Stromal cells in hemangioblastoma: Neuroectodermal differentiation and morphological similarities to ependymoma

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The histogenesis of stromal cells in hemangioblastoma is inconclusive despite a long-term controversy. An immunohistochemical and ultrastructural study was conducted for 17 cases of cerebellar hemangioblastoma. A wide range of immunohistological markers, targeting epithelial, mesenchymal, endothelial and neuroectodermal tissues, was used. In all cases, the microscopic hallmark characterizing hemangioblastomas, that is, lipid-containing stromal cells and a fine capillary network, known as a reticular variant, was noted. Stromal cells showed a variable immunoreactivity for neuroectodermal markers, such as S-100 protein, CD56, CD57, CD99, and neuron-specific enolase. This result, in conjunction with the absence of immunoreactivity for epithelial, mesenchymal, and endothelial markers, likely suggests neuroectodermal differentiation of stromal cells. In three cases, another component, known as a cellular variant, where epithelioid tumor cells were arranged in nests encircled by capillaries and/or in pseudorosette-like structures, was noted. Glial fibrillary acidic protein-immunoreactivity, which was totally absent in cases only showing the reticular pattern, was noted in two of them, suggesting a distinctive sign of glial differentiation in a proportion of hemangioblastomas. Ultrastructurally, microvilli-like projections in intracytoplasmic vacuoles were demonstrated in stromal cells. This result, taken together with the neuroectodermal hypothesis of stromal cells, suggests that hemangioblastomas may occasionally exhibit morphological similarities to ependymomas.

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