The Clinician's Role in Diagnostic Pathways and the Impact of Clinicopathological Collaboration on Outcomes in Patients with Neuroendocrine Neoplasms: Current Perspectives

Introduction: Neuroendocrine neoplasms (NENs) classification and diagnosis have substantially advanced, prompting specialization of pathologists and clinicians in NEN fields and fostering close interdisciplinary collaboration. In these rare diseases, misdiagnosis may undermine therapeutic strategies, highlighting the importance of a strong clinician-pathologist partnership. While the NEN-dedicated pathologist's role is well acknowledged, in clinical practice, accurate histological review depends on the clinician's ability to pose focused diagnostic questions within a well-defined clinical context. Methods: We retrospectively analyzed all NEN histological second opinions performed by a dedicated pathologist at our ENETS Center of Excellence in 01/2023-12/2024. Second opinions were requested by referring clinicians in cases of diagnostic uncertainty or clinical-pathological discordance. Discrepancies between initial and final diagnoses were categorized as "major" (with a substantial impact on patients' management), or "minor". Results: Of 63 reviewed cases, we identified 36 not concordant cases. Among them, we reported 29/36 (81%) cases with significant discrepancies between the initial and the final diagnosis, with a following change in therapeutic strategy in 28 (e.g., shift from surveillance to surgery or modification of systemic therapy). Clinical requests for a histological review were prompted by inconsistency between clinical history and pathological diagnosis, incomplete or incoherent initial pathology report, or need for diagnostic confirmation to support specific clinical indications (e.g., surgery or chemotherapy). Conclusion: Our findings underscore the critical role of clinician's expertise in the multidisciplinary management of NEN patients. Underestimating clinician's role in coordinating the diagnostic process can lead to suboptimal care. Additionally, there is an urgent need to redesign the NEN care pathway, ensuring early access to specialized evaluation since the early diagnostic phase.