José Humberto Damante

Patients with oral squamous cell carcinoma are characterized by increased frequency of suppressive regulatory T cells in the blood and tumor microenvironment

Oral squamous cell carcinoma (OSCC) is a cancerous lesion with high incidence worldwide. The immunoregulatory events leading to OSCC persistence remain to be elucidated. Our hypothesis is that regulatory T cells (Tregs) are important to obstruct antitumor immune responses in patients with OSCC. In the present study, we investigated the frequency, phenotype, and activity of Tregs from blood and lesions of patients with OSCC. Our data showed that >80% of CD4+CD25+ T cells isolated from PBMC and tumor sites express FoxP3. Also, these cells express surface Treg markers, such as GITR, CD45RO, CD69, LAP, CTLA-4, CCR4, and IL-10. Purified CD4+CD25+ T cells exhibited stronger suppressive activity inhibiting allogeneic T-cell proliferation and IFN-γ production when compared with CD4+CD25+ T cells isolated from healthy individuals. Interestingly, approximately 25% of CD4+CD25− T cells of PBMC from patients also expressed FoxP3 and, although these cells weakly suppress allogeneic T cells proliferative response, they inhibited IFN-γ and induced IL-10 and TGF-β secretion in these co-cultures. Thus, our data show that Treg cells are present in OSCC lesions and PBMC, and these cells appear to suppress immune responses both systemically and in the tumor microenvironment.

Oral adverse effects of head and neck radiotherapy: literature review and suggestion of a clinical oral care guideline for irradiated patients

Radiotherapy, alone or associated with surgery or chemotherapy, produces a significant increase in cure rates for many malignancies of the head and neck region. However, high doses of radiation in large areas, including the oral mucosa, may result in several undesired reactions that manifest during or after the completion of therapy. The multidisciplinary management is the best alternative to minimize or even prevent such reactions, and the dentist has a fundamental role in this context. This paper reviews the literature related to the main oral sequelae from head and neck radiotherapy and establishes clinical oral management protocol for these irradiated patients.

Enhanced programmed death 1 (PD-1) and PD-1 ligand (PD-L1) expression in patients with actinic cheilitis and oral squamous cell carcinoma

PD-1 and PD-L1 can be involved in tumor escape, and little is known about the role of these molecules in oral tumors or pre-malignant lesions. In the present study, we investigated the expression of PD-1 and PD-L1 in the blood and lesion samples of patients with actinic cheilitis (AC) and oral squamous cell carcinoma (OSCC). Our results showed that lymphocytes from peripheral blood and tissue samples exhibited high expression of PD-1 in both groups analyzed. Patients with AC presented higher percentage as well as the absolute numbers of CD4+PD-1+ and CD8+PD-1+ lymphocytes in peripheral blood mononuclear cells (PBMC) than healthy individuals, while patients with OSCC presented an increased frequency of CD8+PD1+ in PBMC when compared with controls. On the other hand, increased frequency of CD4+ and CD8+ T cells expressing PD-1+ accumulate in samples from OSCC, and the expression of PD-L1 was intense in OSCC and moderate in AC lesion sites. Lower levels of IFN-γ and higher levels of TGF-β were detected in OSCC samples. Our data demonstrate that PD-1 and PD-L1 molecules are present in blood and samples of AC and OSCC patients. Further studies are required to understand the significance of PD-1 and PD-L1 in oral tumors microenvironment.

Evaluation of some oral postradiotherapy sequelae in patients treated for head and neck tumors

The aim of this study was to evaluate the oral sequelae of radiotherapy in patients treated between 1999 and 2003 for head and neck tumors. One-hundred patients (24 women, 76 men) ranging in age from 30 to 83 years (mean 59.2 years) were examined. Time since radiotherapy ranged from 1 to 72 months (mean 28 months). The total mean radiation dose received by the patients was 5,955 cGy. The evaluation protocol included anamnesis, intraoral and extraoral examination, measurement of stimulated salivary flow and salivary pH. Symptoms reported by the patients included dry mouth (68%), dysphagia (38%), and dysgeusia (30%). In 64% of the patients, the mean stimulated salivary flow rate was less than 0.7 ml/min. The mean salivary pH was 6.97 (+/- 0.714). Stimulated salivary flow increased with increasing postradiotherapy time (p < 0.05). The prevalence of mucositis was associated with higher radiation doses (p < 0.05), and the prevalence of atrophic candidiasis was related to a longer post-treatment period (p < 0.05). Two cases of recurrence of the primary tumor were detected during the study. The main effect of radiotheraphy in the head and neck region was a reduction of the salivary flow rate, even though our study demonstrated that there was a modest late improvement of the salivary flow.

Pyogenic granuloma on the upper lip: an unusual location.

Pyogenic granuloma (PG) is a benign non-neoplastic mucocutaneous lesion. It is a reactional response to constant minor trauma and might be related to hormonal changes. In the mouth, PG is manifested as a sessile or pedunculated, resilient, erythematous, exophytic and painful papule or nodule with a smooth or lobulated surface that bleeds easily. PG preferentially affects the gingiva, but may also occur on the lips, tongue, oral mucosa and palate. The most common treatment is surgical excision. This paper describes a mucocutaneous PG on the upper lip, analyzing the clinical characteristics and discussing the features that distinguish this lesion from other similar oral mucosa lesions. The diagnosis of oral lesions is complex and leads the dentist to consider distinct lesions with different diagnostic methods. This case report with a 4 year-follow-up calls the attention to the uncommon mucocutaneous labial location of PG and to the fact that surgical excision is the safest method for diagnosis and treatment of PG of the lip, even when involving the mucosa and skin

Is podoplanin expression associated with the proliferative activity of ameloblastomas

OBJECTIVES The aim of this study was to investigate the relationship between podoplanin expression and proliferative activity of ameloblastomas and remnants of the odontogenic epithelium from dental follicles (DF) of unerupted teeth. SUBJECTS AND METHODS Thirty-three paraffin-embedded ameloblastomas and thirty-two DF obtained of unerupted teeth were analyzed by immunohistochemistry using anti-human podoplanin and anti-Ki-67 antibodies. Podoplanin expression in odontogenic epithelial cells was evaluated using a scoring method, and the Ki-67 labeling index was determined by the percentage of positive odontogenic cells. RESULTS All ameloblastomas displayed podoplanin expression in ameloblast-like cells of the epithelial islands. Membranous expression of podoplanin in ameloblastomas was stronger than in the remnants of odontogenic epithelium (P = 0.001). Statistically significant difference was observed between the cytoplasmic and membranous expression of podoplanin in the remnants of odontogenic epithelium (P = 0.001). The index of epithelial odontogenic proliferative activity, verified by Ki-67 expression, was higher in ameloblastomas vs remnants of odontogenic epithelium (P < 0.001). No statistically significant correlation was identified between podoplanin and the cellular odontogenic proliferative activity in meloblastomas and DF (P > 0.05). CONCLUSIONS These results provide evidence that there is no connection between podoplanin immunostaining and odontogenic cellular proliferative activity and suggest a role for membranous podoplanin expression in the local invasion of ameloblastomas.

Management of a parotid sialocelein a young patient: case report and literature review

Sialocele is a subcutaneous cavity containing saliva, caused by trauma or infection in the parotid gland parenchyma, laceration of the parotid duct or ductal stenosis with subsequent dilatation. It is characterized by an asymptomatic soft and mobile swelling on the parotid region. Imaging studies are useful and help establishing the diagnosis, such as sialography, ultrasonography, computed tomography and magnetic resonance imaging. This paper describes a recurrent case of a parotid sialocele in a young female patient. She presented a 6 cm x 5 cm swelling on the left parotid region. The ultrasonographic scan of the area revealed a hypoechoic ovoid well defined image suggesting a cyst. A sialography of the left parotid showed a cavitary sialectasia in a panoramic and anteroposterior view. A conservative management was adopted by percutaneous needle aspiration of the swelling, which was useful to provide material for analysis and helped healing. Dentists should be aware of this pathology and the importance in adopting a conservative treatment whenever it is possible.

Psammomatoid juvenile ossifying fibroma: an analysis of 2 cases affecting the mandible with review of the literature

Juvenile ossifying fibroma (JOF) is a rare fibro-osseous neoplasm, defined as a variant of the ossifying fibroma that arises within the craniofacial bones. Two subgroups, juvenile psammomatoid ossifying fibroma (PsJOF) and juvenile trabecular ossifying fibroma, have been delineated by their histology. PsJOF occurs predominantly in the sinonasal and orbital bones. This work reports on 2 cases of extensive PsJOF in the body of the right mandible as well as reviews the literature regarding the radiographic and histologic features, treatment, and prognosis of PsJOF of the jaws.

Monostotic fibrous dysplasia: a 23-year follow-up of a patient with spontaneous bone remodeling.

Fibrous dysplasia is a benign fibro-osseous disease that affects one or more bones. Although its etiology has been defined, the mechanism of spontaneous resolution is still unclear. There is strong evidence indicating the occurrence of stabilization when bone maturation is completed. Deformities that lead to esthetic and functional disorders are observed in almost all cases. Plastic surgery is often recommended when the maxilla and mandible are involved. In the case of mild deformities, careful follow-up during skeletal growth is recommended. We describe here the 23-year follow-up of a patient with monostotic fibrous dysplasia whose disease had stabilized by 13 years of follow-up.

Regulatory T cells in the actinic cheilitis.

BACKGROUND Actinic cheilitis (AC) is an oral potentially malignant lesion which is the counterpart of actinic keratosis of the skin and has potential to develop into squamous cell carcinoma. Regulatory T cells (Tregs) have a critical role in modulating the antitumor immune responses. The presence of regulatory T cells in potentially malignant lesions has not been described. We chose investigate the involvement of regulatory T cells in potentially malignant lesions. METHODS The frequency, phenotype, and activity of CD4+CD25+ T cells isolated from blood and lesion of AC patients were analyzed by flow cytometry. Cytokines were quantified by ELISA. Data were compared with samples from healthy subjects. RESULTS The frequency and suppressor activity of circulating CD4+CD25+ T cells was similar in AC patients and control subjects. However, the frequencies of IL-10-positive Tregs were higher in AC patients, and these cells inhibited interferon-gamma (IFN-γ) and increased interleukin (IL)-10 productions in co-cultures. Furthermore, CD4+CD25+ T cells accumulate in AC lesions. Lesions-derived regulatory T cells suppressed lymphocyte proliferation and pro-inflammatory cytokine production. Moreover, high levels of IL-10 and transforming growth factor-β (TGF-β), and low IFN-γ were detected in the potentially malignant lesions. CONCLUSION Therefore, our data show that Tregs accumulate in AC lesions, and these cells could be suppressing immune responses in a potentially malignant microenvironment.