Extra-Ventricular C11orf95-RELA Fusion Positive Anaplastic Ependymoma with Divergent Histological and Immunohistochemical Features: Report of a Rare Case
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.325311
Source of Support: None, Conflict of Interest: None
Ependymomas commonly involve the ventricular surfaces and central canal of the brain and spinal cord. The occurrence of ependymomas in extra-ventricular cortical location is relatively rare. Further, only occasional cases of ependymoma with divergent histomorphological features have been reported., Amongst various genetic alterations described in ependymal tumors, RELA fusion appeared to be most important for the supratentorial tumors and consider as a separate entity in the recent World Health Organization (WHO) classification. In this report, a case of pediatric extra-ventricular cortical anaplastic ependymoma with distinct but unusual histological features and molecular profile is highlighted.
A 7-year-old girl child presented in the neurosurgery outpatient department (OPD) with a complaint of headache and intermittent vomiting for 1 month along with right-sided weakness for 15 days. Computed tomography (CT) scan revealed a well-circumscribed, heterogeneously enhancing, largely expansile, a solid-cystic lesion in the left frontoparietal region occupying a superficial cortical location close to midline with mass effect and midline shift. Although the left lateral ventricle was effaced by the tumor but the tumor was neither arising or involving it [Figure 1]a, [Figure 1]b, [Figure 1]c. The patient underwent left frontoparietal craniotomy with complete excision of the lesion. Intraoperatively the tumor was grayish red, soft, friable, highly vascular and intraaxial in nature without any connection to lateral ventricles. Postoperative CT scan showed complete removal of the tumor with minimal residual parenchymal edema [Figure 1]d. The patient developed hemiplegia on the right upper and lower limb which gradually improved to the power of grade 2/5 at the time of discharge. The patient underwent 30 cycles of radiotherapy. On follow up after 10 months of surgery, the patient was clinically stable. She could walk with a minimal limp (power on the right-side body of grade 4(+)/5. Contrast magnetic resonance imaging (MRI) showed no residual or recurrent lesion [Figure 1]e and [Figure 1]f.
Histopathological examination showed a highly cellular tumor with a relatively well-defined margin. [Figure 2]a. It was highly cellular and comprising of small round cells. The cells were predominantly arranged in solid sheets with intervening thin-walled vascular channels. Occasional multilayered rosette-like structures with irregular lumen were identified [Figure 2]b. Ependymal true rosettes lined by a single layer of tumor cells were also identified in one focus [Figure 2]c. The individual tumor cells were round to polygonal with high nucleo-cytoplasmic ratio, round nucleus, coarse chromatin, and indistinct nucleoli. Brisk mitotic activity, areas of necrosis, and endothelial proliferation were noted [Figure 2]d and [Figure 2]e.
The tumor cells showed focal immunopositivity for Glial fibrillary acidic protein (GFAP). Staining for EMA and EBP-50 revealed cytoplasmic dot-like immunopositivity. INI-1 and ATRX staining were retained. Interestingly, some of the tumor cells also showed immunopositivity for desmin. The tumor cells were immunonegative for p65/RELA, p53, IDH-1. MIB-1 labeling index was high (approximately 30%).
For the detection of C11orf95–RELA type 1 and 2 fusion transcripts reverse transcription-polymerase chain reaction (RT-PCR) was done using primers as reported in an earlier study. The presence of type I variant fusion was identified, which was further confirmed by Sanger sequencing [Figure 2]l. This analysis was performed on the mRNA isolated from the paraffin blocks.
Anaplastic ependymoma often lacks the apparent histological diagnostic features and mimics a malignant round cell tumor. Although extremely rare, a single tumor with morphological features of ependymoma as well as embryonal tumor with multilayered rosettes (ETMR) has been reported. Nobusawa et al. described a case of anaplastic ependymoma which showed the presence of multilayered ependymoblastic rosette as well as an ependymal true rosette. Similarly, another case of divergent ependymal tumor with ependymoblastoma and anaplastic ependymoma was also reported by Ortiz J et al. However, specific molecular analysis for ETMR (C19MC amplification) or ependymoma was not done in both these cases. In a study, Spence et al. documented the presence of C19MC amplification/overexpression in some cases of PNET with ependymal morphological features. These indicated a subtle morphological overlap anaplastic ependymoma and ETMR which can lead to diagnostic difficulty. Although analysis for C19MC amplification was not done in the present case, it showed the presence of the C11orf95-RELA fusion gene. However, immunohistochemistry for p65/RELA was negative. Discordant results between the molecular method and immunohistochemistry for identification of the RELA fusion gene has been documented by various studies, which may be minimized by using immunohistochemical analysis for both p65RELA and L1CAM together. Till date, there are no recommendations regarding the method which should be used for the assessment of RELA fusion status. However, it is very important to assess the RELA fusion status in cases of supratentorial ependymomas because these group of tumors has worst prognosis as compared to their other counterparts irrespective of the degree of anaplasia. Another unusual feature in the present case was focal desmin expression which may be attributable to the focal myoblastic differentiation as in cases of medullomyoblastoma.
This case is extremely rare in terms of divergent histological features and aberrant immunohistochemical expression. The use of immunohistochemical markers including GFAP, EMA EBP50, p65RELA, L1CAM, etc., in such cases give important clues towards diagnosis and thus help in the judicial use of molecular tests.
The molecular analysis for C11orf95-RELA fusion and immunohistochemistry for p65RELA were performed in the Neuropathology Laboratory, AIIMS, New Delhi. The authors are thankful to Prof. Chitra Sarkar for the same.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
[Figure 1], [Figure 2]