A pineal region mass in a 55-year-old female

Abstract

A 55-year-old female with headache was found on magnetic resonance imaging to have a 2.6 cm contrast enhancing, diffusion restricted pineal mass (Figure 1). Three months later, she presented to the emergency department with confusion, imbalance, headaches, body aches, fatigue, and elevated blood pressure. Physical exam showed bitemporal hemianopsia and a left fourth nerve paresis. Computed tomography imaging at that time revealed enlargement of the mass with peripheral calcification associated with ventriculomegaly and diffuse sulcal effacement, consistent with obstructive hydrocephalus (Figure 1 inset). Urgent external ventricular drain placement was performed resulting in improvement of symptoms. A surgical resection was then pursued. Intraoperatively, the mass showed evidence of prior hemorrhage and was noted to encase internal cerebral veins and the vein of Galen, preventing gross total resection. After a final diagnosis was reached, adjuvant treatment was planned with concurrent radiation therapy and chemotherapy with temozolomide. The patient is currently doing well at an early 3-month follow-up.

H&E-stained sections revealed a markedly hypercellular tumor composed of small cells with high nuclear–cytoplasmic ratios, pleomorphic nuclei, abundant apoptotic bodies, focal areas of necrosis, and mitotic figures (Box 1, Figure 2A,B). Rosettes were not apparent. The immunophenotype of the neoplastic cells was consistent with an embryonal neoplasm: diffuse strong positivity for synaptophysin (Figure 2C), focal positivity for chromogranin A and neurofilament (not shown), and negative staining for OLIG2 (Figure 2C inset) and SALL4 (not shown). There was retained nuclear expression of INI-1 and BRG-1 (not shown). Ki-67 showed an elevated proliferative index (approximately 40%, Figure 2D).

DNA methylation profiling (Illumina MethylationEPIC) was performed and resulted in consensus matches in Heidelberg v12b6 and Bethesda v2 classifiers to the pineoblastoma, miRNA pathway altered, group 1A methylation class with high confidence scores (greater than 0.9). Dimensionality reduction with Uniform Manifold Approximation and Projection (UMAP) placed the sample in the pineoblastoma family (Figure 2E). Copy number variation analysis derived from methylation data revealed an unbalanced genome, with numerous chromosomal gains and losses (Figure 2F), including gains of chromosomes 7 and 18, and losses of chromosomes 2, 3, 5, 6, 9, 16, and 20.

Pineoblastoma, CNS WHO grade 4; DNA methylation profile matching miRNA pathway altered, group 1A methylation class.

This case is an unusual example of a pineoblastoma (PB) arising in an adult. For this age group and location, pineal parenchymal tumors of intermediate differentiation (PPTIDs) and pineocytomas are much more common, but in contrast to this case show an overall more uniform and well-differentiated cellular morphology [1]. Atypical teratoid/rhabdoid tumor and germ cell tumors, also part of the differential diagnosis, were excluded by immunohistochemical workup. PBs are the most aggressive primary tumors of the pineal gland; they are associated with survivals of 4–8 years in pediatric series. Because the adult demographic is exceptional for this tumor type, confirmation with molecular testing was warranted. DNA methylation profiling was chosen over NGS for further workup, as there was insufficient material for both tests. The consensus methylation class pineoblastoma, miRNA pathway altered, group 1A typically occurs in the pediatric population and is associated with copy number alterations and/or mutations in genes implicated in microRNA processing, such as DICER1, DROSHA, or DGCR8 [2].

Prognostic stratification with methylation profiling shows that PBs with abnormalities in microRNA processing fare better than PBs with alterations in RB1 or MYC, which are epigenetically distinct [2]. However, there is insufficient data on the underlying biology and behavior of this tumor in adults, particularly as part of a molecularly defined cohort. Published series' of PBs in adults, albeit limited, suggest that the clinical course may overall be less aggressive than in children and that the extent of disease at presentation is a strong prognostic factor [3].

Aaron McConeghey, Zied Abdullaev, Kenneth Aldape, Steven A. Moore, and Osorio Lopes Abath Neto collected data. Aaron McConeghey and Osorio Lopes Abath Neto drafted the manuscript. Aaron McConeghey, Zied Abdullaev, Kenneth Aldape, Steven A. Moore, and Osorio Lopes Abath Neto reviewed and edited the draft, and approved the final submitted version.

The authors declare no conflicts of interest.