When rarity meets thoracic cancers: a narrative review from ITMIG 2024

Background and Objective: Rare thoracic cancers (RTCs) comprise a heterogeneous group of malignancies characterized by low incidence, high histological diversity, and significant clinical challenges. Their rarity often results in delayed diagnoses, lack of standardized therapeutic approaches, and limited prospective clinical trials. The absence of robust data is compounded by the fragmentation of expertise across institutions, underscoring the need for centralized, multidisciplinary management and international collaboration. This article aims to provide an overview of three representative RTC models, highlighting their unique clinical, pathological, and therapeutic features, and to discuss strategies for optimizing clinical care. Methods: A narrative review was conducted based on a targeted search of PubMed, MEDLINE, and major conference proceedings up to January 2025. The search focused on selected RTCs highlighted during the 2024 ITMIG annual meeting, using terms such as “SMARCA4-deficient undifferentiated tumors”, “thymic neuroendocrine neoplasms”, and “mediastinal germ cell tumors”. Eligible sources included case reports, retrospective series, and narrative reviews. Only English-language publications were considered. Key Content and Findings: We focus on SMARCA4-deficient undifferentiated tumors as examples of rare entities newly defined by molecular profiling; thymic neuroendocrine neoplasms as ultra-rare and biologically aggressive neoplasms; and mediastinal germ cell tumors, which share biological traits with their gonadal counterparts but exhibit unique clinical behaviors. Through these models, we highlight common themes in RTCs management, including diagnostic uncertainty, limited therapeutic options, and emerging directions. Conclusions: We discuss the strengths and limitations of current evidence and future perspectives aimed at enhancing outcomes through dedicated registries and tailored therapeutic strategies.