CASE HISTORY

This 12-month-old boy from Ecuador presented with intractable vomits for 2 months. Imaging studies revealed a 4.3 x 3.2 x 2.9 cm mass involving the right pontocerebellar angle, with compression and displacement of the right cerebellar hemisphere.

Surgery was performed with approximately 80% of tumor resection. The biopsy was initially interpreted as a high-grade pediatric glioma WHO (grade 3) with associated vascular malformation. The case was subsequently sent to Dr. Zambrano for second review, courtesy of Dr. Doris Calle (pediatric oncologist at Hospital del Niño, Guayaquil, Ecuador).

Histomorphologic interpretation of the lesion proved to be very challenging, to a large degree given the extensive thermal artifact present.

However, in the areas of well-preserved tumor, poorly differentiated neoplastic cells with atypical vesicular nuclei and minimal to moderate amounts of eosinophilic

cytoplasm were identified.

Mitotic figures and endothelial proliferation were seen. In addition, a subset of tumor cells was positive for GFAP (not shown), whilst Olig2, synaptophysin, Cam5.2, and AE1/3 were negative. INI1 and H3K27-trimethyl showed preserved nuclear expression. Ki67 proliferation index was estimated as >50%. 

In view of these findings, the tumor was preliminarily diagnosed as a high-grade central nervous system neoplasm with partial glial differentiation, with a differential diagnosis that included embryonal tumor with multilayered rosettes (ETMR) and CNS tumor with BCOR internal tandem duplication (courtesy of Dr. Daniel Marker, UPMC Neuropathology Center of Excellence), and the specimen was submitted for next-generation sequencing (NGS) and DNA methylation array for further classification.

Based on these methylation results, the tumor was classified as an embryonal tumor with multilayered rosettes, non-C19MC-altered. Although these tumors often harbor mutations in DICER1, with the first hit typically involving the germline, no DICER1 gene mutations were identified in this little boy's brain tumor by NGS. In addition to offering definite classification of this tumor, these findings also provide results with genetic counseling impact for the family.