Tumors of nasal cavity and paranasal sinuses (TuNSs) are rare and heterogeneous malignancies, presenting different histological features and clinical behavior. We reviewed the literature about etiology, biology, and clinical features of TuNSs to define pathologic features and possible treatment strategies. From a diagnostic point of view, it is mandatory to have high expertise and perform an immunohistochemical assessment to distinguish between different histotypes. Due to the extreme rarity of these neoplasms, there are no standard and evidence-based therapeutic strategies, lacking prospective and large clinical trials. In fact, most studies are retrospective analyses. Surgery represents the mainstay of treatment of TuNSs for small and localized tumors allowing complete tumor removal. Locally advanced lesions require more demolitive surgery that should be always followed by adjuvant radio- or chemo-radiotherapy. Recurrent/metastatic disease requires palliative chemo- and/or radiotherapy. Many studies emphasize the role of specific genes mutations in the development of TuNSs like mutations in the exons 4–9 of the TP53 gene, in the exon 9 of the PIK3CA gene and in the promoter of the TERT gene. In the near future, this genetic assessment will have new therapeutic implications. Future improvements in the understanding of the etiology, biology, and clinical features of TuNSs are warranted to improve their management.

Introduction. Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE and 90Y-DOTATOC showed efficacy in the metastatic setting of pheocromocytomas (PCCs) and paragangliomas (PGLs) where no standard therapies have been established. Background. A search of peer-reviewed and English articles reporting on 177Lu-DOTATATE and 90Y-DOTATOC efficacy was performed through Medline and Scopus. A subsequent meta-analysis was performed to evaluate the pooled effect size on disease control rate (DCR) with PRRT. Secondary endpoints were description of patients’ genetic characteristics, hematologic toxicity, and time-to-outcome. The pooled effect was estimated with both a mixed-effects model and a random-effects model. Results. Twelve studies met the criteria for this meta-analysis: ten with 177Lu- and two with 90Y-PRRTs (213 patients). The largest one included 46 patients. Median ages ranged from 32.5 to 60.4 years. When reported, mutations of SDHB were the most frequent genetic alterations. The pooled DCRs were 0.83 (95% CI: 0.75–0.88) and 0.76 (95% CI: 0.56–0.89) for 177Lu- and 90Y-PRRT, respectively. The pooled DCR for PRRT was 0.81 (95% CI: 0.74–0.87). Conclusions. We report an updated and solid estimate of DCR achieved with 177Lu- and 90Y-PRRT in PCCs and PGLs, showing that these therapies can be considered in the multidisciplinary treatment of PCCs and PGLs as alternatives to I-131 MIBG and chemotherapy.

Pheochromocytomas (PCCs) and Paragangliomas (PGLs), commonly known as PPGLs to include both entities, are rare neuroendocrine tumors that may arise in the context of hereditary syndromes or be sporadic. However, even among sporadic PPGLs, identifiable somatic alterations in at least one of the known susceptibility genes can be detected. Therefore, about 3/4 of all PPGL patients can be assigned to one of the three molecular clusters that have been identified in the last years with difference in the underlying pathogenetic mechanisms, biochemical phenotype, metastatic potential, and prognosis. While surgery represents the mainstay of treatment for localized PPGLs, several therapeutic options are available in advanced and/or metastatic setting. However, only few of them hinge upon prospective data and a cluster-oriented approach has not yet been established. In order to render management even more personalized and improve the prognosis of this molecularly complex disease, it is undoubtable that genetic testing for germline mutations as well as genome profiling for somatic mutations, where available, must be improved and become standard practice. This review summarizes the current evidence regarding diagnosis and treatment of PPGLs, supporting the need of a more cluster-specific approach in clinical practice.

Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) are rare diseases occurring in the gastrointestinal tract and pancreas. They are characterized by the loss of epithelial tubular gland elements, and by the increased expression of neuroendocrine markers. GEP-NENs are subdivided into two histo-pathological types, gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) and gastro-entero-pancreatic neuroendocrine carcinomas (GEP-NECs). According to WHO 2017 and 2019 classification criteria are graded and staged in four categories, NET-G1, NET-G2, NET-G3, and NEC-G3. The molecular characterization of these tumors can be fundamental for the identification of new diagnostic, prognostic and predictive biomarkers. The main purpose of this study was to analyze the expression of the paralogous 13 HOX genes, normally involved in embryogenic development and frequently deregulated in human cancers, and of the HOX regulating lncRNA HOTAIR in GEP-NENs. The expression of HOX genes is gradually lost in the transition from GEP NET G1 to NET/NEC G3 tumors, while HOTAIR expression, inversely correlated with HOX genes expression and weakly expressed in low-grade GEP NENs, becomes aberrant in NET G3 and NEC G3 categories. Our data highlights their potential role in the molecular stratification of GEP-NENs by suggesting new prognostic markers and potential therapeutic targets.

Nucleocytoplasmic transport has been found dysregulated in many types of cancer and is often described as a poor prognostic factor. Specifically, Exportin-1 (XPO1) has been found overexpressed in many tumors and has become an attractive target in molecular oncology and therapeutics development. The selective inhibitor of nuclear export, Selinexor, is one of the most scientifically interesting drugs that targets XPO1 in clinical development. In this review, we summarized the most relevant preclinical and clinical results achieved for non-solid tumors, sarcomas, and other kind of solid tumors.

Octreotide long-acting repeatable (LAR) is largely used to treat functional and/or metastatic neuroendocrine neoplasms (NENs). Its effect in controlling carcinoid syndrome and partially reduce tumour burden is attributable to the ability of octreotide to bind somatostatin receptors (SSTRs) on the tumour and metastasis, regulating growth hormone secretion and cell growth. Notably, SSTRs are also expressed, at different levels, on Tregs. Tregs, together with myeloid-derived suppressor cells (MDSCs), are key components in the anti-tumour immunoregulation. This is the first prospective study aimed to explore the impact of Octreotide (OCT) LAR on the immune system, with a particular focus on Tregs and MDSC cells. Here, we show that circulating Tregs are elevated in NENs patients compared to healthy donors and that treatment with OCT LAR significantly decrease the level of total Tregs and of the three functional Tregs populations: nTregs, eTregs and non-Tregs. Furthermore, OCT LAR treatment induces a functional impairment of the remaining circulating Tregs, significantly decreasing the expression of PD1, CTLA4 and ENTPD1. A trend in circulating MDSC cells is reported in patients treated with OCT LAR. The results reported here suggest that the effect of OCT LAR on Tregs could tip the balance of the patients’ immune-system towards a durable anti-tumour immunosurveillance with consequent long-term control of the NENs disease.