Influence of epilepsy syndrome on cancer comorbidity.

The relationship between specific epilepsy syndromes and cancer is unclear. We aimed to analyze cancer frequency and its patterns in adults with Idiopathic Generalized Epilepsies (IGE) and Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (MTLE-HS). We retrospectively studied 719 adults (471 IGE; 248 MTLE-HS) followed at a tertiary epilepsy clinic (2016-2023). Data included demographics, epilepsy characteristics, antiseizure medications (ASM), and oncological history, excluding intracranial tumors. Cancer occurred in 4.9% of IGE and 12.9% of MTLE-HS patients (p < 0.001); however, this difference disappeared after age adjustment. Endocrine tumors predominated in IGE (p = 0.031), whereas hematologic malignancies, exclusively of the B-cell lineage, were more common in MTLE-HS (p = 0.033). Five patients (1 IGE; 4 MTLE-HS) developed skin squamous cell carcinoma after long-term sodium channel blocker therapy. Our findings reveal different, syndrome-specific associations between epilepsy and cancer types, likely reflecting a shared genetic susceptibility, with convergent dysregulated immune pathways potentially underlying these patterns. Understanding these relationships may offer insights into pathophysiology and guide the prevention of cancer comorbidities in these patients.