Contributed by Aravind Sekar, MD, Kirti Gupta, MD, Ashish Aggarwal, DNB, M Ch, Pravin Salunke MS, MCh
FINAL DIAGNOSIS
Anaplastic ependymoma (WHO Grade III) with neuropil-like islands.
DISCUSSION
Neuronal differentiation in ependymoma, especially in form of these distinct neuropil-like islands, is extremely rare and finds its mention in the literature in only three case reports to date [1-3]. It was first characterised by Gessi et al in 2005 and was thought to induct the tumor in the category of mixed glio-neuronal tumor [2]. Subsequently, it was better defined in a paper by Rodriguez and colleagues who identified such differentiation at histology, by immunohistochemistry alone or at ultrastructural level in their ependymoma cohort [3]. Their findings suggested this differentiation to be an unusual feature both at histology and immunohistochemical level and ultrastructural features were defined to be the most reliable criterion for its presence. Such a differentiation occurring in a pure glial tumor supported the speculations of its origin from cancer stem cells which were substantiated in landmark paper by Taylor et al [4]. These synaptophysin/MAP-2 positive neuropil islands bordered by tumor cells are a potential diagnostic pitfall as it morphologically mimics pseudo-palisading necrosis of high-grade gliomas, at low magnification. Another differential diagnostic possibility at this location is a ganglioglioma, which is characterized by biphasic histology with presence of dysmorphic ganglion cells. Immunohistochemistry is of special value, as it readily resolves the differentials. Characteristic dot-like positivity for EMA and perivascular accentuation for GFAP are key features of ependymoma.
Neuronal differentiation in ependymoma has so far been observed in supratentorial examples while the index case is in infratentorial location. Given the rarity, the clinical behaviour and prognostic impact of such histologic feature is difficult to predict, however the earlier examples had similar association with anaplastic features as seen in the index case. Hence a close and extended follow-up is advised. Interestingly, the tumor recurrences were devoid of such neuropil -like islands.
More recently, with molecular stratification of supratentorial and infratentorial ependymomas, the genetic landscape of these unusual morphological feature observed in anaplastic ependymoma should be explored. These are likely to be enriched /upregulated for genes associated with neuronal differention. In conclusion, neuronal differentiation is a very rare and an elusive feature; awareness about its occurrence is critical to avoid misdiagnosis. The description of these features in a small case series with follow up data will elucidate its clinical significance in ependymal tumors.
REFERENCES
Contributed by Aravind Sekar, MD, Kirti Gupta, MD, Ashish Aggarwal, DNB, M Ch, Pravin Salunke MS, MCh
International Society of Neuropathology