Difference between revisions of "Hepatocellular carcinoma"

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#redirect [[Liver_neoplasms#Hepatocellular_carcinoma]]
'''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.<ref>{{Ref GLP|588}}</ref>
*Treatments: RFA (radiofrequency ablation), ethanol ablation, liver resection, liver transplant.<ref name=emed_hcc>[http://emedicine.medscape.com/article/282814-overview http://emedicine.medscape.com/article/282814-overview]</ref>
*Mean survival at time of diagnosis ~6 months.<ref name=emed_hcc/>
 
Epidemiology:
*Highest where prevalence of hepatitis B virus (HBV) is high.<ref name=Ref_PBoD924>{{Ref PBoD|924}}</ref>
*HCC generally arises in the setting of [[cirrhosis]].
**Cirrhosis may be regressed and therefore not appreciated.
 
HCCs '''without''' cirrhosis:
*Hepatitis B virus.<ref name=Ref_PBoD924>{{Ref PBoD|924}}</ref>
*Hemochromatosis.
*Fibrolamellar HCC.
 
Risk factors:<ref name=Ref_PBoD924>{{Ref PBoD|924}}</ref><ref name=pmid18333156>{{cite journal |author=Leong TY, Leong AS |title=Epidemiology and carcinogenesis of hepatocellular carcinoma |journal=HPB (Oxford) |volume=7 |issue=1 |pages=5–15 |year=2005 |pmid=18333156 |pmc=2023917 |doi=10.1080/13651820410024021 |url=}}</ref>
*Chronic [[alcoholism]].
*[[Hepatitis C]] virus (HCV) - chronic infection.
*[[Hepatitis B]] virus (HBV) - chronic infection.
*Aflatoxins (food contaminant - mould).<ref name=emed_hcc/>
*Hereditary tyrosinemia.
*[[Hereditary hemochromatosis]].
 
==Gross==
Features:<ref name=Ref_PBoD925>{{Ref PBoD|925}}</ref>
*Unifocal, multifocal or diffusely infiltrative.
**Tumours are multifocal in approx. 50% of cases;<ref name=pmid17696722>{{cite journal |author=Yusuf MA, Badar F, Meerza F, ''et al.'' |title=Survival from hepatocellular carcinoma at a cancer hospital in Pakistan |journal=Asian Pac. J. Cancer Prev. |volume=8 |issue=2 |pages=272–4 |year=2007 |pmid=17696722 |doi= |url=}}</ref><ref name=pmid11676064>{{cite journal |author=Sharieff S, Burney KA, Ahmad N, Salam A, Siddiqui T |title=Radiological features of hepatocellular carcinoma in Southern Pakistan |journal=Trop Doct |volume=31 |issue=4 |pages=224–5 |year=2001 |month=October |pmid=11676064 |doi= |url=}}</ref> some authors have suggested it is upto 75% of cases.<ref name=emed_hcc/>
*Pale in relation to surrounding liver or green (due to bile secretion).
 
==Microscopic==
Requirements:<ref>Adapted from STC (19 Jan 2009).</ref>
*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.<ref name=pmid19177576>{{Cite journal  | last1 = Kojiro | first1 = M. | last2 = Wanless | first2 = IR. | last3 = Alves | first3 = V. | last4 = Badve | first4 = S. | last5 = Balabaud | first5 = C. | last6 = Bedossa | first6 = P. | last7 = Bhathal | first7 = P. | last8 = Bioulac-Sage | first8 = P. | last9 = Brunt | first9 = EM. | title = Pathologic diagnosis of early hepatocellular carcinoma: a report of the international consensus group for hepatocellular neoplasia. | journal = Hepatology | volume = 49 | issue = 2 | pages = 658-64 | month = Feb | year = 2009 | doi = 10.1002/hep.22709 | PMID = 19177576 | url = http://onlinelibrary.wiley.com/doi/10.1002/hep.22709/pdf }}</ref>
 
Additional findings:<ref>Adapted from STC (19 Jan 2009).</ref>
*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:<ref>{{Ref GLP|590-1}}</ref>
*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.<ref>{{Ref GLP|591}}</ref>
 
ASIDE:
*''[[Trabecula]]'' = ''little beam''.
 
DDx:
*[[Cholangiocarcinoma]].
*Combined HCC-CC.<ref name=pmid21559202>{{Cite journal  | last1 = Walther | first1 = Z. | last2 = Jain | first2 = D. | title = Molecular pathology of hepatic neoplasms: classification and clinical significance. | journal = Patholog Res Int | volume = 2011 | issue =  | pages = 403929 | month =  | year = 2011 | doi = 10.4061/2011/403929 | PMID = 21559202 | PMC = 3090128 }}</ref>
 
===Images===
<gallery>
Image:Hepatocellular_carcinoma_low_mag.jpg | HCC - low mag. (WC)
Image:Hepatocellular_carcinoma_intermed_mag.jpg | HCC - intermed mag. (WC)
</gallery>
 
===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.<ref name=pmid16475212>{{Cite journal  | last1 = Stipa | first1 = F. | last2 = Yoon | first2 = SS. | last3 = Liau | first3 = KH. | last4 = Fong | first4 = Y. | last5 = Jarnagin | first5 = WR. | last6 = D'Angelica | first6 = M. | last7 = Abou-Alfa | first7 = G. | last8 = Blumgart | first8 = LH. | last9 = DeMatteo | first9 = RP. | title = Outcome of patients with fibrolamellar hepatocellular carcinoma. | journal = Cancer | volume = 106 | issue = 6 | pages = 1331-8 | month = Mar | year = 2006 | doi = 10.1002/cncr.21703 | PMID = 16475212 }}</ref>
*Individuals usually do '''not''' have the classic risk factors for HCC, i.e. no [[cirrhosis]], no hepatitis.<ref name=pmid16475212/>
 
Clinical:
*AFP usu. not elevated.<ref name=pmid16475212/>
 
====Microscopic====
Features:<ref>{{Ref GLP|595-6}}</ref>
*Large polygonal tumours cells with:
**Graunular eosinophilic cytoplasm.
**Low NC ratio.<ref>STC. 6 December 2010.</ref>
*Layered dense collagen bundles.
 
DDx:
*[[Amyloidosis of the liver]].
 
Note:
*If ''conventional HCC'' is seen focally within the tumour, it is ''conventional HCC''.
 
=====Images=====
<gallery>
Image:Fibrolamellar_hepatocellular_carcinoma_-2-_intermed_mag.jpg | FHCC - intermed. mag. (WC)
Image:Fibrolamellar_hepatocellular_carcinoma_-2-_very_high_mag.jpg | FHCC - very high mag. (WC)
</gallery>
===Sclerosing HCC===
Features:
*Fibrosis. (???)
 
Notes:
*Seen in non-cirrhotic livers.
 
===Grading===
Edmondson-Steiner grading system:<ref name=pmid13160935>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.</ref><ref name=macsween5th>{{Ref MacSween|783}}</ref>
*Well-differentiated.
**Some say "it cannot be diagnosed on biopsy,"<ref>AP. 28 May 2009.</ref> 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:<ref name=macsween5th/>
*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.<ref name=pmid16680226>{{Cite journal  | last1 = Stroescu | first1 = C. | last2 = Herlea | first2 = V. | last3 = Dragnea | first3 = A. | last4 = Popescu | first4 = I. | title = The diagnostic value of cytokeratins and carcinoembryonic antigen immunostaining in differentiating hepatocellular carcinomas from intrahepatic cholangiocarcinomas. | journal = J Gastrointestin Liver Dis | volume = 15 | issue = 1 | pages = 9-14 | month = Mar | year = 2006 | doi =  | PMID = 16680226 }}</ref>
*Glypican-3 +ve (cytoplasmic, granular cytoplasmic or membranous).<ref name=pmid19212669>{{Cite journal  | last1 = Shirakawa | first1 = H. | last2 = Kuronuma | first2 = T. | last3 = Nishimura | first3 = Y. | last4 = Hasebe | first4 = T. | last5 = Nakano | first5 = M. | last6 = Gotohda | first6 = N. | last7 = Takahashi | first7 = S. | last8 = Nakagohri | first8 = T. | last9 = Konishi | first9 = M. | title = Glypican-3 is a useful diagnostic marker for a component of hepatocellular carcinoma in human liver cancer. | journal = Int J Oncol | volume = 34 | issue = 3 | pages = 649-56 | month = Mar | year = 2009 | doi =  | PMID = 19212669 | url = http://www.spandidos-publications.com/serveFile/ijo_34_3_649_PDF.pdf?type=article&article_id=ijo_34_3_649&item=PDF}}</ref>
 
Bile canaliculi:
*CD10 +ve.<ref>{{Cite journal  | last1 = Shousha | first1 = S. | last2 = Gadir | first2 = F. | last3 = Peston | first3 = D. | last4 = Bansi | first4 = D. | last5 = Thillainaygam | first5 = AV. | last6 = Murray-Lyon | first6 = IM. | title = CD10 immunostaining of bile canaliculi in liver biopsies: change of staining pattern with the development of cirrhosis. | journal = Histopathology | volume = 45 | issue = 4 | pages = 335-42 | month = Oct | year = 2004 | doi = 10.1111/j.1365-2559.2004.01927.x | PMID = 15469471 }}</ref>
*pCEA +ve.<ref>{{Cite journal  | last1 = Porcell | first1 = AI. | last2 = De Young | first2 = BR. | last3 = Proca | first3 = DM. | last4 = Frankel | first4 = WL. | title = Immunohistochemical analysis of hepatocellular and adenocarcinoma in the liver: MOC31 compares favorably with other putative markers. | journal = Mod Pathol | volume = 13 | issue = 7 | pages = 773-8 | month = Jul | year = 2000 | doi =  | PMID = 10912937 | URL = http://www.nature.com/modpathol/journal/v13/n7/full/3880134a.html }}</ref>
 
Image:
*[http://www.nature.com/modpathol/journal/v20/n1s/fig_tab/3800682f12.html#figure-title HCC - HepPar-1 (nature.com)].<ref name=pmid17486052>{{Cite journal  | last1 = Goodman | first1 = ZD. | title = Neoplasms of the liver. | journal = Mod Pathol | volume = 20 Suppl 1 | issue =  | pages = S49-60 | month = Feb | year = 2007 | doi = 10.1038/modpathol.3800682 | PMID = 17486052 }}</ref>
 
==Sign out==
===Negative core biopsy===
<pre>
LIVER CORE, BIOPSY:
- CIRRHOSIS.
- HEPATOCYTE CYTOLOGY WITHIN NORMAL LIMITS.
</pre>
 
==See also==
*[[Liver neoplasms]].
 
==References==
{{Reflist|2}}
 
[[Category:Diagnosis]]
[[Category:Liver neoplasms]]

Revision as of 22:25, 11 November 2013

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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