Pediatric germ cell tumors presenting beyond childhood?

Oosterhuis, J. Wolter; Stoop, J.A.; Rijlaarsdam, Martin A.; Biermann, Katharina; Smit, Vincent T.H.B.M.; Hersmus, Remko; Looijenga, Leendert H. J.

doi:10.1111/andr.305

Cited by 30 publications

(17 citation statements)

References 22 publications

(29 reference statements)

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“…Importantly, there is no GCNIS-or gonadoblastoma-like precursor lesion, suggesting that these tumours originate directly from PGC; however, the pathogenesis remains unknown [22,23]. These tumours, mainly mature teratomas, may also occasionally be found in adult men beyond childhood, and can be distinguished from malignant TGCT of young adults by the absence of GCNIS and lack of gain of 12p [24,25].…”

Section: Histopathology and Pathogenesis Of Germ Cell Neoplasmsmentioning

confidence: 99%

Diagnostic markers for germ cell neoplasms: from placental-like alkaline phosphatase to micro-RNAs

Meyts

Nielsen

Skakkebæk

et al. 2015

Folia Histochem Cytobiol.

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This concise review summarises tissue and serum markers useful for differential diagnosis of germ cell tumours (GCT), with focus on the most common testicular GCT (TGCT). GCT are characterised by phenotypic heterogeneity due to largely retained embryonic pluripotency and aberrant somatic differentiation. TGCT that occur in young men are divided into two main types, seminoma and nonseminoma, both derived from a pre-invasive germ cell neoplasia in situ (GCNIS), which originates from transformed foetal gonocytes. In severely dysgenetic gonads, a GCNIS-resembling lesion is called gonadoblastoma. GCT occur rarely in young children (infantile GCT) in whom the pathogenesis is different (no GCNIS/gonadoblastoma stage) but the histopathological features are similar to the adult GCT. The rare spermatocytic tumour of older men is derived from post-pubertal spermatogonia that clonally expand due to gain-of function mutations in survival-promoting genes (e.g. FGFR3, HRAS), thus this tumour has a different expression profile than GCNIS-derived TGCT. Clinically most informative immunohistochemical markers for GCT, except teratoma, are genes expressed in primordial germ cells/gonocytes and embryonic pluripotency-related factors, such as placental-like alkaline phosphatase (PLAP), OCT4 (POU5F1), NANOG, AP-2γ (TFAP2C) and LIN28, which are not expressed in normal adult germ cells. Some of these markers can also be used for immunocytochemistry to detect GCNIS or incipient tumours in semen samples. Gene expression in GCT is regulated in part by DNA and histone modifications, and the epigenetic profile of these tumours is characterised by genome-wide demethylation, except nonseminomas. In addition, a recently discovered mechanism of post-genomic gene expression regulation involves small non-coding RNAs, predominantly micro-RNA (miR). Testicular GCT display micro-RNA profiles similar to embryonic stem cells. Targeted miRNA-based blood tests for miR-371-3 and miR-367 clusters are currently under development and hold a great promise for the future. In some patients miR-based tests may be even more sensitive than the classical serum tumour markers, b-chorio-gonadotrophin (b-hCG), a-fetoprotein (AFP) and lactate dehydrogenase (LDH), which are currently used in the clinic. In summary, research advances have provided clinicians with a panel of molecular markers, which allow specific diagnosis of various subtypes of GCT and are very useful for early detection at the precursor stage and for monitoring of patients during the follow-up.

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Section: Histopathology and Pathogenesis Of Germ Cell Neoplasmsmentioning

confidence: 99%

Diagnostic markers for germ cell neoplasms: from placental-like alkaline phosphatase to micro-RNAs

Meyts

Nielsen

Skakkebæk

et al. 2015

Folia Histochem Cytobiol.

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“…The presence of IT components and their extent are assumed to predict YST differentiation that may either be histologically undetectable but present at first diagnosis or developed at relapse. Within the group of older children and adolescents, it is difficult to distinguish late onset childhood‐type tumors (Type I), which have also been reported to be present beyond puberty and show a more favorable outcome, from early onset adult GCT (Type II), with an unfavorable clinical course . Consequently, risk adapted therapy is a challenge since prognosis is difficult to predict …”

Section: Introductionmentioning

confidence: 99%

Chromosomal gains of 12p and 1q are not associated with inferior outcome of pediatric and adolescent germ cell tumors

Greimelmaier¹,

Calaminus

Kristiansen

et al. 2019

Pediatric Blood & Cancer

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Background Pediatric germ cell tumors (GCT) are rare and very heterogeneous neoplasms that show a high diversity in tumor biology and histology. The clinical behavior cannot be predicted based on morphology or immunohistochemistry. The aim of this study was to investigate a large number of pediatric GCT regarding chromosomal gains of 12p and 1q. Methods One hundred and eighty pediatric nonseminomatous GCT, that is, mature teratomas, immature teratomas, yolk sac tumors, and mixed germ cell tumors, from three age groups were evaluated for 1q and 12p gains by fluorescence in situ hybridization in tissue micro arrays. The results were correlated with tumor biology and clinical data. Results Eleven out of 143 GCT showed gains of 1q. In 29/157 GCT a gain of 12p was found. Prepubertal patients (≤6 years of age) more often displayed gains of 1q compared to pubertal/adolescent patients (11‐17 years of age), whereas pubertal/adolescent patients showed gains of 12p most frequently. Twenty‐one out of 155 patients suffered from relapse or metachronous disease. Patients with and without gains of 1q or 12p did not differ in frequency of these events. However, the likelihood of occurrence of these clinical events varied depending on the histological type of the tumor. Conclusion The biological behavior of pediatric GCT depends more on the histological type of the tumor than on the genetic aberrations examined in this study. Gains of 1q and 12p are not suitable to predict the clinical outcome of GCT in childhood. Nevertheless, both genetic alterations might be used as biomarkers to distinguish different histological types of GCT and therefore could be of diagnostic value, especially in borderline cases.

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“…Furthermore, postpubertal types can occur in prepubertal individuals who have disorders of sex development. Although it is well documented that prepubertal type neoplasms can present at an age beyond childhood, they nevertheless maintain discrete characteristics that distinguish them from adult type testicular GCTs [9].…”

Section: Classification Of Germ Cell Neoplasmsmentioning

confidence: 99%

“…A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 9 Yolk sac tumor is histologically complex, and various histological patterns have been described (Fig. 5).…”

Section: Pure Yolk Sac Tumormentioning

confidence: 99%