No abstract

We herein report an uncommon association of intimately admixed atypical carcinoid (AC) and large cell neuroendocrine (NE) carcinoma (LCNEC) of the thymus, occurring in two 20- and 39-year-old Caucasian males. Both tumors were treated by maximal thymectomy. The younger patient presented with a synchronous lesion and died of disease after 9 months, while the other patient was associated with a recurrent ectopic adrenocorticotropic hormone Cushing's syndrome and is alive with disease at the 2-year follow-up. MEN1 syndrome was excluded in either case. Immunohistochemically, disarrayed cytoplasmic and nuclear ß-catenin expression was seen alongside an intra-tumor Ki-67 antigen labeling index (LI) ranging from 2 to 80% in the younger patient's tumor and from 3 to 45% in the other. Both exhibited upregulated cyclin D1 and retinoblastoma, while vimentin was overexpressed in the recurrent LCNEC only. Next-generation sequencing revealed CTNNB1, TP53, and JAK3 mutations in the synchronous tumor and CTNNB1 mutation alone in the metachronous tumor (the latter with the same mutation as the first tumor of 17 years prior). None of the 23 T-NET controls exhibited this hallmarking triple alteration (p = 0.003). These findings suggested that LCNEC components developed from pre-existing CTNNB1-mutated AC upon loss-of-function TP53 and gain-of-function JAK3 mutations in one case and an epithelial-mesenchymal transition upon vimentin overexpression in the other case. Both tumors maintained intact cyclin D1-retinoblastoma machinery. Our report challenges the concept of secondary LCNEC as an entity that develops from pre-existing AC as a result of tumor progression, suggesting a paradigm shift to the current pathogenesis of NET.

Non-small-cell lung cancer is still considered a difficult disease to manage because of its aggressiveness and resistance to common therapies. Chemotherapy remains the gold standard in nearly 80% of lung cancers, but clinical outcomes are discouraging, and the impact on median overall survival (OS) barely reaches 12 months.At the end of the last century, the discovery of oncogene-driven tumours completely changed the therapeutic landscape in lung cancers, harbouring specific gene mutations/translocations. Epidermal growth factors receptor (EGFR) common mutations first and anaplastic lymphoma kinase (ALK) translocations later led new insights in lung cancer biology knowledge. The use of specific tyrosine kinases inhibitors overturned the biological behaviour of EGFR mutation positive tumours and became a preclinical model to understand the heterogeneity of lung cancers and the mechanisms of drug resistance. In this review, we summarise the employment of targeted agents against the most representative biomolecular alterations and provide some criticisms of the therapeutic strategies.

Aim: We investigated outcomes in patients with advanced non-small-cell lung cancer (NSCLC) and peritoneal involvement. Patients & methods: NSCLC patients with peritoneal carcinomatosis (PC) were included. We evaluated mOS1 (overall survival [OS] from NSCLC diagnosis) and mOS2 (OS from diagnosis of PC). Results: In total, 60 NSCLC patients were diagnosed with PC, 12 (20%) patients had a diagnosis of NSCLC and synchronous PC with a median OS of 9 months. Smokers had a shorter mOS1 and mOS2 compared with never-smokers; EGFR-mutated patients on tyrosine kinase inhibitors had longer mOS1 and mOS2 than EGFR wild-type patients. Conclusion: Metachronous PC is correlated to a short survival, irrespective of treatment line. Never-smokers and EGFR-mutated patients had improved mOS1 and mOS2 when compared with smokers and EGFR wild-type population.

SUNCT is a rare headache disorder, first described by Sjaastad et al. in 1989 (1) and recently codified by the International Classification of Headache Disorders as a primary headache (2). The literature, however, discloses some cases of secondary SUNCT syndrome, particularly due to lesions in the posterior fossa or involving the pituitary gland (3-10). The pharmacological treatment of this syndrome is problematic. Some encouraging results have been recently suggested with lamotrigine (11-15), gabapentin (16, 17) and topiramate (18, 19); all previous attempts at treatment with drugs used for other short-lasting headaches were unsuccessful (20). It is noteworthy that two reports (21, 22) even reported a worsening effect of verapamil in patients affected by SUNCT. We describe a patient with SUNCT syndrome and an ischaemic lesion in the posterior fossa, who was successfully treated with verapamil.