Hepatocellular carcinoma

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Hepatocellular carcinoma
Diagnosis in short

Hepatocellular carcinoma.
LM architectural changes - liver plate thickness >3 cells thick, +/-nuclear changes of malignancy (very common), variable architecture (pseudoglandular, trabecular, fibrolamellar, solid)
Subtypes sclerosing HCC, fibrolamellar HCC
LM DDx cholangiocarcinoma, occasionally liver metastasis, high-grade dysplasia
Stains reticulin (thickened liver plate)
IHC CD34 +ve sinusoids, HepPar-1 +ve (usu.), AFP +ve (usu.), CK8/18 +ve, glypican-3 +ve
Gross usu. cirrhosis (micronodular or macronodular)
Site liver - see liver neoplasms
Associated Dx causes of cirrhosis, e.g. chronic alcoholism, Hepatitis C, Hepatitis B, hereditary hemochromatosis, others
Prevalence most common malignant primary liver tumour, less common than metastases
Blood work +/-AFP elevation
Prognosis moderate to poor
Clin. DDx liver metastasis, other liver tumours

Hepatocellular carcinoma, abbreviated HCC, is the most common malignant primary liver tumour. It 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).

Images

  • HCC. (WC)

  • HCC. (WC)

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]
  • TTF-1 +ve cytoplasmic staining.[22]
    • Benign liver also has cytoplasmic staining.

Bile canaliculi:

Image:

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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. ↑ Pollet A. 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. ↑ Mishra, M.; Morgan, V.; Hamati, AK.; Al-Abbadi, M. (Jan 2012). "Carcinoma of unknown primary: check the liver... thanks to TTF-1.". Tenn Med 105 (1): 35-6, 40. PMID 22359993.
  23. ↑ 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.
  24. ↑ 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.
  25. ↑ 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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