Non-seminomatous germ cell tumors
2023-04-24 Andres M. Acosta, MD Affiliation1.Department of Pathology, Indiana University, Indianapolis, IN
Classification
Definition
Non-seminomatous germ cell tumors (NSGCTs) comprise neoplasms with pure non-seminoma histology, as well as mixed tumors (which may include a component of seminoma). Among NSGCTs, mixed tumors are more frequent than pure tumors (~70% versus ~30%). The different histologic types of NSGCTs include embryonal carcinoma, post-pubertal yolk sac tumor (YSTs), post-pubertal teratoma, and trophoblastic neoplasms (the most frequent being choriocarcinoma).
| Non-seminomatous germ cell tumors | Genetic Event(s) |
|---|---|
| Embryonal carcinoma (EC) | Genomic findings are overall similar in seminoma and non-seminomatous germ cell tumors (GCTs). However, there are some differences including a slightly lower mdeian ploidy (~2.8 versuss ~3.1) and different patterns of recurrent losses of chromosomal arms. 1 Unlike pure seminomas, nonseminomas invariably harbor gains of sequences of 12p and/or i(12p) but KIT, KRAS and NRAS mutations are relatively rare. 1 The rpocesses that drive the reprogramming of non-seminomatous GCTs are though to be driven largely by epigenetic mechanisms. 2 Like seminoma, embryonal carcinoma expresses miR-371-3p. 1,3 |
| Yolk sac tumour (YST), postpubertal-type | Yolk sac tumor postubertal type (YST) is expected to have a lower median ploidy and different patterns of recurrent chromosomal losses than seminomas. 1 Unlike pure seminomas, YST, postpubertal type almost invariably harbor gains of sequences of 12p and/or i(12p). 1 The rpocesses that drive the reprogramming of non-seminomatous GCTs are though to be driven largely by epigenetic mechanisms. 2 YST, postpubertal type does not demonstrate significant expression of miR-371-3p 1,3. |
| Choriocarcinoma | Choriocarcinoma is expected to have a lower median ploidy and different patterns of recurrent chromosomal losses than seminomas. 1 Choriocarcinoma harbors gains of sequences of 12p and/or i(12p). 1 The rpocesses that drive the reprogramming of non-seminomatous GCTs are though to be driven largely by epigenetic mechanisms. 2 Chriocarcinoma is not expected to express miR-371-3p 1,3. |
| Placental site trophoblastic tumour | No specific genetic findings so far. |
| Epithelioid trophoblastic tumour | No specific genetic findings so far. |
| Cystic trophoblastic tumour | No specific genetic findings so far. |
| Teratoma, postpubertal-type | It occurs in adults mainly as a component of a mixed germ cell tumor and most commonly after chemotherapy. Cystic trophoblastic tumor typically demonstrate overrepresentation of sequences of 12p/i(12p) .4 |
| Teratoma with somatic-type malignancy | "Somatic-type" malignancies associated with teratoma demonstrate gains of 12p/i(12p), distinct methylation profiles, a high degreee of aneuploidy and relatively frequent alteration of genes of the TP53 pathway. 5-8 So called "somatic-type" malignancies arising in teratoma are often resistant to cisplatin-based chemotherapy regimens. 9 |
| Mixed germ cell tumors of the testis | Mixed germ cell tumors have molecular features similar to nonseminomas. |
| Regressed germ cell tumors | No specific genetic findings so far. |
Article Bibliography
| Reference Number | Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|---|
| 1 | 29898407 | 2018 | Integrated Molecular Characterization of Testicular Germ Cell Tumors. | Shen H et al |
| 2 | 31413324 | 2019 | Human germ cell tumours from a developmental perspective. | Oosterhuis JW et al |
| 3 | 33158661 | 2021 | Integrated Expression of Circulating miR375 and miR371 to Identify Teratoma and Active Germ Cell Malignancy Components in Malignant Germ Cell Tumors. | Nappi L et al |
| 4 | 32144540 | 2020 | Histology, 12p status, and IMP3 expression separate subtypes in testicular teratomas. | Semjén D et al |
| 5 | 15167939 | 2004 | Fluorescence in situ hybridization analysis of chromosome 12p in paraffin-embedded tissue is useful for establishing germ cell origin of metastatic tumors. | Kernek KM et al |
| 6 | 31478941 | 2019 | Fluorescent In Situ Hybridization Analysis for 12p Alterations in Sarcomatoid Yolk Sac Tumors. | Idrees MT et al |
| 7 | 35438203 | 2022 | Morphological spectrum and molecular features of somatic malignant transformation in germ cell tumours. | Lobo J et al |
| 8 | 36030288 | 2022 | Molecular correlates of male germ cell tumors with overgrowth of components resembling somatic malignancies. | Wyvekens N et al |
| 9 | 35803413 | 2022 | Somatic-type malignancies in testicular germ cell tumors. | Guo CC et al |
Citation
Andres M. Acosta, MD
Non-seminomatous germ cell tumors
Atlas Genet Cytogenet Oncol Haematol. 2023-04-24
Online version: http://atlasgeneticsoncology.org/solid-tumor/209117/non-seminomatous-germ-cell-tumors
