Primary and Metastatic Paraganglioma of the Cranial Vault

Introduction: Paragangliomas (PGs) are extra-adrenal neuroendocrine tumors that are extremely rare. Multiple lesions in the central nervous system raise suspicion of a metastatic process. Lack of consensus on their distinction and management warrants the categorization of existing literature to evaluate management options.

Methods: A systematic review of the literature on PG within the cranial vault was completed in accordance with PRISMA guidelines using the PubMed database. The management parameters and immunohistochemistry of all documented cases of primary and metastatic PG within the cranial vault were descriptively assessed, and the published cases' demographics, and respective treatment pathways quantitatively compared. This review was augmented by comparison with our center's case of a 48-year-old man diagnosed with metastatic PG originating in the cauda equina and seeding in the cerebellum ([Figs. 1] and [2]). Histological parameters within the literature was also investigated.

Results: The systematic review yielded 52 published papers. Also, 78% of primary PGs were within the sellar region, 21% in the cerebellum and the remaining in the supratentorial compartment. In contrast, 36% of PG metastases occurred in the cerebellum, 29% in the cerebral parenchyma and the remainder in the dura and sella.

In fifth-sixths of cases of surgically treated cerebral PG no adjuvant therapy was used. Recurrence within a year was seen in two-sixths of the cases. The majority of the primary cerebellar PG (n = 8) were bilateral and invading the cerebellopontine angle ([Fig. 3]). Adjuvant radiotherapy was used in three-eighths of cases and associated with the longest progression-free survival. No recurrence was observed in any of the cases.

The majority of cerebral metastases were in the temporal lobe. Dural metastases accounted for 13% of metastatic intracranial PGs. Overall, 53% of metastases were within the cerebellum (n = 8). Most metastatic cerebellar PGs were slow growing and had their primary source from the cauda equina. Longer progression-free survival was seen with cases that opted for adjunct radiotherapy. Three cases of sellar metastases were documented in the literature. The overall recurrence rate was 4 to 10%.

A total of 98% intracranial PGs noted zellballen architecture ([Fig. 4]). The chief cells in primary PG stained for chromogranin A, synaptophysin, and neurospecific enolase (NSE) 50% of the time. Sustentacular stain for S-100 tested positive in 50% of cases. Cerebellar metastatic chief cells stained positive for chromogranin A, synaptophysin, cytokeratin, NSE, and neurofilament protein (NFP) in 60, 60, 60, 40, and 20%, respectively. Sustentacular cells stained for S-100 40% of the time, with a K_i-67 labeling index of 8.8%. Chief cells in primary sellar PGs stained for chromogranin A, synaptophysin, NFP, NSE, and cytokeratin 96, 71, 21, 19, and 19% respectively. Sustentacular stain for S-100 and GFAP was 37.5 and 17% with a K_i-67 labeling index of 3.1%.

Conclusion: Metastatic PG is an insidiously silent condition. Patients should undergo regular neuroradiological surveillance of the complete neural axis to assess for early metastatic seeding to the intracranial cavity. Adjuvant radiotherapy with gross total resection resulted in the longest documented progression-free survival. Further prospective studies evaluating operative intervention ± radiation and chemotherapy for both primary and secondary disease is warranted to elucidate the optimal systemic management.

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Publication History

Article published online:
12 February 2021