Peripheral hemangioblastoma: clinicopathologic characterization in a series of 22 cases.

Hemangioblastoma is a rare tumor of uncertain histotype that typically arises in the cerebellum, quite often in the setting of Von Hippel-Lindau syndrome (VHL). Exceptional cases of hemangioblastoma arising outside the central nervous system have been reported, but little is known about their clinicopathologic and immunohistochemical features. Twenty-two cases of hemangioblastoma arising at peripheral sites were identified in consultation files. Clinical, morphologic, and immunohistochemical features were evaluated. Outcome data were obtained from referring pathologists. Twelve patients were female and 10 male; the median age was 58 years (range, 27 to 79 y). All the tumors were solitary (except 1) and arose in spinal nerve roots (12), kidney (3), intestine (2), orbit (1), forearm (1), peritoneum (1), periadrenal soft tissue (1), and flank (1). Five patients had VHL; another 5 had lesions suggestive of VHL. One patient had tuberous sclerosis. The median tumor size was 4 cm (range, 1.3 to 15 cm). Most tumors were well circumscribed; 6 were poorly marginated-3 eroded the adjacent bone and 1 extended into the pleura. All tumors were composed of an admixed population of plump spindle cells and microvacuolated cells with palely eosinophilic or clear cytoplasm, which often mimicked lipoblasts or renal cell carcinoma. In 5 cases the microvacuolated cells were scant. Spindle cell nuclei were hyperchromatic or vesicular with inconspicuous nucleoli. Four tumors showed marked nuclear pleomorphism. Mitotic activity was low (range, 0 to 2/10 HPF). All tumors had a complex capillary network, with admixed larger thin-walled or thick-walled vessels in a solid and often lobular growth pattern, similar to central nervous system hemangioblastoma. In 9 cases the larger vessels showed a branching hemangiopericytoma-like pattern. No necrosis or lymphovascular invasion was identified. Tumor cells expressed inhibin in 95% (20/21), neuron-specific enolase in 79% (15/19), and S100 protein in 65% (13/20); they also expressed GLUT1 (7/10, mostly weak), SMA (4/5), epithelial membrane antigen (2/8, focal), PAX8 (1/10), and desmin (1/4). Brachyury was consistently negative (0/19), as were keratin, HMB-45, melan-A, and GFAP. CD31 and CD34 highlighted tumor vasculature. Follow-up information was available for 17 patients (range, 5 to 117 mo; median 36 mo). Three patients had locally persistent disease after incomplete resection. True local recurrence or distant metastasis has not been identified in any patient so far. One patient died of metastatic renal cell carcinoma. Peripheral hemangioblastoma is rare, often associated with VHL syndrome, and may mimic some malignant tumors. The immunohistochemical profile can aid diagnosis. Unresectable cases may be locally aggressive, but complete excision appears to be curative. Recognition of this tumor may identify patients in whom testing for VHL syndrome is warranted.