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Histogenesis of intracranial germ cell tumors: primordial germ cell vs. embryonic stem cell

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Abstract

Introduction

Intracranial germ cell tumor (iGCT) is a rare disorder and often occurs during childhood and adolescence. iGCTs are frequently localized in pineal region and hypothalamic–neurohypophyseal axis (HNA). In spite of well-established clinical and pathological entity, histogenesis of iGCTs remains unsettled. Current theories of histogenesis of iGCTs include germ cell theory (from primordial germ cells (PGCs) of aberrant migration) and stem cell theory (transformed embryonic stem (ES) cells). In order to comprehend the histogenesis, we revisit the origin, migration, and fate of the human PGCs, and their transformation processes to iGCT.

Discussion

In “germ cell theory,” transformation of ectopic PGCs to iGCT is complex and involves multiple transcription factors. Germinoma is derived from ectopic PGCs and is considered a prototype of all GCTs. Non-germinomatous germ cell tumors (NGGCTs) develop from more differentiated counterparts of embryonic and extra-embryonic tissues. However, there is a distinct genomic/epigenomic landscape between germinoma and NGGCT. ES cells transformed from ectopic PGCs through molecular dysregulation or de-differentiation may become the source of iGCT. “Stem cell theory” is transformation of endogenous ES cells or primitive neural stem cell to iGCTs. It supports histological diversity of NGGCTs because of ES cell’s pluripotency. However, neural stem cells are abundantly present along the subependymal zone; therefore, it does not explain why iGCTs almost exclusively occur in pineal and HNA locations. Also, the vast difference of methylation status between germinoma and NGGCT makes it difficult to theorize all iGCTs derive from the common cellular linage.

Conclusion

Transformation of PGCs to ES cells is the most logical mechanism for histogenesis of iGCT. However, its detail remains an enigma and needs further investigations.

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Abbreviations

ES:

Embryonic stem

GCT:

Germ cell tumor

HNA:

Hypothalamic-neurohypophyseal axis

iGCT:

Intracranial germ cell tumor

iPSC:

Induced pluripotent stem cell

NGGCT:

Non-germinomatous germ cell tumor

PGC:

Primordial germ cell

SCF:

Stem cell factor

wpc:

Week post-conception

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Acknowledgements

Tadanori Tomita is endowed by Yeager Professorship of Pediatric Neurosurgery.

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  1. Division of Pediatric Neurosurgery, Ann & Robert H. Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Emma L. Burnham & Tadanori Tomita

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Emma L. Burnham and Tadanori Tomita reviewed pertinent articles in the literature. Emma L. Burnham and Tadanori Tomita wrote the manuscript text. All authors reviewed the manuscript.

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Burnham, E.L., Tomita, T. Histogenesis of intracranial germ cell tumors: primordial germ cell vs. embryonic stem cell. Childs Nerv Syst 39, 359–368 (2023). https://doi.org/10.1007/s00381-022-05808-w

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