. We identified some chromosomal imbalances and genes mapped in the chromosomes 2, 3, 4, 6, 7, 11, 14, 17, 18 and 22 as putative linked to chemoradioresistance and chemoradiosensitivity. We also observed that gains in short arm of chromosomes 6, 7, 8 and 18 were acquired after treatment of the primary tumor. We identified losses of VHL gene and promoter methylation of WT1 and GATA5 genes, as predictors of relapses. CONCLUSIONS: A common clonal origin for the diagnosed relapses was observed and we identified some putative candidate biomarkers of prognosis, relapse risk and treatment response that could guide the development of management strategies for these patients.

Early detection and personalized treatment in oral cancer: the impact of omics approaches.

BACKGROUND: Oral cancer is one of the most common malignant lesions of the head and neck. This cancer is an aggressive and lethal disease with no significant improvements in the overall survival in the last decades. Moreover, the incidence of oral HPV-positive tumors is rising, especially in young people. This oral neoplasm develops through numerous molecular imbalances that affect key genes and signaling pathways; however, the molecular mechanisms involved in the pathogenesis and progression of oral tumors are still to be fully determined. In order to improve the quality of life and long-term survival rate of these patients, it is vital to establish accurate biomarkers that help in the early diagnosis, prognosis and development of target treatments. Such biomarkers may possibly allow for selection of patients that will benefit from each therapy modality, helping in the optimization of intensity and sequence of the treatments in order to decrease side effects and improve survival. CONCLUSION: In this review we discuss the current knowledge of oral cancer and the potential role of omics approaches to identify molecular biomarkers in the improvement of early diagnosis, treatment and prognosis. The pursuit to improve the quality of life and decrease mortality rates of the oral patients needs to be centralized on the identification of critical genes in oral carcinogenesis. Understanding the molecular biology of oral cancer is vital for search new therapies, being the molecular-targeted therapies the most promising treatment for these patients.

WT1, MSH6, GATA5 and PAX5 as epigenetic oral squamous cell carcinoma biomarkers - a short report.

PURPOSE: Oral squamous cell carcinoma (OSCC) is a frequently occurring aggressive malignancy with a heterogeneous clinical behavior. Based on the paucity of specific early diagnostic and prognostic biomarkers, which hampers the appropriate treatment and, ultimately the development of novel targeted therapies, we aimed at identifying such biomarkers through a genetic and epigenetic analysis of these tumors. METHODS: 93 primary OSCCs were subjected to DNA copy number alteration (CNA) and methylation status analyses using methylation-specific multiplex ligation-dependent probe amplification (MS-MPLA). The genetic and epigenetic OSCC profiles obtained were associated with the patients' clinic-pathological features. RESULTS: We found that WT1 gene promoter methylation is a predictor of a better prognosis and that MSH6 and GATA5 gene promoter methylation serve as predictors of a worse prognosis. GATA5 gene promoter methylation was found to be significantly associated with a shorter survival rate. In addition, we found that PAX5 gene promoter methylation was significantly associated with tongue tumors. To the best of our knowledge, this is the first study that highlights this specific set of genes as epigenetic diagnostic and prognostic biomarkers in OSCC. CONCLUSIONS: Our data highlight the importance of epigenetically assessing OSCCs to identify key genes that may serve as diagnostic and prognostic biomarkers and, potentially, as candidate therapeutic targets.

Cervical abscess in an immunocompetent patient with Mycobacterium malmoense pulmonary disease.

BACKGROUND: Mycobacterium malmoense is a nontuberculous mycobacteria seen mainly in two age groups and with different clinical presentations. Most patients are male adults presenting clinical symptoms and signs similar to those of pulmonary tuberculosis. The second group is formed by immunocompetent children with localized cervical lymphadenitis. Although cervical adenitis is the main extrapulmonary manifestation of M. malmoense, virtually all cases of cervical disease were documented in children. Disseminated disease is rare and has been reported in patients with severely impaired immunity. CASE REPORT: We report a case of a 47-year-old immunocompetent man with a cervical abscess, in whom we identified a M. malmoense pulmonary disease with multiple cervical, thoracic and abdominal adenopathies. CONCLUSION: Extrapulmonary infection due to M. Malmoense needs to be considered on the differential diagnosis of cervical masses and adenopathies, not only in pediatric patients but also in adults with no impaired immunity. A high index of suspicion for nontuberculous mycobacteria is essential for the diagnosis and prognosis.