Liver & intrahepatic bile ducts
Hepatocellular carcinoma
Undifferentiated variant

Topic Completed: 7 May 2019

Minor changes: 24 September 2020

Copyright: 2019-2021,, Inc.

PubMed Search: Undifferentiated[TI] hepatocellular carcinoma

Daffolyn Rachael Fels Elliott, M.D., Ph.D.
Ryan M. Gill, M.D., Ph.D.
Page views in 2020: 1,608
Page views in 2021 to date: 536
Cite this page: Fels Elliott DR, Gill RM. Undifferentiated variant. website. Accessed April 14th, 2021.
Definition / general
  • Primary liver tumor that can be diagnosed as carcinoma based on immunohistochemistry but cannot be further classified (Surg Pathol Clin 2013;6:367)
  • May show molecular abnormalities supporting a diagnosis of hepatocellular carcinoma (HCC)
Essential features
  • Primary liver tumor that can be diagnosed as carcinoma based on immunohistochemistry (e.g. cytokeratin+) but hepatocellular immunostains are negative (e.g. arginase1- and HepPar1-)
  • Solid or trabecular growth pattern with high N/C ratios and nuclear pleomorphism
  • May be albumin in situ hybridization (ISH)+
ICD coding
  • ICD-10: C22.7 - Other specified carcinomas of liver
Clinical features
Prognostic factors
Case reports
Microscopic (histologic) description
  • Solid or trabecular growth pattern
  • High N/C ratio
  • Pleomorphism
  • No histologic features of classic HCC
Microscopic (histologic) images

Images hosted on other servers:

Scattered multinucleated hyperchromatic cells, necrosis

Positive stains
Negative stains
Molecular / cytogenetics description
Sample pathology report
  • Liver, mass, core biopsy:
    • Poorly differentiated carcinoma; see comment
    • Comment: This tumor shows a poorly differentiated carcinoma with tumor cells positive for pancytokeratin and negative for CK7, CK19, mucicarmine and hepatocellular markers (HepPar1, arginase1 and glypican 3). Albumin in situ hybridization is positive in tumor cells. We favor consideration as an undifferentiated hepatocellular carcinoma; correlation with molecular testing can be helpful (e.g. next generation sequencing cancer gene panel).
Differential diagnosis
Board review style question #1
Which of the following features is true regarding the undifferentiated variant of hepatocellular carcinoma (HCC)?

  1. Albumin ISH is always negative
  2. Arginase1 is usually positive
  3. Cytokeratin is usually negative
  4. Has a better prognosis in comparison to classic HCC
  5. May show solid or trabecular growth pattern
Board review style answer #1
E. May show solid or trabecular growth pattern

Reference: Undifferentiated hepatocellular carcinoma

Comment Here
Board review style question #2
Which variant of hepatocellular carcinoma is characterized by positive cytokeratin but albumin ISH and all hepatocellular markers are negative?

  1. Fibrolamellar
  2. Lymphoepithelioma-like
  3. Sarcomatoid
  4. Scirrhous
  5. Undifferentiated
Board review style answer #2
Back to top
Image 01 Image 02