Embryonal tumors with abundant neuropil and true rosettes: a distinctive CNS primitive neuroectodermal tumor

Abstract

Embryonal neoplasms of the central nervous system (CNS) generally arise in the early years of life and behave in a clinically aggressive manner, but vary somewhat in their microscopic appearance. Several groups have reported examples of an embryonal tumor with combined histologic features of ependymoblastoma and neuroblastoma, a lesion referred to as "embryonal tumor with abundant neuropil and true rosettes" (ETANTR). Herein, we present 22 new cases, and additional clinical follow-up on our 7 initially reported cases, to better define the histologic features and clinical behavior of this distinctive neoplasm. It affects infants and arises most often in cerebral cortex, the cerebellum and brainstem being less frequent sites. Unlike other embryonal tumors of the CNS, girls are more commonly affected than boys. On neuroimaging, the tumors appear as large, demarcated, solid masses featuring patchy or no contrast enhancement. Five of our cases (18%) were at least partly cystic. Distinctive microscopic features include a prominent background of mature neuropil punctuated by true rosettes formed of pseudo-stratified embryonal cells circumferentially disposed about a central lumen (true rosettes). Of the 25 cases with available follow-up, 19 patients have died, their median survival being 9 months. Performed on 2 cases, cytogenetic analysis revealed extra copies of chromosome 2 in both. We believe that the ETANTR represents a histologically distinctive form of CNS embryonal tumor.

FIGURE 1

Neuroradiologic features of ETANTR: the MRI of case 19 showed a well-demarcated T2 hyperintense right frontal lesion (A). The proton nuclear magnetic resonance spectroscopy revealed a choline peak (Cho) and a high ratio of Cho/NAA suggesting a highly cellular tumor (B). Case 20 had a well-demarcated T2 hyperintense (C) and T1 hypointense lesion (D) in the pons. Case 29 showed a T2 hyperintense thalamic lesion (E) with no contrast enhancement (F). ETANTR indicates embryonal tumor with abundant neuropil and true rosettes; MRI, magnetic resonance imaging; NAA, N-acetyl aspartate.

FIGURE 2

Histopathologic features of ETANTR: at high magnification, the hypercellular areas were composed by small hyperchromatic cells with round to oval nuclei and indistinct cell borders (A–B). Ependymoblastic rosettes, the distinctive feature of this tumor, were easily identifiable (C–D). In case 9, the tumor was composed of large elements with pleomorphic nuclei among which distinctive ependymoblastic rosettes were evident (E). The relapsing tumor of case 19 was also composed of large “anaplastic” elements with pleomorphic nuclei, but lacking rosettes (F). ETANTR indicates embryonal tumor with abundant neuropil and true rosettes.

FIGURE 3

Immunohistochemical features of ETANTR: the neoplastic cells, composing the rosettes showed a high proliferation index and scattered mitotic figures (A). The neuropil-like matrix was intensely stained for neurofilaments (B). In case 22, the tumor showed also an unusual sarcomatous-like area composed by elongated spindle-like cells (C), positive for smooth muscle actin (D). ETANTR indicates embryonal tumor with abundant neuropil and true rosettes.