Small cell astrocytoma: An aggressive variant that is clinicopathologically and genetically distinct from anaplastic oligodendroglioma

BACKGROUND: Small cell glioblastoma (GBM) is a variant with monomorphous, deceptively bland nuclei that often is misdiagnosed as anaplastic oligodendroglioma. METHODS: To elucidate its clinicopathologic and genetic features, the authors studied 71 adult patients (median age, 57 years), including 22 patients who were identified from a set of 229 GBMs (10%) that had been characterized previously by epidermal growth factor receptor (EGFR)/EGFR-vIII variant immunohistochemistry. Tumors also were analyzed by fluorescence in situ hybridization for 1p, 19q, 10q, and EGFR copy numbers. RESULTS: Radiologically, 37% of tumors that were not selected for grade showed minimal to no enhancement. Similarly, 33% of tumors had no endothelial hyperplasia or necrosis histologically, qualifying only as anaplastic astrocytoma (Grade III) using World Health Organization criteria. Nevertheless, such tumors progressed rapidly, with mortality rates that were indistinguishable from their Grade IV counterparts. The median survival for 37 patients who were followed until death was 11 months. Oligodendroglioma-like histology included chicken-wire vasculature (86%), haloes (73%), perineuronal satellitosis (58%), and microcalcifications (45%), although mucin-filled microcystic spaces were lacking. No small cell astrocytomas had 1p/19q codeletions, whereas EGFR amplification and 10q deletions were present in 69% and 97% of small cell astrocytomas, respectively. The tumors expressed EGFR and EGFR-vIII more commonly than nonsmall cell GBMs (83% vs. 35% P < 0.001; 50% vs. 21% P < 0.001 respectively). CONCLUSIONS: Small cell astrocytoma is an aggressive histologic variant that behaved like primary GBM, even in the absence of endothelial hyperplasia and necrosis. Despite considerable morphologic overlap with anaplastic oligodendroglioma, clinicopathologic and genetic features were distinct. Fifty percent of small cell astrocytomas expressed the constitutively activated vIII mutant form of EGFR, and molecular testing for 10q deletion improved the diagnostic sensitivity over EGFR alone.