Hepatocellular carcinoma

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Hepatocellular carcinoma, abbreviated HCC, is a common primary malignant liver tumour that most often arises in the context of cirrhosis.

General

Clinical:

  • Serum AFP elevated - in approx. 50% of patients.[1]
  • Treatments: RFA (radiofrequency ablation), ethanol ablation, liver resection, liver transplant.[2]
  • Mean survival at time of diagnosis ~6 months.[2]

Epidemiology:

  • Highest where prevalence of hepatitis B virus (HBV) is high.[3]
  • HCC generally arises in the setting of cirrhosis.
    • Cirrhosis may be regressed and therefore not appreciated.

HCCs without cirrhosis:

  • Hepatitis B virus.[3]
  • Hemochromatosis.
  • Fibrolamellar HCC.

Risk factors:[3][4]

Gross

Features:[5]

  • Unifocal, multifocal or diffusely infiltrative.
    • Tumours are multifocal in approx. 50% of cases;[6][7] some authors have suggested it is upto 75% of cases.[2]
  • Pale in relation to surrounding liver or green (due to bile secretion).

Microscopic

Requirements:[8]

  • Architectural changes.
    • Liver plate more than 3 cells thick - key feature.
    • Loss of reticulin scaffold - incomplete loss is considered significant.
    • CD34+ staining cells, suggesting loss of epithelial cells that form the sinusoids.
    • Loss of structures seen in a normal liver lobule (bile ductules, portal triad).
    • Invasion of the portal tract - useful in well-diff. lesions.[9]

Additional findings:[10]

  • Nuclear changes.
    • Increased NC ratio - key feature if present.
    • Nuclear hyperchromasia.
    • Abnormal nuclear contour.
    • Mitoses.
  • Cytoplasmic changes.
    • Cytoplasmic hyperchromasia, clearing or lighter staining.

Varied architecture - may be:[11]

  • Pseudoglandular - can be confused with adenocarcinoma.
  • Trabecular.
  • Fibrolamellar.
  • Solid.

Notes:

  • HCC with trabecular morphology has some resemblance to normal liver - but has extra cells.
  • Fibrolamellar - better prognosis, classically in young adults.
  • Stroma is usually scant.[12]

ASIDE:

DDx:

Images

  • HCC - low mag. (WC)

  • HCC - intermed mag. (WC)

Fibrolamellar hepatocellular carcinoma

  • Abbreviated fibrolamellar HCC, FL-HCC, and FHCC.

General

  • Rare variant.
  • Classically afflicts younger patients.
    • Mean age at onset ~27 years in one study.[14]
  • Individuals usually do not have the classic risk factors for HCC, i.e. no cirrhosis, no hepatitis.[14]

Clinical:

  • AFP usu. not elevated.[14]

Microscopic

Features:[15]

  • Large polygonal tumours cells with:
    • Graunular eosinophilic cytoplasm.
    • Low NC ratio.[16]
  • Layered dense collagen bundles.

DDx:

Note:

  • If conventional HCC is seen focally within the tumour, it is conventional HCC.
Images

  • FHCC - intermed. mag. (WC)

  • FHCC - very high mag. (WC)

Sclerosing HCC

Features:

  • Fibrosis. (???)

Notes:

  • Seen in non-cirrhotic livers.

Grading

Edmondson-Steiner grading system:[17][18]

  • Well-differentiated.
    • Some say "it cannot be diagnosed on biopsy,"[19] as it cannot be reliably differentiated from a regenerative nodule.
  • Moderately differentiated.
    • Round, regular nuclei, some hyperchromatism, nucleoli present, increase NC ratio.
  • Poor differentiated.
    • Very prominent nucleoli, pronounced nuclear irregularity.
  • Undifferentiated.
    • Anaplastic giant cells.

Simplified description - based on MacSween:[18]

  • Well-differentiated = cytologically near normal.
  • Moderate = looks like a cancer, small nucleoli.
  • Poor = bad cancer, raisin-like (irregular) nuclear membrane, large nucleoli (~1/3 of nucleus).
  • Undifferentiated = death on a slide, huge cells (3-4x the size of other cells).

IHC

  • CD34 +ve sinusoids; sinusoids in normal liver are CD34 -ve.
  • HepPar-1 +ve; may be neg. in high grade tumours.
  • AFP +ve; may be neg. even if the serum AFP is elevated.
  • CK8/18 +ve.[20]
  • Glypican-3 +ve (cytoplasmic, granular cytoplasmic or membranous).[21]

Bile canaliculi:

Image:

Sign out

Negative core biopsy

LIVER CORE, BIOPSY:
- CIRRHOSIS.
- HEPATOCYTE CYTOLOGY WITHIN NORMAL LIMITS.

See also

References

  1. ↑ Iacobuzio-Donahue, Christine A.; Montgomery, Elizabeth A. (2005). Gastrointestinal and Liver Pathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 588. ISBN 978-0443066573.
  2. ↑ 2.0 2.1 2.2 2.3 http://emedicine.medscape.com/article/282814-overview
  3. ↑ 3.0 3.1 3.2 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. 924. ISBN 0-7216-0187-1.
  4. ↑ Leong TY, Leong AS (2005). "Epidemiology and carcinogenesis of hepatocellular carcinoma". HPB (Oxford) 7 (1): 5–15. doi:10.1080/13651820410024021. PMC 2023917. PMID 18333156. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2023917/.
  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. 925. ISBN 0-7216-0187-1.
  6. ↑ Yusuf MA, Badar F, Meerza F, et al. (2007). "Survival from hepatocellular carcinoma at a cancer hospital in Pakistan". Asian Pac. J. Cancer Prev. 8 (2): 272–4. PMID 17696722.
  7. ↑ Sharieff S, Burney KA, Ahmad N, Salam A, Siddiqui T (October 2001). "Radiological features of hepatocellular carcinoma in Southern Pakistan". Trop Doct 31 (4): 224–5. PMID 11676064.
  8. ↑ Adapted from STC (19 Jan 2009).
  9. ↑ Kojiro, M.; Wanless, IR.; Alves, V.; Badve, S.; Balabaud, C.; Bedossa, P.; Bhathal, P.; Bioulac-Sage, P. et al. (Feb 2009). "Pathologic diagnosis of early hepatocellular carcinoma: a report of the international consensus group for hepatocellular neoplasia.". Hepatology 49 (2): 658-64. doi:10.1002/hep.22709. PMID 19177576. http://onlinelibrary.wiley.com/doi/10.1002/hep.22709/pdf.
  10. ↑ Adapted from STC (19 Jan 2009).
  11. ↑ Iacobuzio-Donahue, Christine A.; Montgomery, Elizabeth A. (2005). Gastrointestinal and Liver Pathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 590-1. ISBN 978-0443066573.
  12. ↑ Iacobuzio-Donahue, Christine A.; Montgomery, Elizabeth A. (2005). Gastrointestinal and Liver Pathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 591. ISBN 978-0443066573.
  13. ↑ Walther, Z.; Jain, D. (2011). "Molecular pathology of hepatic neoplasms: classification and clinical significance.". Patholog Res Int 2011: 403929. doi:10.4061/2011/403929. PMC 3090128. PMID 21559202. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3090128/.
  14. ↑ 14.0 14.1 14.2 Stipa, F.; Yoon, SS.; Liau, KH.; Fong, Y.; Jarnagin, WR.; D'Angelica, M.; Abou-Alfa, G.; Blumgart, LH. et al. (Mar 2006). "Outcome of patients with fibrolamellar hepatocellular carcinoma.". Cancer 106 (6): 1331-8. doi:10.1002/cncr.21703. PMID 16475212.
  15. ↑ Iacobuzio-Donahue, Christine A.; Montgomery, Elizabeth A. (2005). Gastrointestinal and Liver Pathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 595-6. ISBN 978-0443066573.
  16. ↑ STC. 6 December 2010.
  17. ↑ Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. EDMONDSON HA, STEINER PE. Cancer. 1954 May;7(3):462-503. PMID 13160935.
  18. ↑ 18.0 18.1 Burt, Alastair D.;Portmann, Bernard C.;Ferrell, Linda D. (2006). MacSween's Pathology of the Liver (5th ed.). Churchill Livingstone. pp. 783. ISBN 978-0-443-10012-3.
  19. ↑ AP. 28 May 2009.
  20. ↑ Stroescu, C.; Herlea, V.; Dragnea, A.; Popescu, I. (Mar 2006). "The diagnostic value of cytokeratins and carcinoembryonic antigen immunostaining in differentiating hepatocellular carcinomas from intrahepatic cholangiocarcinomas.". J Gastrointestin Liver Dis 15 (1): 9-14. PMID 16680226.
  21. ↑ Shirakawa, H.; Kuronuma, T.; Nishimura, Y.; Hasebe, T.; Nakano, M.; Gotohda, N.; Takahashi, S.; Nakagohri, T. et al. (Mar 2009). "Glypican-3 is a useful diagnostic marker for a component of hepatocellular carcinoma in human liver cancer.". Int J Oncol 34 (3): 649-56. PMID 19212669. http://www.spandidos-publications.com/serveFile/ijo_34_3_649_PDF.pdf?type=article&article_id=ijo_34_3_649&item=PDF.
  22. ↑ Shousha, S.; Gadir, F.; Peston, D.; Bansi, D.; Thillainaygam, AV.; Murray-Lyon, IM. (Oct 2004). "CD10 immunostaining of bile canaliculi in liver biopsies: change of staining pattern with the development of cirrhosis.". Histopathology 45 (4): 335-42. doi:10.1111/j.1365-2559.2004.01927.x. PMID 15469471.
  23. ↑ Porcell, AI.; De Young, BR.; Proca, DM.; Frankel, WL. (Jul 2000). "Immunohistochemical analysis of hepatocellular and adenocarcinoma in the liver: MOC31 compares favorably with other putative markers.". Mod Pathol 13 (7): 773-8. PMID 10912937.
  24. ↑ Goodman, ZD. (Feb 2007). "Neoplasms of the liver.". Mod Pathol 20 Suppl 1: S49-60. doi:10.1038/modpathol.3800682. PMID 17486052.
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