Difference between revisions of "Gestational trophoblastic disease"

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Revision as of 22:26, 23 May 2012

Gestational trophoblastic disease (GTD) includes choriocarcinoma and hydatidiform moles.

Overview

Most common

Overview of gestational trophoblastic disease:

Gross Nuclear atypia Villi IHC DNA content Micrographs
Complete mole "snowstorm" +/- ? yes, all abnormal [1] p57(KIP2) -ve Paternal, diploid complete mole + intermed. trophoblast (WC), complete mole (WC)
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 (webpathology.com)

More comprehensive overview

Benign abnormal looking placenta:

Abnormal fertilization:

Tumours:

Entities

Choriocarcinoma

General

Gross

  • Dark, shaggy, focally hemorrhagic & friable/necrotic-appearing.
  • Invasive border.

Microscopic

Features:

  • Two cell populations:
  1. Cytotrophoblasts - key feature.
    • Clear cytoplasm.
    • Polygonal shaped cells in cords/masses.
    • Distinct cell borders.
    • Single uniform nucleus.
  2. 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.
  • The dual cell population may not be evident at first.
    • Hemorrhage and marked nuclear pleomorphism are suggestive of the diagnosis.

Images:

IHC

Hydatidiform moles

General

  • Significance: increased risk for choriocarcinoma (in complete moles).
  • Non-neoplastic proliferation.

Etymology:

  • Hydatid is literally watery vesicle.[8]

Types

  1. Partial mole - see partial mole.
  2. Complete mole - see complete mole.

Extent:

  • Invasive mole - not a subtype.
    • 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]

Mole vs. normal

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 lack the maternal genome; thus, p57(KIP2) immunostaining (in the cytotrophoblasts and villous stromal cells) is absent.[12][13]
      • Intermediate trophoblasts and maternal tissue are positive controls.[13]
    • Memory device:
      • p57 is positive in partial moles.
      • 3 Ps - partial moles are triploid.

Molecular

Partial hydatidiform mole

  • AKA partial mole.

General

Genetics:

  • Usually triploid (e.g. 69XXY).

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.
  • "Norwegian fjord periphery"[16] - jagged border / irregular sawtooth-like periphery.
    • Complete moles tend to have a smooth border

Images:

Complete hydatidiform mole

  • AKA complete mole, AKA classic mole.

General

Epidemiology:

Genetics:

  • Diploid - most are 46XX.
  • Male derived, i.e. arise from DNA in sperm; empty egg fertilized.

Gross/Radiology

  • "Snowstorm" appearance on ultrasound.[18]
  • May be described as "grape-like" on gross exam.[19]

Image:

Microscopic

Features:

  • No normal villi.
  • No fetal parts seen.
    • Very rarely nucleated RBCs.

Images:

Invasive hydatidiform mole

  • AKA invasive mole.

General

Microscopic

Features:

  • Chorionic villi - abnormal +/- normal.
  • Trophoblastic cells within uterine muscle +/- vessels - key feature.

DDx:

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, dyscohesive +/-multinucleation MIB1 high, p63 -ve, CD146 +ve EPS, choriocarcinoma Other? (webpathology.com)
Epithelioid trophoblastic tumour (ETT) nests of cells in hyaline stroma eosinophilic cytoplasm, central nucleus MIB1 low, p63 +ve, CD146 -ve squamous carcinoma Other? (webpathology.com)
Choriocarcinoma polygonal cells with clear cytoplasm (cytotrophoblasts) multinucleated cells with smudged nuclei (syncytiotrophoblasts), no chorionic villi beta-hCG +ve, p63 +ve invasive hydatidiform mole, PSTT elevated beta-hCG (serum); not intermediate trophoblast derived. (webpathology.com)

Placental site nodule

  • Abbreviated PSN.

General

  • Benign.
  • Intermediate trophoblast remnants from a previous gestation.[20]

Clinical:

  • Vaginal bleed.

Microscopic

Features:[20]

  • Paucicellular with hyaline material scattered cells.
  • Variable cell population:
    • Small-large cells.
    • Clear to eosinophilic cytoplasm.
    • +/-Multinucleation.

Notes:

  • No mitotic activity.

Images:

DDx:

Exaggerated placental site

  • Abbreviated EPS.

General

  • Benign.

Definition:

Note:

  • Used to go by a terrible old term: syncytial endometritis:[21]
    • Not syncytial -- mostly.
    • Not inflammatory.

Microscopic

Features:[21]

  • 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.
  • Ectatic blood vessels.

DDx:

IHC

  • MIB1 ~0%.
    • Used to differentiate from PSTT.

Placental site trophoblastic tumour

  • Abbreviated PSTT.
  • Malignant counterpart of exaggerated placental site (abbreviated EPS).

General

  • Derived from intermediate trophoblast.
  • Follows pregnancy.
  • May be associated with nephrotic syndrome[22] with granular IgM staining.[23]

Clinical:

  • Raised (serum) beta-hCG - but usually not has high as in choriocarcinoma.
    • In ~70% < 1000 IU/L.[24]
    • In a series of 55 cases the average beta-hCG was ~700 IU/L.[25]
  • Prognosis dependent on time of diagnosis from last pregnancy.
    • <48 months = good prognosis.[24]

Microscopic

Features:

  • Large cells:
    • Nuclear pleomorphism.
    • Cytoplasm:
      • Abundant.
      • Solid, i.e. not vesicular.
      • Light basophilic, not clear - key feature.
    • NC ratio ~ normal.
  • +/-Multinucleated cells.
  • Ectatic blood vessels.

Note:

DDx:

Images:

IHC

Features:[27]

  • CD146 +ve.
  • p63 -ve.
  • Ki-67 ~14+/-7%.
    • Choriocarcinoma ~69+/-20%.

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:[28]

  • Architecture: nests in hyaline matrix.
  • Cytoplasm: abundant, eosinophilic.

DDx:

Images:

IHC

Features:[29]

  • Cyclin E +ve (nuclear).
  • p16 -ve.
    • +ve (nuclear) in squamous cell carcinoma of the cervix.

Others:

  • HMCK -ve.
    • SCC +ve.

Note:

  • p63 not useful... +ve in both SCC and ETT.

See also

References

  1. http://pathologyoutlines.com/placenta.html#completemole
  2. 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.
  3. URL: http://www.webpathology.com/image.asp?n=4&Case=36. Accessed on: 8 February 2011.
  4. 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.
  5. 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. 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/.
  7. 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.
  8. URL: http://dictionary.reference.com/browse/hydatid.
  9. URL: http://www.ihcworld.com/_newsletter/2003/focus_mar_2003.pdf. Accessed on: 28 May 2011.
  10. URL: http://pathologyoutlines.com/placenta.html#hydatgeneral.
  11. 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.
  12. 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.
  13. 13.0 13.1 Fukunaga, M. (Dec 2002). "Immunohistochemical characterization of p57(KIP2) expression in early hydatidiform moles.". Hum Pathol 33 (12): 1188-92. doi:10.1053/hupa.2002.129421. PMID 12514787.
  14. http://jcp.bmjjournals.com/cgi/reprint/51/6/438.pdf
  15. URL: http://pathologyoutlines.com/placenta.html#incompletemole. Accessed on: 9 August 2011.
  16. 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.
  17. 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.
  18. URL:http://www.jultrasoundmed.org/cgi/content/abstract/18/9/589. Accessed on: 27 July 2010.
  19. Abike, F.; Temizkan, O.; Payasli, A.; Avsar, F.; Karahan, N.; Baspinar, S. (Jan 2008). "Postmenopausal complete hydatidiform mole: a case report.". Maturitas 59 (1): 95-8. doi:10.1016/j.maturitas.2007.10.005. PMID 18162339.
  20. 20.0 20.1 20.2 20.3 20.4 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.
  21. 21.0 21.1 URL: http://moon.ouhsc.edu/kfung/IACP-OLP/TC-Text/TC-01-Supp.pdf. Accessed on: 15 August 2011.
  22. Bonazzi, C.; Urso, M.; Dell'Anna, T.; Sacco, S.; Buda, A.; Cantú, MG. (Aug 2004). "Placental site trophoblastic tumor: an overview.". J Reprod Med 49 (8): 585-8. PMID 15457847.
  23. Komatsuda, A.; Nakamoto, Y.; Asakura, K.; Yasuda, T.; Imai, H.; Miura, AB. (May 1992). "Case report: nephrotic syndrome associated with a total hydatidiform mole.". Am J Med Sci 303 (5): 309-12. PMID 1580319.
  24. 24.0 24.1 Schmid, P.; Nagai, Y.; Agarwal, R.; Hancock, B.; Savage, PM.; Sebire, NJ.; Lindsay, I.; Wells, M. et al. (Jul 2009). "Prognostic markers and long-term outcome of placental-site trophoblastic tumours: a retrospective observational study.". Lancet 374 (9683): 48-55. doi:10.1016/S0140-6736(09)60618-8. PMID 19552948.
  25. Baergen, RN.; Rutgers, JL.; Young, RH.; Osann, K.; Scully, RE. (Mar 2006). "Placental site trophoblastic tumor: A study of 55 cases and review of the literature emphasizing factors of prognostic significance.". Gynecol Oncol 100 (3): 511-20. doi:10.1016/j.ygyno.2005.08.058. PMID 16246400.
  26. URL: http://www.webpathology.com/image.asp?n=3&Case=588. Accessed on: 1 January 2012.
  27. Shih, IM.; Kurman, RJ. (Jan 1998). "Ki-67 labeling index in the differential diagnosis of exaggerated placental site, placental site trophoblastic tumor, and choriocarcinoma: a double immunohistochemical staining technique using Ki-67 and Mel-CAM antibodies.". Hum Pathol 29 (1): 27-33. PMID 9445130.
  28. 28.0 28.1 URL: http://www.webpathology.com/image.asp?case=589&n=2. Accessed on: 15 August 2011.
  29. 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.