Over the last few years, a great advance has been made in the comprehension of the molecular pathogenesis underlying thyroid cancer progression, particularly for the papillary thyroid cancer (PTC), which represents the most common thyroid malignancy. Putative cancer driver mutations have been identified in more than 98% of PTC, and a new PTC classification into molecular subtypes has been proposed in order to resolve clinical uncertainties still present in the clinical management of patients. Additionally, the prognostic stratification systems have been profoundly modified over the last decade, with a view to refine patients’ staging and being able to choose a clinical approach tailored on single patient’s needs. Here, we will briefly discuss the recent changes in the clinical management of thyroid nodules, and review the current staging systems of thyroid cancer patients by analyzing promising clinicopathological features (i.e., gender, thyroid auto-immunity, multifocality, PTC histological variants, and vascular invasion) as well as new molecular markers (i.e., BRAF/TERT promoter mutations, miRNAs, and components of the plasminogen activating system) potentially capable of ameliorating the prognosis of PTC patients.

In 2010, the definition of cachexia was jointly developed by the European Society for Clinical Nutrition and Metabolism (ESPEN) Special Interest Groups (SIG) "Cachexia-anorexia in chronic wasting diseases" and "Nutrition in geriatrics". Cachexia was considered as a synonym of disease-related malnutrition (DRM) with inflammation by the ESPEN guidelines on definitions and terminology of clinical nutrition. Starting from these concepts and taking into account the available evidence the SIG "Cachexia-anorexia in chronic wasting diseases" conducted several meetings throughout 2020-2022 to discuss the similarities and differences between cachexia and DRM, the role of inflammation in DRM, and how it can be assessed. Moreover, in line with the Global Leadership Initiative on Malnutrition (GLIM) framework, in the future the SIG proposes to develop a prediction score to quantify the individual and combined effect(s) of multiple muscle and fat catabolic mechanisms, reduced food intake or assimilation and inflammation, which variably contribute to the cachectic/malnourished phenotype. This DRM/cachexia risk prediction score could consider the factors related to the direct mechanisms of muscle catabolism separately from those related to the reduction of nutrient intake and assimilation. Novel perspectives in the field of DRM with inflammation and cachexia were identified and described in the report.

Multiple primary malignant neoplasms are multiple tumors with different pathogenetic origin. They may be synchronous or metachronous. The management of these conditions represents an interesting clinical scenario. A crucial aspect is the decision regarding which tumor to treat initially, and how to schedule further treatments according to individual tumor risk. This process involves a multidisciplinary physician team to ensure favorable outcomes. We describe a case report of a female patient affected by primary synchronous tumors of the breast and pectoral skin, which raised a series of diagnostic, etiological and therapeutic issues persuading us to carry out a critical review of the literature.

The pathophysiology of cancer anorexia is complex and serum biomarkers, including growth and differentiation factor(s) (GDF), may be modulated. We explored the association(s) between GDF-15 serum levels and anorexia and, secondarily, with low muscle mass and body weight loss in cancer patients. We considered gastrointestinal and lung cancer patients (CP) and healthy BMI-matched controls. The FAACT-questionnaire was administered to diagnose anorexia and we calculated the L3-SMI by CT scan to assess low muscularity, setting their cutoff values at the lowest tertile. GDF-15 serum levels were assessed by ELISA. We enrolled 59 CP and 30 controls; among CP, 25 were affected by gastrointestinal and 34 by lung cancer. Anorexia was present in 36% of CP. Gastrointestinal CP resulted more anorexic compared to lung CP (p = 0.0067). Low muscle mass was present in 33.9% of CP and L3-SMI was lower in gastrointestinal compared to lung CP (p = 0.049). The GDF-15 levels were higher in CP vs. controls (p = 0.00016), as well as in anorexic vs. non-anorexic CP (p = 0.005) and vs. controls (p < 0.0001). Gastrointestinal CP showed higher GDF-15 levels vs. lung CP (p = 0.0004). No difference was found in GDF-15 between CP with low muscle mass and those with moderate/high muscularity and between patients with body weight loss and those with stable weight. Our data support the involvement of GDF-15 in the pathogenesis of cancer anorexia. The mechanisms of action of GDF-15 in cancer should be further clarified also regarding the changes in muscularity.

The new immunotherapy targeting the programmed cell death 1 (PD-1) receptor and its cognate ligand PD-L1 has renewed hopes of eradicating the most difficult human cancers to treat. Among these, there are the poorly differentiated and anaplastic thyroid cancers, unresponsive to all the therapies currently in use. In the present review we will summarize information regarding the expression of PD-L1 in the different thyroid cancer histotypes, its correlation with clinicopathological features, and its potential prognostic value. Then, we will evaluate the available data indicating the PD-1/PD-L1 axis as a promising target for thyroid cancer therapy.