Papillary Tumor of the Pineal Region: Diagnosis

Abstract

Papillary tumor of the pineal region (PTPR) has been recently included in the 2007 World Health Organization (WHO) “Classification of tumors of the central nervous system.” PTPRs are considered to originate from the subcommissular organ (SCO), which consists of secretory ependymocytes. The origin of the tumor is reflected in the neuroradiological, microscopic, immunohistochemical, and ultrastructural findings. In non-contrast T1-weighted magnetic resonance imaging (MRI) scans, the lesion is represented as a heterogeneous hyperintense area due to the presence of secretory glycoprotein inclusions. PTPRs are most frequently misdiagnosed as ependymomas or choroid plexus (CP) tumors owing to the morphological similarity among these tumors. PTPRs are histologically characterized by loose papillary and densely cellular diffuse, patternless areas showing pseudorosettes with fibrovascular cores covered by several layers of columnar or cuboidal cells. PTPRs are composed of a greater number of epithelial cells than that in ependymomas and lesser number of papillary cells than choroid plexus (CP) tumors. Characteristic immunohistochemical findings of PTPRs include characteristic small ring- and dot-like staining patterns indicative of cytokeratin 18 immunoreactivity, which are similar to those obtained for CP tumors. Furthermore, both PTPRs and CP tumors showed focal transthyretin (prealbumin; TTR) immunoreactivity. On the other hand, PTPRs and ependymomas occasionally showed immunoreactivities to epithelial membranous antigen (EMA), glial fibrillary acidic protein (GFAP), and neural cell adhesion molecule (NCAM). In addition to the abovementioned makers, strong diagnostic markers for PTPRs and factors that distinguish PTPRs from ependymomas or CP tumors are expression of neuronal markers, including microtubule-associated protein 2 (MAP2), neuron-specific enolase (NSE), and neuronal nuclei (NeuN). These findings can be attributed to the extensive involvement of SCO in neuronal differentiation. Ultrastructural examination of PTPRs showed the presence of microvilli and desmosomes—characteristics of ependymoma cells—and abundant rough endoplasmic reticulum, lipid droplets, etc.—characteristics of CP tumor cells.