Laura de Campos Hildebrand

Spatial distribution of cancer stem cells in head and neck squamous cell carcinomas

BACKGROUND CD44 and aldehyde dehydrogenase 1 (ALDH1) are considered putative markers of highly tumorigenic cells (i.e., cancer stem-like cells) in head and neck squamous cell carcinomas. This small subset of cells is believed to be the primary responsible for tumor initiation and progression. The objectives of this study were (i) to evaluate the patterns of CD44 and ALDH1 expression in the tumor center and in the invasive front, as well as in adjacent non-tumor epithelium, and (ii) to correlate these findings with clinical parameters. MATERIALS AND METHODS The sample comprised 44 patients with primary head and neck squamous cell carcinomas. Hematoxylin and eosin (HE) staining was used for histopathological tumor grading and for morphological analysis of adjacent non-tumor epithelium. Semiquantitative analysis was performed in histological sections immunostained for CD44 and ALDH1. RESULTS ALDH1 immunostaining in the invasive front showed positive association with tumor size, regional metastasis, tumor histopathological grading, and disease progression. Moreover, expression of this marker in both tumor invasive front and adjacent non-tumor epithelium was related with more aggressive tumors. CD44 immunostaining was heterogeneous in all areas evaluated and did not show association with clinical data. CONCLUSION Collectively, these data suggest that ALDH1 immunostaining in the invasive front and in adjacent non-tumor epithelium may help identify tumors with a more aggressive behavior, potentially contributing to improving treatment customization and the monitoring of patients with head and neck cancer.

Tufted Angioma in Children: Report of Two Cases and a Review of the Literature

Tufted angioma (TA) is a benign vascular tumor with endothelial origin. It is extremely rare in oral mucosa; only seven cases have been reported in the literature so far. Here, we describe two cases of tufted angioma observed in children and we also present a review of the literature about this pathology, concerning the differential diagnosis and management of this lesion in children.

Intramuscular 30% polymethylmethacrylate (PMMA) implants in a non-protein vehicle: an experimental study in rats

INTRODUCTION: In the present study, the stability and biocompatibility of a 30% polymethylmethacrylate (PMMA) filling material implanted in the masseter muscle of rats were investigated according to the cytologic characteristics presented in the graft versus host reaction. METHODS: The study included 20 rats, which were divided into 4 groups: groups I, II, III, and IV corresponded to animals evaluated 7, 14, 45, and 60 days after surgery, respectively. The implant was placed in the right masseter muscle at the level of the mandibular angle. RESULTS: After 7 days, lymphoplasmacytic inflammatory infiltrates, a fibrous capsule, a large number of neutrophils, macrophages, and exudate were observed. The second group (14 days) showed granulation tissue composed of a lymphoplasmacytic inflammatory infiltrate, newly formed vessels, and a fibrous capsule. However, the second group also exhibited regeneration of the muscle fibers, and a decreased number of neutrophils and exudate. After 45 and 60 days, the inflammatory infiltrate decreased in intensity compared to the first 2 groups. CONCLUSIONS: The inflammatory reaction caused by PMMA is transient and does not compromise the function and the shape of the masseter muscle tissue, suggesting that PMMA is biocompatible.

Functional oral self-mutilation in physically healthy pediatric patients: Case report and analysis of 27 literature cases

Self-mutilation is a form of intentional injury or tissue destruction inflicted upon one’s own body without suicidal intent [1–3]. Van Sell et al. have estimated that 3 million people in the United States present self-injurious behavior, including cutting, burning, and other types of tissue destruction [4]. However, the exact prevalence of self-mutilation in the world population is uncertain and probably above the average reported [2], taking into consideration that such behaviors are not considered socially acceptable and therefore usually hidden from others [1]. In self-mutilation, physical pain is inflicted against one’s own body in an attempt to override intense emotional pain. Some authors identify self-inflicted injury as a ‘‘cry for help,’’ but the behavior is also associated with shame and consequently hidden practice [1,3,5,6,16]. Self-mutilation can affect all types of people, without distinction of sex, age, socioeconomic status, or educational level [1,7,8]. However, a higher incidence of self-inflicted injury has been reported among women and adolescents [3,6,8]. The etiology of self-mutilation can be classified into two categories: organic and functional [7]. In organic self-mutilation, injuries are inflicted unknowingly, unintentionally, and compulsively [7,9], e.g. as observed in comatose patients [10], patients with genetic syndromes, biochemical or enzymatic deficiencies such as Lesch-Nyhan, De Lange, and Tourette syndromes, congenital insensitivity to pain, and Leigh syndrome [7,11,12]. In turn, functional self-mutilation refers to self-injuries performed knowingly by physically healthy patients without detectable genetic defects [1,7], therefore representing a far greater diagnostic challenge to health professionals [9]. Functional self-mutilation is further divided into three subcategories: (A) injuries superimposed upon a pre-existing lesion; (B) injuries secondary to a chronic destructive habit (e.g. dummysucking); and (C) injuries of unknown or complex etiology (often including a psychological component). In the last subcategory, patients usually deny that they are producing the injury [13]. In addition to the etiologic classification of self-mutilation, differential diagnoses should bemade between this condition and other behaviors, such as cosmetic procedures, masochistic acts, and mental illnesses (e.g., depression followed or not by suicide attempt) [1]. Some cosmetic or esthetic procedures, such as body piercing, tattooing and plastic surgery, have been socially and culturally determined and can cause damage to oral tissues, but cannot be considered as self-mutilation [14]. Also, individuals who inflict injuries on themselves cannot be considered masochists, because the latter derive pleasure from their own pain, whereas self-mutilators seek relief fromoverwhelming emotional pain [1]. Finally, physical self-mutilation cannot be considered a suicide attempt, because self-mutilators do not intend to die, but rather to obtain relief [8,15]. With this regard, some authors have noted that suicide is a permanent solution to a temporary problem, whereas self-mutilation is a temporary solution to a permanent problem [15,16]. Oral self-mutilation is not uncommon. A literature search conducted in the PubMed database using the term oral selfmutilation yielded 296 papers. However, only 14 of these articles were found to describe cases of functional mutilation in nonsyndromic pediatric patients (these 14 articles are listed in Table 1) [5,7,13,17–27]. In cases of oral self-mutilation, the gingival area is the site most frequently affected, typically among pediatric female patients [5,7,13,17–19,21,23,26,27]. The most commonmethods of gingival self-inflicted injury are pocking with a pencil or scratching with fingernails [5,13,17,19,20,22,23,25–27], and etiologic factors usually include an emotional component, e.g. parent divorce, problems at school, birth or death of a sibling, or an unhappy home environment [5,13,19,20,23]. Treatment is based on correct diagnosis after a careful and thorough clinical examination, once functional oral self-mutilation is often denied or hidden by both the patient and family members [5–7,13,17–20,23,25–27]. Patients need to cease the habit [3,14], and psychological therapy acquires special importance in this process [1,5,16,17]. International Journal of Pediatric Otorhinolaryngology 75 (2011) 880–883

Focal adhesion kinases in head and neck squamous cell carcinoma

BACKGROUND Focal adhesion kinase (FAK) phosphorylation contributes to the regulation of growth factors that promote cellular adhesion, mobility, and survival, being a key factor in tumor development. The objective of this study was to evaluate the immunohistochemical expression patterns of FAK and its phosphorylated forms, FAK Tyr-576 and FAK Tyr-925, in head and neck squamous cell carcinoma and non-neoplastic adjacent epithelial tissue (AE). METHODS The percentage of immunohistochemistry stained cells and its correlation with clinicopathological variables and prognosis were determined using samples from 54 patients. RESULTS FAK, FAK Tyr-576, and FAK Tyr-925 overexpression was observed in tumor zones and AE. FAK Tyr-576 immunostaining showed a relationship with tumor clinicopathological parameters. Moreover, positive immunostaining of FAK Tyr-576 in AEsue was associated with patients prognoses. CONCLUSIONS Increased expression of FAK Tyr-576 could enable identification of tumors with a more aggressive behavior and epithelial alterations before the appearance of clinical or histological manifestations.

Location of injected polymethylmethacrylate microspheres influences the onset of late adverse effects : an experimental and histopathologic study

Polymethylmethacrylate (PMMA) has been widely used in the correction of wrinkles because of its long-lasting cosmetic improvements. However, side effects and complications may occur, and its clinical appearance on the oral mucosa can be similar to that of inflammatory or neoplastic disease. The aim of this research was to compare the clinical and histopathologic responses to PMMA injected by two different methods. Twenty-two rats received an injection of PMMA using the tunneling technique (gold standard), with subcutaneous deposition of the filler in the face, or a variation of the technique with transcutaneous submucosal deposition of the filler in the cheek. The tissue reaction was analyzed clinically every 24 hours during the first week, then once a week for the following 3 months. Histologic evaluation was based on the local inflammatory response to the filler. No clinical changes were observed during the initial evaluation period (0–14 days). After 14 days, only the submucosal group showed extra-oral enlargement (n=4, 18.2%). Histopathologic analysis revealed nodule formation in four animals (18.2%) in the submucosal group, with no nodules observed in the subcutaneous group. The data obtained in this study demonstrate that the technique used to deliver the filler may influence the risk of adverse reactions.

Carcinoma verrugoso en paciente joven

espanolEl carcinoma verrucoso es una variacion de bajo grado de malignidad del carcinoma de celulas escamosas oral, y la mayoria surge en la mucosa oral de individuos que mascan tabaco de forma cronica (6, 8, 10). Estas lesiones encontradas predominantemente en hombres, con mas de 55 anos de edad (edad promedio de 65 a 70 anos) y las regiones de mayor frecuencia en mucosa bucal incluyen vestibulo mandibular, mucosa yugal y palato duro (6, 8). La lesion aparece como una placa espesa, difusa, bien demarcada e indolora, con proyecciones superficiales papilares o verruciformes. Microscopicamente, se observa la presencia de crestas interpapilares anchas y alargadas y produccion abundante de ceratina (2). La metastasis es un evento raro en los carcinomas verrucosos (6, 8, 9). El tratamiento de eleccion es la excision quirurgica, asociada o no a la radioterapia. Los autores relatan un caso clinico de una paciente de 13 anos de edad con lesion comprometiendo todo lo vermellion del labio inferior. El tratamiento inicial propuesto fue la radioterapia asociado a la quimioterapia, decido a la edad de la paciente, localizacion y extension de la lesion. Despues de una dosis total de 70Gy, hubo la regresion total de la lesion. Siendo asi, el tratamiento del carcinoma verrucoso asociando a la radioterapia y quimioterapia se mostro adecuado en este caso. EnglishThe verrucous carcinoma is a low grade variant of oral squamous cell carcinoma, and it mostly appears in the oral mucosa of individuals who chew tobacco chronically 6, 8, 10. The lesions are mainly found in men over 55 years old (average age 65 to 70 years) and the most common regions in the oral mucosa include the mandibular vestibule, jugal mucosa and hard palate 6, 8. The lesion appears as a well-defined painless diffuse thick plaque with superficial papillary or verruciform projections. Under the microscope the presence of wide elongated interpapilIary ridges and copious keratin production are observed2. Metastasis is a rare event in verrucous carcinomas 6, 8, 9. The treatment of choice is surgical excision, optionally combined with radiotherapy. The authors report a clinical case of a 13-year-old patient with a lesion compromising the whole lower Iip vermilion. The initial treatment proposed was radiotherapy combined with chemotherapy, due to the patients age and the localization and extent of the lesion. After a total dose of 70Gy, full regression of the lesion took place. Thus, treatment of verrucous carcinoma by combining radiotherapy with chemotherapy proved satisfactory in this case