Anaplastic ependymoma (WHO grade III) with granular cell features.
Besides "true" granular cell tumors (GCT), that mainly occur in the sellar region, granular cell features can be identified occasionally in other CNS tumors, including gliomas, medulloblastomas schwannomas and meningiomas (1, 2). Classically, the granular cells in all these tumors are described as elements with medium-sized or large, eosinophilic, granular PAS-positive cytoplasms. They mostly show an eccentrically located nuclei, which may vary in size. In most cases, the granular feature of cytoplasm depends on accumulation of autophagolysosomes or residual bodies and it is mainly considered a degenerative phenomenon (1, 2).
Granular cell features among ependymomas are extremely rare. Although uncommon histotypes are not infrequent by ependymomas occurring in about 1% of cases, only few cases with granular cell features have been described to date (3). Two cases of cerebral ependymoma showing a granular cell component have been initially published only in abstract form by Yang. (4). Two additional cases have been reported recently (5). The first two cases reported by Yang (4) and the first case described by Shintaku (5) share some clinical and pathological aspects with our case (4, 5). All cases affected pediatric patients and two, as our case, were hemispheric (frontal lobe), while the third case was localized in the posterior fossa. In these three cases, the PAS positive, "granular cells" formed a well delimitated, easily recognizable area with a similar immunohistochemical profile (GFAP+, S100 protein+, CD68 +).
If the granular cell areas or the granular cell ependymomas have specific molecular features, it is yet to be determined. The only case studied cytogenetically presented a 49, XY (+2, +11, +12) karyotype but it is not clear whether these changes were specific for the granular cell component or for the whole tumor (5).
The clinical and prognostic significance of granular cell features in ependymomas are not only unknown but also difficult to be determined given the rarity of such cases. Only one of the published cases had a long-term follow up (4): this tumor showed aggressive clinical behavior despite the absence of anaplastic features. In our case, the ependymoma showed unequivocally anaplastic features in its non-granular component. After the histopathological diagnosis, our patient received radiotherapy (2x 1.0 Gy per day; up to 68 Gy in total), accompanied by chemotherapy with vincristin (1/week; 1.5 mg/m2).
Among gliomas, diffuse low- and high- grade astrocytomas are the most common tumors which can more frequently present granular cell features (1, 6). Whereas granular cell astrocytomas have been in the past considered a specific tumor variant characterized by an aggressive clinical behavior (6), they are currently not included in the revised WHO classification of brain tumors (7), because they are now retained to be only an unusual phenotypic variation rather than a specific astrocytoma subtype. (7).
In conclusion, granular cells represent a very unusual feature in ependymoma. In the future, the description of new cases or small case series with follow-up data may facilitate to elucidate its possible clinical significance in ependymal tumors.
Contributed by Marco Gessi, Gerrit H. Gielen, Raoul Hinze, Hans-Peter Vinz, Christian GŁttel and Torsten Pietsch