Edema is a precursor to central nervous system peritumoral cyst formation

Abstract

Despite the common occurrence and frequent clinical effects of peritumoral cysts in the central nervous system (CNS), the mechanism underlying their development and evolution is not understood. Because they commonly produce peritumoral cysts and because serial magnetic resonance imaging (MRI) is obtained in von Hippel-Lindau disease patients, hemangioblastomas provide an opportunity to examine the pathophysiology of CNS peritumoral cyst formation. Serial MRI was correlated with the clinical findings in 16 von Hippel-Lindau disease patients with 22 CNS hemangioblastomas (11 spinal cord; 11 cerebellar) that were associated with the appearance and evolution of peritumoral cysts. Hemangioblastoma-associated cyst wall histomorphological analysis was performed on postmortem tissues from three von Hippel-Lindau disease patients (not in the clinical series). Comparative proteomic profiling was performed on peritumoral cyst fluid and serum. Vascular endothelial growth factor levels were determined in peritumoral cysts. MRI clearly showed peritumoral edema that developed and slowly and progressively evolved into enlarging hemangioblastoma-associated cysts in all tumors (mean follow-up, 130 +/- 38 months; mean +/- standard deviation). Postcontrast MRI demonstrated convective leakage of gadolinium into cysts. Mean time required for edema to evolve into a cyst was 36 +/- 23 months (range, 8-72 months). Thirteen (59%) hemangioblastoma-cysts became symptomatic (mean time to symptom formation after cyst development, 35 +/- 32 months; range, 3-102 months) and required resection. Protein profiles of cyst fluid and serum were similar. Mean cyst fluid vascular endothelial growth factor concentration was 1.5 ng/ml (range, 0-5.4 ng/ml). Histology of the cyst walls was consistent with reactive gliosis. CNS peritumoral cyst formation is initiated by increased tumor vascular permeability, increased interstitial pressure in the tumor, and plasma extravasation with convective distribution into the surrounding tissue. When the delivery of plasma from the tumor exceeds the capacity of the surrounding tissue to absorb the extravasated fluid, edema (with its associated increased interstitial pressure) and subsequent cyst formation occur.

Solid Cerebellar Hemangioblastoma with Peritumoral Edema: 5-Years Follow up

“…As the plasma ultrafiltrate enters the interstitial space of the tumor, interstitial pressure increases and plasma extravasates with convective distribution into the surrounding tissue. If the delivery of plasma from the tumor exceeds the capacity to absorb the extravasated fluid of the surrounding tissue, edema and subsequent cyst formation occur (2). However, this case showed a solid HB with peritumoral edema and aggravated edema at the 5-year follow up.…”

Surgical management of cerebellar hemangioblastomas in patients with von Hippel–Lindau disease

“…35,36,39 These studies conclude that the mechanisms of formation differ for intratumoral and peritumoral cysts. Whereas intratumoral cyst formation occurs primarily by intratumoral necrosis, peritumoral cysts develop as a result of a tumor interstitial process that begins with generation of edema.…”

“…37,66 It has been found that VHL-associated hemangioblastomas are frequently associated with peritumoral edema and/or cysts. 39,40,66 Tumor progression, expanding peritumoral edema, and cyst formation/propagation underlie the clinical signs and symptoms associated with CNS hemangioblastoma. Patients with VHL disease who have CNS hemangioblastomas typically develop symptoms early in life (mean age at presentation 33 years).…”

“…Once extravasation of fluid from the tumor overcomes the capacity of the surrounding tissue to resorb the excess fluid, edema and subsequent cyst formation occur. 39 Tumor-Related Effects on Symptom Formation. Larger tumors were associated with signs and symptoms, and tumors that caused symptoms were significantly larger than those that did not (Fig.…”

Terminal syringomyelia mimicing intramedullary tumor: case report

“…Although concomitant hindbrain malformation exists with syringomyelia in the majority of cases (5), terminal syringomyelia in the lower third of the spinal cord is more commonly seen with spinal dysraphism, especially tethered cord (6,7). Syringomyelia also rarely develops in association with primary spinal intramedullary tumors (11,17) or intradural metastases (9). The pathogenesis, natural history and management of terminal syringomyelia remain controversial (18).…”