Phd in ANGIO-CARDIO-THORACIC PATHOPHYSIOLOGY AND IMAGING

Thesis title: Neoplasie neuroendocrine polmonari resecate: analisi clinicopatologica, immunoistochimica e prognostica in una coorte monocentrica

Background: Pulmonary neuroendocrine neoplasms (NENs) encompass a wide histologic spectrum ranging from well-differentiated typical and atypical carcinoids to poorly differentiated large-cell (LCNEC) and small-cell carcinomas (SCLC). Surgical resection remains the mainstay of treatment in early-stage disease, but reliable prognostic markers are still needed. Methods: A retrospective study was conducted on 59 patients who underwent curative-intent pulmonary resection for NENs between 2007 and 2025. Demographic, surgical, histopathological, and immunohistochemical data (Ki-67, INSM1, RB1, p53, DLL3, PD-L1) were analyzed. Survival outcomes were assessed using Kaplan–Meier and Cox proportional hazards models according to the 9th TNM IASLC classification. Results: Median age was 68 years; 61% were males. Histologic distribution was: typical carcinoid 32%, atypical carcinoid 19%, LCNEC 29%, SCLC 17%, others 3%. Median Ki-67 was 45% (IQR 18–78). RB1 loss and p53 alteration were seen in 64% and 61% of NECs, respectively. At a median follow-up of 48 months, 27.9% developed recurrence and 33.9% died. Five-year overall survival (OS) and disease-free survival (DFS) were 59.8% and 55.1%, respectively. On multivariate Cox analysis, independent adverse prognostic factors for OS were histologic subtype (NEC vs carcinoid, HR 3.74, p=0.002), nodal involvement (HR 2.68, p=0.012), Ki-67 ≥50% (HR 2.51, p=0.019), and non-radical resection (HR 1.89, p=0.041). Conclusions: Pulmonary NENs resected surgically display wide biological heterogeneity. Histologic grade, nodal status, proliferative index, and RB1/p53 profile independently predict outcome. Ongoing molecular investigations, including NGS and PD-L1 assessment, may refine biological stratification and identify potential therapeutic targets in high-grade NECs.