Tumor necrosis in paragangliomas is associated with a higher rate of metastasis, larger tumor volume, and increased cardiovascular risk, while cystic alterations alone do not affect clinical presentation.
Cystic alterations were highly prevalent in paragangliomas but did not affect clinical presentation regardless of their pathomorphological subtype.
Necrotic alterations in paragangliomas were associated with a significantly higher rate of metastasis compared to non-cystic/non-necrotic tumors.
Necrotic paragangliomas were associated with significantly larger tumor volume than non-cystic/non-necrotic lesions.
Necrotic paragangliomas were associated with more pronounced clinical signs and symptoms compared to tumors without cystic or necrotic lesions.
Necrotic paragangliomas were significantly more frequently associated with cardiovascular complications than cystic paragangliomas in the meta-analysis.
The prevalence of both cystic and necrotic lesions was higher in adrenal paragangliomas (pheochromocytomas) than in extra-adrenal paragangliomas.
This research suggests that paragangliomas — rare tumors arising from nerve tissue that can occur near the adrenal glands or elsewhere in the body — frequently develop internal structural changes, including cyst-like (fluid-filled) spaces and areas of tissue death (necrosis). In a study of 103 patients treated over a decade at a single center, over 60% of these tumors showed some form of cystic change, but these cystic changes did not appear to make patients sicker or change how the disease behaved. By contrast, tumors with true necrosis (dead tissue) were far more dangerous: three-quarters of patients with necrotic tumors had metastatic (spreading) disease, compared to only 10% of those without these changes, and the necrotic tumors were also much larger on average. A broader analysis combining data from 235 patients confirmed these findings: necrotic paragangliomas were significantly more likely to spread to other parts of the body and were strongly linked to cardiovascular complications such as heart problems, compared to tumors with only cystic changes. These cardiovascular risks were dramatically more common in the necrotic group (statistically significant at p < 0.0001). This research suggests that identifying necrosis in a paraganglioma — whether through imaging before surgery or pathology examination afterward — could be an important warning sign for clinicians. Patients whose tumors show necrotic changes may need closer monitoring for cancer spread and more careful management of heart and blood pressure risks. Incorporating assessment of necrosis into routine evaluation and follow-up plans for paraganglioma patients could help tailor care to those at highest risk.
Wiejak A, Constantinescu G, Zygiene G, Robledo M, Ziegler C, Kühn J, et al.. (2026). 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.. Endocrine pathology. https://doi.org/10.1007/s12022-026-09931-1