CNS neuroblastoma, FOXR2-activated

Central nervous system neuroblastoma, FOXR2-activated is a novel brain tumor entity recently included in the WHO brain tumor classification ¹.

Terminology

Central nervous system neuroblastoma with FOXR2 activation was identified in 2016 as a new molecular entity, distinguished from primitive neuroectodermal tumors of the central nervous system based on its specific genetic and histopathological alterations ².

It was included in the 5^th edition (2021) of the WHO brain tumor classification among the “other CNS embryonic tumors” ¹.

Epidemiology

Central nervous system neuroblastoma, FOXR2-activated is a rare tumor and occurs in young children (range 1-9.4 years old) ³.

Clinical presentation

Due to its rarity, not much clinical data are available although their presentation is presumably indistinguishable from other tumors in similar locations.

Pathology

Location

Central nervous system neuroblastoma, FOXR2-activated is a supratentorial tumor with seldom an interventricular localization ³.

Microscopic appearance

It usually demonstrates poorly differentiated cells with embryonic appearance, high nucleus: cytoplasm ratio, round-shaped nuclei, and sometimes brisk mitotic proliferation. It may show necrosis, high vascularity, endothelial proliferation, nuclear pleomorphism, and perivascular pseudorosettes ^1-3.

Immunochemistry

Synaptophysin and OLIG2 are often positive, whereas vimentin and GFAP are absent in most cases. The Ki-67 index is high ranging from 12%-50% ^1-3.

Molecular markers

Alterations of the FOXR2 locus on chromosome Xp11.21 and a specific methylation profile are characteristic of this tumor.

Radiographic features

Central nervous system neuroblastoma, FOXR2-activated appears as mixed cystic and solid supratentorial mass with sharp margins and necrosis ³. In some cases, leptomeningeal dissemination has been described ¹.

MRI

• T1/T2 sequences: heterogeneous signal with mild perilesional edema
• DWI: solid component may show moderate or high restriction of diffusivity
• T1 C+ (Gd): heterogeneous enhancement ³

Treatment and prognosis

Data about treatment and prognosis are still limited. 

Differential diagnosis

Differential diagnosis includes the other CNS embryonic tumors such as:

• atypical teratoid/rhabdoid tumor
• cribriform neuroepithelial tumor (provisional inclusion)
• embryonal tumor with multilayered rosettes (ETMR)
• CNS tumor with BCOR internal tandem duplication
• CNS embryonal tumor