Márcio Ajudarte Lopes

Clinicopathological and immunohistochemical analysis of twenty-five head and neck osteosarcomas

The aim of this study was to analyze the clinicopathological features and immunohistochemical expression of p53, MDM2, CDK4, PCNA and Ki67 proteins in 25 head and neck osteosarcomas registered in a single institution. The mean age of the patients was 29 years and the most common site was the mandible (60%). The predominant histological type was the chondroblastic (72%) and 52% of the cases were classified as intermediate-grade of malignancy. The immunohistochemical analysis displayed positivity in 52% of the cases for p53, 24% for MDM2, 84% for CDK4, 92% for PCNA and 88% for Ki-67. The majority of cases were treated with surgery alone or associated with chemotherapy. Five patients developed local recurrences, four had distant metastasis and six had persistent disease after initial treatment. The overall 5-year and 10-year survival rates were 59% and 49%, respectively, and the most important prognostic factors were prior history of radiation exposure and osteoblastic histological type.

Multivariate survival analysis of 128 cases of oral cavity minor salivary gland carcinomas

Minor salivary gland carcinomas are uncommon tumors of the oral cavity. The decision regarding treatment remains controversial. The main objective of this paper is to report on the survival results of 128 patients treated in a single institution.

Myofibroblasts in the stroma of oral cancer promote tumorigenesis via secretion of activin A

Myofibroblasts are essential during wound healing and are often found in the stroma of oral squamous cell carcinomas (OSCC). Although the molecular mechanisms by which myofibroblasts influence OSCC remain largely unknown, previous studies demonstrated that presence of myofibroblast in OSCC stroma is an important risk factor of patients shortened survival. Here we showed that some growth factors are produced in higher levels by tumor-associated myofibroblasts compared to tumor-associated fibroblasts, including activin A. Myofibroblast-conditioned media containing activin A significantly increased OSCC cell proliferation and tumor volume, whereas down-regulation of activin A in the conditioned media decreased proliferation. In addition, myofibroblasts induced in vitro invasion of OSCC cells, which was accompanied by an increased production of matrix metalloproteinases (MMP). In vivo, a significant correlation between presence of myofibroblasts and activities of MMP-2 and MMP-9 was observed in OSCC samples. However, blockage of activin A synthesis by myofibroblasts did not affect invasion and MMP production by OSCC cells. Together, our data demonstrate that activin A is required for the proliferative effects of myofibroblasts on OSCC cells. We conclude that myofibroblasts in the stroma of OSCC may influence proliferation and invasion, resulting in more aggressive tumor.

Oral leiomyosarcoma: review of the literature and report of two cases with assessment of the prognostic and diagnostic significance of immunohistochemical and molecular markers

Leiomyosarcoma of the oral cavity is a very rare tumor that is associated with aggressive clinical behavior and low survival. In this paper, we report two new cases of leiomyosarcoma affecting the mandibular gingiva and mandible of a 35-year-old male and the mandible of a 51-year-old female. Given the difficulty in the histopathologic discrimination between benign and malignant smooth muscle tumors and the absence of reliable histologic parameters for prognostication of leiomyosarcomas, we evaluated the diagnostic and prognostic value of various immunohistochemical and molecular markers. By means of immunohistochemistry and quantitative real-time PCR analysis, we detected protein expression of PCNA, bcl-2, CDK4, p53 and MDM2 in both our cases and MDM2 amplification in our second case. The literature, pertinent to oral leiomyosarcoma and to molecular analysis of smooth muscle tumors, is reviewed.

Dental Alterations Associated with X-Linked Hypophosphatemic Rickets

The X-linked hypophosphatemic rickets is a rare metabolic disorder characterized by low serum phosphate levels caused by a decreased renal tubular reabsorption of inorganic phosphates. The initial complaints are a delay in the development of walking caused by deformity of the legs. Oral findings include poorly mineralized dentin, enlarged pulp chambers and root canals, and periradicular abscesses in caries-free teeth. We present three patients from the same family with X-linked hypophosphatemic rickets showing bone and dental alterations.

Patterns of Demineralization and Dentin Reactions in Radiation-Related Caries

Radiation-related caries is a unique form of rampant decay and is a complication of head and neck radiotherapy that frequently causes generalized dental destruction and impairs quality of life in cancer patients. The aim of this study was to investigate the patterns of demineralization of caries in irradiated patients and to establish whether direct radiogenic damage to the dentition might be important in the progression of radiation-related caries. Teeth from patients who had concluded radiotherapy were examined histologically by polarized light microscopy, and the ultrastructure was examined by scanning backscattered electron microscopy. Cervical caries and incisal caries, a very unusual sort of lesion, were widely detected. Additionally, diffuse brown discoloration of the smooth surface of enamel was frequently observed. Polarized light microscopy suggested that these areas were incipient caries. Evidence of normal odontoblast function was observed in the detection of reactionary dentin and intratubular dentin deposition. In conclusion, radiation-related caries seems to have the same morphological and demineralization pattern as ordinary caries, with the presence of demineralized dentin, a translucent zone, dentin dead tracts, reactionary dentin and intratubular dentin deposition. Based on these findings, direct radiogenic destruction of the teeth seems to be not essential to the microscopic progression of radiation-related caries.

Oral pigmented lesions: Clinicopathologic features and review of the literature

Diagnosis of pigmented lesions of the oral cavity and perioral tissues is challenging. Even though epidemiology may be of some help in orientating the clinician and even though some lesions may confidently be diagnosed on clinical grounds alone, the definitive diagnosis usually requires histopathologic evaluation. Oral pigmentation can be physiological or pathological, and exogenous or endogenous. Color, location, distribution, and duration as well as drugs use, family history, and change in pattern are important for the differential diagnosis. Dark or black pigmented lesions can be focal, multifocal or diffuse macules, including entities such as racial pigmentation, melanotic macule, melanocytic nevus, blue nevus, smoker’s melanosis, oral melanoacanthoma, pigmentation by foreign bodies or induced by drugs, Peutz-Jeghers syndrome, Addison´s disease and oral melanoma. The aim of this review is to present the main oral black lesions contributing to better approach of the patients. Key words:Pigmentation, melanin, oral, diagnosis, management.

Oral myofibromas: report of two cases and review of clinical and histopathologic differential diagnosis

Myofibroma is a benign mesenchymal neoplasm composed of myofibroblasts which has been described with different synonyms since the first report in 1951. It may show clinical and histologic features that may be misinterpreted as a malignancy. We describe 2 cases of oral myofibromas affecting infants; the first one showed a rapid growth with teeth displacement and ulceration; the second one presented a relatively slow growth with an indolent course. Differential diagnosis included benign and malignant mesenchymal neoplasms, salivary gland tumors, and reactive processes. Microscopic analysis of both lesions revealed a spindle cell tumor with immunoreactivity for vimentin, muscle-specific actin, and specific smooth muscle isoform alpha-actin, rendering the diagnoses of myofibroma. The patients were treated with surgical excision, and both are in follow-up without any signs of recurrence. Myofibroma presents a wide range of differential diagnosis, including benign and malignant neoplasms. Therefore, accurate diagnosis may avoid an unnecessary aggressive therapy.

Clinicopathological features and immunohistochemical expression of p53, Ki-67, Mcm-2 and Mcm-5 in proliferative verrucous leukoplakia.

BACKGROUND Proliferative verrucous leukoplakia (PVL) is a distinct and aggressive type of oral leukoplakia which affects elderly women without risk behavior and presents high rates of malignant transformation. The objective of the present study was to evaluate the clinicopathological characteristics and the distribution of cell proliferation markers, aiming to elucidate the distinct biological behavior of the PVL. METHODS Clinical and microscopical features of 12 patients with PVL were reviewed. Immunohistochemical analysis for p53, Ki-67, Mcm-2 and Mcm-5 were performed and the data were correlated. RESULTS All patients were women, above 50 years of age, 91.7% were non-smoker and 100% were non-habitual drinker. Alveolar ridge (66.6%), tongue (50%) and buccal mucosa (41.6%) were the most affected sites. Four patients developed squamous cell carcinoma (SCC). The immunohistochemical findings showed higher positivity for p53, Ki-67, Mcm-2 and Mcm-5 in SCCs. However, some patients with mild or moderate dysplasia, specially the patients who developed SCC, presented high expression of Mcm-2 and Mcm-5. CONCLUSIONS High immunoexpression of Mcm-2 and Mcm-5 in mild and moderate dysplasia could be helpful to predict the malignant transformation of PVL.

Head and neck chondrosarcoma: Analysis of 16 cases

OBJECTIVE Head and neck chondrosarcomas are rare, accounting for less than 12% of all chondrosarcomas. Few studies with larger series approach the clinicopathological characteristics of these tumours. The aim of this study was describe clinical findings, management and outcome of 16 cases of head and neck chondrosarcoma from a single institution. STUDY DESIGN The files of the Cancer Hospital A.C. Camargo were reviewed, and data from patients with head and neck chondrosarcoma were collected. RESULTS Mean age was 36 years, with slight male predilection. The most common site affected was maxilla (43%). Surgery was the main modality treatment performed in 10 patients. Overall 5-year survival rate was 56.4%. Although it was not statistically significant, the most important factor affecting overall survival was tumour size. CONCLUSION Early diagnosis and adequate surgical resection are important to get better survival rates.