L. Pastore

Oral Manifestations of Celiac Disease

Introduction Contrary to early beliefs, celiac disease (CD) is relatively common; however, it still remains underdiagnosed since most cases are atypical, with few or no gastrointestinal symptoms and predominance of extraintestinal manifestations. As a consequence, the diagnosis of the disorder often requires a multidisciplinary approach. Also some oral ailments have been described in celiac patients. In this study, we review the papers that have reported oral manifestations in subjects with CD. Methods A comprehensive literature search was conducted in Medline and Embase databases using appropriate key words. Additional papers were selected by cross-referencing from the retrieved articles. Results Dental enamel defects are the oral lesions most closely related to CD. There are conflicting data on the association between CD and recurrent aphthous stomatitis. A correlation of CD with atrophic glossitis has been reported, although robust evidence in support of it is lacking. Patients with CD have caries indexes seemingly lower than healthy individuals, but they may experience delay in tooth eruption. Occurrence of other oral mucosal lesions in CD subjects is likely occasional. Conclusions Patients with systematic dental enamel defects should be screened for CD even in the absence of gastrointestinal symptoms. CD screening tests for patients with oral aphthae or idiopathic atrophic glossitis should be selectively considered during a medical evaluation that focuses on all aspects of the patients status.

Effect of p63 expression on survival in oral squamous cell carcinoma.

Background: P63 is the protein codified by p63 gene, a p53 gene homolog, known for its pivotal role in cell cycle regulation, and involved in the tumor differentiation. Aims of the present study were to assess the frequency and pattern of p63 protein expression in oral squamous cell carcinoma (OSCC) in relation to the main tumour characteristics and to verify whether p63 can be considered a marker of prognosis in patients with OSCC. Material and Methods: In a retrospective study, a cohort of 64 OSCC patients was investigated for p63 protein expression and its cellular localization by immunohistochemistry (monoclonal mouse anti-human p63 protein-clone 4A4). After grouping by p63 expression, OSCCs were statistically analyzed for the variables age, gender, histological grading (G), TNM, staging, recurrence, and overall survival rate. Results: The overall frequency of p63 overexpressed was of 57.8 percent. Various p63 staining patterns were observed according to G score, with a significant correlation between p63 overexpression and the lowest G score (P < 0.0001). No statistically significant difference was found between p63 pattern expression and age, sex, staging. OSCC patients with p63 overexpressed were found to have a poorer survival rate with respect to OSCCs with a normal pattern of expression (P = 0.024). Conclusions: On the basis of these results, it is possible to suggest p63 pattern expression as a reliable indicator of histological grading and an early marker of poor prognosis.

Orally Based Diagnosis of Celiac Disease: Current Perspectives

Celiac disease (CD) is a lifelong immune-mediated disorder caused by the ingestion of wheat gluten in genetically susceptible persons. Most cases of CD are atypical and remain undiagnosed, which exposes the individuals to the risk of life-threatening complications. Serologic endomysial and tissue transglutaminase antibody tests are used to screen at-risk individuals, although a firm diagnosis requires demonstration of characteristic histopathologic findings in the small-intestinal mucosa. A gluten challenge, with a repeat biopsy to demonstrate recurrence of histopathologic changes in the intestinal mucosa after the re-introduction of gluten, is considered for those persons in whom diagnosis remains in doubt. In this paper, we review studies that evaluated: (1) the possibility of using oral mucosa for the initial diagnosis of CD or for local gluten challenge; and (2) the possibility of using salivary CD-associated antibodies as screening tests. Our review shows that orally based diagnosis of CD is attractive and promising, although additional evaluations with standardized collection and analysis methods are needed. There is some evidence of a dissociation between systemic and oral mucosal immune responses in CD. The hypothesis that gluten could stimulate naïve lymphocytes directly in the oral cavity would have important implications for the understanding, diagnosis, and management of CD.

Squamous Cell Carcinoma of the Lower LIP: Fas/Fasl Expression, Lymphocyte Subtypes and Outcome

Squamous cell carcinoma (SCC) of the lip is a relatively common malignancy of the head and neck region. Tumour thickness, grading and perineural invasion are significant prognostic indicators. However, there is still the need of new reliable biological markers able to predict the prognosis of the single cases with an unfavourable biological behaviour unpredictable by the classic clinical-pathological parameters. 32 cases of (SCC) of the lower lip were analysed for their clinicopathologic features, and immunohistochemical expression of Fas/FasL in neoplastic cells and in inflammatory infiltrate. Moreover the density and phenotype of tumour-infiltrating lymphocytes (TIL) were analysed. The results were related with the follow-up of the patients ranging from 2 to 6 years. The cases with over-expression of Fas/FasL in neoplastic cells and Fas+ in T cells preferentially showed a more aggressive clinical behaviour (p<0.01). Moreover we found an alteration of the normal expression of CD4 and CD8 lymphocyte types in ten cases. This data suggest that the Fas/FasL pathway is involved in the close relation between neoplastic cells and T cells and so in the biological behaviour of these tumours.

The Production of the Oral Mucosa of Antiendomysial and Anti—Tissue-Transglutaminase Antibodies in Patients with Celiac Disease: A Review

Celiac disease (CD) is a lifelong, T cell—mediated enteropathy, triggered by the ingestion of gluten and related prolamins in genetically susceptible subjects, resulting in minor intestinal mucosal injury, including villous atrophy with crypt hyperplasia and intraepithelial lymphocytosis, and subsequent nutrient malabsorption. Although serological tests for antiendomysial (EMA) and anti—tissue transglutaminase (anti-tTG) autoantibodies are used to screen and follow up on patients with CD, diagnostic confirmation is still based on the histological examination of the small intestinal mucosa. Although the small intestinal mucosa is the main site of the gut involved in CD, other mucosal surfaces (such as gastric, rectal, ileal, and esophageal) belonging to the gastrointestinal tract and the gut-associated lymphoid tissue (GALT) can also be involved. A site that could be studied less invasively is the mouth, as it is the first part of the gastrointestinal system and a part of the GALT. Indeed, not only have various oral ailments been reported as possible atypical aspects of CD, but it has been also demonstrated that inflammatory changes occur after oral supramucosal application and a submucosal injection of gliadin into the oral mucosa of CD patients. However, to date, only two studies have assessed the capacity of the oral mucosa of untreated CD patients to EMA and anti-tTG antibodies. In this paper, we will review studies that evaluate the capacity of the oral mucosa to produce specific CD autoantibodies. Discrepancies in sensitivity from the two studies have revealed that biopsy is still not an adequate procedure for the routine diagnostic purposes of CD patients, and a more in-depth evaluation on a larger sample size with standardized collection and analysis methods is merited. However, the demonstration of immunological reactivity to the gluten ingestion of the oral mucosa of CD, in terms of IgA EMA and anti-tTG production, needs to be further evaluated in order to verify whether the oral mucosa is colonized by lymphocytes activated in the intestine or if gluten could stimulate naïve lymphocytes directly in the oral mucosa. This would have important implications for the pathogenesis, diagnosis, and treatment of CD.

Efficacy of famciclovir in the treatment of oral hairy leukoplakia

production. Barnadas et al. report a patient who developed angiomatous lesions after anti-IL-2 therapy. Angiomatous lesions have also been reported in patients in whom IL-2 levels are low, e.g. those with extensive burns and chronic mucocutaneous candidiasis. Treatment appears extremely difficult. Shave, excision, cryotherapy and electrocautery have all been unsuccessful in the three previously published cases. Curettage and cautery and radiotherapy were unsuccessful in our patient. Thalidomide is antiangiogenic and can be helpful in GVHD, but failed when given to two of the three patients reported. Our patient also received thalidomide: no change was noted clinically, and the drug was stopped because of nausea and fatigue. We report the fourth case of eruptive angiomas associated with GVHD. Despite its benign histological appearance, treatment has been recalcitrant in all cases and it appears to have a poor prognosis, probably because of its association with active GVHD. We suggest that more targeted treatment for cGVHD will be necessary before resolution of the angiomas is obtained.

Multiple masses on the tongue of a patient with generalized mucocutaneous lesions.

Luca Pastore and colleagues discuss the differential diagnosis and management of a 62-year-old man who presented with a 6-cm fungating mass on the dorsum of the tongue.