pediatric germ cell tumors

The germ cell tumors (GCTs) are a rare and complex group of heterogenous neoplasms that comprise both benign and malignant
histologies.

Despite their heterogeneity, they are all presumed to arise from totipotent primordial germ cells (PGC).

Benign GCTs are called teratomas. Of the malignant GCT histologies, seminomatous tumors (testicular seminomas, ovarian dysgerminomas, and
extragonadal germinomas) recapitulate the undifferentiated and pluripotent PGC phenotype, whereas nonseminomatous tumors [e.g., yolk sac tumors (YST)] display lineage specific differentiation.

Amixture of histologic subtypes may be present within any single GCT, suggesting a close interrelationship between the different histologies and the cell of origin.

Many epidemiologic and clinical differences exist between GCTs arising in adulthood and those arising in childhood (defined in United Kingdom as 0–16 years of age), with tumors in adolescents showing a degree of overlap with GCTs in both age groups.

Because of these differences, GCTs of identical histology are treated differently depending on patient age and country of residence. Despite overall success in managing children with GCTs, there are subgroups of patients in whom
the prognosis is less favorable.

Moreover, adoption of adult derived chemotherapeutic schedules in the treatment of pediatric malignant GCTs has resulted in significant toxicity and long-term morbidity, which may be avoidable.

It is therefore essential to obtain a greater understanding of the biology of pediatric malignant GCTs, not least so that children can be given the most
appropriate treatment.

CGH

 11528555 (51 cases)

With the exception of some testicular and ovarian tumors, malignant GCTs in children do not show chromosomal gain of 12p, which is characteristic of GCTs in adult patients. (11528555)

Irrespective of the primary site, childhood GCTs show chromosomal imbalances of chromosome 1 (loss of distal 1p, gain of 1q), deletion of 4q and 6q as well as gain of 20q at a high frequency. (11528555)

Management

The first Intergroup protocols confirmed that stage I malignant testicular germ cell tumors and immature teratomas at all sites in children could be treated with surgery alone followed by close observation.

Future protocols currently in the planning stages may extend this low-risk category to stage I ovarian germ cell tumors of all histologic types.

Low-stage extragonadal germ cell tumors may be placed in a new intermediate risk category.

See also

 foci of endodermal sinus tumors in low-stage immature teratomas
 extragonadal germ cell tumors
 malignant germ cell tumors (MGCTs)

References

Expression profiling and miRNA

 Pediatric primary central nervous system germ cell tumors of different prognosis groups show characteristic miRNome traits and chromosome copy number variations. Wang HW, Wu YH, Hsieh JY, Liang ML, Chao ME, Liu DJ, Hsu MT, Wong TT. BMC Genomics. 2010 Feb 24;11:132. PMID: 20178649 [Free]

 Pediatric malignant germ cell tumors show characteristic transcriptome profiles. Palmer RD, Barbosa-Morais NL, Gooding EL, Muralidhar B, Thornton CM, Pett MR, Roberts I, Schneider DT, Thorne N, Tavaré S, Nicholson JC, Coleman N; Children’s Cancer and Leukaemia Group. Cancer Res. 2008 Jun 1;68(11):4239-47. PMID: 18519683

Pathology

 Pediatric germ cell tumors: protocol update for pathologists. Perlman EJ, Hawkins EP. Pediatr Dev Pathol. 1998 Jul-Aug;1(4):328-35. PMID: 10463297

 Schneider DT, Schuster AE, Fritsch MK, et al. Genetic analysis of childhood germ cell tumors with comparative genomic hybridization. Klin Padiatr 2001; 213: 204–11 (11528555)