Successful treatment with rituximab of IgG4-related disease coexisting with adult-onset asthma and periocular xanthogranuloma.

Immunoglobulin G4-related disease (IgG4RD) is a systemic fibro-inflammatory disease of unknown aetiology, which is characterized by tumefactive lymphoplasmatocytic infiltrative lesions, with a predominance of IgG4 positive plasma cells, fibrosis and obliterative phlebitis. Adult-onset asthma and periocular xanthogranuloma (AAPOX) is a rare disease of unknown aetiology characterized by violaceous or yellow cutaneous papules and nodules usually accompanied with adult-onset asthma. We report a case of IgG4RD associated with AAPOX. We also conducted a literature search with keywords including IgG4RD and AAPOX. A 36-year-old woman presented with bilateral exophthalmos and periorbital oedema. Keratoconjunctivitis sicca, painless left parotid gland and submandibular left lymph node enlargement were also noted. Two and half years ago biopsy of yellow plaques of her right lower eyelid confirmed periorbital xanthogranuloma. She underwent parotid gland biopsy which showed IgG4RD. She was treated with steroids and two cycles of rituximab with complete remission. The literature review revealed 8 articles describing 14 cases with IgG4RD and AAPOX, 9 men and 5 women (ratio M:F = 1.8:1) were affected. The age at diagnosis was greater in men compared to women. In the majority of patients, ophthalmic presentation included bilateral upper and lower eyelid swelling while systemic features were asthma, lacrimal and parotid involvement, lymphadenopathy, sclerosing pancreatitis and sclerosing cholangitis. Prednisone and rituximab were effective treatments. It has to be clarified whether the association between IgG4RD and AAPOX represents shared pathophysiology, a common underlying cause or coincidence. Rituximab added to steroids resulted in complete remission of the two entities.

ki-67 and Topoisomerase IIa proliferation markers in colon adenocarcinoma.

Aberrant cell proliferation is a major cause in the development and progression of carcinogenic process. Epithelia characterized by increased mitotic rates accumulate easily gross numerical and structural chromosomes (polysomy/aneuploidy) and specific gene (deletions, amplifications, point mutations, translocations) deregulations that lead to their progressive neoplastic and finally malignant transformation. Molecules that are critical for evaluating the proliferation status of the corresponding tissues include mainly ki-67 (cytogenetic band: 10q26.2), and also Topoisomerase IIa/Topo IIa (cytogenetic band: 17q21.2). Both of them demonstrate different expression patterns in every cell cycle phase and their estimated expression as Nuclear Labeling Index (NLI) is a very useful tool for assessing the aggressiveness of the examined pre- and malignant tissues. In fact, ki-67 expression increases as a cell progresses through the cell cycle, with highest expression being seen in G2/M phase cell, whereas Topo IIa is expressed in proliferating cells in the late S phase with a peak in G2-M phases. Concerning colon adenocarcinoma, high expression levels of them seem to correlate with advanced disease and also with modified response rates to specific chemotherapeutic agents, such as doxorubicin, an inhibitor of Topo IIa. In the current molecular review we explored the role of these proliferative markers in colon adenocarcinoma and their influence in the tumor biological behavior.

Molecular aspects in HPV-dependent laryngeal and oropharyngeal carcinoma.

Human papillomavirus (HPV)-mediated cervical carcinogenesis represents a well analyzed model of viral implication in epithelial malignant transformation. Mechanisms of high risk (HR) HPV-related infection seem to demonstrate a similar action regarding its implication in head and neck (HN) carcinomas, predominantly in squamous cell carcinoma (SCC) histological type. The prevalence of HR HPV subtypes - mainly HPV16 - is characterized by a broad geographic heterogeneity. Furthermore, HPV-associated HNSCCs demonstrate differences regarding sexual, molecular, epidemiological, and prognostic features compared to alcohol and tobacco dependent ones. Based on these differences, HPV-derived HNSCC appear to be a specific well-defined entity mostly affecting young to middle-aged - male mainly - non-smokers. This is a strong reason of detecting an increased HR-HPV DNA levels -due to viral transmission - in oropharyngeal and laryngeal anatomic regions. Additionally, different response rates to chemoradiation and targeted therapeutic regimens are another significant field for handling these SCC malignancies in the corresponding patients. In the current special article we explored the role of HPV-related carcinogenesis in oropharyngeal and laryngeal SCC focused on the latest molecular aspects.

Aspergillosis in immunocompromised patients with haematological malignancies.

Aspergillosis, which is saprophytic in nature, is known to cause massive destruction of paranasal sinuses in immunocompromised hosts, but in immunocompetent individuals invasive aspergillosis is rare. Diagnosis is posed from history, physical examination including anterior and posterior rhinoscopy, endoscopy of the nose and paranasal sinuses, radiological findings (CT and/or MRI), fungus cultures and histopathological examination. Non-specific presenting symptoms provide time for infection to extent from sinuses to vital surroundings such as bony, vascular and central nervous system structures, thereby increasing morbidity and mortality. Mass lesions involving the sinuses are initially misdiagnosed as tumors, inflammatory pseudotumors or pituitary adenomas. Therefore, diagnosis should be always confirmed by histopathology. Aspergillus sinusitis is a potentially fatal complication of immunosupression or of chemotherapy-induced leucopenia. Concerning patients with hematologic malignancies, it seems that its incidence is progressively increased. A combination of early diagnosis and application of specific antifungals provides the perfect management and prognosis in the corresponding patients. In the current special review, we present new data regarding the infection in patients with hematologic malignancies.

Chromosomal instability in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) demonstrates an increasing rate due to high risk Human Papilloma Virus (HR-HPV) persistent infection, and also to chronic cigarette and alcohol consumption. Gross chromosomal alterations (polysomy, aneuploidy, intra-chromosome rearrangements) and specific gene aberrations such as amplifications, deletions, point mutations combined or not with epigenetic ones (promoter methylations and miRNA deregulations) are responsible for the progressive transformation of normal squamous cell epithelia to the corresponding malignant. Chromosomal instability (CI) -based on structural or numerical abnormalities- leads to specific abnormal karyotypes combined or not with functional suppressor gene inactivation and oncogene overactivation in solid malignancies, including OSCC. Extensive cytogenetic analyses have shown that gross alterations (gains/losses) in chromosomes 3, 4, 7, 8, 9, 11, 14, 17, 18, 19 and also 20 form different CI patterns in OSCC, which in conjunction with an aggressive phenotype (presence of lymph nodal metastasis) negatively affect the prognosis in the corresponding patients. In the majority of OSCC cases, loss of chromosomal bands are almost equally detected compared with gains regarding the chromosomes referred above. In the current special molecular paper we explored the role of CI in the progression and biological behavior of OSCCs.

p53 mutations in oral cavity carcinoma.

Head and neck squamous cell carcinoma (HNSCC) includes a variety of SCCs derived from the anatomic regions of the oral and nasal cavity and also of the pharynx and larynx. Oral cavity SCC (OCSCC) demonstrates an increasing rate due to viral -related (High Risk Human Papilloma Virus-HR HPV) persistent infection, cigarette smoking and alcohol consumption. Gross chromosomal alterations (polysomy, aneuploidy) and specific gene aberrations such as amplifications, deletions, point mutations combined or not with epigenetic ones (promoter methylations and miRNA deregulations) are responsible for the progressive transformation of normal squamous epithelia to the corresponding malignant. In the majority of OCSCC cases, critical genes, such as p53 are found to be inactivated, leading to an overactivated cell cycle correlated to carcinogenetic process. P53 (gene location: 17p13.1) is a suppressor gene acting as a key regulator of the cell's genomic stability, function and homeostasis. P53 aberrant overexpression is frequently observed in OCSCC tissues as a result of point mutation or deletion. In the current special article we explored the role of the p53 gene deregulation - especially focused on its mutation status - in OCSCCs.

HPV infection in oropharyngeal squamous cell carcinomas: correlation with tumor size.

PURPOSE: Human papillomavirus (HPV) is implicated in carcinogenesis of a variety of epithelia, including oropharyngeal and laryngeal. High risk (HR) HPV persistent infection in head and neck squamous cell carcinomas (HNSCC) is a significant event, but its influence regarding the prognosis and survival in these patients remains under consideration. Our aim was to analyze a series of oropharyngeal (OP) SCCs at the HPV DNA level, correlating them to the survival status of the corresponding patients. METHODS: Using HPV DNA polymerase chain reaction (PCR) microarray technology, 28 formalin-fixed, paraffinembedded primary OPSCCs were cored and analyzed. RESULTS: Positive DNA amplicons for HPV infection were detected in 3 SCC cases (sub types: HPV 31/35/70). Interestingly, HPV persistent infection was associated with larger tumors (p=0.029) which also affected survival status (p=0.007) in the corresponding patients. Overall survival was also significantly dependent on the stage of the malignancies (p=0.022). Furthermore, tumor size was significantly and negatively correlated with age (p=0.015), meaning that younger patients will probably develop larger tumors. CONCLUSIONS: HPV-depended OPSCCs - although not so common as the laryngeal ones, but still not so rare in the rural population in Greece - are characterized by a combination of specific features. Our results showed that survival was adversely effected by the stage of the disease and tumor size and indirectly by the presence of HPV - especially in young adults - while the combined surgery/radiotherapy/ chemotherapy therapy seems to prolong survival. Additionally, HPV co-existence seems to be associated with larger tumors and poor survival.

Deregulation of p53/survivin apoptotic markers correlated to PTEN expression in pterygium neoplastic cells.

PURPOSE: Pterygium is a distinct clinicopathological entity characterized by degenerated and neoplastic-like features. Concerning its rise on normal conjunctiva epithelia, the role of specific gene deregulations including apoptotic/anti-apoptotic factors and significant suppressor genes in signaling transduction pathways is under investigation. In the current study, we co-analyzed p53, survivin and PTEN proteins in pterygia and normal conjunctiva. METHODS: Using a liquid-based cytology assay, 50 cell specimens were obtained by a smooth scraping on conjunctiva epithelia and fixed accordingly. Among them, 38 were pterygia and the remaining (n=12) normal epithelia (control group). Immunocytochemistry assays were implemented on the corresponding slides by applying ani-p53, survivin, and PTEN antibodies. Digital image analysis was performed for evaluating objectively the corresponding immunostaining intensity levels. RESULTS: The majority of the examined pterygia cases overexpressed the markers p53:22/38-57.9%, survivin:30/38-78.9%, and PTEN:25/38-65.7%. Interestingly, overall p53/PTEN co-expression was found to be statistically significant (p=0.022). CONCLUSIONS: Survivin overexpression leads to an increased anti-apoptotic activity playing a central molecular role in the pathogenesis and progression of pterygia. Furthermore, although p53 expression is observed in these lesions, its impact seems to be low compared to survivin's influence on them. Additionally, the role of PTEN in the process is potentially significant providing a suppressor balance to the p53/ survivin complex.

Intracranial meningioma: Experience with stereotactic radiotherapy.

PURPOSE: Definitive radiotherapy is a treatment option for patients with inoperable meningiomas. The purpose of this study was to evaluate the results of stereotactic radiotherapy as first-line treatment for intracranial meningiomas that were diagnosed radiologically. METHODS: Between January 2010 and June 2016, 56 patients with intracranial meningioma treated with Cyberknife- based Stereotactic Radiosurgery (SRS) or hypofractionated stereotactic radiotherapy (hFSRT) were included. The median prescribed radiation dose was 16 Gy (range 13-18) for SRS and 25 Gy (range 18-33) for hFSRT. hFSRT doses were delivered in 3 to 5 fractions. RESULTS: Median follow-up was 58 months (range 6-97). Overall survival (OS) for the whole group was 89.2%; for SRS group it was 100% and for hFSRT group 87.5% (p=0.29). Progression free survival (PFS) for the whole group was 89.3%; for SRS group it was 87.5% and for hFSRT 89.5% at 5 years (p=0.93). CONCLUSION: SRS and hFSRT were effective with excellent local control rates and they can be an alternative treatment option for patients with inoperable meningiomas.

DNA mismatch repair deficiency in lung and oral cavity carcinomas: the role of histogenetic origin.

DNA mismatch repair system (DNA MMR) is a crucial genetic mechanism for DNA homeostasis in prokaryotic and eukaryotic cells. During DNA replication and also recombination, point intra-nucleotide errors including base deletion, insertion, and mis-incorporation happen. These raised abnormalities in the newly synthesized DNA strand could affect negatively the stability of the molecule and the function of the corresponding genes. DNA MMR proteins prevent these errors by recognizing and repairing them, securing directly the normal anatomy of the DNA double strand and indirectly the expression of the genes. Specific genomic alterations - mutations, loss of heterozygosity (LOH), or promoter hypermethylation - regarding the MMR genes (human homologues) hMLH1, hMSH2, hMSH3, hMSH6, hPMS1 and hPMS2 modify negatively their expression leading to loss of their function in repairing the corresponding base to base errors. The result known as microsatellite instability (MSI) was initially recognized in colonic carcinoma, especially in its inherited aspect - the Lynch syndrome -, the most common form of hereditary colon carcinoma. Since then, acquired deficiencies in specific DNA MMR genes have been detected in a broad spectrum of malignancies including different anatomic regions and histologies such as stomach, prostate, esophageal, endometrial, lung and head & neck. In the current special review we explored the role of DNA MMR deficiency in lung and oral cavity carcinomas in order to identify similarities and differences regarding the corresponding genes alterations.

mTOR deregulation in oral cavity squamous cell carcinoma.

Signal transduction pathways consist of a variety of inter- and intra-cellular molecules. They act as supporting mechanisms for cell survival and homeostasis. Among them, the phosphatidylinositol 3-kinase (PI3K)/tumor suppressor phosphatase and tensin homologue deleted on chromosome ten (PTEN)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway plays a crucial role in regulating normal cell growth based on growth factor receptors (GFRs) interaction, including epidermal GFR (type II-HER2) and insulin GFR (IGF). mTOR protein acts as a serine-threonine kinase that belongs to the PI3K-related kinase family. It mediates protein and lipid synthesis, mitochondrial metabolism, biogenesis, proliferation and also negatively regulates autophagy. Two distinct multiprotein complexes have been mainly identified and cloned: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). mTOR is deregulated predominantly due to mutations, deletions, loss of heterozygosity (LOH) or abnormal phosphorylation of the upstream molecules inside the current pathway. Pure mTOR mutations are very rare. Development of specific inhibitors at the basis of targeted therapeutic strategies such as rapamycin (rapalogs) is an evolution in handling patients with mTOR abnormal overactivity. In the current special article we explored the role of the gene deregulation leading to abnormal protein expression in oral cavity squamous cell carcinoma (SCC).

Topoisomerase I deregulation in laryngeal squamous cell carcinomas based on tissue microarray analysis.

PURPOSE: Topoisomerases (types: I/IIa-b/IIIa-b) represent a super-family of nucleic enzymes involved in the DNA replication, transcription, recombination, and also chromosome topological formation. Topoisomerase's I (Topo I- gene location: 20q12) aberrant expression is a frequent genetic event in a variety of solid malignancies. Topo I inhibition promotes cell death due to DNA damage and for this reason it is a target for specific targeted chemotherapy (camptothecin, topotecan, irinotecan). Our aim was to investigate the role of abnormal Topo I protein expression in laryngeal squamous cell carcinomas (LSCC) in which there are very limited data regarding the influence of the marker. METHODS: Using tissue microarray (TMA) technology, 50 formalin-fixed, paraffin-embedded primary laryngeal SCCs were cored and re-pembedded into one recipient block. Immunohistochemistry was performed using anti- Topo I antibody. Digital image analysis was also implemented for evaluating objectively the protein expression levels on the corresponding stained nuclei. RESULTS: Topo I protein overexpression (moderate to high staining intensity values) was observed in 32/50 (64%) tissue cores, whereas low expression rates were detected in 18/50 (36%) cases. Topo I overall expression was strongly associated with the differentiation grade of the examined tumors (p=0.021). No other statistical correlations were identified. CONCLUSIONS: Topo I overexpression is observed in a significant subset of LSCCs affecting the level of differentiation in them. Additional molecular studies focused on the mechanism of Topo I gene/protein deregulation (i.e. amplification, abnormal epigenetic promoter methylation, mRNA aberrant expression) are necessary discriminating the eligible patients for applying specific chemotherapeutic strategies based on anti-Topo I agents.

Novel molecular and metabolic aspects in osteosarcoma.

Osteosarcoma (OS) is the most frequent bone-forming malignancy in children and adolescents. Concerning its molecular landscape, there is no a direct relationship with a specific gene, but a combination of genetic events. A broad spectrum of activated oncogenes and downregulated suppressor genes has been already explored and considered crucial for its progressive pathogenesis. Mechanisms of gene deregulation include amplifications, point mutations, allelic losses and also epigenetic abnormalities such as aberrant promoter methylation. Although a significant progress in understanding the molecular nature of the OS has been achieved, its aggressive phenotype - characterized by high metastatic potential - remains unexplored. Novel targeted therapeutic strategies include monoclonal antibodies (mABs) and also tyrosine-kinase inhibitors (TKIs). Additionally, sophisticated and innovative diagnostic techniques, such as 18 fluorodeoxyglucose positron emission tomography plus CT (18F-FDG/PET/CT), provide critical data regarding its biological behavior. In the current paper, we present novel molecular and metabolic advances by analyzing OS genetic profile and biochemical microenvironment.

Impact of the functional neck dissection in maxillofacial surgical oncology: its role in robotic-based surgery era.

Head and neck cancers demonstrate an increased prevalence worldwide. The main therapeutic approaches are still surgery and radiotherapy, although in selective cases novel targeted therapeutic strategies based on monoclonal antibodies (ie anti-EGFR) are also applied. Concerning maxillofacial surgical oncology, a variety of methods has been developed. Among them the functional neck dissection technique seems to be a reliable and significant surgical approach, especially in removing identified cervical metastatic lymph node(s). In this technical paper, we focused on the method, its modifications adding our experience and also the challenges that arise in the modern robotic-based era regarding head and neck surgery.

Deregulation of p53-MDM2 auto-regulatory pathway in breast carcinoma.

PURPOSE: p53 tumor suppressor protein (17p13.1) regulates critically the cell cycle and thus it is involved in cancer initiation and prevention. The gene is frequently mutated in breast cancer patients and the mutations have been associated with poor prognosis and response rates to chemotherapy. The purpose of this study was to correlate p53 expression with MDM2, a proto-oncogene (12q14.3), which acts as a major negative regulator in p53-MDM2 auto-regulatory pathway. METHODS: Seventy breast adenocarcinoma cases were included in the study. Sixty tumors were pathologically categorized as invasive ductal adenocarcinomas, whereas the rest of them were diagnosed as pure in situ carcinomas. Immunohistochemistry (IHC) was applied using anti-p53 and anti-MDM2 antibodies in the corresponding tissue sections. RESULTS: Overexpression of p53 protein was observed in 39/60 (65%) invasive cases, while 40/60 (66.7%) expressed MDM2 protein. Interestingly, in 26/60 (43%) cases a combined p53/ MDM2 co-expression was detected, whereas in 7/60 (11%) a combined loss of expression was identified (overall co-expression: p=0.999). Concerning in situ carcinomas, co-expression of p53/MDM2 was observed in 7/10 (70%) cases. CONCLUSIONS: MDM2 oncogene overexpression - predominantly due to gene amplification - is a frequent and critical genetic event in both in situ and invasive breast adenocarcinomas. Accumulation of p53 protein in the nucleus of tumor cells harboring mutant p53 - as the result of its overexpression - does not mean necessarily decreased expression of MDM2. MDM2 directly binds to p53 and represses its transcriptional activity promoting p53 degradation. So targeting the molecule, p53's crucial tumor suppressor function is normally regulated.

E-cadherin/α-catenin deregulated co-expression in thyroid carcinoma based on tissue microarray digital image analysis.

PURPOSE: Deregulation of cell-to-cell adhesion molecules is a common and also critical genetic event in epithelial malignancies leading to an increasing metastatic potential. Among them, e-cadherin and catenins--especially α and ß--, act as oncogenes during the carcinogenetic process affecting specific signaling transduction pathways (i.e. Wnt/ b-catenin). Concerning thyroid carcinoma, decreased or loss of expression in these proteins seems to affect the biological behavior of the neoplasm increasing its aggressiveness. The aim of this study was to investigate the deregulation of e-cadherin/α-catenin complex in thyroid carcinomas. METHODS: Thirty-five paraffin-embedded tissue samples including thyroid carcinomas (N=20) and also 15 cases of benign follicular nodules were cored at 1 mm diameter and transferred to a microarray block. Immunohistochemistry (IHC) was performed using anti-e-cadherin/α-catenin antibodies. Digital image analysis was also implemented for measuring the corresponding protein expression levels. RESULTS: E-cadherin/α-catenin protein expression demonstrated a significant progressive decrease regarding benign and malignant lesions (p=0.001). Simultaneous e-cadherin/α-catenin reduced or loss of expression was observed in 10/20 (50%) cancer cases correlated to advanced stage (especially nodal metastasis) of the examined tumours (p=0.02). Concerning the histological type, combined loss of e-cadherin/α-catenin expression was predominantly associated with follicular and anaplastic histology (p=0.001). Interestingly, α-catenin protein expression pattern was significantly correlated with the grade of differentiation of the examined malignancies (p=0.01). CONCLUSIONS: Progressive loss of e-cadherin mainly and also α-catenin expression is associated with an aggressive phenotype (low differentiation, increased metastatic activity/advanced stage) in thyroid carcinomas. Based on their aberrant protein expression, novel agents have been developed for restoring their normal function.

Molecular assays in detecting EGFR gene aberrations: an updated HER2-dependent algorithm for interpreting gene signals; a short technical report.

Purpose: Among oncogenes that have already been identified and cloned, Epidermal Growth Factor Receptor (EGFR) remains one of the most significant. Understanding its deregulation mechanisms improves critically patients' selection for personalized therapies based on modern molecular biology and oncology guidelines. Anti-EGFR targeted therapeutic strategies have been developed based on specific genetic profiles and applied in subgroups of patients suffering by solid cancers of different histogenetic origin. Detection of specific EGFR somatic mutations leads to tyrosine kinase inhibitors (TKIs) application in subsets of them. Concerning EGFR gene numerical imbalances, identification of pure gene amplification is critical for targeting the molecule via monoclonal antibodies (mAbs). In the current technical paper we demonstrate the main molecular methods applied in EGFR analyses focused also on new data in interpreting numerical imbalances based on ASCO/ACAP guidelines for HER2 in situ hybridization (ISH) clarifications.

Chromosome 7 deregulation in non-small cell lung carcinoma molecular landscape.

Lung cancer exhibits an increasing incidence and a high mortality rate worldwide. Non-small cell lung carcinoma (NSCLC)constitutes the majority of patients with lung cancer (about 85% of all pathologically defined lung cancer cases). A broad spectrum of genomic imbalances, including chromosome polysomy/aneuploidy or specific gene deregulation mechanisms, such as point mutations, deletions and amplifications has been already identified in the corresponding patients, modifying their response rates to novel targeted therapeutic regimens, and affecting also their life span. Among all chromosomes, chromosome 7 seems to play a critical role in NSCLC development and progression. Aberrations in significant genes located on it, such as EGFR, cMET, BRAF combined with numerical abnormalities of the whole chromosome are cytogenetic events that lead to specific molecular signatures in patients with NSCLC. Detection of these chromosome/gene imbalances based on polymerase chain reaction (PCR) and in situ hybridization provides to oncologists the right genetic substrate for handling these patients in a rational therapeutic way regarding their isolated molecular profile. In the current paper, we present the structural and functional profile of chromosome 7 focused on its alterations in NSCLC.

Solitary Fibrous Tumor of the Masticator Space with Unusual Extension: a Case Report.

Background: We present the case of a patient with solitary fibrous tumor of the masticator space with unusual extension. Case presentation: A 43-year-old woman presented with a painless mass with intraoral extension on the right cheek. The B-scan sonograph and magnetic resonance imaging revealed the extension of the tumor. The biopsy performed under local anesthesia raised the suspicion of a solitary fibrous tumor. Tumor excision included a preoperative tumor embolization. The surgical removal of the tumor included a partial parotidectomy on the right side, insertion of masseteric and temporalis muscle, resection of the middle part of the zygomatic bone and stabilization of the bone with a plate, mobilization of the tumor from the maxillary sinus and the pterygopalatine fossa through an endoscopic approach and an approach via partial resection of the anterior wall of the maxillary sinus after identifying and sparing the infraorbital nerve. Ôhe histological findings confirmed the diagnosis of solitary fibrous tumor. The patient's treatment completed with radiation therapy, and 2.5 years later, there was recurrence in the right temporal area. Conclusion:To our knowledge, this is the second reported case of solitary fibrous tumor arising in the masticator space and the only case with extension intraorally and in the paranasal sinuses. Tumor embolization and complete surgical excision are the most frequently recommended treatments.

PTEN Deregulation Mechanisms in Salivary Gland Carcinomas.

Among the tumour suppressor genes that affect critically cell functions and homeostasis, phosphatase and tensin homolog deleted in chromosome 10 (PTEN- gene locus: 10q21) regulates the PI3K/Akt/mTOR signalling pathway. PTEN is deleted, mutated or epigenetically hyper-methylated in a variety of human solid malignancies. Salivary gland carcinomas (SGCs) belong to the head and neck carcinomas (HNCs) super category of solid malignancies. Histo-pathologically, they demonstrate a significant diversity due to a variety of distinct and mixed subtypes. Genetically, they are characterized by a broad spectrum of gene and chromosomal imbalances. Referring specifically to suppressor genes, PTEN deregulation plays a critical role in signaling transduction in the corresponding SGC pre- and malignant epithelia modifying the response rates to potential targeted therapeutic strategies. In the current review, we explored the role of PTEN deregulation mechanisms that are involved in the onset and progression of SGCs.