Fibrosis as a Risk Factor for Cutaneous Squamous Cell Carcinoma in Recessive Dystrophic Epidermolysis Bullosa: A Systematic Review.

Recessive dystrophic epidermolysis bullosa (RDEB) is a severe subtype of epidermolysis bullosa caused by changes in collagen VII with a high risk of early development of cutaneous squamous cell carcinoma (cSCC). This review aimed to discuss the relationship between the recurrent healing process, the appearance of fibrosis, and malignant epithelial transformation in RDEB. We searched PubMed, the Regional Portal of the Virtual Health Library, and Embase for articles on the relationship between blistering, recurrent scarring, and fibrosis in the context of cSCC and RDEB. That alterations of collagen VII result in blister formation, scar deficiency associated with inflammation, and increased expression of transforming growth factor ß. These events promote the differentiation of myofibroblasts and the expression of profibrotic proteins, leading to structural changes and the establishment of a microenvironment favorable to carcinogenesis. Patients with RDEB and areas of recurrent scarring and fibrosis may be more prone to the development of cSCC.

Epidermolysis bullosa in oral health: clinical manifestations and salivary alterations.

Epidermolysis bullosa (EB) is an inherited disease characterized by the fragility of the skin and mucous membranes. All types/subtypes of EB can lead to alterations in the mouth and glands. OBJECTIVE: To evaluate clinical manifestations of EB on the oral mucosa and alterations in salivary flow. MATERIALS AND METHODS: Sociodemographic and clinical data were obtained from EB individuals. The salivary flow analysis was performed in EB and in non-EB patients. Fischer's exact test was applied to the qualitative variables, and the Mann-Whitney test was applied to the quantitative data. RESULTS: A total of 11 cases of EB were evaluated, and 3 types of EB were diagnosed (recessive dystrophic-RDEB; junctional-JEB; and simplex-EBS). Only individuals with RDEB or JEB showed the oral manifestation of the disease. The most affected sites were the lips (54%), hard palate (36%), and oral mucosa (27%). Ulcer and ankyloglossia were diagnosed in all RDEB cases. Regarding salivary flow, an intragroup comparison revealed an increase in stimulated versus unstimulated collection in the control sample (p = 0.0064). The EB group showed no difference (p = 0.6086). We also observed no differences in salivary volume between the control and EB groups (p = 0.7117 and p = 0.5557, unstimulated and stimulated flows, respectively). CONCLUSIONS: No oral manifestations were observed in EBS subjects. It is unclear whether individuals with EB are predisposed to manifest hyposalivation. CLINICAL RELEVANCE: Severe cases of EB show broad alterations in the oral mucosa, whereas the saliva needs to be better evaluated.

Immunohistochemical Study of Laminin-332 γ2 Chain and MMP-9 in High Risk of Malignant Transformation Oral Lesions and OSCC.

OBJECTIVES: Oral squamous cell carcinoma is associated with alterations in basement membrane. Laminin-332 is present in basal lamina and performs multiple biologic effects by γ2 chain. Matrix metalloproteinase acts disrupting extracellular components and was related to poor prognosis in cancer. Here, molecular profile of laminin-332 γ2 chain and matrix metalloproteinase-9 was assessed in oral lesions. MATERIAL AND METHODS: The expression of laminin-332 γ2 chain and matrix metalloproteinase-9 (MMP-9) was examined by immunohistochemistry in 10 patients with high risk of malignant transformation oral lesions and 26 cases of oral squamous cell carcinoma (OSCC). Associations between microscopic and clinicopathologic features were established. RESULTS: Immunostaining of laminin-332 γ2 chain in high risk oral lesions was most detected in basement membrane which is continuous, while the majority of OSCC cases showed a discontinuous membrane (P = 0.001). It was observed a positive reaction for γ2 chain in invasive fronts and a higher expression in epithelial compartment of smoking patients with OSCC (P < 0.0001). In epithelium, MMP-9 expression was presented in all layers with no difference between lesions. However, an elevated immunostaining in stromal cells was associated with male patients (P = 0.0054), older than 60 years (P = 0.0101) and with OSCC. CONCLUSIONS: Present study results support the hypothesis of changes in molecules expression in high risk oral lesions and oral squamous cell carcinoma. A relation between clinical and molecule profile was observed. Those molecules may represent a useful tool to predict oral cancer behaviour.

Fibrosis and Mast Cells in Colorectal Lesions: Significance in Adenoma-Colorectal Cancer Sequence and Association with Diet.

PURPOSE: Adenoma is the most common benign neoplasm with potential to progress into colorectal cancer (CRC), a disease responsible for high rates of mortality. However, it is not possible yet to establish which lesions will evolve into CRC. We aimed to investigate the intrinsic factors, diet profile, and microenvironment as factors involved in adenoma-CRC progression. METHODS: We evaluated nutritional profile and microscopic features. Adenomas and CRC lesions were stained with Mallory's trichrome to reveal fibrosis and Alcian blue to identify mast cells. RESULTS: A total of 143 patients was selected, 66 % diagnosed with normal mucosa, 28.4 % with benign lesion, and 5.6 % with CRC. A higher frequency of lesions was associated with patients older than 50 years (26.57 %) and women (18.18 %), but men were more likely to develop CRC. Regarding microscopic aspects, epithelium-connective tissue interface with disorganization feature was significantly higher in CRC when compared to adenoma (P = 0.0007). A greater fibrosis around vessels was also observed in CRC (P = 0.01). The statistical analysis indicated a significant correlation between mast cell population and patients older than 50 years (P < 0.01), male (P < 0.01), with right colon lesion (P < 0.05) and CRC. Low consumption of leafy greens (P < 0.001) and carotenoids (P < 0.01) and elevated consumption of red meat (P < 0.001) were associated with a high density of mast cells. CONCLUSIONS: An association between clinical, diet profile, and microscopic features in colorectal lesions was observed, with a progressive change in the microenvironment during adenoma-CRC sequence.

Oral lichen planus: clinical profile and determination of oral epithelial dysplasia / Liquen plano oral: perfil clínico y determinación de la displasia epitelial oral

Oral lichen planus (OLP) is the most common noninfectious oral disease and is considered a potentially malignant disorders (OPMDs). The etiology and pathogenesis of OLP are not completely understood and the malignant transformation remains under discussion. The aim was to asses the cytological and histological features of OLP, and establish relationship between clinical and microscopic profiles. A total of 10 patients diagnosed with OLP were investigated. Slides were prepared and stained with Hematoxylin­Eosin to identify 8 histological features and 8 cytological alterations. Finally, oral epithelial dysplasia degree was determined. Hyperplasia and loss of polarity of basal cells were detected in 90 % of cases. Anisonucleosis, nuclear pleomorphism and hyperchromasia affected 100 % of the sample. Six cases were classified as mild-grade OED, with no cases of severe-grade. Microscopic alterations were higher in women (P <0.0001) and moderate-grade OED was diagnosed only in this group (P <0.0014). The findings demonstrated that microscopic and clinical data association should be analyzed to a better understand of disease behavior. OED was absence only in one case, so the periodic follow-up of patients diagnosed with OLP is mandatory to avoid the malignant transformation.

El liquen plano oral (LPO) es la enfermedad no infecciosa más común y se considera un trastorno potencialmente maligno. La etiología y la patogénesis del LPO no se conoce y la transformación maligna sigue siendo objeto de debate. El objetivo de este estudio fue evaluar las características citológicas e histológicas del LPO y establecer la relación entre los perfiles clínicos y microscópicos. Un total de 10 pacientes diagnosticados con LPO fueron investigados. Secciones histológicas se prepararon y tiñeron con hematoxilina-eosina para identificar 8 características histológicas y 8 alteraciones citológicas. Finalmente, se determinó el grado de displasia epitelial. La hiperplasia y la pérdida de la polaridad de las células basales se detectaron en el 90 % de los casos. Anisonucleosis, pleomorfismo nuclear e hipercromasia afectaron al 100 % de las muestras. Seis casos fueron clasificados como displasia epitelial oral (DEO) de grado leve y no se reportaron casos de grado severo. Las alteraciones microscópicas fueron mayores en las mujeres (p <0,0001) y DEO de grado moderado fue diagnosticado sólo en este grupo (p <0,0014). Los resultados demostraron que la asociación de datos microscópicos y clínicos deben ser analizados para una mejor comprensión del comportamiento de la enfermedad. La DEO estuvo ausente sólo en un caso, por lo que el seguimiento periódico de los pacientes diagnosticados con LPO es necesario para evitar la transformación maligna.