An 11 Year Old Child with a Right Parieto‐Occipital Lesion

Clinical history

An 11 years old male patient suffered from a blunt head injury after tumbling in consequence of a short episode of vertigo and visual disturbances. Thereafter, the patient was not responsive to verbal stimuli for approximately 10 minutes and presented a retrograde amnesia. No aconuresis was observed. In the first clinical examination, the patient showed an anisocoria with a smaller pupil on the left side and only a partial light reaction. A prominent dysdiadochokinesia could be observed. EEG did not detect any epileptogenic foci but a focal wave slowing compatible with a right parieto‐occipital tumor or with an intracerebral bleeding. The consecutive MRI of the neuroaxis showed an intra‐axial lesion with solid parts and contrast enhancing, cystic areas (Fig. 1a), located in the right occipital lobe. Notably, the skull bone in the proximity of the lesion appeared thinned (Fig. 1a, arrow) but without any signs of infiltration. MRI imaging of the spine was without pathological findings. The family history was not suspicious for cancer predisposition syndromes. The lesion was surgically completely resected (Fig. 1a) and submitted to neuropathological examination (Fig. 1b). The postoperative course was uneventful.

Figure 1.

 

Histopathological findings

The histopathological examination revealed a highly cellular, glial tumor (Fig. 1c). The tumor presented perivascular architecture with evidence of perivascular pseudorosettes (Fig. 1c). The tumor cells mostly showed hyperchromic nuclei with rounded shaped contour and scant cytoplasm (Fig. 1c). Mitoses were evident. No areas of necrosis were observed. Focally, the tumor showed an area composed by cells with large, eosinophilic, granular, PAS positive cytoplasms (Fig. 1d and 1e). This area, which appeared well demarcated from the surrounding tumor tissue (Fig. 1f), presented a moderate cellularity and no marked nuclear polymorphism (Fig. 1d). No mitoses were present herein.

Both tumor components were GFAP positive (Fig. 1g) and showed a variable staining intensity with MAP2C. A dot‐like and ring‐like immunohistochemical staining pattern of EMA was focally present (Fig. 1h). Moreover, the tumor cells were negative for Olig‐2. Immunostainings with antibodies against p53, synaptophysin, CD34 and neurofilament protein resulted negative. The proliferation activity evaluated with Ki‐67 (MIB‐1) antibody was comprised between 20–25% in the highly cellular areas (Fig. 1ij), but only 2–3% in granular cell areas (Fig. 1j). What is your diagnosis?

Diagnosis

Anaplastic ependymoma (WHO grade III) with granular cell features.

Discussion

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 and only few cases with granular cell features have been described to date. 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 3. The first two cases reported by Yang 4 and the first case described by Shintaku 3 share some clinical and pathological aspects with our case. 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 3.

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 (2 × 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. Whereas granular cell astrocytomas have been in the past considered a specific tumor variant characterized by an aggressive clinical behavior, they are currently not included in the revised WHO classification of brain tumors, because they are now retained to be only an unusual phenotypic variation rather than a specific astrocytoma subtype. 1.

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