Germ cell tumours
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This article covers germ cell tumours which classicaly arise in the gonads (ovary, testis). They are also found in the midline and make appearances in neuropathology (e.g. pineal gland) and in the mediastinum.
Overview
- Germ cell tumours (GCTs).
- Intratubular germ cell neoplasia.
- Germinoma/Seminoma/Dysgerminoma.
- Yolk sac tumour (endodermal sinus tumour).
- Embryonal carcinoma.
- Choriocarcinoma.
- Teratoma.
- Mixed GCT - 60% of GCTs are mixed.
- Common combinations:
- teratoma + embryonal carcinoma + endodermal sinus tumour (yolk sac tumour) (TEE).
- seminoma + embryonal (SE).
- embryonal + teratoma (TE).
- Common combinations:
IHC for GCTs
ABCDs of GCTs:
- AFP - yolk sac tumour.
- Beta-hCG - choriocarcinoma.
- CD30 - embryonal carcinoma.
- D2-40 - seminoma.
Tabular summary of GCTs
| Tumour | Key feature | Microscopic | IHC | Other | Image |
|---|---|---|---|---|---|
| Intratubular germ cell neoplasia (ITGCN) | nests of small fried egg cells | large central nucleus, clear cytoplasm, squared-off nuclear membrane, nucleoli[1] |
CD117 | appearance similar to seminoma | [1], [2] |
| Germinoma / Seminoma / Dysgerminoma | fried egg cells | fried egg-like cells (central nucleus, clear cytoplasm) with squared-off nuclear membrane, nucleoli, lymphocytic infiltrate, granulomata, syncytiotrophoblastic giant cells[2] |
D2-40 | seminoma = male version of this tumour; dysgerminoma = female version of this tumour | [3], [4] |
| Yolk sac tumour (endodermal sinus tumour) | Schiller-Duval bodies | Schiller-Duval b. = central blood vessel surrounded by epithelial-like cells a space and more epithelial-like cells, variable arch. | AFP | patterns: microcystic, solid, hepatoid | hepatoid YST |
| Embryonal carcinoma | prominent nucleoli, vescicular nuclei | var. arch.: tubulopapillary, glandular, solid, embryoid bodies (ball of cells in surrounded by empty space on three sides), +/-nuclear overlap, mitoses common | CD30 | usu. part of a mixed GCT | [5], [6], [7] |
| Choriocarcinoma | clear cytoplasm | cells with abundant clear cytoplasm and eccentric atypical nuclei (cytotrophoblast), very large (multinucleated) cells with abundant eosinophilic cytoplasm and extreme nuclear atypia (syncytiotrophoblast) | beta-hCG | other | [8], [9] |
| Teratoma, immature | primitive neuroepithelium | pseudostratified epithelium in rosettes (gland-like arrangement) | None | teratoma are always malignant in males | [10] |
| Mixed germ cell tumour | NA | common combinations: teratoma + embryonal carcinoma + endodermal sinus tumour (yolk sac tumour) (TEE); seminoma + embryonal (SE); embryonal + teratoma (TE) | NA | - | - |
![[1]](http://commons.wikimedia.org/wiki/File:Intratubular_germ_cell_neoplasia_high_mag.jpg){kind=link}
![[2]](http://commons.wikimedia.org/wiki/File:Intratubular_germ_cell_neoplasia_high_mag_cropped.jpg){kind=link}
![[3]](http://commons.wikimedia.org/wiki/File:Seminoma_high_mag.jpg){kind=link}
![[4]](http://commons.wikimedia.org/wiki/File:Seminoma_intermed_mag.jpg){kind=link}
![[5]](http://commons.wikimedia.org/wiki/File:Embryonal_carcinoma_intermed_mag.jpg){kind=link}
![[10]](http://commons.wikimedia.org/wiki/File:Primitive_neuroepithelium_intermed_mag.jpg){kind=link}
Germinoma
Comes in three flavours:
- Germinoma.
- Seminoma.
- Dysgerminoma.
Germinoma
Is the generic version of this tumour. It is found in the midline (brain, mediastinum).
Seminoma
Main article: Testis#Seminoma
A common GCT in males.
Dysgerminoma
Main article: Ovarian tumours#Dysgerminoma
A common GCT in females.
Yolk sac tumour
General
- Tumour also known as endodermal sinus tumour.
Epidemiology
- Most common GCT in infants and young boys.
Microscopy
Classic feature:
- Schiller-Duval bodies.
- Look like glomerulus - central blood vessel surrounded by epithelial-like cells a space and more epithelial-like cells
- Architecure - variable.
- Most common microcystic pattern.[3]
Image:
Variants:
- Hepatoid pattern.[4]
- Vaguely resembles liver.
- Hyaline globules (light red well-circumscribed globs).
- Bile canaculi.
- Vaguely resembles liver.
- Solid pattern.[5]
- Vaguely resembles seminoma.
Image:
IHC
- AFP +ve.
- Glypican 3 +ve.
- More sensitive than AFP.[6]
- Alpha-1 AT +ve.
- Cytokeratin +ve. ???
DDx
- Embryonal carcinoma.
Embryonal carcinoma
General
- Affects young adults.
- May be seen in women.
Microscopic
Features:[7]
- Nucleoli - key feature.
- Vesicular nuclei (clear, empty appearing nuclei) - key feature.
- Nuclei overlap.
- Necrosis - common.
- Not commonly present in seminoma.
- Indistinct cell borders
- Mitoses - common.
- Variable architecture:
- Tubulopapillary.
- Glandular.
- Solid.
- Embryoid bodies - ball of cells in surrounded by empty space on three sides.
Notes:
- Cytoplasmic staining variable (eosinophilic to basophilic).
Images:
- Set 1:
- Set 2:
DDx
- Yolk sac tumour.
IHC
- AE1/AE3 +ve.
- CD30 +ve.
Choriocarcinoma
General
- Aggressive clinical course.
Microscopic
Features:
- Cytotrophoblasts - key feature.
- Clear cytoplasm.
- Polygonal shaped cells in cords/masses.
- Distinct cell borders.
- Single uniform nucleus.
- +/-Hemorrhage.
- +/-Necrosis.
- Syncytiotrophoblasts - may be absent.[8]
- Large + many irreg. or lobular hyperchromatic nuclei.
- Eosinophilic vacuolated cytoplasm (contains hCG).
Image(s):
- Choriocarcinoma - low mag. (webpathology.com).
- Choriocarcinoma (webpathology.com).
- Choriocarcinoma (webpathology.com).
Notes:
- See: Chorionic villi.
IHC
- beta-hCG +ve.
Teratoma
General
- Consists of all three germ layers:[9]
- Endoderm:
- Skin, CNS.
- Mesoderm:
- Muscle, bone, connective tissue, blood.
- Ectoderm:
- Internal organs.
- Endoderm:
Classification
- Divided into:
- Mature.
- Immature.
Immature
- Immature if neural tissue is present:[10]
- Vaguely resembles pseudostratified respiratory epithelium.
- Islands of small hyperchromatic cells - "blastema".
- +/-Cartilage.
- +/-Adipocytes.
- +/-Colonic type mucosa.
- +/-Stratified squamous epithelium (skin).
Images:
- Primitive neuroepithelium - high mag. (WC).
- Primitive neuroepithelium - intermed mag. (WC)
- Teratoma - mature components (WC).
Other images:
- Immature teratoma - myxomatous stroma (webpathology.com).
- Immature teratoma - blastema (webpathology.com).
- Immature teratoma - primitive neuroepithelium (webpathology.com).
- Immature teratoma - primitive neuroepithelium (pathconsultddx.com).
- Immature teratoma - primitive neuroepithelium (ouhsc.edu).
Grading
Based on quantity of immature neuroepithelium:[11][12][13]
- G0 - mature teratoma; no immature neuroepithelium.
- G1 - less than one lower power field (LPF) of immature neuroepithelium; LPF defined field at 4X magnification.
- G2 - 1-3 LPFs.
- G3 - more than 3 LPFs.
Note:
- LPF not adequately defined - see LPFitis. Same BS as HPF.
IHC (immature)
Features:
- Primitive neuroepithelium:[14]
- Neuron-specific enolase (NSE) +ve.
- Neuron-specific B tubulin +ve.
- Synaptophysin +ve.
See also
References
- ↑ Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 538. ISBN 978-0443066771.
- ↑ Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 542. ISBN 978-0443066771.
- ↑ URL: http://webpathology.com/image.asp?case=34&n=1. Accessed on: March 8, 2010.
- ↑ URL: http://webpathology.com/image.asp?case=34&n=6. Accessed on: March 8, 2010.
- ↑ URL: http://webpathology.com/image.asp?case=34&n=8. Accessed on: March 8, 2010.
- ↑ Emerson, RE.; Ulbright, TM. (Jun 2010). "Intratubular germ cell neoplasia of the testis and its associated cancers: the use of novel biomarkers.". Pathology 42 (4): 344-55. doi:10.3109/00313021003767355. PMID 20438407.
- ↑ Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 549. ISBN 978-0443066771.
- ↑ URL: http://www.webpathology.com/image.asp?n=4&Case=36. Accessed on: 8 February 2011.
- ↑ Moore, Keith L.; Persaud, T.V.N. (2002). The Developing Human: Clinically Oriented Embryology (7th ed.). Saunders. pp. 83. ISBN 978-0721694122.
- ↑ RS. 2 May 2010.
- ↑ Harms D, Zahn S, Göbel U, Schneider DT (2006). "Pathology and molecular biology of teratomas in childhood and adolescence". Klin Padiatr 218 (6): 296–302. doi:10.1055/s-2006-942271. PMID 17080330.
- ↑ Ulbright TM (February 2005). "Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues". Mod. Pathol. 18 Suppl 2: S61–79. doi:10.1038/modpathol.3800310. PMID 15761467. http://www.nature.com/modpathol/journal/v18/n2s/full/3800310a.html.
- ↑ O'Connor DM, Norris HJ (October 1994). "The influence of grade on the outcome of stage I ovarian immature (malignant) teratomas and the reproducibility of grading". Int. J. Gynecol. Pathol. 13 (4): 283–9. PMID 7814189.
- ↑ Craver RD, Lipscomb JT, Suskind D, Velez MC (October 2001). "Malignant teratoma of the thyroid with primitive neuroepithelial and mesenchymal sarcomatous components". Ann Diagn Pathol 5 (5): 285–92. doi:10.1053/adpa.2001.27918. PMID 11598856.