Paraneoplastic syndromes in ovarian cancer: Clinical manifestations, mechanisms and management challenges

Paraneoplastic syndromes encompass an enigmatic spectrum of clinical manifestations precipitated by various malignancies but not attributable to direct tumor invasion, metastatic dissemination, or hormone secretion from the affected organ. In ovarian cancer, a notably heterogeneous malignancy with a predilection for presentation at the advanced stage, paraneoplastic manifestations may arise from multiple organ systems, thereby complicating diagnosis, altering clinical trajectories, and exerting profound impact on both short- and long-term patient outcomes. These phenomena, observed across both epithelial and nonepithelial ovarian tumors, are often mediated through immune cross-reactivity, ectopic hormone secretion, or cytokine dysregulation. Notable manifestations include neurological syndromes, such as cerebellar degeneration, anti-N-methyl-D-aspartate receptor encephalitis, and metabolic disturbances like hypercalcemia, Cushing's syndrome, and thromboembolic states. Despite significant advancements, the diverse clinical presentations of paraneoplastic syndromes continue to pose substantial diagnostic ambiguities, with challenges in surgical planning and operative intricacies. This narrative review aims to elucidate an expansive analysis of the extant data on epidemiological patterns of ovarian cancer-associated paraneoplastic syndromes, their underlying molecular and immunological drivers, and management strategies. The review utilized extensive search across PubMed, EMBASE, Medline, Scopus, and Cochrane Library databases from January 2000 to March 2024. Inclusion criteria included peer-reviewed studies reporting ovarian cancer patients with clinically confirmed paraneoplastic syndromes, definite investigations, and clinical outcomes. Furthermore, it emphasizes the critical importance of multidisciplinary approaches to deliver holistic perioperative care, while addressing the systemic perturbations induced by paraneoplastic processes.