Clear cells are associated with proliferative activity in ependymoma: a quantitative study

Abstract

Ependymomas comprise WHO Grade (G) II tumors (ependymomas) and WHO Grade III tumors (anaplastic ependymomas). Clear cell ependymoma, a subtype of ependymoma characterized by proliferation of clear cells, generally corresponds to WHO Grade III. On the other hand, clear cells are common in otherwise conventional ependymomas. This study aims to reveal the direct relationship between clear cells and proliferative activity in ependymomas. A total of 14 ependymomas with clear cells, comprising 6 WHO Grade II tumors and 8 Grade III tumors, were studied. The sections were stained with hematoxylin and eosin (H&E), and also immunostained with PHH3, a marker of mitosis, and MIB-1, an anti-Ki-67 antibody. Each case was assessed on H&E sections for necrosis and microvascular proliferation, and semi-quantified for clear cells in an increasing order as Grades I - III (clear cell grade). Mitoses were counted on H&E and PHH3-stained sections, under a light microscope, in 4 areas showing a high amount of mitosis. The MIB-1 index was manually determined on 4 images captured from the area showing the highest amount of Ki-67-positive nuclei. The results were as follows: 1) Necrosis or microvascular proliferation was present irrespective of the clear cell grade (amount of clear cells). 2) A higher amount of clear cells was associated with a higher proliferative activity. These results indicate that clear cells could be an independent prognostic factor other than necrosis, microvascular proliferation, or the WHO grade. It seems important to assess clear cells, apart from the concept of clear cell ependymoma, when diagnosing an ependymoma.