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Germ Cell Tumors

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Abstract

Central nervous system (CNS) germ cell tumors (GCT) are a rare heterogeneous group of malignant tumors that present in children and young adults. CNS GCTs are classified based on their histology and immunohistochemical profile; they are divided into pure germinoma and nongerminomatous GCT (NGGCTs) with the latter including teratomas, yolk sac tumors, embryonal carcinoma, choriocarcinoma, and mixed GCTs. CNS GCTs typically occur in the midline, involving primarily the suprasellar and pineal region, with rare occurrence in the basal ganglia and thalamus. Clinical presentation varies based on tumor location and age. Patients with pineal tumors present with signs and symptoms of hydrocephalus, whereas vision loss and diabetes insipidus are common presenting features of suprasellar tumors. Diagnosis is usually made with a combination of magnetic resonance imaging (MRI) and the presence of tumor markers (beta-human chorionic gonadotropin [βhCG] and alpha-fetoprotein [AFP]) in the serum and/or cerebrospinal fluid (CSF). Biopsy is indicated for midline lesions with negative tumor markers in serum and CSF. The role for aggressive surgical resection at diagnosis is controversial in CNS GCTs, with the exception of mature and immature teratomas for which a maximal safe surgical resection is desired. The exact pathogenesis of CNS GCTs remains unclear, with conventional thought being that GCTs arise from the aberrant migration of progenitor germ cells. KIT mutations are the most commonly found abnormality in whole genome sequencing, particularly in germinomas. This is followed by genes involved in the MAPK signaling and AKT/mTOR pathways. There is currently no universal standard of care for the treatment of CNS GCT. Germinomas respond exceptionally well to chemotherapy and radiation therapy with survival rates well in excess of 90% with irradiation alone. Current clinical trials are testing the role of adjuvant chemotherapy followed by reduced dose and volume of irradiation. Conversely, NGGCTs are more resistant to therapy with poor survival rates, requiring more intensive chemotherapy as well as higher doses of irradiation.

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Abbreviations

AFP:

Alpha-fetoprotein

AuHCR:

Autologous hematopoietic cell rescue

CBTRUS:

Central Brain Tumor Registry of the United States

CCKBR:

Cholecystokinin B receptor

CGH:

Comparative genomic hybridization

CNS:

Central nervous system

COG:

Children’s Oncology Group

CR:

Complete response

CSF:

Cerebrospinal fluid

CSI:

Craniospinal irradiation

CT:

Computed tomography

ETV:

Endoscopic third ventriculostomy

FISH:

Fluorescent in situ hybridization

GCT:

Germ cell tumor

Gy:

Gray

IFR:

Involved field radiation

miRNA:

microRNA

MMGCT:

Mixed malignant germ cell tumor

MRI:

Magnetic resonance imaging

NGGCT:

Nongerminomatous germ cell tumor

OS:

Overall survival

PFS:

Progression-free survival

PLAP:

Placental alkaline phosphatase

PR:

Partial response

qRT-PCR:

Quantitative reverse transcriptase polymerase chain reaction

RT:

Radiation therapy

SFOP:

Société Française d’Oncologie Pédiatrique

SIOP:

Société Internationale d’Oncologie Pédiatrique

SNRPN:

Small nuclear ribonucleoprotein polypeptide N

VP:

Ventricular peritoneal

WBI:

Whole brain irradiation

WES:

Whole exome sequencing

WHO:

World Health Organization

WVI:

Whole ventricular irradiation

YST:

Yolk sac tumors

βhCG:

β Human chorionic gonadotropin

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Authors and Affiliations

  1. Children’s Hospital Los Angeles, Los Angeles, CA, USA

    Kee Kiat Yeo M.D. & Girish Dhall M.D.

  2. Keck School of Medicine of University of Southern California, Los Angeles, CA, USA

    Kee Kiat Yeo M.D. & Girish Dhall M.D.

  3. Neuro-Oncology Program, Children’s Hospital Los Angeles, Los Angeles, CA, USA

    Kee Kiat Yeo M.D. & Girish Dhall M.D.

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  1. Kee Kiat Yeo M.D.
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  2. Girish Dhall M.D.
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Correspondence to Girish Dhall M.D. .

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Editors and Affiliations

  1. Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Amar Gajjar

  2. Children’s National Medical Center, George Washington University, Silver Spring, WA, USA

    Gregory H. Reaman

  3. Cincinnati, OH, USA

    Judy M. Racadio

  4. Medpace, Cincinnati, OH, USA

    Franklin O. Smith

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Yeo, K.K., Dhall, G. (2018). Germ Cell Tumors. In: Gajjar, A., Reaman, G., Racadio, J., Smith, F. (eds) Brain Tumors in Children. Springer, Cham. https://doi.org/10.1007/978-3-319-43205-2_11

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