Histological predictors of outcome in ependymoma are dependent on anatomic site within the central nervous system

Abstract

Ependymomas originate in posterior fossa (PF), supratentorial (ST) or spinal cord (SC) compartments. At present, grading schemes are applied independent of anatomic site. We performed detailed histological examination on 238 World Health Organization grade II and III ependymomas. Among PF ependymomas, the presence of hypercellular areas, necrosis, microvascular proliferation and elevated mitotic rate (all P < 0.01) were significantly associated with worse progression-free survival (PFS), while extensive ependymal canal formation was not (P = 0.89). Similar to the PF tumors, microvascular proliferation (P = 0.01) and elevated mitotic rate (P = 0.03) were significantly associated with worse PFS in the ST tumors. However, in contrast to PF tumors, extensive ependymal canals (P = 0.03) were associated with worse clinical outcome in ST ependymomas, but hypercellularity (P = 0.57) and necrosis (P = 0.47) were not. On multivariate Cox regression, after adjusting for relevant clinical variables, individual histological factors and a composite histological score remained significant among ST and PF ependymoma. In contrast to both PF and ST ependymoma, histological features were not found to be associated with PFS in SC tumors. Taken together, the clinical relevance of specific histological features in ependymoma appears to be related to the anatomic site of origin and suggests that site-specific grading criteria be considered in future classification systems.

Keywords: ependymoma; histology; progression-free survival.

Figure 1

An illustration of selected histological features, including. A. Areas of low cellularity, B. areas of hypercellularity, C. mitoses, D. microvascular proliferation, E. extensive ependymal canals and F. tumor interface with the adjacent brain parenchyma.

Figure 2

Kaplan–Meier survival curves showing the effect of the extent of World Health Organization (WHO) grade III features on progression‐free survival among ependymomas arising from the three different compartments. Blue = WHO grade III features absent; Red = <50%; Green = >50%. Values based on univariate Cox regression analysis.

Figure 3

Kaplan–Meier survival curves showing the effects of the presence of hypercellularity and necrosis on progression‐free survival among ependymomas arising from posterior fossa, supratentorial and spinal cord compartments. Blue = absent; Red = present. P‐values based on univariate Cox regression analysis.

Figure 4

Kaplan–Meier survival curves showing the effects of the presence of microvascular proliferation (MVP) and mitotic rate (at a cut‐off value of ≥5 per 10 high‐power fields) on progression‐free survival among ependymomas arising from posterior fossa, supratentorial and spinal cord compartments. Blue = absent; Red = present. P‐values based on univariate Cox regression analysis.

Figure 5

Kaplan–Meier survival curves showing the effect of the extent of ependymal canals on progression‐free survival among ependymomas arising from the posterior fossa, supratentorial and spinal cord compartments. Blue = <25%; Red = >25%. P‐values based on univariate Cox regression analysis.

Figure 6

Kaplan–Meier analyses showed three distinct groups of ependymomas with significant differences in progression‐free survival when the histological score was combined with the gene expression‐derived metagene score. Ependymomas with favorable metagene scores and favorable histological scores (green) had significantly longer progression‐free survival vs. tumors with unfavorable metagene scores and unfavorable histological scores (red).