Liver & intrahepatic bile ducts

Hepatocellular carcinoma

HCC - lymphocyte rich

Editorial Board Member: Monika Vyas, M.D.
Deputy Editor-in-Chief: Catherine E. Hagen, M.D.
Daffolyn Rachael Fels Elliott, M.D., Ph.D.
Ryan M. Gill, M.D., Ph.D.

Last author update: 6 September 2022
Last staff update: 6 September 2022

Copyright: 2019-2023,, Inc.

PubMed Search: Lymphocyte rich / lymphoepithelioma-like hepatocellular carcinoma

Daffolyn Rachael Fels Elliott, M.D., Ph.D.
Ryan M. Gill, M.D., Ph.D.
Page views in 2022: 1,238
Page views in 2023 to date: 935
Cite this page: Fels Elliott DR, Gill RM. HCC - lymphocyte rich. website. Accessed October 2nd, 2023.
Definition / general
  • Rare subtype of hepatocellular carcinoma (HCC) designated by the WHO; characterized by a dense lymphoid infiltrate with more lymphocytes than tumor cells
Essential features
  • Striking lymphocytic infiltrate is a defining feature
  • Not associated with Epstein-Barr virus (EBV) or microsatellite instability
ICD coding
  • ICD-10: C22.7 - other specified carcinomas of liver
  • Liver
Clinical features
  • Very rare tumor with limited clinical and outcome data
  • Imaging modalities for diagnosis of HCC: multiphasic computed tomography (CT) or magnetic resonance imaging (MRI)
  • Tissue biopsy is indicated if imaging is not diagnostic of HCC
  • Elevation in serum alpha fetoprotein (AFP)
Radiology description
  • Dynamic perfusion pattern of arterial hyperenhancement and venous or delayed phase washout is characteristic of HCC
Radiology images

Images hosted on other servers:

CT scan

Prognostic factors
Case reports
Gross description
Microscopic (histologic) description
  • Cords and trabeculae of tumor cells in a dense lymphoid stroma (lymphocytes outnumber tumor cells in most fields)
  • Lymphoid infiltrate predominantly T cells with scattered B cells and germinal centers
  • May show piecemeal necrosis
  • Histologic grade usually well to moderately differentiated
  • If poorly differentiated, the term lymphoepithelioma-like HCC may be used (Gastroenterol Clin North Am 2017;46:365)
  • May have focal syncytial growth
Microscopic (histologic) images

Contributed by Ryan M. Gill, M.D., Ph.D.

Lymphocyte rich HCC


Lymphoepithelioma-like HCC


Positive stains
Negative stains
Molecular / cytogenetics description
  • Most cases negative for EBV in situ hybridization (ISH); EBV positivity reported in one study (Diagn Mol Pathol 2004;13:183)
  • Tumor infiltrating lymphocytes not associated with microsatellite instability (Am J Surg Pathol 2015;39:304)
  • Lymphocyte rich hepatocellular carcinoma has been shown to have focal amplification of chromosome 11q13.3, which is considered to be an immune checkpoint signature, making them a promising target for immunotherapy (J Pathol 2019;249:166)
Sample pathology report
  • Liver, mass, core biopsy:
    • Lymphocyte rich hepatocellular carcinoma (see comment)
    • Comment: The tumor shows histologic features of lymphocyte rich hepatocellular carcinoma with nests and cords of hepatoid cells within a dense lymphoid stroma. The tumor cells are positive for pancytokeratin, HepPar1 and glypican 3, and negative for CK7, CK19 and mucicarmine. EBV in situ hybridization is negative.
Differential diagnosis
Board review style question #1

Which variant of hepatocellular carcinoma is shown in the image?

  1. Fibrolamellar
  2. Lymphoepithelioma-like
  3. Sarcomatoid
  4. Scirrhous
  5. Undifferentiated
Board review style answer #1
B. Lymphoepithelioma-like

Comment Here

Reference: Lymphocyte rich hepatocellular carcinoma
Board review style question #2
Which of the following features is characteristic of lymphocyte rich hepatocellular carcinoma (HCC)?

  1. Cytokeratin is usually negative
  2. Has a worse prognosis in comparison to classic HCC
  3. It is one of the more common variants of HCC
  4. Lymphocytes outnumber tumor cells in most fields
  5. Most cases are positive for Epstein-Barr virus in situ hybridization
Board review style answer #2
D. Lymphocytes outnumber tumor cells in most fields

Comment Here

Reference: Lymphocyte rich hepatocellular carcinoma
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