Hemangioblastoma-associated mast cells in von Hippel-Lindau disease are tumor derived

摘要

von Hippel-Lindau disease (VHL) is a tumor syndrome resulting from an inherited mutation in the VHL gene. The primary neoplastic manifestation in VHL are CNS hemangioblastomas1 that develop after loss of the second wild-type VHL allele (loss of heterozygosity [LOH]). Histologically, hemangioblastomas are composed of stromal cells, blood vessels, and mast cells.2,3 The VHL-deficient neoplastic stromal cell expresses markers reflective of pluripotent embryologic hemangioblasts.4 These cells can differentiate into tumor-derived endothelial and hematopoietic progeny in vitro.5 In vivo, tumor-derived extramedullary hematopoiesis results in VHL-deficient erythrocytes.6 Although the tumor origin of hemangioblastoma-associated stromal cells, reactive blood vessels, and intratumoral erythrocytes has been established, the origin of the abundant intratumoral mast cells is not known.