Tumor Necrosis is Associated with an Increased Metastatic and Cardiovascular Risk in Paragangliomas: A Single-Center Series and Meta-Analysis Comparing Necrosis and Cystic Degeneration in Paragangliomas

Paragangliomas (PGLs) are rare neural crest-derived tumors with highly variable morphology and clinical behavior. These tumors can present with cystic and necrotic alterations that may influence the clinical presentation of affected patients. However, prevalence and clinical significance of these pathological alterations remain poorly understood. In this retrospective study (2011-2021), 103 patients with confirmed PGLs were examined for cystic and necrotic alterations based on imaging and pathology reports as well as pathological re-evaluation. Cystic alterations, including microscopic, macroscopic, and pseudocystic alterations, were observed in 61.8% of PGLs. Regardless of their pathomorphological presentation, cystic alterations did not affect the clinical presentation of these patients. In contrast, necrotic alterations were identified in 3.9% of PGLs and were associated with a higher rate of metastasis (75% vs. 10%, p = 0.0124), larger tumor volume (53.6 cm3 vs. 6.6 cm3p = 0.0339), and more pronounced signs and symptoms, including hypertension, palpitations, and weakness compared to patients without cystic/necrotic lesions. The prevalence of cystic and necrotic lesions was higher in adrenal than extra-adrenal PGLs. An additional meta-analysis of 235 patients with PGLs confirmed the increased rate of metastasis in necrotic PGLs (16% vs. 4.5%, p = 0.0369), which were also significantly more frequently associated with cardiovascular complications (p < 0.0001) than cystic PGLs. Considering pathological alterations, particularly necrotic lesions, may substantially affect the clinical management of patients with PGLs. Incorporating these features into preoperative management and follow-up strategies might be crucial, given the higher metastatic potential and increased cardiovascular risk associated with necrotic PGLs.