Difference between revisions of "Gestational trophoblastic disease"
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=Entities= | =Entities= | ||
==Choriocarcinoma== | ==Choriocarcinoma== | ||
{{Main|Choriocarcinoma}} | |||
===General=== | ===General=== | ||
*Classified as a [[germ cell tumour]]. | *Classified as a [[germ cell tumour]]. | ||
*May be preceded by a complete hydatidiform mole.<ref name=Ref_PBoD1110-1>{{Ref PBoD|1110-1111}}</ref> | *May be preceded by a complete hydatidiform mole.<ref name=Ref_PBoD1110-1>{{Ref PBoD|1110-1111}}</ref> | ||
===Microscopic=== | ===Microscopic=== | ||
Features: | Features: | ||
*[ | *Two cell populations: | ||
* | #'''C'''ytotrophoblasts - '''key feature'''. | ||
* | #*'''C'''lear cytoplasm. | ||
#*Polygonal shaped cells in cords/masses. | |||
#*Distinct cell borders. | |||
#*Single uniform nucleus. | |||
#Syncytiotrophoblasts - may be absent.<ref>URL: [http://www.webpathology.com/image.asp?n=4&Case=36 http://www.webpathology.com/image.asp?n=4&Case=36]. Accessed on: 8 February 2011.</ref> | |||
#*Large + many irreg. or lobular hyperchromatic nuclei. | |||
#*Eosinophilic vacuolated cytoplasm (contains hCG). | |||
*+/-Hemorrhage. | |||
*+/-Necrosis. | |||
Notes: | |||
*[ | *No ''[[chorionic villi]]'' should be present. | ||
* | **If chorionic villi are present... it is likely a type of [[hydatidiform mole]]. | ||
*The dual cell population may not be evident at first. | |||
**Hemorrhage and marked nuclear pleomorphism are suggestive of the diagnosis. | |||
Images: | |||
* | *www: | ||
**[http://www.webpathology.com/image.asp?n=5&Case=36 Choriocarcinoma - low mag. (webpathology.com)]. | |||
**[http://www.webpathology.com/image.asp?case=36&n=1 Choriocarcinoma (webpathology.com)]. | |||
**[http://www.webpathology.com/image.asp?n=4&Case=36 Choriocarcinoma (webpathology.com)]. | |||
**[http://chestjournal.chestpubs.org/content/138/1/220.full Choriocarcinoma (chestjournal.chestpubs.org)].<ref>{{Cite journal | last1 = Venkatram | first1 = S. | last2 = Muppuri | first2 = S. | last3 = Niazi | first3 = M. | last4 = Fuentes | first4 = GD. | title = A 24-year-old pregnant patient with diffuse alveolar hemorrhage. | journal = Chest | volume = 138 | issue = 1 | pages = 220-3 | month = Jul | year = 2010 | doi = 10.1378/chest.09-2688 | PMID = 20605823 }}</ref> | |||
**[http://oac.med.jhmi.edu/Pathology/Repro/Placenta/279B_Full.html Choriocarcinoma - uterus (med.jhmi.edu)]. | |||
*[[WC]]: | |||
**[http://commons.wikimedia.org/wiki/File:Choriocarcinoma_-2-_high_mag.jpg Choriocarcinoma - high mag. (WC)]. | |||
**[http://commons.wikimedia.org/wiki/File:Choriocarcinoma_-2-_very_high_mag.jpg Choriocarcinoma - very high mag. (WC)]. | |||
===IHC=== | ===IHC=== | ||
*beta-hCG +ve.<ref name=pmid19145204>{{cite journal |author=Kalhor N, Ramirez PT, Deavers MT, Malpica A, Silva EG |title=Immunohistochemical studies of trophoblastic tumors |journal=Am. J. Surg. Pathol. |volume=33 |issue=4 |pages=633–8 |year=2009 |month=April |pmid=19145204 |doi=10.1097/PAS.0b013e318191f2eb |url=}}</ref> | *beta-hCG +ve.<ref name=pmid19145204>{{cite journal |author=Kalhor N, Ramirez PT, Deavers MT, Malpica A, Silva EG |title=Immunohistochemical studies of trophoblastic tumors |journal=Am. J. Surg. Pathol. |volume=33 |issue=4 |pages=633–8 |year=2009 |month=April |pmid=19145204 |doi=10.1097/PAS.0b013e318191f2eb |url=}}</ref> | ||
**Classically said to be produced by syncytiotrophoblasts.<ref name=pmid20735820>{{Cite journal | last1 = Cole | first1 = LA. | title = Biological functions of hCG and hCG-related molecules. | journal = Reprod Biol Endocrinol | volume = 8 | issue = | pages = 102 | month = | year = 2010 | doi = 10.1186/1477-7827-8-102 | PMID = 20735820 | PMC = 2936313 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2936313/ }} | |||
</ref> | |||
***Cytotrophoblasts also produce some.<ref name=pmid20735820/><ref name=pmid12242037>{{Cite journal | last1 = Kovalevskaya | first1 = G. | last2 = Genbacev | first2 = O. | last3 = Fisher | first3 = SJ. | last4 = Caceres | first4 = E. | last5 = O'Connor | first5 = JF. | title = Trophoblast origin of hCG isoforms: cytotrophoblasts are the primary source of choriocarcinoma-like hCG. | journal = Mol Cell Endocrinol | volume = 194 | issue = 1-2 | pages = 147-55 | month = Aug | year = 2002 | doi = | PMID = 12242037 }}</ref> | |||
==Hydatidiform moles== | ==Hydatidiform moles== | ||
Revision as of 04:09, 28 December 2011
Gestational trophoblastic disease (GTD) includes choriocarcinoma and hydatidiform moles.
Overview
Most common
Overview of gestational trophoblastic disease:
| Gross | Nuclear atypia | Villi | IHC | DNA content | Images | |
| Complete mole | "snowstorm" | +/- ? | yes, all abnormal [1] | p57(KIP2) -ve | Paternal, diploid | Complete mole (pathconsultddx.com) |
| Partial mole | grape-like clusters |
+/- | large villi, villi with cisterns, villi with cytotrophoblastic inclusions |
p57(KIP2) +ve | Maternal & paternal, tripoid | Partial mole (utah.edu) |
| Choriocarcinoma | haemorrahagic, necrotic | marked | none | beta-hCG +ve | ? | Choriocarcinoma - testicular (webpathology.com) |
More comprehensive overview
Benign abnormal looking placenta:
- Placental site nodule (PSN).
- Exaggerated placental site (EPS).
Abnormal fertilization:
Tumours:
- Invasive mole.
- Choriocarcinoma.
- Placental site trophoblastic tumour (PSTT).
- Epithelioid trophoblastic tumour (ETT).
Entities
Choriocarcinoma
Main article: Choriocarcinoma
General
- Classified as a germ cell tumour.
- May be preceded by a complete hydatidiform mole.[2]
Microscopic
Features:
- Two cell populations:
- Cytotrophoblasts - key feature.
- Clear cytoplasm.
- Polygonal shaped cells in cords/masses.
- Distinct cell borders.
- Single uniform nucleus.
- Syncytiotrophoblasts - may be absent.[3]
- Large + many irreg. or lobular hyperchromatic nuclei.
- Eosinophilic vacuolated cytoplasm (contains hCG).
- +/-Hemorrhage.
- +/-Necrosis.
Notes:
- No chorionic villi should be present.
- If chorionic villi are present... it is likely a type of hydatidiform mole.
- The dual cell population may not be evident at first.
- Hemorrhage and marked nuclear pleomorphism are suggestive of the diagnosis.
Images:
- www:
- WC:
IHC
- beta-hCG +ve.[5]
Hydatidiform moles
General
- Significance: increased risk for choriocarcinoma (in complete moles).
- Non-neoplastic proliferation.
Etymology:
- Hydatid is literally watery vesicle.[8]
Types
- Partial mole - see partial mole.
- Complete mole - see complete mole.
- Invasive mole.
- Within uterine muscle +/- vessels.
Microscopic
Hydropic changes:
| Entity | Villi (outline) | Cisterns | Blood vessels | Nucleated RBCs | p57 / Ki-67[9] staining | Ploidy | Image |
| Complete mole | bizarre; often not ovoid; fissures/slit-like gaps | well-developed | canalicular (thin walled) / few (???) | rare | -ve / ~70% | diploid / tetraploid | [1], [2], [3], [4] |
| Partial mole | jagged, still quasi ovoid | poorly developed / small | present | common | +ve / ~70% | triploid | [5], [6] |
| Hydropic abortus | smooth | poorly developed / small | common | common | +ve / ~20% | diploid | [7] |
![[1]](http://commons.wikimedia.org/wiki/File:Hydatidiform_mole_%281%29_complete_type.jpg){kind=link}
![[2]](http://commons.wikimedia.org/wiki/File:Hydatidiform_mole_%282%29_complete_type.jpg){kind=link}
![[3]](http://commons.wikimedia.org/wiki/File:Hydatidiform_mole_%283%29_complete_type.jpg){kind=link}
![[4]](http://commons.wikimedia.org/wiki/File:Hydatidiform_mole_%284%29_complete_type.jpg){kind=link}
Mole vs. normal
- Moles have large chorionic villi with edema and abnormal blood vessels.[10]
Non-molar vs. partial vs. complete - short version
Features:[11]
- Non-molar pregnancy: polar proliferation of trophoblastic tissue.
- Partial mole: Norwegian fjord periphery, circumferential or multifocal trophoblastic proliferation, fetal parts.
- Complete mole: grapes grossly, large villi with round borders.
IHC
- p57(KIP2) - the gene is strongly paternally imprinted and the paternal copy is inactived; its expression is from the maternal gene.
- Complete moles lacks the maternal genome; thus, p57(KIP2) immunostaining is absent.[12]
- Memory device:
- p57 is positive in partial moles.
- 3 Ps - partial moles are triploid.
Molecular
- The type of mole can be determined by cytogenetics.[13]
Partial hydatidiform mole
- AKA partial mole.
General
Genetics:
- Polypoid - usually triploid (e.g. 69XXY).
Images: [8]
Microscopic
Features:
- Abnormal chorionic villi.
- Villi too large (>0.1 mm ?).
- Villi with cisterns.
- Contain fluid in the centre, i.e. are "hydropic".
- Villi with cytotrophoblastic inclusions.
- Cytotrophoblast in the core of a villus (normally it is only at the surface of the villus).
- May have fetal parts, such as nucleated RBCs.
- Trophoblastic proliferation.
- Without atypia.[14]
- "Norwegian fjord periphery"[15] - jagged border / irregular sawtooth-like periphery.
- Complete moles tend to have a smooth border
Images:
Complete hydatidiform mole
General
Epidemiology:
- May precede choriocarcinoma[16] ~ 1-2% risk.
Genetics:
- Diploid - most are 46XX.
- Male derived, i.e. arise from DNA in sperm; empty egg fertilized.
Radiology
- "Snowstorm" appearance on ultrasound.[17]
Microscopic
Features:
- No normal villi.
- No fetal parts seen.
- Very rarely nucleated RBCs.
Image:
Entities - intermediate trophoblast
| Entity | Key feature | Other histologic features | IHC | DDx | Other | Image |
|---|---|---|---|---|---|---|
| Placental site nodule (PSN) | paucicellular, hyaline material | no mitotic activity | IHC? | EPS ??? | post-partum | (ijpmonline.org) |
| Exaggerated placental site (EPS) | abundant intermediate trophoblasts - between muscle | no mitotic activity | MIB1 ~0% | PSTT, PSN | post-partum | Image? |
| Placental site trophoblastic tumour (PSTT) | abundant cytoplasm - not clear | +/-multinucleation | MIB1 high | EPS | Other? | (webpathology.com) |
| Epithelioid trophoblastic tumour (ETT) | nests of cells in hyaline stroma | eosinophilic cytoplasm, central nucleus | MIB1 low | squamous carcinoma | Other? | (webpathology.com) |
| Choriocarcinoma | polygonal cells with clear cytoplasm (cytotrophoblasts) | multinucleated cells with smudged nuclei (syncytiotrophoblasts), usu. no chorionic villi | beta-hCG | DDx? | elevated beta-hCG (serum); not intermediate trophoblast derived. | (webpathology.com) |
Placental site nodule
- Abbreviated PSN.
General
- Benign.
- Intermediate trophoblast remnants from a previous gestation.[18]
Microscopic
Features:[18]
- Paucicellular with hyaline material scattered cells.
- Variable cell population:
- Small-large cells.
- Clear to eosinophilic cytoplasm.
- +/-Multinucleation.
Notes:
- No mitotic activity.
Images:
- PSN (ijpmonline.org).[18]
- PSN (gfmer.ch) - includes images from Jacob and Mohapatra.[18]
DDx:
- Invasive (cervical) squamous cell carcinoma.
- Can be sorted-out with IHC (SCC will typically be: p16 +ve, MIB1 +ve).
- Exaggerated placental site.
- Different histomorphology than PSN; EPS:[18] syncytiotrophoblastic tissue, in cords/nests, no hyaline nodules.
Exaggerated placental site
- Abbreviated EPS.
General
- Benign.
Definition:
- "Increased number" of implantation-site intermediate trophoblastic cells.
Note:
- Used to go by a terrible old term: syncytial endometritis:[19]
- Not syncytial -- mostly.
- Not inflammatory.
Microscopic
Features:[19]
- Intermediate trophoblast:
- Abundant (eosinophilic) cytoplasm.
- Usu. adjacent to:
- Chorionic villi.
- Decidua - endometrial stromal cells with a nucleus central, eosinphilic cytoplasm, well-defined cell borders.
- No mitotic activity.
DDx:
- PSTT.
IHC
- MIB1 ~0%.
- Used to differentiate from PSTT.
Placental site trophoblastic tumour
- Abbreviated PSTT.
- Malignant counterpart of exaggerated placental site (abbreviated EPS).
General
Clinical
- Raised beta-hCG - but usually not has high as in choriocarcinoma.[20]
- Derived from intermediate trophoblast.
Epidemiology
- Usually follows a normal pregnancy ~ 75% of cases.[20]
Microscopic
Features:
- Large cells.
- Nuclear pleomorphism.
- Cytoplasm:
- Abundant.
- Solid, i.e. not vesicular.
- Light basophilic, not clear - key feature.
- NC ratio ~ normal.
- +/-Multinucleated cells.
DDx:
EPS vs. PSTT:
- EPS has a low MIB1 (Ki-67).
Images:
Epithelioid trophoblastic tumour
- Abbreviated ETT.
General
- Often in endocervix.
- Malignant counterpart of placental site nodule or PSN.
Clinical:
- Vaginal bleeding.
- Elevated beta-hCG.
Microscopic
Features:[21]
- Architecture: nests in hyaline matrix.
- Cytoplasm: abundant, eosinophilic.
DDx:
- Invasive squamous cell carcinoma.
Images:
IHC
Features:[22]
- Cyclin E +ve (nuclear).
- p16 -ve.
- +ve (nuclear) in squamous cell carcinoma of the cervix.
See also
- Hydatid disease - due to Echinoccus spp. such as E. granulosus.
- Chorionic villi.
- Ectopic pregnancy.
- Placenta.
- Arias-Stella reaction - benign atypical changes of the endometrium associated with trophoblastic tissue.
References
- ↑ http://pathologyoutlines.com/placenta.html#completemole
- ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1110-1111. ISBN 0-7216-0187-1.
- ↑ URL: http://www.webpathology.com/image.asp?n=4&Case=36. Accessed on: 8 February 2011.
- ↑ Venkatram, S.; Muppuri, S.; Niazi, M.; Fuentes, GD. (Jul 2010). "A 24-year-old pregnant patient with diffuse alveolar hemorrhage.". Chest 138 (1): 220-3. doi:10.1378/chest.09-2688. PMID 20605823.
- ↑ Kalhor N, Ramirez PT, Deavers MT, Malpica A, Silva EG (April 2009). "Immunohistochemical studies of trophoblastic tumors". Am. J. Surg. Pathol. 33 (4): 633–8. doi:10.1097/PAS.0b013e318191f2eb. PMID 19145204.
- ↑ 6.0 6.1 Cole, LA. (2010). "Biological functions of hCG and hCG-related molecules.". Reprod Biol Endocrinol 8: 102. doi:10.1186/1477-7827-8-102. PMC 2936313. PMID 20735820. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2936313/.
- ↑ Kovalevskaya, G.; Genbacev, O.; Fisher, SJ.; Caceres, E.; O'Connor, JF. (Aug 2002). "Trophoblast origin of hCG isoforms: cytotrophoblasts are the primary source of choriocarcinoma-like hCG.". Mol Cell Endocrinol 194 (1-2): 147-55. PMID 12242037.
- ↑ URL: http://dictionary.reference.com/browse/hydatid.
- ↑ URL: http://www.ihcworld.com/_newsletter/2003/focus_mar_2003.pdf. Accessed on: 28 May 2011.
- ↑ URL: http://pathologyoutlines.com/placenta.html#hydatgeneral.
- ↑ Howat, AJ.; Beck, S.; Fox, H.; Harris, SC.; Hill, AS.; Nicholson, CM.; Williams, RA. (Jul 1993). "Can histopathologists reliably diagnose molar pregnancy?". J Clin Pathol 46 (7): 599-602. PMID 8157742.
- ↑ Merchant SH, Amin MB, Viswanatha DS, Malhotra RK, Moehlenkamp C, Joste NE (February 2005). "p57KIP2 immunohistochemistry in early molar pregnancies: emphasis on its complementary role in the differential diagnosis of hydropic abortuses". Hum. Pathol. 36 (2): 180–6. doi:10.1016/j.humpath.2004.12.007. PMID 15754295.
- ↑ http://jcp.bmjjournals.com/cgi/reprint/51/6/438.pdf
- ↑ URL: http://pathologyoutlines.com/placenta.html#incompletemole. Accessed on: 9 August 2011.
- ↑ Howat, AJ.; Beck, S.; Fox, H.; Harris, SC.; Hill, AS.; Nicholson, CM.; Williams, RA. (Jul 1993). "Can histopathologists reliably diagnose molar pregnancy?". J Clin Pathol 46 (7): 599-602. PMID 8157742. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC501384/?page=3.
- ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1111. ISBN 0-7216-0187-1.
- ↑ URL:http://www.jultrasoundmed.org/cgi/content/abstract/18/9/589. Accessed on: 27 July 2010.
- ↑ 18.0 18.1 18.2 18.3 18.4 Jacob, S.; Mohapatra, D.. "Placental site nodule: a tumor-like trophoblastic lesion.". Indian J Pathol Microbiol 52 (2): 240-1. PMID 19332926. http://www.ijpmonline.org/text.asp?2009/52/2/240/48931.
- ↑ 19.0 19.1 URL: http://moon.ouhsc.edu/kfung/IACP-OLP/TC-Text/TC-01-Supp.pdf. Accessed on: 15 August 2011.
- ↑ 20.0 20.1 URL: http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675(06)70463-6. Accessed on: 23 September 2009.
- ↑ 21.0 21.1 URL: http://www.webpathology.com/image.asp?case=589&n=2. Accessed on: 15 August 2011.
- ↑ Mao, TL.; Seidman, JD.; Kurman, RJ.; Shih, IeM. (Sep 2006). "Cyclin E and p16 immunoreactivity in epithelioid trophoblastic tumor--an aid in differential diagnosis.". Am J Surg Pathol 30 (9): 1105-10. doi:10.1097/01.pas.0000209854.28282.87. PMID 16931955.