Choriocarcinoma

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Choriocarcinoma is a rare aggressive germ cell tumour.

Choriocarcinoma
Diagnosis in short

Choriocarcinoma. H&E stain.

LM cytotrophoblasts, syncytiotrophoblast (often wrapped around the cytotrophoblasts) - multinucleated, hemorrhage (very common), necrosis (common)
LM DDx mixed germ cell tumour, invasive hydatidiform mole, placental site trophoblastic tumour
IHC beta-hCG +ve, CD10 +ve, p63 +ve, OCT3 -ve, GATA3 +ve, CK7 +ve
Gross dark friable, hemorrhagic/necrotic-appearing mass with an invasive border
Grossing notes orchiectomy grossing
Staging testicular cancer staging
Site ovary, testis, uterus

Associated Dx complete hydatidiform mole
Clinical history often preceded by pregnancy
Signs testicular mass (male)
Symptoms vaginal bleeding (female)
Prevalence rare
Blood work beta-hCG markedly elevated (usu. >10,000 IU)
Prognosis often poor
Treatment surgery and chemotherapy

General

  • Aggressive clinical course.
  • Usually a mixed tumour, i.e. pure choriocarcinoma is rare, e.g. dysgerminoma + choriocarcinoma.

Clinical

  • High beta-hCG -- usually > 10,000 IU.
    • Median in one series of testicular choriocarcinoma ~ 200,000 IU.[1]
    • Elevation may be seen in other (non-trophoblastic) tumours.[2]
  • Vaginal bleeding or testicular mass.
  • Occasionally thyrotoxicosis.[3]

Note:

  • Beta-hCG is negative ~3 weeks after pregnancy.[4]

Epidemiology

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.[6]
    • Large + many irreg. or lobular hyperchromatic nuclei.
    • Eosinophilic vacuolated cytoplasm (contains hCG).
  • +/-Hemorrhage - classically in the centre of the lesion.
  • +/-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.

DDx:

Images

Case

Case

www

IHC

ISUP consensus paper by Ulbright et al.:[8]

  • Beta-hCG +ve.
  • Glypican 3 +ve/-ve.
  • OCT3 -ve.
  • AFP -ve.

Others:

Notes:

  • Beta-hCG is classically said to be produced by syncytiotrophoblasts.[15]
    • Cytotrophoblasts also produce some[15][16] - usually no staining.

See also

References

  1. Alvarado-Cabrero, I.; Hernández-Toriz, N.; Paner, GP. (Jan 2014). "Clinicopathologic analysis of choriocarcinoma as a pure or predominant component of germ cell tumor of the testis.". Am J Surg Pathol 38 (1): 111-8. doi:10.1097/PAS.0b013e3182a2926e. PMID 24145647.
  2. Mann, K.; Saller, B.; Hoermann, R. (1993). "Clinical use of HCG and hCG beta determinations.". Scand J Clin Lab Invest Suppl 216: 97-104. PMID 7690985.
  3. O'Reilly, S.; Lyons, DJ.; Harrison, M.; Gaffney, E.; Cullen, M.; Clancy, L.. "Thyrotoxicosis induced by choriocarcinoma a report of two cases.". Ir Med J 86 (4): 124, 127. PMID 8395487.
  4. Haenel, AF.; Hugentobler, W.; Brunner, S.. "[The postpartum course of the HCG titer of maternal blood and its clinical relevance].". Z Geburtshilfe Perinatol 190 (6): 275-8. PMID 2436389.
  5. 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.
  6. URL: http://www.webpathology.com/image.asp?n=4&Case=36. Accessed on: 8 February 2011.
  7. 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.
  8. Ulbright TM, Tickoo SK, Berney DM, Srigley JR (August 2014). "Best practices recommendations in the application of immunohistochemistry in testicular tumors: report from the international society of urological pathology consensus conference". Am. J. Surg. Pathol. 38 (8): e50–9. doi:10.1097/PAS.0000000000000233. PMID 24832161.
  9. Mittal, K.; Soslow, R.; McCluggage, WG. (Mar 2008). "Application of immunohistochemistry to gynecologic pathology.". Arch Pathol Lab Med 132 (3): 402-23. doi:10.1043/1543-2165(2008)132[402:AOITGP]2.0.CO;2. PMID 18318583.
  10. Park, SY.; Lee, DE.; Park, HJ.; Kim, KC.; Kim, YH. (Nov 2014). "Retroperitoneal nongestational choriocarcinoma in a 25-year-old woman.". Obstet Gynecol Sci 57 (6): 544-8. doi:10.5468/ogs.2014.57.6.544. PMID 25469347.
  11. Hemati, S.; Esnaashari, O.; Mohajeri, M.; Sarvizadeh, M. (May 2011). "Choriocarcinoma of the breast; a case report and review of literatures.". J Res Med Sci 16 (5): 707-11. PMID 22091297.
  12. Mao, TL.; Kurman, RJ.; Huang, CC.; Lin, MC.; Shih, IeM. (Nov 2007). "Immunohistochemistry of choriocarcinoma: an aid in differential diagnosis and in elucidating pathogenesis.". Am J Surg Pathol 31 (11): 1726-32. doi:10.1097/PAS.0b013e318058a529. PMID 18059230.
  13. Kalhor, N.; Ramirez, PT.; Deavers, MT.; Malpica, A.; Silva, EG. (Apr 2009). "Immunohistochemical studies of trophoblastic tumors.". Am J Surg Pathol 33 (4): 633-8. doi:10.1097/PAS.0b013e318191f2eb. PMID 19145204.
  14. Osman H, Cheng L, Ulbright TM, Idrees MT (February 2016). "The utility of CDX2, GATA3, and DOG1 in the diagnosis of testicular neoplasms: an immunohistochemical study of 109 cases". Hum Pathol 48: 18–24. doi:10.1016/j.humpath.2015.09.028. PMID 26772394.
  15. 15.0 15.1 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/.
  16. 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.