Wilfredo Alejandro González-Arriagada

Intraoral sclerosing perineurioma: a case report and review of the literature

Sclerosing perineurioma is an extraneural soft tissue lesion that has been reported in the extremities of young adults. It is composed of oval epithelioid or plump spindled cells scattered to form ill-defined fascicles in a storiform, whorled, or trabecular pattern and dermal sclerosis represented by thickened collagen bundles in a lamellar array that express epithelial membrane antigen and are negative for S-100 protein. The treatment is surgical excision, and no recurrence or metastases are expected. Herein is presented the first case of intraoral sclerosing perineurioma of the lower lip, emphasizing its histopathologic and immunohistochemical features.

Expression pattern of PLUNC proteins as an auxiliary tool for the diagnosis of high-grade mucoepidermoid carcinoma of the salivary gland

BACKGROUND Mucoepidermoid carcinomas are the most frequent malignant neoplasia of the salivary glands and are histologically classified as low, intermediate, and high grade. At present, histochemical stains such as periodic acid-Schiff or mucicarmine are useful tools in making a diagnosis. Recently, expression of the PLUNC proteins has been described in mucin-producing salivary gland tumors, with the suggestion that they could provide a powerful tool for the diagnosis of difficult cases. METHODS This study evaluates the expression of PLUNC proteins in 30 cases of salivary gland mucoepidermoid carcinomas. Tumors were reviewed and classified according to histological grade. Periodic acid-Schiff, mucicarmine, and immunohistochemical staining for SPLUNC1, LPLUNC1, SPLUNC2, and LPLUNC2 were carried out. Immunostaining was classified as positive or negative. RESULTS The majority of the tumors (63%) were classified as low grade, 13% were intermediate grade, and 23% were high grade. SPLUNC1 (90%) and LPLUNC1 (93%) were positive in the majority of cases, mainly in mucous cells, mucin plugs, and intermediate cells. SPLUNC2 and LPLUNC2 did not present significative expression within the tumors; however, LPLUNC2 was found to stain positively in mast cells in 83% of the samples. CONCLUSIONS SPLUNC1 and LPLUNC1 showed a similar pattern of expression and could prove useful in the diagnosis of high-grade cases because of the differential staining in intermediate and epidermoid cells. The expression of LPLUNC2 in mast cells has not previously been reported, but further studies are necessary to validate this finding and to determine its significance.

Criterios de Evaluación Odontológica Pre-Radioterapia y Necesidad de Tratamiento de las Enfermedades Orales Post-Radioterapia en Cabeza y Cuello

RESUMEN: El objetivo de esta revision es presentar criterios de evaluacion odontologica pre-radioterapia y cualesson las principales necesidades de tratamiento de estos pacientes despues del tratamiento de radiacion. Fueron revisadosarticulos en ingles, espanol y portugues entre 1995 y 2009 indexados en Pubmed y Scielo. Las palabras claves fueron:cancer oral y radioterapia, complicaciones de la radioterapia en cabeza y cuello, evaluacion oral pre-radioterapia.Los efec-tos colaterales de la radioterapia en la region de cabeza y cuello pueden ser temporales o tardios. Aquellos que son tardios,como la caries de radiacion y la osteorradionecrosis pueden estar directamente relacionados con el hecho de no haberrealizado una evaluacion odontologica previa y pueden afectar severamente la calidad de vida del paciente.La participaciondel cirujano-dentista en el equipo multidisciplinario y la evaluacion odontologica de los pacientes que seran sometidos aradioterapia en la region de cabeza y cuello son de vital importancia en mejorar la calidad de vida post-operatoria de estospacientes.

Efficacy of low-level laser therapy as an auxiliary tool for management of acute side effects of head and neck radiotherapy

ABSTRACT Introduction: Head and neck radiotherapy (HNRT) is associated with acute and chronic side effects, some of which result in great morbidity. The aim of this study was to determine the efficacy of low-level laser therapy (LLLT) as an oral care tool for the management of these effects. Materials and Methods: Clinical information was collected from 216 patients undergoing HNRT; these individuals were divided into a control group without laser therapy (n = 108) and a laser group (n = 108). The intervention of the laser group was performed in a different period to the control group and was applied three times weekly. All data were analyzed by a descriptive statistical analysis. Results: The presence and severity of mucositis were similar between the groups. However, the laser group showed a lower frequency of interruption of oncologic therapy related to mucositis (p = 0.030) and the need of nasogastric tube nutrition during the HNRT (p = 0.027). In addition, trismus was less intense in the laser group (p = 0.023). Conclusions: The introduction of laser therapy in the supportive care for patients undergoing HNRT showed benefits for the patient and the medical system, reducing morbidity and costs associated with side-effects.

Proteostasis and Mitochondrial Role on Psychiatric and Neurodegenerative Disorders: Current Perspectives

Proteostasis involves processes that are fundamental for neural viability. Thus, protein misfolding and the formation of toxic aggregates at neural level, secondary to dysregulation of the conservative mechanisms of proteostasis, are associated with several neuropsychiatric conditions. It has been observed that impaired mitochondrial function due to a dysregulated proteostasis control system, that is, ubiquitin-proteasome system and chaperones, could also have effects on neurodegenerative disorders. We aimed to critically analyze the available findings regarding the neurobiological implications of proteostasis on the development of neurodegenerative and psychiatric diseases, considering the mitochondrial role. Proteostasis alterations in the prefrontal cortex implicate proteome instability and accumulation of misfolded proteins. Altered mitochondrial dynamics, especially in proteostasis processes, could impede the normal compensatory mechanisms against cell damage. Thereby, altered mitochondrial functions on regulatory modulation of dendritic development, neuroinflammation, and respiratory function may underlie the development of some psychiatric conditions, such as schizophrenia, being influenced by a genetic background. It is expected that with the increasing evidence about proteostasis in neuropsychiatric disorders, new therapeutic alternatives will emerge.

Agrin has a pathological role in the progression of oral cancer

BackgroundThe extracellular matrix modulates the hallmarks of cancer. Here we examined the role of agrin—a member of this matrix—in progression of oral squamous cell carcinoma (OSCC).MethodsWe evaluated the immunohistochemical expression of agrin in OSCC and dysplasias. Benign lesions were used as control. In subsequent experiments, we investigated whether the silencing of agrin interferes with tumour expansion both in vitro as well as in vivo. To gain insights into the role of agrin, we identified its protein network (interactome) using mass spectrometry-based proteomics and bioinformatics. Finally, we evaluated the clinical relevance of agrin interactome.ResultsAgrin was elevated in malignant and premalignant lesions. Further, we show that agrin silencing interferes with cancer cell motility, proliferation, invasion, colony and tumour spheroid formation, and it also reduces the phosphorylation of FAK, ERK and cyclin D1 proteins in OSCC cells. In orthotopic model, agrin silencing reduces tumour aggressiveness, like vascular and neural invasion. From a clinical perspective, agrin contextual hubs predict a poor clinical prognosis related with overall survival.ConclusionsAltogether, our results demonstrate that agrin is a histological marker for the progression of oral cancer and is a strong therapeutic target candidate for both premalignant and OSCC lesions.

Diagnostic approach to intramasseteric nodules

Intramuscular nodules can be the clinical presentation of several groups of lesions, such as reactive disorders and benign and malignant tumors. Here, we present three cases with similar clinical features and image aspects on Doppler ultrasonography. Two of the lesions were diagnosed as intramasseteric hemangioma and the third as intramasseteric metastasis from high-grade pleomorphic sarcoma of the thigh. The diagnosis of intramasseteric nodules is challenging, and various differential diagnoses must be considered. Clinical features, evolution time, and information from complementary examinations, such as Doppler ultrasonography and fine-needle aspiration cytology, are useful in making a precise diagnosis and providing appropriate treatment.

Kohlschütter-Tönz Syndrome - Report of an additional case

Kohlschütter-Tönz Syndrome is a rare disorder clinically characterized by amelogenesis imperfecta, epilepsy and progressive mental deterioration. We present an additional case of this syndrome of a nine year-old boy who was referred by pigmented teeth. The mental deterioration was associated with speech delay, impulsive behavior, attention-deficit/hyperactivity disorder, and learning problems. The physical examination revealed a reduction of lower third, slightly palpebral fissures, low ear and hair implantation, coarse hair and hypertrichosis. The intraoral examination showed alteration in teeth pigmentation diagnosed as amelogenesis imperfecta. Although rare, the present case report illustrates a syndrome that has dental anomalies and systemic alterations. It is important to recognize this syndrome as early as possible and paediatric dentist may contribute to the diagnosis and consequently to better manage the patients. Key words:Kohlschütter-Tönz syndrome, amelogenesis imperfecta, seizures, mental deterioration.

Combining discovery and targeted proteomics reveals a prognostic signature in oral cancer

Different regions of oral squamous cell carcinoma (OSCC) have particular histopathological and molecular characteristics limiting the standard tumor−node−metastasis prognosis classification. Therefore, defining biological signatures that allow assessing the prognostic outcomes for OSCC patients would be of great clinical significance. Using histopathology-guided discovery proteomics, we analyze neoplastic islands and stroma from the invasive tumor front (ITF) and inner tumor to identify differentially expressed proteins. Potential signature proteins are prioritized and further investigated by immunohistochemistry (IHC) and targeted proteomics. IHC indicates low expression of cystatin-B in neoplastic islands from the ITF as an independent marker for local recurrence. Targeted proteomics analysis of the prioritized proteins in saliva, combined with machine-learning methods, highlights a peptide-based signature as the most powerful predictor to distinguish patients with and without lymph node metastasis. In summary, we identify a robust signature, which may enhance prognostic decisions in OSCC and better guide treatment to reduce tumor recurrence or lymph node metastasis.Oral cancer has region-specific histopathological and molecular characteristics, complicating its classification by the standard tumor-node-metastasis system. Here, the authors combine discovery and targeted proteomics with IHC to identify region-specific and saliva biomarkers for oral cancer prognosis.

Clinicopathological significance of chemokine receptor (CCR1, CCR3, CCR4, CCR5, CCR7 and CXCR4) expression in head and neck squamous cell carcinomas

BACKGROUND Head and neck squamous cell carcinoma shows high prevalence of lymph node metastasis at diagnosis, and despite the advances in treatment, the overall 5-year survival is still under 50%. Chemokine receptors have a role in the development and progression of cancer, but their effect in head and neck carcinoma remains poorly characterised. This study aimed to assess the prognostic value of CCR1, CCR3, CCR4, CCR5, CCR7 and CXCR4 in head and neck squamous cell carcinomas. METHODS Immunohistochemical expression of chemokine receptors was evaluated in a retrospective cohort of 76 cases of head and neck squamous cell carcinoma. Clinicopathological associations were analysed using the chi-square test, survival curves were analysed according to the Kaplan-Meier method, and the Cox proportional hazard model was applied for multivariate survival analysis. RESULTS The chemokine receptors were highly expressed in primary carcinomas, except for CCR1 and CCR3. Significant associations were detected, including the associations between CCR5 expression and lymph node metastasis (N stage, P = .03), advanced clinical stage (P = .003), poor differentiation of tumours (P = .05) and recurrence (P = .01). The high expression of CCR5 was also associated with shortened disease-free survival (HR: 2.85, 95% CI: 1.09-8.14, P = .05), but the association did not withstand the Cox multivariate survival analysis. At univariate analysis, high expression of CCR7 was associated with disease-free survival and low levels of CXCR4 were significantly associated with both disease-specific and disease-free survival. CONCLUSIONS These findings show that chemokine receptors may have an important role in head and neck squamous cell carcinoma progression, regional lymph node metastasis and recurrence.