Review article
Pineal germ cell tumors: Two cases with review of histopathologies and biomarkers

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Highlights

Abstract

Pineal germ cell tumors (GCTs) are primarily seen in pediatric and Asian populations. These tumors are divided into germinomatous and non-germinomatous GCTs (NGGCTs). GCTs are thought to arise by misplacement of totipotent stem cells en route to gonads during embryogenesis. Intracranial GCTs display an affinity to develop along the pineal-suprasellar axis and have variable manifestations dependent upon the location of the tumor. Management and outcomes are driven by histopathologies. In this study, we highlight two cases of pineal GCTs and present a review of the literature with an emphasis on 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)

  • S.J. Rogers et al.

    Radiotherapy of localised intracranial germinoma: time to sever historical ties?

    Lancet Oncol

    (2005)
  • S.H. Yen et al.

    Optimal treatment for intracranial germinoma: can we lower radiation dose without chemotherapy?

    Int J Radiat Oncol Biol Phys

    (2010)
  • D.T. Yang et al.

    Primary pontomedullary germinoma in a 12 year old boy

    J Clin Neurosci

    (2009)
  • Y. Li et al.

    Primary mature teratoma presenting as an adrenal tumor in a child

    Urology

    (2011)
  • S.L. Rodriguez et al.

    Primary embryonal carcinoma of the orbit in a 10-month-old female: a seven-year follow-up

    Am J Ophthalmol

    (2005)
  • H. Kiratli et al.

    Primary orbital endodermal sinus tumor (yolk sac tumor)

    J AAPOS

    (2008)
  • D.M. Bell et al.

    Primary sinonasal choriocarcinoma

    Ann Diagn Pathol

    (2009)
  • T. Yamagami et al.

    Choriocarcinoma arising from the pituitary fossa with extracranial metastasis: a review of the literature

    Surg Neurol

    (1983)
  • K.W. Ngan et al.

    Immunohistochemical expression of OCT4 in primary central nervous system germ cell tumours

    J Clin Neurosci

    (2008)
  • S. Suster et al.

    Germ cell tumors of the mediastinum and testis: a comparative immunohistochemical study of 120 cases

    Hum Pathol

    (1998)
  • D.M. Green

    The diagnosis and treatment of yolk sac tumors in infants and children

    Cancer Treat Rev

    (1983)
  • F.E. von Eyben

    A systematic review of lactate dehydrogenase isoenzyme 1 and germ cell tumors

    Clin Biochem

    (2001)
  • M.T. Jennings et al.

    Intracranial germ-cell tumors: natural history and pathogenesis

    J Neurosurg

    (1985)
  • T.J. Eberts et al.

    Primary intracranial endodermal sinus tumor. Case report

    J Neurosurg

    (1979)
  • K. Jellinger

    Primary intracranial germ cell tumours

    Acta Neuropathol

    (1973)
  • H.J. Hoffman et al.

    Intracranial germ-cell tumors in children

    J Neurosurg

    (1991)
  • I.J. Lin et al.

    Primary intracranial germ-cell tumor in children

    Chin Med J

    (1997)
  • J. Kuratsu et al.

    Epidemiological study of primary intracranial tumors: a regional survey in Kumamoto Prefecture in the southern part of Japan

    J Neurosurg

    (1996)
  • K. Ueki et al.

    Treatments and prognoses of pineal tumors–experience of 110 cases

    Neurol Med Chir

    (1980)
  • L. Wang et al.

    Novel somatic and germline mutations in intracranial germ cell tumours

    Nature

    (2014)
  • WHO Classification of Tumours of the Central Nervous System, 4th ed., Lyon, France: International Agency for Research...
  • L. Liang et al.

    MRI of intracranial germ-cell tumours

    Neuroradiology

    (2002)
  • T. Yamagami et al.

    An immunohistochemical study of intracranial germ cell tumours

    Acta Neurochir

    (1987)
  • C.E. Hoei-Hansen et al.

    New evidence for the origin of intracranial germ cell tumours from primordial germ cells: expression of pluripotency and cell differentiation markers

    J Pathol

    (2006)
  • R.J. Packer et al.

    Intracranial germ cell tumors

    Oncologist

    (2000)
  • J.A. Murovic et al.

    Manifestations and therapeutic considerations in pineal yolk-sac tumors. Case report

    J Neurosurg

    (1981)
  • J. Bjornsson et al.

    Intracranial germ cell tumors: pathobiological and immunohistochemical aspects of 70 cases

    J Neuropathol Exp Neurol

    (1985)
  • T. Fujimaki et al.

    CT and MRI features of intracranial germ cell tumors

    J Neurooncol

    (1994)
  • T. Chang et al.

    CT of pineal tumors and intracranial germ-cell tumors

    AJNR Am J Neuroradiol

    (1989)
  • A.P. Kyritsis

    Management of primary intracranial germ cell tumors

    J Neurooncol

    (2010)
  • M.E. Echevarria et al.

    Pediatric central nervous system germ cell tumors: a review

    Oncologist

    (2008)
  • G. Calaminus et al.

    Intracranial germ cell tumors: a comprehensive update of the European data

    Neuropediatrics

    (1994)
  • D.I. Sung et al.

    Midline pineal tumors and suprasellar germinomas: highly curable by irradiation

    Radiology

    (1978)
  • C. Balmaceda et al.

    Current advances in the diagnosis and management of intracranial germ cell tumors

    Curr Neurol Neurosci Rep

    (2004)
  • H.L. Weiner et al.

    Surgery in the management of primary intracranial germ cell tumors

    Childs Nerv Syst

    (1999)

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