Liver & intrahepatic bile ducts
Hepatocellular carcinoma
Lymphocyte rich

Topic Completed: 28 May 2019

Minor changes: 17 March 2021

Copyright: 2019-2021,, Inc.

PubMed Search: Lymphoepithelioma-like hepatocellular carcinoma

Daffolyn Rachael Fels Elliott, M.D., Ph.D.
Ryan M. Gill, M.D., Ph.D.
Page views in 2020: 713
Page views in 2021 to date: 240
Cite this page: Fels Elliott DR, Gill RM. Lymphocyte rich. website. Accessed April 19th, 2021.
Definition / general
  • Rare variant characterized by pleomorphic tumor cells in a dense lymphoid stroma
Essential features
  • Cords of pleomorphic epithelial cells in a dense lymphoid stroma
  • Very rare variant of hepatocellular carcinoma (HCC)
  • Most cases negative for Epstein-Barr virus (EBV)
  • Previously called Lymphoepithelioma-like variant
ICD coding
  • ICD-10: C22.7 - Other specified carcinomas of liver
Clinical features
Radiology images

Images hosted on other servers:

CT scan

Prognostic factors
Case reports
Gross description
Microscopic (histologic) description
  • Cords and trabecula of pleomorphic epithelial cells in a dense lymphoid stroma
  • May have focal syncytial growth
Microscopic (histologic) images

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

Dense lymphoid infiltrate

Inconspicuous tumor cells


Positive stains
Negative stains
Molecular / cytogenetics description
Sample pathology report
  • Liver, mass, core biopsy:
    • Lymphoepithelioma-like hepatocellular carcinoma (see comment)
    • Comment: The tumor shows histologic features of lymphoepithelioma-like carcinoma with pleomorphic tumor cells arranged in nests and cords 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
  • Lymphoepithelioma-like cholangiocarcinoma:
    • Syncytial growth of glands and cords of epithelial cells in a lymphoid stroma
    • May have luminal or cytoplasmic mucin
    • CK7+, CK19+, EBV ISH+, negative hepatocellular markers
  • Classic HCC with increased lymphocytes:
    • Tumors with only mild to moderate increase in lymphocytes should be classified as conventional HCC
  • Lymphoma (primary hepatic lymphoma or secondary involvement by systemic disease):
    • Dense infiltrate of atypical B or T cells
    • No intermixed neoplastic hepatocytes
    • Positive hematolymphoid markers (depends on the entity), negative cytokeratin and hepatocellular markers
  • Inflammatory myofibroblastic tumor:
    • Tumor of myofibroblasts with plasma cells, lymphocytes and eosinophils
    • ALK+ spindle cells (subset)
  • IgG4 related disease:
    • Abundant IgG4+ plasma cells, systemic disease, elevated serum IgG4
  • Inflammatory variant of angiomyolipoma:
    • Mature adipose tissue, smooth muscle cells and thick walled blood vessels with an inflammatory infiltrate
    • HMB45+, MelanA+, SMA+
  • Inflammatory pseudotumor-like follicular / fibroblastic dendritic cell sarcoma:
    • Neoplastic spindle cells are positive for CD21 (follicular differentiation) or SMA (fibroblastic differentiation), EBV ISH+
  • Inflammatory pseudotumor (nonneoplastic):
    • Mixed inflammation, granulomas, necrosis / abscess, rule out AFB, T. pallidum, parasites
    • No intermixed neoplastic hepatocytes
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

Reference: Lymphocyte rich hepatocellular carcinoma

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Board review style question #2
Which of the following features is characteristic of Lymphocyte rich hepatocellular carcinoma?

  1. Composed of pleomorphic epithelial cells in a dense lymphoid stroma
  2. Cytokeratin is usually negative
  3. Has a worse prognosis in comparison to classic HCC
  4. It is one of the more common variants of HCC
  5. Most cases are positive for Epstein-Barr virus in situ hybridization
Board review style answer #2
A. Composed of pleomorphic epithelial cells in a dense lymphoid stroma

Reference: Lymphocyte rich hepatocellular carcinoma

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