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Thyroid nodules are very common, and their frequency is four to five times higher in women than in men. Most of them are benign, with only a very little percentage revealing a malignant neoplasm. About 50% of thyroid nodules are detected by self-palpation of neck, whereas the other 50% are diagnosed by neck ultrasonography and following fine-needle aspiration. Management of thyroid nodules is very difficult, because benign nodules are prevalent, whereas thyroid carcinoma is uncommon, representing only 1% of all malignancies. A standard diagnostic approach is represented by 'first-level' exams, consisting in neck ultrasonography and serum thyroid-stimulating hormone measurement, followed, only for nodules that are suspicious of malignancy, by 'second-level' exams, consisting of fine-needle aspiration and mutational test, which does detect particular DNA mutations present only in malignant cells. In this review, we will analyze the genetics of thyroid cancer and its heterogeneity, and we will briefly describe the current available diagnostic and therapeutic approaches.

Oral cavity mucosal melanomas (OCMM) represent only 3% of all malignant melanomas. Surgery is the mainstay of treatments and it is often followed by adjuvant radiotherapy. The role of adjuvant immunotherapy and/or chemotherapy is still debated and to date neither treatment is routinely used. From January 1990 to January 2010, we have collected from our database data of 20 patients with a histologically proven diagnosis of OCMM. Upfront surgery, followed by adjuvant radiotherapy was performed in 16/20 (80%) patients. Immunohistochemical analysis was carried out on all tissue samples and the following markers were assessed: Ki-67, HMG-45, Melan-A, S-100, CD31, CD35, CD20, CD21, and CD3. Although Ki-67, HMG-45, Melan-A, and S-100 were assessed in tumor cells, the analysis of CD31, CD21, CD20, CD3, and CD35 was carried out on the tumor-infiltrating lymphocytes. Patient outcome was analyzed and associated with clinical and Immunohistochemical tumor characteristics. The median overall survival (OS) was 12 months, with a 2-year OS rate of 30%. The median progression-free survival (PFS) was 9 months, with a 2-year PFS rate of 25%. Grade of lymphocyte infiltration (CD20 and CD3 expression) correlated strongly with prognosis. Interestingly, overexpression of CD21 along with downregulation of CD31 was significantly associated with better OS and PFS, whereas the reversal features correlated with a poor prognosis. Our report shows that patients affected by OCMM have a poor prognosis despite the administration of multimodal treatments. Moreover, our analysis suggests that the evaluation of several biomarkers, especially in tumor-infiltrating lymphocytes, may identify categories of patients with distinct immune response against the tumor and possibly different treatment response and prognosis.

The Comprehensive Geriatric Assessment (CGA) represents the future of the geriatric oncology to reduce toxicities and treatment-related hospitalization in the elderly. Most patients receiving docetaxel for metastatic castration-resistant prostate cancer are in their seventies or older. We explored the efficacy of the CGA in predicting chemotherapy feasibility and response to docetaxel in a cohort of 24 patients aged at least 70. This was an observational, prospective study involving 24 patients who were 70 years of age or older and about to start chemotherapy with docetaxel for metastatic castration-resistant prostate cancer; we performed a CGA including five domains and divided our patients into 'healthy' and 'frail'; the relations between general condition and (i) early chemotherapy discontinuation and (ii) response to docetaxel were explored. We found a statistically significant relationship between frailty assessed by CGA and early docetaxel discontinuation; we also found an association between frailty and response to chemotherapy, but this did not reach statistical significance. A geriatric assessment before starting chemotherapy may help clinicians to recognize frail patients, and hence to reduce toxicities and early treatment discontinuation. Further analyses are required to simplify the CGA tools and to facilitate its incorporation into routine clinical practice.

Oncogenic viruses may have a significant impact on the therapeutic management of several malignancies besides their well-known role in tumor pathogenesis. Epstein-Barr virus (EBV) induces neoplastic transformation of epithelial cells of the nasopharynx by various molecular mechanisms mostly involving activation of oncogenes and inactivation of tumor-suppressor genes. EBV infection can also induce the expression of several immunogenic peptides on the plasma membrane of the infected cells. Importantly, these virus-related antigens may be used as targets for antitumor immunotherapy-based treatment strategies. Two different immunotherapy strategies, namely adoptive and active immunotherapy, have been developed and strongly improved in the recent years. Furthermore, EBV infection may influence the use of targeted therapies for nasopharyngeal carcinoma (NPC) considering that the presence of EBV can induce important modifications in cell signaling. As an example, latent membrane protein type 1 is a viral transmembrane protein mainly involved in the cancerogenesis process, which can also mediate overexpression of the epidermal growth factor receptor (EGFR) in NPC cells, rendering them more sensitive to anti-EGFR therapy. Finally, EBV may induce epigenetic changes in the infected cells, such as DNA hypermethylation and histone deacetylation, that can sustain tumor growth and can thus be considered potential targets for novel therapies. In conclusion, EBV infection can modify important biological features of NPC cells, rendering them more vulnerable to both immunotherapy and targeted therapy.