Clinical significance of molecular alterations in histologically negative surgical margins of head and neck cancer patients

The development of locoregional recurrence is the main reason for treatment failure in head and neck squamous cell carcinomas (HNSCC) and the remaining of tumor cells in surgical margins is associated with recurrence. Surgical margins are considered negative based on histologic assessment of the pathological specimen. However, this method lacks sensitivity in identifying cells that already started malignant transformation but have not yet developed a pathologic phenotype. We investigated the usefulness of assessing the expression of PTHLH, EPCAM, MMP9, LGALS1 and MET for the detection of molecular alterations in histologically negative surgical margins and determine the correlation of these tumor-related alterations with clinical and prognostic parameters. Differential gene expression was determined by quantitative RT-PCR analyses in normal mucosa, HNSCC and negative margin samples. Thirty-eight percent of the histologically negative surgical margins examined were margin-positive for overexpression of at least one of the genes evaluated. Moreover, MMP9 and PTHLH overexpression in the surgical margins was associated with the development of second primary tumors (p = 0.002) and lower rates of local control (log rank test p = 0.022; HR = 4.186; p = 0.035), respectively. These findings demonstrate that the overexpression of tumor-related genes in histologically negative surgical margins is a frequent event. the use of qRT-PCR may be an useful tool in detecting actually negative HNSCC surgical margins and the overexpression of specific genes in these margins could be helpful in the identification of patients with a higher risk of developing second primary tumors and local recurrences, thus aiding the surgeon in the delineation of the HNSCC resection extent and helping in the planning of adjuvant therapy. (C) 2011 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Lab Mol Canc Biol, Dept Biol Sci, BR-04039032 São Paulo, BrazilHosp Canc AC Camargo, Fundacao Antonio Prudente, Dept Head & Neck Surg, BR-01509010 São Paulo, BrazilHosp Canc AC Camargo, Fundacao Antonio Prudente, Dept Pathol, BR-01509010 São Paulo, BrazilHosp Canc Barretos, Dept Head & Neck Surg, Fundacao PIO 12, BR-14784400 Barretos, SP, BrazilUniversidade Federal de São Paulo, Lab Mol Canc Biol, Dept Biol Sci, BR-04039032 São Paulo, BrazilFAPESP: 2007/56245-0FAPESP: 2008/58460-9CNPq: 302360/2008-5Web of Scienc

Giant pleomorphic adenoma of the parotid gland

Pleomorphic adenoma is the most common type of all benign and malignant salivary gland tumors, involving more frequently the parotid gland. It is a benign tumor with a slow and continuous growth that without treatment can reach an enormous size. We present a case of a giant pleomorphic adenoma in a 78-year-old man with a history of more than 30 years of a growing lesion in the parotid gland. Clinical examination revealed a giant mass on the right side of the face, however without any sign of facial nerve damage. The tumor was completely resected by total parotidectomy and preservation of the facial nerve. Macroscopically, the tumor measured 28cm and weighed 4.0 Kg. On the histological examination there was a predominance of epithelial and mioepithelial cells in a hyaline and mixoid stroma. It was not found any area of malignant transformation. In the post-operatory the aesthetic and functional results were excellent

Incidental thyroid carcinoma: Correlation between FNAB cytology and pathological examination in 1093 cases

Objective: To investigate Incidental Thyroid Carcinoma (ITC) by comparing the results of Fine Needle Aspiration Biopsy (FNAB) cytology and the postoperative pathological findings. Methods: Data of 1479 patients who underwent total thyroidectomy were retrieved. Three hundred eighty-six patients were excluded due to insufficient data. Each surgical specimen studied received two histopathological diagnoses: the local diagnosis ‒ for the same area in which the FNAB was performed; and the final diagnosis, which includes a study of the entire surgical specimen. Results: A thousand and ninety-three patients were investigated. FNAB result was malignant in 187 patients, benign in 204, suspicious or indeterminate in 668 cases, and inconclusive in 34 cases. The prevalence of ITC was 15.1%. Most of the ITC in this series was less than 0.5 cm. The incidence of ITC was higher in Bethesda III (17.5% ITC) and IV (19% ITC) than in Bethesda II cases (1.5% false negatives and 9% ITC). Conclusion: Although the incidence of false-negative results in Bethesda II nodules is only 1.5%, 9% of these patients had ITC in the thyroid parenchyma outside the nodule that underwent preoperative FNAB. The incidence of ITC in the same scenario was even higher in Bethesda III (17.5%) and Bethesda IV cases (19%). Ultrasonography-guided FNAB is an excellent method for the assessment of thyroid nodules. However, biopsy sites should be carefully selected. Despite the high incidence of incidentalomas, total thyroidectomy should not always be the treatment of choice due to its rare but potentially serious complications. The findings of the present study can assist future clinical decisions towards active surveillance strategies for the management of papillary thyroid carcinoma

TIMP3 and CCNA1 hypermethylation in HNSCC is associated with an increased incidence of second primary tumors

Background: Hypermethylation in the promoter regions is associated with the suppression of gene expression and has been considered a potential molecular marker for several tumor types, including head and neck squamous cell carcinomas (HNSCC).Methods: To evaluate the gene hypermethylation profile as a prognostic marker, this retrospective study used a QMSP approach to determine the methylation status of 19 genes in 70 HNSCC patients.Results: the methylation profile analysis of primary HNSCC revealed that genes CCNA1, DAPK, MGMT, TIMP3 and SFRP1 were frequently hypermethylated, with high specificity and sensitivity. TIMP3 and CCNA1 hypermethylation was significantly associated with lower rates of second primary tumor-free survival (p = 0.007 and p = 0.001; log-rank test, respectively).Conclusion: This study, for the first time, presents CCNA1 and TIMP3 hypermethylation as a helpful tool to identify HNSCC subjects at risk of developing second primary carcinomas.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Dept Biol Sci, Lab Mol Canc Biol, BR-04039020 São Paulo, BrazilBarretos Canc Hosp, Stat & Epidemiol Ctr, BR-14784400 Barretos, BrazilAC Camargo Hosp, Dept Head & Neck Surg, BR-01509010 São Paulo, BrazilBarretos Canc Hosp, Dept Head & Neck Surg, BR-14784400 Barretos, BrazilDuke NUS Grad Med Sch, Canc & Stem Cell Biol Program, Singapore 169857, SingaporeUniversidade Federal de São Paulo, Dept Biol Sci, Lab Mol Canc Biol, BR-04039020 São Paulo, BrazilWeb of Scienc

Decreased CD1a + and CD83 + cells in tonsillar squamous cell carcinoma regardless of HPV status

Dendritic cells (DCs) are specialized antigen-presenting cells that play a critical role in the immune response against human papillomavirus (HPV) infection, and represent a therapeutic target in cancer. Objective: To identify and quantify DCs in tonsillar squamous cell carcinoma (TSCC) under the influence of HPV infection. Methodology: CD1a and CD83 antibodies were used to identify immature dendritic cells and mature dendritic cells by immunohistochemistry in 33 primary TSCC and 10 normal tonsils (NTs), respectively. For the TSCC samples, the number of DCs per area was evaluated in the intra- and peritumoral compartments. For the NTs, the quantification of DCs was evaluated in the intra- and peritonsillar compartments. HPV detection methods were determined according to the ASCO Clinical Practice Guidelines from the College of American Pathologists Guideline (2018). Results: There were fewer intratumoral CD1a+ DCs in the HPV-positive and HPV-negative TSCC groups than in the NT group (p<0.05). In the peritumoral compartment, there were fewer CD83+ DCs in the HPV-positive and HPV-negative TSCC groups than in the NT group (p<0.001). The quantification of DCs subtypes showed no statistical differences between HPV-positive and HPV-negative TSCC groups (p>0.137). Patients with HPV-positive TSCC had significantly better overall survival rate than those with HPV-negative TSCC (p=0.004). Conclusion: Tumor activity contributes to DC depletion regardless of intralesional HPV positivity. An improved prognosis has been reported in patients with HPV-positive TSCC

Malignant Transformation Of An Odontogenic Cyst In A Period Of 10 Years.

Primary intraosseous carcinoma of the jaws (PIOSCC) might arise from odontogenic epithelium, more commonly from a previous odontogenic cyst. The aim of this case is to illustrate that the clinician should consider that an apparent benign dentigerous cyst can suffer malignant transformation and that all material removed from a patient must be evaluated histologically. A 44-year-old man presented in a routine periapical X-ray an impacted lower left third molar with radiolucency over its crown. Ten years later, the patient complained of pain in the same region and the tooth was extracted. After one month, the patient still complained of pain and suffered a fracture of the mandible. A biopsy was performed and carcinoma was diagnosed. The patient was treated surgically with adjuvant radio- and chemotherapy and after 8 years, he is well without signs of recurrences. This report describes a central mandibular carcinoma probably developed from a previous dentigerous cyst.201476296

The pesticides use and the risk for head and neck cancer:a review of case-control studies

Tobacco, alcohol consumption, and HPV infection are the most common risk factors for head and neck cancer (HNC). Despite of this, recent evidences are growing on the association between long-term exposure to pesticides and the risk of chronic diseases, including different types of cancer. The present review evaluated in current literature evidence of an association between exposure to pesticides and the occurrence of HNCs. A literature search of the case-control studies was conducted in the PubMed, Web of science and Cochrane databases. Methodological quality of each study was rated with the Scottish Intercollegiate Guidelines Network (SIGN 50) checklist. One thousand and thirty-five studies were identified and twelve met all criteria and, therefore, considered for quality assessment and data extraction. According to SIGN 50 criteria, six studies received an overall high-quality. All the studies considered of high quality found a positive association between exposure to pesticides and different HNC sites, including larynx, pharynx and nasal cavity. In addition, the increased risk was associated with the frequency of exposure. Finally, improving pesticide users' awareness of their risks and proper handling, as well as adopting protective measures such as the use of personal protective equipment, appear to be effective in reducing human health damage

Genomic profile of a squamous cell carcinoma ex pleomorphic adenoma compared to a head and neck squamous cell carcinoma

FAPESPUniv Estadual Campinas UNICAMP, Dept Patol, Fac Ciencias Med, Campinas, SP, BrazilUniv Estadual Campinas UNICAMP, Fac Ciencias Med Cirurgia Cabeca & Pescoco, Campinas, SP, BrazilAC Camargo Canc Ctr, Dept Cirurgia Cabeca & Pescoco, Sao Paulo, SP, BrazilUniv Sao Paulo UNIFESP, Inst Biociencias, Dept Genet & Biol Evolucionaria, Sao Paulo, SP, BrazilUniv Sao Paulo UNIFESP, Inst Biociencias, Dept Genet & Biol Evolucionaria, Sao Paulo, SP, BrazilFAPESP: 2011/23204-5FAPESP: 2011/23366-5SciEL

Epidemiology and survival outcomes of lip, oral cavity, and oropharyngeal squamous cell carcinoma in a southeast Brazilian population

Lip, oral cavity, and oropharyngeal squamous cell carcinoma (SCC) represent a major health problem in the global scenario. In South America, the highest incidence rates are seen in Brazil. Therefore, the epidemiological and clinical profile and survival outcomes of lip, oral cavity, and oropharyngeal SCC was studied in São Paulo State, Brazil. The clinicopathological data of 12,099 patients with lip, oral cavity, and oropharyngeal SCC were obtained from hospital cancer registries of the Fundação Oncocentro de São Paulo, Brazil (2010?2015). Survival rates and other analyses were performed using SPSS software. A clear male predominance was observed, particularly for patients with oropharyngeal SCC (88.3%). The average age of patients was higher for lip cases (65 ± 13.5 years) compared to other sites. The schooling level was low for most patients, especially in lip cases (87.9%). Most of the patients with oral cavity (71.8%) and oropharyngeal (86.3%) SCC had advanced-stage (III?IV) disease. However, the majority of lip cases (83.3%) were at an early stage (I?II). Surgical excision was the main treatment for lip (72%) and oral cavity SCC (23.5%), and chemoradiotherapy was the main treatment for oropharyngeal SCC (40.2%). The 5-year overall survival (OS) for patients with lip, oral cavity, and oropharyngeal SCC were 66.3, 30.9, and 22.6%, respectively. Multivariate analysis revealed that the determinants of OS were different for lip, oral cavity, and oropharyngeal SCC, except for those at the clinical stage, which was an independent predictor for all sites. OS-independent determinants varied according to the affected site. Oral cavity and oropharyngeal SCC presented worse survival rates than those for lip SCC