TLR4 down-regulation identifies high risk HPV infection and integration in head and neck squamous cell carcinomas.

TLRs are main actors of the innate immune response against HPV. There are very few studies on the role of TLRs mediated HPV clearance in Head and Neck oncology. Our aim was to evaluate whether TLR4 expression identifies HPV infection and/or HR-HPV integration status in oral and oropharyngeal cancers. By immunohistochemistry we assessed TLR4 levels in OSCC/OPSCC. To detect viral integration or episomic status In situ hybridization for HPV-DNA and Pyro-sequencing techniques have been performed. The relationship between TLR4 expression with HPV infection status has been investigated. ISH HPV positive samples have reported lower levels of TLR4 intensity than negative samples (p = .002). There was no statistical correlation between TLR4 intensity and PCR HPV results (p more than 0.0.5). Point-biserial correlation coefficient revealed significant association between TLR4 expression and HR-HPV integration status (p = .0001) and between TLR4 expression index and HR-HPV infection (p = .001). These data have shown that TLR4 down-regulation is strongly associated to both HPV-16 infection and its integration into the host DNA.

Immune activation and chronic inflammation as the cause of malignancy in oral lichen planus: is there any evidence ?

The association of chronic inflammation with a variety of epithelial malignancies has been recognised for centuries. Well established examples include, among many others, oesophageal adenocarcinoma associated with chronic oesophagitis and bowel cancer associated with chronic inflammatory bowel diseases. By now no data, other than clinical observation, have been available in understanding the pathogenesis of these inflammation-related tumours. However, recent molecular studies on the relationship between solid malignancies and the surrounding stroma have given new insights. There is now enough evidence to accept that the chronic inflammatory process per se is able to provide a cytokine-based microenvironment which is able to influence cell survival, growth, proliferation, differentiation and movement, hence contributing to cancer initiation, progression, invasion and metastasis. Here it is discussed whether also oral lichen planus (OLP), being a chronic inflammatory autoimmune disease which has been clinically associated with development of oral squamous cell carcinoma, might be categorised among these disorders. With this aim, we critically reviewed and detailed the presence, in OLP subepithelial infiltrate, of inflammatory cells and cytokine networks that might act to promote squamous tumorigenesis.

Localized amyloidosis of the upper gingiva: a case report.

INTRODUCTION: Localized amyloidosis in the head and neck is a rare and generally benign condition. In the oral cavity, amyloidosis usually involves the tongue or buccal mucosa. We present the second case of oral amyloidosis arising in the gingiva ever reported, to the best of our knowledge. CASE PRESENTATION: A 73-year-old White Spanish man presented a persistent nodular mass involving his upper gingiva. The lesion was surgically resected and the histological examination revealed a subepithelial, multinodular amorphous and fibrillar accumulation. Staining of the specimen for Congo red proved positive, exhibiting a reddish colour under light microscopy and apple-green birefringence under polarized light. With immunohistochemical tests, pentagonal amyloid component was demonstrated. An extensive study excluded any systemic involvement; a diagnosis of localized primary amyloidosis was made. After 2 years of follow-up, no clinical progression to systemic amyloidosis or local recurrence was observed. CONCLUSIONS: Localized amyloidosis of the gingiva is an extremely rare condition that seems to show no clinically distinct feature. Histologic examination is the first step towards diagnosis, followed by immunohistochemical tests. The diagnosis of localized amyloidosis should always be integrated with blood tests, a bone marrow biopsy, echocardiography and digestive endoscopy to intercept systemic involvement.

The role of EBV in the pathogenesis of Burkitt's Lymphoma: an Italian hospital based survey.

The exact worldwide incidence of Burkitt's lymphoma is not known. There are three distinct clinical variants of Burkitt's lymphoma, each manifesting differences in epidemiology, clinical presentation, morphology, biology and genetic features: the endemic (African), the sporadic (non-endemic), and the immunodeficiency-associated form. In particular, we reported data regarding Burkitt's lymphoma incidence in the world and across different European countries. Finally, we described clinic-pathological data of 48 Burkitt's lymphomas occurred in Italy from 2003 to 2013, in 4 different hospitals, two of which located in east side, and the other ones located in the west-coast. Forty Burkitt's lymphomas occurs in children (age range 3-12), and 8 were adulthood Burkitt's lymphomas (age range 18-87). In the pediatric group the Male:Female ratio (M:F) was of 4:1, whereas the group of the adult patients has a M:F of 1:1.67. Immunohistochemical detection of Latent Membrane Protein 1 (LMP1) expression and Epstein-Barr virus Encoded RNA (EBER) In Situ Hybridization (ISH) procedures have been performed. Lymphocyte B monoclonal spread has been demonstrated using a Polymerase Chain Reaction (PCR) based method to amplify Fragment Restriction FR1, FR2 and FR3 immunoglobulin heavy chains DNA fragments. Only 38 cases out of 48 were analyzed for LMP-1 showing various percentage of stained cells in 47.4% of the patients. Considering ISH for EBER detection results: 1 out 2 (50%) adult analyzed cases was positive, with 50% of stained tumor cells (this patient was a 22 years old female, coming from Napoli);15 out 24 (62.5%) children analyzed Burkitt's lymphomas resulted as positive for EBER;the overall positivity has been observed in 16/26 Burkitt's lymphomas (61.53%).Finally, EBV has been detected in children and adult patients, one of them with deregulation of the oncogene c-MYC by chromosomal translocation.

High-dose intravenous 'pulse' methylprednisone in the treatment of severe oropharyngeal pemphigus: a pilot study.

BACKGROUND: High-dose intravenous (i.v.) methylprednisolone has been used therapeutically in severe blistering diseases to avoid the complications and side-effects of long-term orally administered glucocorticoid therapy. The aim of the study is to evaluate the capacity of methylprednisolone i.v. 'pulse' therapy to induce remission in the treatment of severe oropharyngeal pemphigus. METHODS: Twelve patients, all of whom had oropharyngeal severe pemphigus, were included in the analysis. There were eight women and four men whose ages ranged from 22 to 78 years (mean age: 50.75 years) with a disease duration of 1-3 months(mean duration: 55 days). In order to obtain a rapid clinical remission of extensive mucosal lesions, we performed 'pulse' therapy with intravenous methylprednisolone (30 mg/kg body weight to a maximum of 1 g per dose on each of 3-5 consecutive days)evaluating the clinical response and the short-term side-effects. RESULTS: Our therapy was generally safe and well tolerated with a very low rate of side-effects. All patients responded to i.v. methyl-prednisolone with evidence of a decrease in signs and symptoms within l week of commencing treatment and in all cases remission was observed after the second or the third cycle of 'pulse'. The most common adverse events during treatment were flushing and hyperglycaemia; in a few cases we observed a metallic taste in the mouth, pruritus, headaches ranging from mild to moderate, palpitations, mood alterations, insomnia and fatigue. CONCLUSIONS: High-dose 'pulse' administration of glucocorticoids is a potentially effective therapy to be considered in the treatment of patients with severe oropharyngeal pemphigus. Similar patients treated with conventional oral administered doses of prednisone or deflazacort had protracted courses requiring months of glucocorticoid therapy with no long-term remissions. However, further well-designed, long-term comparative trials are required to confirm this.