A tumor-specific cellular environment at the brain invasion border of adamantinomatous craniopharyngiomas

Abstract

Craniopharyngiomas (CP) are benign epithelial tumors of the sellar region and can be clinicopathologically distinguished into adamantinomatous (adaCP) and papillary (papCP) variants. Both subtypes are classified according to the World Health Organization grade I, but their irregular digitate brain infiltration makes any complete surgical resection difficult to obtain. Herein, we characterized the cellular interface between the tumor and the surrounding brain tissue in 48 CP (41 adaCP and seven papCP) compared to non-neuroepithelial tumors, i.e., 12 cavernous hemangiomas, 10 meningiomas, and 14 metastases using antibodies directed against glial fibrillary acid protein (GFAP), vimentin, nestin, microtubule-associated protein 2 (MAP2) splice variants, and tenascin-C. We identified a specific cell population characterized by the coexpression of nestin, MAP2, and GFAP within the invasion niche of the adamantinomatous subtype. This was especially prominent along the finger-like protrusions. A similar population of presumably astroglial precursors was not visible in other lesions under study, which characterize them as distinct histopathological feature of adaCP. Furthermore, the outer tumor cell layer of adaCP showed a distinct expression of MAP2, a novel finding helpful in the differential diagnosis of epithelial tumors in the sellar region. Our data support the hypothesis that adaCP, unlike other non-neuroepithelial tumors of the central nervous system, create a tumor-specific cellular environment at the tumor-brain junction. Whether this facilitates the characteristic infiltrative growth pattern or is the consequence of an activated Wnt signaling pathway, detectable in 90% of these tumors, will need further consideration.

Insights into the Infiltrative Behavior of Adamantinomatous Craniopharyngioma in a New Xenotransplant Mouse Model

“…All xenografts showed a typical bordering zone between tumor tissue and the surrounding brain. This area, marked by a distinct gliosis and appearance of undifferentiated neuroepithelial cells, was similar to that seen in human adaCP (8). Even the growth behavior was comparable between the primary tumor and the xenograft model.…”

Preclinical transgenic and patient‐derived xenograft models recapitulate the radiological features of human adamantinomatous craniopharyngioma

“…Unusually, nuclear-cytoplasmic localization of activated b-catenin is found in only a small proportion of tumor cells, either as small cell clusters, which broadly correlate with epithelial whorls, or otherwise dispersed in a minority of cells throughout the tumor (9,11). We have recently described the 3D structure of human ACP using high resolution micro-CT (m-CT) imaging (2), and corroborated the presence of clusters at the leading invasive edge of tissue invasion (8,26).…”

Surgical Strategies in Childhood Craniopharyngioma

“…Karavitaki et al (2005) found after a 10-year follow-up phase up to 40% of patients suffering from obesity. As known from histological specimen resected during surgery, the tumors show finger-like invasion into brain tissue (Burghaus et al, 2010). The surgical attempt to resect these parts will damage the adjacent brain tissue.…”