Review articlePineal germ cell tumors: Two cases with review of histopathologies and biomarkers
Introduction
Pineal germ cell tumors (GCTs) are rare, comprising less than 5% and 18% of primary brain tumors in Western and Asian countries, respectively [1], [2], [3], [4], [5], [6], [7], [8]. Pineal GCTs account for nearly 50% of intracranial GCTs (IGCTs) and are more common in males [8]. Histologically, these tumors are categorized as germinomatous or non-germinomatous [1]. Germinomatous GCTs include germinomas and germinomas with syncytiotrophoblastic giant cells (STGCs). Non-germinomatous GCTs (NGGCTs) include teratomas, embryonal carcinomas, yolk sac tumors, and choriocarcinomas [9].
IGCTs commonly develop along the pineal-suprasellar axis. Computed tomography (CT) demonstrates punctate hyperdensities, which indicate tumoral calcifications embedded in a hypodense, enhancing mass [10], [11]. Magnetic resonance imaging (MRI) remains the diagnostic modality of choice, and reveals a T1- and T2-isointense vividly enhancing mass. Management and prognoses of these tumors are driven by histopathological subtype.
Advances in immunohistochemistry and next-generation sequencing have furthered our understanding of the origin and pathomolecular mechanisms underlying the development of GCTs. DNA damage response (DDR) signaling and the ATM-ChK2-p53 pathway, which are involved in the development of solid tumors, have been shown to be downregulated in germinomas and other subtypes of primary GCTs [12]. This pattern is also observed in testicular GCTs. Mutations in the KIT/RAS and AKT1/mTOR pathways, among others, have also been demonstrated in IGCTs [8]. Here we report two cases of pineal GCTs (yolk sac tumor and germinoma). The literature is reviewed with an emphasis on histopathologies and biomarkers.
Section snippets
Cases
All patients gave informed consent for the treatments described below. Institutional Review Boards at each respective institution did not require consent for this type of article. Nevertheless, details that might disclose the identities of the subjects are omitted. Permission to reproduce images was appropriately obtained. The slides depicted in this paper are not from the patients herein described and are for non-CNS GCTs.
Discussion
In this report, we described two cases of pineal GCTs. These patients provided the rationale for conducting a review of the literature with an emphasis on histopathologies and biomarkers. The PubMed database was queried using relevant search terms. A total of 298 IGCTs, comprised of 193 germinomas (64.8%), 52 teratomas (17.4%), 20 choriocarcinomas (6.7%), 19 yolk sac tumors (6.4%), and 14 embryonal carcinomas (4.7%) were identified (Table 1). Our analysis represents the aggregated data from the
Conclusion
GCTs are rare tumors and more common in Asians and males. These tumors display an affinity to develop along the pineal-suprasellar axis. We herein presented two cases of pineal GCTs (germinoma and yolk sac tumor), which inspired a review of the literature on IGCTs with an emphasis on histopathologies and biomarkers. Germinomas are most common and appear as a mix of lymphocytes and undifferentiated large cells with clear cytoplasm, round nuclei, and prominent nucleoli. Germinomas rarely
Conflicts of interest/disclosures
None.
Acknowledgements
Carlito Lagman is supported by a Gurtin Skull Base Research Fellowship. Lawrance K. Chung is supported by an AMA Foundation Seed Grant and an AΩA Carolyn L. Kuckein Student Research Fellowship. Timothy T. Bui is a recipient of the David Geffen Medical Scholarship. Seung J. Lee is a recipient of the American Academy of Neurology Medical Student Summer Research Scholarship. Isaac Yang (senior author) is partially supported by a Visionary Fund Grant, an Eli and Edythe Broad Center of Regenerative
References (90)
- et al.
Patterns of DNA damage response in intracranial germ cell tumors versus glioblastomas reflect cell of origin rather than brain environment: implications for the anti-tumor barrier concept and treatment
Mol Oncol
(2014) - et al.
Radiation therapy for intracranial germ cell tumors
Int J Radiat Oncol Biol Phys
(2003) - et al.
Germ cell tumours of the central nervous system: treatment consideration based on 111 cases and their long-term clinical outcomes
Eur J Cancer
(1998) - et al.
Radiation therapy for primary intracranial germ-cell tumors
Int J Radiat Oncol Biol Phys
(1995) - et al.
Pineal and CNS germ cell tumors: Royal Marsden Hospital experience 1962–1987
Int J Radiat Oncol Biol Phys
(1990) - et al.
Radiotherapy of primary intracranial germinomas: the case against routine craniospinal irradiation
Int J Radiat Oncol Biol Phys
(1988) - et al.
Pineal region tumors: analysis of treatment results
Int J Radiat Oncol Biol Phys
(1984) - et al.
Treatment results of intracranial germinoma as a function of the irradiated volume
Int J Radiat Oncol Biol Phys
(1988) - et al.
Long-term follow-up of dose-adapted and reduced-field radiotherapy with or without chemotherapy for central nervous system germinoma
Int J Radiat Oncol Biol Phys
(2010) - et al.
Low-dose craniospinal irradiation as a definitive treatment for intracranial germinoma
Radiother Oncol
(2009)