# Papillary Tumor of the Pineal Region Identified by DNA Methylation Leads to the Incidental Finding of Germline Mutation PTEN G132D Associated with PTEN Hamartoma Tumor Syndrome: A Case Report and Systematic Review

## TL;DR

A rare brain tumor was correctly identified using DNA methylation profiling, revealing a genetic mutation linked to a syndrome that increases cancer risk.

## Contribution

This is the first case report linking papillary tumor of the pineal region with PTEN Hamartoma Tumor Syndrome.

## Key findings

- DNA methylation profiling correctly identified the tumor as a papillary tumor of the pineal region (PTPR), Group B.
- A pathogenic PTEN p.G132D mutation was found in both the tumor and germline, indicating PTEN Hamartoma Tumor Syndrome (PHTS).
- Systematic review showed inconsistencies in PTPR diagnostics and underuse of molecular testing in clinical practice.

## Abstract

Distinct subgroups of rare brain tumors can be molecularly classified using whole genome DNA methylation profiling and next-generation sequencing. Furthermore, these tools can identify germline mutations contributing to carcinogenesis. Access to molecular testing in the clinical setting is vital for pathology laboratories to make an accurate diagnosis. One molecularly unique brain tumor requiring such tools is the papillary tumor of the pineal region (PTPR). Herein, we present a case report of a 21-year-old male presenting with macrocephaly and obstructive hydrocephalus due to the PTPR. Next-generation sequencing identified a pathogenic PTEN p.G132D mutation in the tumor and matched germline findings further identified PTEN Hamartoma Tumor Syndrome (PHTS). The case report tumor was initially misdiagnosed as ependymoma while methylation profiling classified it more specifically as a PTPR, Group B. To better understand the current status of PTPRs, we conducted a systematic review of recent cases reporting on the diagnostics, treatments, and outcomes for PTPR patients. To our knowledge, this is the first case report for PTPRs revealing an association with PHTS. Our review revealed inconsistencies in diagnostics, treatments, and outcomes for PTPR, and an underutilization of definitive molecular testing.