Search

The distinction between follicular adenomas (FAs) and well differentiated follicular and papillary carcinomas is often a demanding task and sometimes only intuitive.We report an histomorphological evaluation of follicular neoplasms [FAs, follicular carcinomas (FCs), and follicular variant of papillary carcinomas (FVPTCs)], supported by a qualitative and quantitative image analysis and by a molecular characterization.Tumor fibrosis and haemorrhage, neoplastic capsule thickness, follicle diameter, number of neoplastic cells, nuclear diameter of neoplastic cells, vessels density, vessels area and intratumoral distribution were evaluated. Ras and BRAF mutations, RET/PTC1, RET/PTC3, and PAX8/PPARγ rearrangements were analyzed. Correlations with clinico-pathological features have been studied.We found that FAs had a more extensive intratumoral haemorrhage, while malignant neoplasms were characterized by an evident fibrosis, higher cellularity and larger size. FVPTCs had higher nuclear diameter; cells count was higher in the minimally invasive follicular thyroid carcinomas, as well as a thickener neoplastic capsule. The CD34 stain showed a higher microvessel density in the FVPTCs group. A higher peripheral vessels distribution was observed only in malignant neoplasms. We observed overall Ras mutations in 2.4% of adenomas, in 41.5% of FVPTCs, and in 44.8% of FCs. It is outstanding that there is a marked difference in the Ras mutation distribution between the benign and malignant tumors in our series.We found that genotyping of Ras gene family together with an accurate analysis of selected morphological features could help in the differential diagnosis of follicular-derived thyroid neoplasms.

Emerging evidence indicates that interactions between chemokine receptors and their ligands may have a critical role in several steps of tumor development, including tumor growth, progression, and metastasis. In this report, we retrospectively evaluated CXCR4 expression in a consecutive series of 200 papillary thyroid carcinomas. We investigated the relationship between the clinicopathological features of the tumors and mutations in the BRAF gene to verify whether overexpression of CXCR4 is linked to more aggressive behavior in thyroid tumors. CXCR4 protein expression was evaluated by immunohistochemical staining. A final staining score was calculated by adding the score representing the percentage of positive cells to the intensity score. The CXCR4 expression of each papillary thyroid carcinoma sample was normalized by calculating the z score for each final staining score. Univariate analysis was used to correlate CXCR4 expression with the papillary thyroid carcinoma variant, the degree of neoplastic infiltration, the American Joint Commission on Cancer stage, the presence of lymphocytic thyroiditis and the mutation status of the BRAF gene. Multiple regression analysis confirmed a strong association between CXCR4, BRAF mutation and the degree of neoplastic infiltration. These data clearly indicate that the chemokine receptor expression induced by oncogenic activation could be the major determinant of the local aggressiveness of neoplastic cells. In conclusion, our data indicate that CXCR4 expression and BRAF mutation status could cooperatively induce and promote a more aggressive phenotype in papillary thyroid carcinoma through several pathways and specifically increase the tumors' spread outside of the thyroid gland.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a recently identified death factor that acts as a potent apoptosis inducer in ameloblastomas.The expression of TRAIL and its receptors (TRAIL-R), and the location of apoptotic cells were evaluated in 15 cases of ameloblastoma using immunohistochemistry and an in situ DNA nick-end labeling method. The proliferative activity of ameloblastomas was analyzed by determining the Ki-67 labeling index.TRAIL and TRAIL-R were diffusely expressed in ameloblastomas, without clear correlation with the location of apoptotic cells. Apoptosis and proliferation were opposite in the peripheral and central components of the ameloblastomas. In some ameloblastoma variants, apoptosis and proliferation seemed to modify in the same direction.TRAIL and its receptors might be involved in neoplastic transformation of odontogenic epithelium and might suggest some intrinsic regulation of neoplastic cell proliferation and death in ameloblastomas, thus explaining their slow growth and inability to metastasize.

Skin manifestations of tuberculous infection (Mycobacterium tuberculosis) are represented by miliary tuberculosis of the skin, tuberculous chancre, scrofuloderma, tuberculosis verrucosa cutis, periorificial tuberculosis, and lupus vulgaris (LV). Among this group, LV is the most common skin condition, diagnosed in 10% of tuberculotic patients. The authors report herein a case of squamous cell carcinoma (SCC) arising from long-standing (50-year) LV and underline the need of an extensive follow-up of tuberculotic lesions.