Cancer stem cells enrichment with surface markers CD271 and CD44 in human head and neck squamous cell carcinomas.

Head and neck squamous cell carcinoma (HNSCC) has a poor 5-year survival rate of 50%. One potential reason for treatment failure is the presence of cancer stem cells (CSCs). Several cell markers, particularly CD44, have been used to isolate CSCs. However, isolating a pure population of CSC in HNSCC still remains a challenging task. Recent findings show that normal oral stem cells were isolated using CD271 as a marker. Thus, we investigated the combined use of CD271 and CD44 to isolate an enriched subpopulation of CSCs, followed by their characterization in vitro, in vivo, and in patients' tissue samples. Fluorescent-activated cell sorting was used to isolate CD44+/CD271+ and CD44+/CD271- from two human HNSCC cell lines. Cell growth and self-renewal were measured with MTT and sphere/colony formation assays. Treatment-resistance was tested against chemotherapy (cisplatin and 5-fluorouracil) and ionizing radiation. Self-renewal, resistance, and stemness-related genes expression were measured with qRT-PCR. In vivo tumorigenicity was tested with an orthotopic immunodeficient mouse model of oral cancer. Finally, we examined the co-localization of CD44+/CD271+ in patients' tissue samples. We found that CD271+ cells were a subpopulation of CD44+ cells in human HNSCC cell lines and tissues. CD44+/CD271+ cells exhibited higher cell proliferation, sphere/colony formation, chemo- and radio-resistance, upregulation of CSCs-related genes, and in vivo tumorigenicity when compared to CD44+/CD271- or the parental cell line. These cell markers showed increased expression in patients with the increase of the tumor stage. In conclusion, using both CD44 and CD271 allowed the isolation of CSCs from HNSCC. These enriched CSCs will be more relevant in future treatment and HNSCC progression studies.

Epidemiology and Patient Distribution of Oral Cavity and Oropharyngeal SCC in Canada.

BACKGROUND: Oral cavity cancers (OCCs) and oropharyngeal cancers (OPCs) continue to be a major source of morbidity and mortality worldwide requiring the shared effort of numerous specialists. Tobacco and alcohol consumption have long been identified as risk factors for both OCC and OPC. In addition, human papilloma virus (HPV) is gaining its position as the main causal agent for OPC. OBJECTIVE: The objective of this study is to analyze the epidemiology of OCC and OPC in Canada. METHODS: Data pertaining to the year of diagnosis, the patient's sex, age at the time of diagnosis, province/territory, city and postal code of oral cavity, and oropharyngeal malignancies diagnosed during 1992-2010 were extracted from the Canadian Cancer Registry and Le Registre Québécois du Cancer. RESULTS: In total, 21 685 OCC cases and 15 965 OPC cases were identified from 1992 to 2010. Of those, 84.97% were oral cavity squamous cell carcinomas (SCCs), 88.10% were oropharyngeal SCCs, and both had a significant male predominance. While oral cavity SCC incidence stabilized over the study period, oropharyngeal SCC continued to increase. Oral cavity SCC incidence increased with age, while oropharyngeal SCC incidence peaked in the 50- to 59-year age group. Detailed geographic distribution analysis of patients at the provincial/territorial, city, and postal code levels identified several patient clusters. CONCLUSIONS: This work highlights important epidemiological differences in trends between oral and oropharyngeal cancers, identifies high-incidence postal codes for each malignancy, and correlates incidence/mortality with known risk factors including alcohol/tobacco use and HPV infections, therefore providing a comprehensive understanding of epidemiology for these cancers in Canada.

Successful management of pediatric oral pemphigus vulgaris with topical corticosteroid monotherapy.

Pemphigus vulgaris (PV) is an autoimmune intraepithelial bullous disease that affects the skin and mucous membranes. Typically, the management of PV is challenging, with systemic corticosteroids being the mainstay of treatment. We describe the case of a 14-year-old girl who was diagnosed with oral PV and successfully treated with topical corticosteroids alone. This case details a pediatric mucosal PV case successfully managed solely with topical corticosteroids.

Acute herpetic gingivostomatitis in adults: a review of 13 cases, including diagnosis and management.

OBJECTIVE: To present to general dentists the typical signs and symptoms associated with adult acute (primary) herpetic gingivostomatitis. The pertinent laboratory tests, management options and current pharmacotherapy are also reviewed. REVIEW DESIGN: The clinical files of 13 adult patients were reviewed. All had no history of herpes simplex virus infection and presented with oral lesions suggestive of primary herpetic infection. The subjects were all patients of one of the investigators, and their workup included Tzanck testing and viral culture. RESULTS: The patients ranged in age from 18 to 79 (mean 37.2, standard deviation 19.6) years. Nine (69%) were men. Viral culture was confirmed as the gold standard for diagnosis. The sensitivity of Tzanck testing was 77% (10/13), slightly higher than that reported previously (40% to 50%). In this patient group the febrile lymphadenopathic profile was typical of younger patients (18 to 42 years of age), whereas older patients presented with predominantly oral symptoms. CONCLUSIONS: Primary herpetic gingivostomatitis is not limited to children but can affect people of any age. Proper diagnosis and treatment are essential, particularly in elderly and immunocompromised patients. Tzanck testing may serve as a useful adjunct in diagnosis. Antiviral agents such as valacyclovir and famciclovir should be considered part of early management. Dentists are often the first health care professionals to be consulted by patients with this condition, and recognition of the infection is paramount.

Use of fluorescent light in detecting malignant and premalignant lesions in the oral cavity: a prospective, single-blind study.

OBJECTIVE: To determine the usefulness of the VELscope in detecting malignant and premalignant oral cavity lesions. STUDY DESIGN: Prospective clinical study. SETTING: Head and neck oncology clinic at an academic tertiary care centre. SUBJECTS AND METHODS: Eighty-five patients with a history of smoking, alcohol use, and/or head and neck cancer were recruited into the study. The VELscope was used to examine patients' oral cavities after a clinical examination. Biopsies were then taken from suspicious areas. RESULTS: Of the 85 patients included in the study, 33 underwent biopsies prompted by a clinical examination, the VELscope, or both. Biopsy results that showed invasive malignancy or dysplasias were considered positive. Five positive biopsies for premalignant lesions were detected only by the VELscope and were not visible on clinical examination. On the other hand, only one positive biopsy for a premalignant lesion was detected by the clinical examination only and not seen on the VELscope. Seven positive biopsies were detected by both methods. This indicates that the diagnostic yield from a regular examination was 47% (95% CI 23-72) and that the diagnostic yield from the addition of the VELscope was an additional 31% (95% CI 11-59). Sensitivity and specificity for the VELscope were 92% and 77%, respectively. CONCLUSION: The Velscope may add sensitivity to the clinical examination and be a useful adjunct in high-risk patients.

Sclerosing mucoepidermoid carcinoma of the salivary gland: Case report and literature review.

Sclerosing mucoepidermoid carcinoma (SMEC) is an extremely rare variant of mucoepidermoid carcinoma with unique histologic features. To the best of our knowledge, only 14 cases of salivary gland SMEC have been previously reported in the English-language literature since it was discovered in 1987. We report a new case of salivary gland SMEC, and we review the literature. Because of SMEC's distinctive histologic features and rarity, its diagnosis can be difficult. Moreover, no clear treatment strategy has emerged with regard to adjuvant postoperative radiotherapy. We attempt to elucidate a natural course of this disease, and we propose a conservative approach to postoperative management.

Orofacial granulomatosis presenting as persistent lip swelling: review of 6 new cases.

PURPOSE: Orofacial granulomatosis (OFG) is an uncommon disease, which presents usually as a persistent swelling of the soft tissues in the orofacial region and is characterized histologically by a granulomatous inflammation. The term orofacial granulomatosis is used in the literature to describe a nonspecific granulomatous inflammation. A subset, cheilitis granulomatosa (CG), which presents clinically as persistent lip swelling, is a granulomatous inflammation of unknown origin of the lips. CG may also be part of the triad of the Melkersson-Rosenthal syndrome (MRS) and some consider it as an oligosymptomatic form of MRS. PATIENTS AND METHODS: In a retrospective study, we reviewed the clinical records of all patients between the years 1990 and 2002 with the histologic diagnosis of granulomatous inflammation of the lip from the Department of Pathology at the Montreal General Hospital. The age at biopsy, sex, site of lesion, other signs of MRS, signs and symptoms of systemic granulomatous disease, and the treatment were compiled. RESULTS: Six subjects were included in the study, 5 females and 1 male. Four had swelling of the lower lip and 2 of the upper lip. In one patient a history of facial nerve palsy was reported and in another one a mild fissured tongue was present. No signs or symptoms of systemic granulomatous disease were noted. The treatment consisted of intralesional steroids with good results in 5 out of 6 patients. CONCLUSION: A thorough work-up to eliminate other etiologies of granulomatous disease is essential when a patient presents with granulomatous inflammation of the lip. CG seems to respond well to steroid treatment and the need for surgery is minimal and should be reserved for recalcitrant cases.

HER2/neu and Ki-67 as prognostic indicators in mucoepidermoid carcinoma of salivary glands.

INTRODUCTION: Mucoepidermoid carcinoma is the most common salivary gland malignancy, representing up to 30% of all cases. Despite attempts to correlate histopathologic grades to clinical outcomes, some histologically "low"-grade lesions continue to behave aggressively despite appropriate treatment. OBJECTIVE: This preliminary study will attempt to evaluate the use of immunohistochemical markers HER2/neu and Ki-67 as prognostic markers of biologic aggressiveness for mucoepidermoid carcinoma of the salivary glands. DESIGN AND METHODS: A retrospective chart review of 42 patients with mucoepidermoid carcinoma of major and minor salivary glands treated between 1970 and 1995 was conducted. A combination of primary resection with or without postoperative irradiation was used. Histologic grading and correlation with outcome analyses are provided. RESULTS: In the current study, positive HER2/neu staining and strong Ki-67 staining occurred in patients with high-grade mucoepidermoid carcinoma, whereas low-grade carcinoma was correlated with negative or weak staining. CONCLUSION: These preliminary results indicate that, overall, the overexpression of both the HER2/neu and the Ki-67 oncoproteins may serve as prognostic markers for poor outcome in salivary gland mucoepidermoid carcinoma.

Involvement of interleukin-18 in the inflammatory response against oropharyngeal candidiasis.

BACKGROUND: Oral candidiasis is a collective name for a group of disorders caused by the dimorphic fungus Candida albicans (C. albicans). Host defenses against C. albicans essentially fall into two categories: specific immune mechanisms and local oral mucosal epithelial cell defenses. The rationale of this study was to investigate the involvement of IL-18 in the inflammatory response against oral candidiasis. MATERIAL/METHODS: We first used human oral mucosa tissue and saliva to assess the production of Il-18. Second, we engineered human oral mucosa using only normal human oral epithelial cells and fibroblasts. Tissues were infected with C. albicans at different time points. RESULTS: Tissue and saliva analyses demonstrated that constitutively produced and secreted IL-18 was up-regulated following Candida-infection. With our engineered model, we showed that C. albicans significantly increased the secretion of active IL-18 by infected epithelial cells. Interestingly, a significant secretion of IFNg functionally supported the up-regulation of active IL-18 in C. albicans-infected tissues. We also showed that rhIL-18 increased the expression and production of endogenous IL-18 and ICE in C. albicans-infected tissues, which was paralleled by a significant increase in IFNg secretion. CONCLUSIONS: These data suggest that (i) oral epithelial cells are involved in local host defenses against C. albicans infections, via IFNg induced-IL-18, and (ii) that IL-18 and IFNg secretions may be related to epithelial cells. Given that our experimental model closely mimics the natural interface between the oral mucosa and C. albicans, it appears that IL-18 meets the requirements of being a cytokine that epithelial cells use to control C. albicans infections.