Pleomorphic Adenoma of Minor Salivary Glands: a Rare Case Report.

Pleomorphic adenoma is a non-cancerous neoplasm that develops in the salivary glands. Originating from minor salivary glands, it is extremely uncommon and primarily affects females. The peak incidence is observed between 40 and 60 years of age. It usually presents as a slowly growing, painless, solid tumor that does not cause ulcers on the overlying mucosa. Here, a 47-year-old woman experienced repeated swelling on the buccal mucosa following surgical extraction of a pleomorphic adenoma three years ago. The swelling was solid with clearly defined boundaries. An excisional biopsy was conducted under general anesthesia, resulting in total mass removal. The histological evaluation revealed the existence of a recurring pleomorphic adenoma. This instance emphasizes the significance of addressing this entity as a potential etiology for persistent painless and intraoral swellings.

Clinical Impact of C-myc Oncogenic Diversity on Solid and Lymphoid Malignancies.

INTRODUCTION: Onset and progression of malignant tumors is a multistep process including a variety of gross chromosomal and specific genes' deregulation. Among oncogenes that are frequently altered in solid and also in hematological malignancies, the C-myc (gene locus: 8q24.21) plays a pivotal role. C-myc is a proto-oncogene encoding for a nuclear phosphoprotein implicated in cell cycle progression, apoptosis and cellular differentiation and transformation. OBJECTIVE: The purpose of the current molecular review was to explore the differences of C-myc oncogenic activity in solid and lymphoid malignancies that modify its clinical impact on them. MATERIAL AND METHOD: A systematic review of the literature in the international database PubMed was carried out. The year 2010 was set as a prominent time limit for the publication date of articles in the majority of them, whereas specific references of great importance and historical value in the field of C-myc gene discovery and analysis were also included. The following keywords were used: C-myc, oncogene, signaling pathway, malignancies, carcinoma, lymphoma. A pool of 43 important articles were selected for the present study at the basis of combining molecular knowledge with new targeted therapeutic strategies. RESULTS: C-myc oncogene demonstrates two different mechanisms of deregulation: amplification, mutation and translocation patterns. These particular aspects of gene alteration are unique for solid and non-solid (hematological) malignancies, respectively. CONCLUSIONS: C-myc is characterized by diversity regarding its deregulation mechanisms in malignancies derived from different tissues. C-myc translocation is sporadically combined with amplification ("complicon" formation) or mutations creating exotic genetic signatures. This "bi-phasic" C-myc deregulation model in the corresponding malignant tumor categories clinically affects the corresponding patients, also modifying the targeted therapeutic strategies on them.

C-Jun Transcription Factor Oncogenic Activation in Oral Carcinoma.

INTRODUCTION: Oral carcinogenetic is based on a variety of genomic imbalances (gross chromosome or specific gene alterations) that drive the normal oral mucosa to its neoplastic/dysplastic epithelial form and finally to a totally malignant tissue transformation. In this multi-step procedure, down-regulation of suppressor genes combined with overactivation of oncogenes are two crucial and partially early genetic events involved in the onset and progression of neoplastic/malignant epithelia transformation. More specifically, deregulation of strong transcription factors negatively affects the normal expression of a broad spectrum of genes that are involved in cell proliferation and signalling transduction to the nucleus. OBJECTIVE: The purpose of the current molecular review was to explore the c-Jun (chromosome location: 1p32-p31) transcription factor transformation mechanisms to oncogene in oral squamous cell carcinoma (OSCC). MATERIAL AND METHOD: A systematic review of the literature was carried out by searching in PubMed international database. The year 2010 was set as a prominent time limit for the publication date of the articles in the majority of them, whereas specific references of great importance and historical value in the field of the c-Jun gene discovery and analysis were also included. The following keywords were used: c-Jun, oncogene, signaling pathway, oral, carcinoma, transcription. A pool of 45 important articles were selected for the present study at the basis of combining molecular knowledge with new targeted therapeutic strategies. RESULTS: C-Jun - as a part of the c-Jun/c-Fos transcription factors' complex -critically regulates the expression levels in a variety of genes inside the cellular microenvironment. A broad spectrum of malignancies, including OSCC, demonstrate c-Jun alterations driving the gene to its oncogenic phenotype. Interestingly, c-Jun oncogenic activation is mediated by high-risk human papilloma virus (HR-HPV) persistent infection in significant subsets of these malignancies. CONCLUSIONS: C-Jun was the first oncogene - acting as a strong transcription factor - that was discovered and cloned 35 years ago. C-Jun is the living history of oncogenes and its discovery marks a significant step in the evolution of molecular biology.

Impact of Amplified Oncogenes on Salivary Gland Carcinomas.

In normal epithelia, proto-oncogenes regulate critical intra- or intercellular functions, including cell growth and proliferation, apoptosis, and signaling transduction from the cell periphery (extracellular space) to the nucleus mediated by different pathways. Oncogenes are the mutated or amplified forms of the corresponding proto-oncogenes that are crucially involved in cell neoplastic and malignant transformation during carcinogenesis. Salivary gland carcinomas (SGCs) demonstrate a variety of histogenetic types. They are characterized by a broad spectrum of chromosomal and gene alterations. In particular, amplifications in specific genes [human epidermal growth factor receptor 2 (HER2), human epidermal growth factor receptor 4 (HER4), epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), Mouse double minute 2 homolog (MDM2), androgen receptor (AR), programmed death (ligand 1 (PD-L1), neurogenic differentiation factor 2 (NEUROD2), phosphatidylinositol 3,4,5-trisphosphate-dependent RAC exchanger 1 protein (PREX1), cyclin-dependent kinase4/6 (CDK4/6), proline-rich acidic protein 1 (PRAP1), kell antigen system (KEL), glutamate receptor subunit epsilon 2 (GRIN2D), Ewing sarcoma RNA-binding protein 1 (EWSR1), MYC proto-oncogene (MYC)] combined or not with chromosomal numerical imbalances (aneuploidy/ polysomy/monosomy) form different genetic signatures affecting the response to monoclonal antibody-based, oncologicaly targeted regimens. Different SGC histotypes demonstrate specific combinations of mutated/amplified genes that modify their clinicohistological features. In the current molecular review, we present the most important amplified oncogenes and their impact on the biological behavior of SGCS.

Mutational Signatures in Salivary Gland Carcinomas.

Salivary gland carcinomas belong to the head and neck carcinoma super category of malignancies. They are characterized by histopathological diversity and comprise a variety of entities and subtypes. Mucoepidermoid, adenoid cystic and salivary duct carcinomas represent the most prominent malignancies. Concerning their corresponding genetic background, a broad spectrum of gene and chromosomal imbalances has been detected. Point mutations and deletions, amplifications and translocations, combined or not with chromosomal aneuploidy/polysomy/monosomy, create a landscape of specific genetic signatures that affect the biological behavior of these tumors and modify response rates to potential targeted therapeutic strategies. In the current molecular review, we focused on the categorization and description of the most important mutational signatures in salivary gland carcinomas.

Brain Perfusion Changes in a Patient with Facial Trauma.

A 69-year-old male was admitted to our hospital because of left facial trauma with bone fractures, including the maxillary sinus, zygomatic arch, and ethmoid and sphenoid bones. Brain computed tomography was unremarkable but regional cerebral blood flow with hexamethyl-propylene-amine oxime single-photon emission computed tomography (SPECT) showed hypoperfusion of the left hemisphere, which was reversible since a repeat SPECT 4 months later was substantially improved. Brain perfusion SPECT may provide information on cerebrovascular status in some cases of facial injury.

Anti-EGFR/BRAF-Tyrosine Kinase Inhibitors in Thyroid Carcinoma.

Alterations in significant genes located on chromosome 7 - including epidermal growth factor receptor (EGFR) and also v-Raf murine sarcoma viral oncogene homolog B (BRAF) as a mitogen-activated protein kinase (MAPK)  - combined or not with numerical imbalances of the whole chromosome (aneuploidy-polysomy) are crucial genetic events involved in the development and progression of malignancies. Identification of EGFR/BRAF-dependent specific somatic mutations and other mechanisms of deregulation (i.e., amplification) is critical for applying targeted therapeutic approaches [tyrosine kinase inhibitors (TKIs] or monoclonal antibodies (mAbs). Thyroid carcinoma is a specific pathological entity characterized by a variety of histological sub-types. Follicular thyroid carcinoma (FTC), papillary thyroid carcinoma (PTC), medullary thyroid carcinoma (MTC), and anaplastic thyroid carcinoma (ATC) represent its main sub-types. In the current review, we explore the role of EGFR/BRAF alterations in thyroid carcinoma in conjunction with the corresponding anti-EGFR/BRAF TKI-based novel therapeutic strategies for patients with specific genetic signatures.

Intraductal Carcinoma of the Parotid Gland as a Rare Neoplasm: A Case Report and Literature Review.

Background: Intraductal carcinoma is a rare low grade neoplasm of salivary glands with an excellent prognosis. It most frequently occurs in the parotid gland. Ectopic localizations are quite rare. Methods: This case report describes a man in his 60's who was referred to ear, nose and throat outpatient department with 1-month history of painless swelling of the right parotid region. Results: Ultrasound-guided fine-needle aspiration unveiled a cytologic specimen judged as "suspicious for malignancy" and patient underwent a partial superficial parotidectomy. Immunohistochemistry confirmed diagnosis of intraductal carcinoma of right parotid gland. Conclusions: There are few reported cases concerning this clinical entity following thorough review of the literature and recent developments with reference to the contribution of cytology and histopathology will probably modify its classification and management.

[Dysphagia with no obvious cause: globus pharyngeus]. / Une dysphagie sans cause évidente : le globus pharyngé.

Globus pharyngeus or globus sensation is an ordinary ENT referral. It comprises a persistent or intermittent painless feeling of a lump or foreign body in the throat and may be outlined as a tightening or choking sensation. It is usually long-lasting and has a tendency to recur. There are no established guidelines concerning diagnosis or treatment. History and clinical examination represent essential elements as they enable the practitioner to narrow the differential diagnosis and consider red flags. Therapeutic trial using PPI is recommended as initial first line treatment in the absence of red flags and paraclinical assessment can be proposed in nonresponsive patients. Management of this clinical condition consists of reassurance and offering speech therapy for refractory cases.

Le globus pharyngé est une plainte fréquente en consultation ORL. Il est défini comme une sensation, généralement chronique, de masse, blocage ou corps étranger persistant ou intermittent dans la gorge. Il n'existe pas de standards clairs concernant son diagnostic ou son traitement. L'anamnèse et l'examen clinique sont des éléments essentiels puisqu'ils permettent d'affiner les diagnostics différentiels et d'envisager une origine oncologique en présence de drapeaux rouges (tabagisme, consommation alcoolique). En l'absence de facteurs de risque, un traitement d'épreuve par IPP (inhibiteurs de la pompe à protons) est la première ligne de traitement. En l'absence d'amélioration, on peut proposer un bilan paraclinique. La prise en charge thérapeutique consiste à rassurer le patient et lui proposer des séances de logopédie pour les cas sévères.

Evaluation of Cheek Edema in an Infant Reveals Langerhans Cell Histiocytosis.

BACKGROUND: Langerhans cell histiocytosis is a rare hematological disorder. Skin rash is the typical early feature, and bony involvement is the second most common presentation. METHODS: We present a case of a 5-month-old female infant with left hemifacial swelling, initially treated for infection with antibiotics. However, due to persistence of swelling and new onset fever, further evaluation with ultrasonography, CT scan, FDG PET/CT and eventually biopsy was performed. RESULTS: Imaging methods revealed mandibular osteolysis indicative of either osteomyelitis or histiocytosis X. Tissue biopsy was diagnostic for Langerhans cell histiocytosis. CONCLUSION: Langerhans cell histiocytosis may present in infancy with a variety of symptoms, included an isolated bony lesion. Langerhans cell histiocytosis, despite its rarity, should be included in the differentiated diagnosis, when bone osteolysis is found.

Impact of SARS-CoV-2 infection on oral carcinoma patients.

Coronavirus-related Severe Acute Respiratory Syndrome (SARS-CoV) in 2002/2003, Middle-East Respiratory Syndrome (MERS-Cov) in 2012/2013, and especially the current 2019/2020 Severe Acute Respiratory Syndrome-2 (SARS-CoV-2) tested the national health systems' endurance worldwide. In order to fight this emergency situation, a variety of pharmaceutical companies focused on the design and development of efficient vaccines that are considered necessary for providing a level of normalization in totally affected human social-economical activity worldwide. COVID-19 led to an increased uncertainty in the field of oncological patients' management disrupting the normal conditions of therapeutic and monitoring procedures. In the current article, we explored the impact of SARS-CoV-2 infection on oral carcinoma patients. We observed COVD-19 pandemic negatively affects the normality regarding early diagnosis and optimal management (surgical operation, post-operational follow up/monitoring) in HNSCC/OSCC patients. Understanding the involvement of SARS-CoV-2 in the progression of malignancies is the first critical step for targeting the virus by efficient monoclonal antibodies and vaccines.

Reconstructing carcinoma of the lip commissure and buccal mucosa: an oncosurgical alternative approach.

PURPOSE: To describe a new technique of surgical treatment of the lip commissure or buccal mucosa carcinomas, where we use local flaps (skin, buccal mucosa) of the sliding type. METHODS: According to the current technique, the ectomy ranges horizontally and in a cuneiform shape towards the side of the buccal cavity, and in the whole thickness of the layer (skin - mucosa), where the neoplastic focus is enclosed. RESULTS: The difference in our technique consists of the following: To the vertical bi-cuneiform part of the wound a horizontal cuneiform part (with the top showing upwards) is added, with extent and width analogous to those of the cancerous injury (tri-cuneiform ectomy). The width of the gap across its horizontal part is larger on the side of the mucosa (continuous line), compared to the one along the side of the skin (punctuated line), since the mucosa, as a more versatile tissue, can be sutured easily, in contrast to the buccal skin, which is of greater thickness and shows lack of versatility, so that it can be pulled on with difficulty in order to be sutured. The planning of the injury, according to our described technique, facilitates the broad ectomy of the intraoral injuries in the area of the lip commissure and the buccal mucosa, with immediate suture of the flaps (buccal and skin gap), and the occlusion of the wound by primary intention. CONCLUSIONS: Using this specific technique, in the cases of extended injuries infiltrating the skin or the subcutaneous tissue, the harming use of transposition (sliding or free) flaps is avoided.

Diagnosis and treatment of limbic encephalitis in the cancer patient.

Limbic encephalitis is an inflammatory process involving the limbic structures of the brain, manifested with short-term memory deficits, confusion, depression and seizures. It is usually a paraneoplastic condition but it may also appear as a nonparaneoplastic syndrome. Patients with this condition may exhibit a variety of antibodies in their serum or/and cerebrospinal fluid targeting basement membrane components that bind to a variety of neurotransmitter receptors such as α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid and GABA B and proteins associated to the ion channels such as LGI1, Caspr2 or intracellular components. Flurodeoxyglucose PET/computed tomography usually demonstrates increased uptake in the limbic structures, and it may reveal the site of the primary tumor. Treatment consists of tumor removal if possible. Symptomatic treatment includes steroids, gamma immune globulin, plasma exchange, immunosuppressive therapies and anti-epileptic drugs. Prognosis is better when it is associated with antibodies against basement membrane rather than intracellular antibodies.

Cochlear involvement in patients with systemic autoimmune rheumatic diseases: a clinical and laboratory comparative study.

PURPOSE: Inner ear involvement has been reported in systemic rheumatic disease while detection of cochlin-specific antibodies has been reported in patients with idiopatic sensorineural hearing loss, suggesting cochlin's strong link to autoimmune hearing loss. The aim of this cross-sectional study was to calculate the prevalence of sensorineural hearing loss (SNHL) in patients with systemic rheumatic diseases, and to investigate any potential correlation with human antibodies to cochlin. METHODS: Patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren's syndrome (SS) and systemic sclerosis (SSc) according to the criteria of American College of Rheumatology were included in the study. All patients underwent a complete ear-nose-throat physical examination and audiological evaluation with pure tone audiometry and impedance audiometry. Pure tone average was calculated, taking as a starting point the hearing loss in dB according to the recommendation 02/1 of "Bureau International d' Audiophonologie" (BIAP) so as an average hearing threshold value. Sera of all patients were tested for the presence of IgG antibodies to human cochline (COCH-IgG). Sex and age-matched healthy subjects were included as controls to each group. RESULTS: A total of 133 patients were studied; 60 with RA, 41 with SLE, 24 with SS and 8 with SSc. 61.4% of patients reported vertigo, 41% hyperacousis, 39% hearing loss, 38% tinnitus, 37.9% headache and 2.1% sensation of ear pressure with unremarkable otoscopy. The prevalence of SNHL calculated for patients affected by RA, SLE, SS and SSc was 66.6%, 31.71%, 54.17%, and 75% respectively. The calculated average hearing thresholds value in RA was increased in comparison to SLE (p < 0.05). In addition it was also higher in patients with RA and secondary SS, in comparison to RA patients (p > 0.05). There was statistically significant correlation of average hearing threshold with disease activity score 28 (DAS28) in RA, but no correlation observed with disease activity index (SLEDAI) in SLE. COCH-IgG antibodies were detected in only two samples. The results were compared with those of their respective sex and age-matched healthy subjects. CONCLUSION: Our study revealed increased prevalence of SNHL in patients with systemic autoimmune rheumatic disease but no correlation of hearing loss with COCHIgG antibodies. The mechanism of inner ear damage remains unknown; thus, additional prospective studies will be needed to elucidate its pathogenesis.

Combined EGFR/ALK Expression Analysis in Laryngeal Squamous Cell Carcinoma.

BACKGROUND/AIM: Epidermal growth factor receptor (EGFR) acts as an oncogene in malignancies. Our aim was to examine the role of combined EGFR/ anaplastic lymphoma kinase (ALK) expression as molecular markers in laryngeal squamous cell carcinoma (LSCC) patients. MATERIALS AND METHODS: Fifty (n=50) tissue sections derived from twenty-five (n=25) primary LSCCs were analyzed by immunohistochemistry (IHC). RESULTS: EGFR overexpression was observed in 17/25 (68%) cases. Concerning ALK, 23/25 (92%) demonstrated low expression. EGFR expression was associated with grade (p=0.049), whereas ALK expression was correlated with stage (p=0.048). ALK overexpression was detected at advanced-stage EGFR-positive cases. A biphasic EGFR protein expression pattern was observed in five (n=5) LSCC cases, whereas ALK expression was stable in all cases. CONCLUSION: EGFR overexpression is frequently observed in LSCC combined with low ALK expression. LSCC patients with EGFR/ALK protein overexpression should be eligible for targeted therapeutic strategies.

Numerical Imbalances of Chromosome 7 in Oral Squamous Cell Carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is an aggressive neoplasm. Many chromosomal and gene alterations have been identified in OSCC, including structural and numerical changes. In this study, we implemented a molecular assay of chromosome 7 (Chr7) in order to investigate the level of its numerical instability in OSCC. MATERIALS AND METHODS: Using tissue microarray technology, 30 primary OSCCs were cored and re-embedded into one recipient block. Chromogenic in situ hybridization assay was performed based on Chr7 centromeric probedetection. RESULTS: Chr 7 numerical analysis detected polysomy (trisomy/ tetrasomy) in 4/30 (13.3%) of the examined tissue OSCC cores. Statistical significance was assessed correlating Chr7 numerical aberrations with stage (p=0.015), especially detected in cases not related to human papillomavirus (HPV) (p=0.01). CONCLUSION: Although Chr7 polysomy is a relatively rare gross genetic event in OSSC, it affects their biological behavior leading toa progressively aggressive phenotype (advanced stage). Furthermore, Chr7 polysomy is observed more frequently in non-viral (HPV) cases.