Germ cell tumor [Neurosurgery Wiki]

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====== Germ cell tumor ======

A germ cell [[tumor]] (GCT) is a neoplasm derived from [[germ cell]]s. Germ cell tumors can be cancerous or non-cancerous tumors. Germ cells normally occur inside the gonads (ovary and testis). Germ cell tumors that originate outside the gonads may be birth defects resulting from errors during the development of the embryo.

===== General information =====

When they arise in the CNS, they are homologs of germ cell tumors of the gonads and other sites. GCTs occur in the midline in the suprasellar and/or pineal region (simultaneous suprasellar and pineal region lesions are diagnostic of a GCT; so-called synchronous germ cell tumors comprise 13% of GCTs and are highly sensitive to XRT). In the pineal region, these tumors occur predominantly in males. In females, GCTs are more common in the suprasellar region. Aside from benign [[teratoma]]s,
all intracranial GCTs are malignant and may metastasize via CSF and systemically. 



===== Epidemiology =====
Primary germ cell tumors (PGCT) of the central nervous system usually develop in the [[third ventricle]] area, and most frequently in the [[pineal region]]. The [[suprasellar region]] is the second preferential site for development of these tumors which are rarely simultaneously present in these two sites.

Germ cell malignancies are common and increasing in males. However, a handful of cases have reported the rare occurrence of testicular germ cell tumours some years after initial extragonadal presentation
((Peat DS, Trowell JE. Testicular seminoma in a patient with pineal germinoma. Journal of Clinical Pathology. 1994;47(8):771–772.))
((Trentini GP, Miaorana A, de Benedittis A. Metachronous seminoma of the pineal region and right testis: case report. Applied Pathology. 1985;3(3):129–133.))
((Chi LH, Deruytter MJ. Dual occurrence of pineal germinoma and testicular seminoma: case report and review of the literature. Pediatric Neurosurgery. 2005;42(1):38–44.))
((Maity A, Shu H-KG, Judkins AR, Fisher MJ, Dwyer-Joyce LEA, Vaughn DJ. Testicular seminoma 16 years after treatment for CNS germinoma. Journal of Neuro-Oncology. 2004;70(1):83–85)).

Of all anterior [[mediastinal tumor]]s, 15-20% are germ cell tumors of which approximately 50% are benign [[teratoma]]s.


===== Classification =====

[[Intracranial germ cell tumor]]

[[Extragonadal germ cell tumor]].

The WHO classification of CNS tumours divides intracranial germ cell tumours into: 

[[Germinoma]] (account for 60-80% of all cases) 

embryonal carcinoma

yolk sac tumor

choriocarcinoma

[[Teratoma]]

immature

mature

teratoma with malignant transformation

mixed germ cell

----

Germ cell tumors are broadly divided in two classes:

The germinomatous or seminomatous germ cell tumors (GGCT, SGCT) include only germinoma and its synonyms dysgerminoma and seminoma.

===Nongerminomatous===
see [[nongerminomatous germ cell tumor]].

===== Types =====

1. [[germinoma]]s: malignant tumors of primitive germ cells that occur in the gonads (called testicular
seminomas in males, dysgerminomas in females) or in the CNS. Survival with these is much better than with nongerminomatous tumors

● variant: syncytiotrophoblastic giant cell variant

2. [[nongerminomatous germ cell tumor]]s (NGGCT) include:

a) embryonal carcinoma:

b) choriocarcinoma

c) [[endodermal sinus tumor]] (EST) AKA yolk sac carcinoma: usually malignant

d) [[teratoma]].A germ cell tumor composed of at least two of the three germ cell layers: ectoderm,
endoderm, & mesoderm. 

Subclassifications:

● mature: composed of mature skin, skin appendage organs (sweat glands, hair follicles...)
adipose tissue cartilage, bone...

● immature: contain immature embryonic or fetal tissue alone or in combination with
mature tissues

● exhibiting malignant transformation: [[teratoma]]s that contain a component resulting from
malignant transformation of a somatic tissue (usually a carcinoma or sarcoma)

3. mixed germ cell tumor.


===== Etiology =====
It is generally thought that the germ cell tumour represents a second primary tumour, as opposed to metastases. Previous reports have suggested that genetic mutations contribute to their development 
((Silva VB, Azevedo AL, Costa IM, Mafra MS, Passos-Coelho JL, Bravo-Marques JM. Mixed testicular germ cell tumour in a patient with previous pineal germinoma. Journal of Neuro-Oncology. 2011;101(1):125–128.))
((Coffey J, Linger R, Pugh J, et al. Somatic KIT mutations occur predominantly in seminoma germ cell tumors and are not predictive of bilateral disease: report of 220 tumors and review of literature. Genes Chromosomes and Cancer. 2008;47(1):34–42.))
((Rapley EA, Crockford GP, Teare D, et al. Localization to Xq27 of a susceptibility gene for testicular germ-cell tumours. Nature Genetics. 2000;24(2):197–200.)).

A genetic basis has been proposed for these tumours. Mutations in the KIT gene at codon 816 are associated with gonadal and extragonadal germ cell tumours.
Furthermore, it is thought such mutations occur very early during embryogenesis, prior to the migration of germ cells to gonadal and extragonadal locations. Coffey et al. found a KIT mutation in a patient who suffered from a pineal germinoma and a testicular seminoma
((Coffey J, Linger R, Pugh J, et al. Somatic KIT mutations occur predominantly in seminoma germ cell tumors and are not predictive of bilateral disease: report of 220 tumors and review of literature. Genes Chromosomes and Cancer. 2008;47(1):34–42.))

Some investigators suggest that this distribution arises as a consequence of abnormal migration of germ cells during embryogenesis. Others hypothesize a widespread distribution of germ cells to multiple sites during normal embryogenesis, with these cells conveying genetic information or providing regulatory functions at somatic sites.

Extragonadal germ cell tumors were thought initially to be isolated metastases from an undetected primary tumor in a gonad, but it is now known that many germ cell tumors are congenital and originate outside the gonads. The most notable of these is [[sacrococcygeal teratoma]], the single most common tumor diagnosed in babies at birth.

===== Diagnosis =====


[[Germ cell tumor diagnosis]]





===== Treatment =====
The management of intracranial germ-cell tumours is complex because of varied clinical presentations, tumour sites, treatments and outcomes, and the need for multidisciplinary input. Participants of the 2013 Third International CNS Germ Cell Tumour Symposium (Cambridge, UK) agreed to undertake a multidisciplinary Delphi process to identify consensus in the clinical management of intracranial germ-cell tumours. 77 delegates from the symposium were selected as suitable experts in the field and were invited to participate in the Delphi survey, of which 64 (83%) responded to the invitation. Invited participants represented multiple disciplines from Asia, Australasia, Europe, and the Americas. 38 consensus statements encompassing aspects of intracranial germ-cell tumour work-up, staging, treatment, and follow-up were prepared. To achieve consensus, statements required at least 70% agreement from at least 60% of respondents. Overall, 34 (89%) of 38 statements met consensus criteria. This international Delphi approach has defined key areas of consensus that will help guide and streamline clinical management of patients with intracranial germ-cell tumours. Additionally, the Delphi approach identified areas of different understanding and clinical practice internationally in the management of these tumours, areas which should be the focus of future collaborative studies. Such efforts should translate into improved patient outcomes
((Murray MJ, Bartels U, Nishikawa R, Fangusaro J, Matsutani M, Nicholson JC.
Consensus on the management of intracranial germ-cell tumours. Lancet Oncol. 2015
Sep;16(9):e470-7. doi: 10.1016/S1470-2045(15)00244-2. Review. PubMed PMID:
26370356.
)).

===== Case reports =====

Combination of Germinoma with Teratoma is very rare. A case of Mixed Malignant Germ cell tumor of third ventricle with recurrence with emphasis on histopathological and radiological findings
((Kishore M, Monappa V, Rao L, Kudva R. Mixed malignant germ cell tumour of
third ventricle with hydrocephalus: a rare case with recurrence. J Clin Diagn
Res. 2014 Nov;8(11):FD03-5. doi: 10.7860/JCDR/2014/9866.5124. Epub 2014 Nov 20.
PubMed PMID: 25584231; PubMed Central PMCID: PMC4290250.
)).