Liver & intrahepatic bile ducts

Hepatocellular carcinoma

HCC - cytology

Editorial Board Members: Monika Vyas, M.D., Marc Pusztaszeri, M.D.
Deputy Editor-in-Chief: Catherine E. Hagen, M.D.
Lawrence Hsu Lin, M.D., Ph.D.
Tamar C. Brandler, M.D., M.S.

Last author update: 16 March 2022
Last staff update: 18 May 2022

Copyright: 2002-2023,, Inc.

PubMed Search: Hepatocellular carcinoma cytology

Lawrence Hsu Lin, M.D., Ph.D.
Tamar C. Brandler, M.D., M.S.
Page views in 2022: 6,245
Page views in 2023 to date: 3,695
Cite this page: Lin LH, Brandler TC. HCC - cytology. website. Accessed June 9th, 2023.
Definition / general
  • Most common primary malignancy of the liver
  • Hepatocytic differentiation
  • Fine needle aspiration is a useful tool in the diagnosis of hepatocellular carcinoma (HCC)
Essential features
  • 70 - 90% arise in cirrhotic patients
  • Elevated alpha fetoprotein (AFP)
  • Accuracy of cytopathologic diagnosis of HCC is high (> 90%) (J Surg Oncol 1991;48:246, Diagn Cytopathol 2002;26:283, Acta Cytol 2013;57:332)
  • Common pitfalls:
    • False negative: well differentiated HCC mistaken as benign lesion or nonneoplastic liver (false nondiagnostic)
    • False positive: dysplastic nodules and benign hepatic tumors mistaken for well differentiated HCC
    • Misdiagnosis: poorly differentiated HCC mistaken for metastatic carcinoma
  • Cell blocks are useful to confirm hepatocellular differentiation with immunohistochemical stains (arginase1, HepPar1, glypican 3)
CTP coding
  • 88172 - determination of adequacy of specimen
  • 88173 - FNA interpretation
  • 88305 - cell block preparation
  • Liver
  • Common metastatic sites: lymph nodes and lungs
  • Less common metastatic sites: adrenal glands, bone, kidney, spleen and ovary
  • Elevated alpha fetoprotein (AFP)
Radiology description
  • Ultrasound typically shows a distinct hepatic nodule; when a nodule is detected through ultrasound, diagnosis is complemented by CT and MRI (Eur J Radiol 2018;101:72)
  • Dynamic CT or MRI (contrast enhanced imaging) shows a typical pattern of intense enhancement during arterial phase when compared to surrounding parenchyma and progressive decrease during venous phases (wash out) (Eur J Radiol 2018;101:72)
  • When the typical findings are present, a biopsy is not always mandatory for the diagnosis of HCC (Eur J Radiol 2018;101:72)
  • Liver Imaging Reporting and Data System (LI-RADS) classifies liver nodules detected on dynamic CT / MRI into categories depending on the risk of malignancy (Eur J Radiol 2018;101:72, Radiology 2018;289:816):
    • LI-RAD 1: definitely benign
    • LI-RAD 2: probably benign
    • LI-RAD 3: intermediate probability of malignancy
    • LI-RAD 4: probably HCC
    • LI-RAD 5: definitely HCC
Radiology images

Contributed by Lawrence Hsu Lin, M.D., Ph.D. and Tamar C. Brandler, M.D., M.S.
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Rounded mass (ultrasound)

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Lobulated mass (ultrasound)

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Heterogeneous echotexture (ultrasound)

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Hypodense mass (CT)

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Ill defined area (CT)

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Large hepatic mass (MRI)

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Poorly defined mass (MRI)

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Ultrasound guided biopsy

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CT guided biopsy

Case reports
Cytology description
Cytology images

Contributed by Lawrence Hsu Lin, M.D., Ph.D. and Tamar C. Brandler, M.D., M.S.
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High cellularity with bare nuclei

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High cellularity and normal appearing hepatocytes

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Thickened trabeculae

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Pseudoglandular structures

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Endothelial wrapping

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Transgressing vessel

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Transversing vessel

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Enlarged nuclei and increased N/C ratio

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Enlarged nuclei and prominent nucleoli

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Multinucleated tumor cells

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Bile production

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Cell block - well differentiated HCC

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Cell block - poorly differentiated HCC

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Cell block - multinucleated tumor cells

Images hosted on other servers:

Well differentiated neoplasm

Moderately differentiated neoplasm

Poorly differentiated neoplasm (marked nuclear pleomorphism)

Trabecular and pseudoacinar patterns

Pseudoacinar pattern

Fatty change

Mallory hyaline

Fibrolamellar variant

Sarcomatoid change

HepPar1, CEA and CD31 IHC

Reticulin stain

Sample pathology report
  • Liver, mass, ultrasound guided aspiration biopsy (smears and cell block):
    • Moderately differentiated hepatocellular carcinoma, positive for malignancy (see comment)
    • Comment: Cellular sample showing atypical monotonous cells with enlarged nuclei, abundant granular cytoplasm arranged in trabecular and pseudoglandular patterns with transgressing vessels. Single bare nuclei are present in the background. Immunohistochemical stains show that the neoplastic cells are reactive for HepPar1, arginase1, glypican 3. Polyclonal CEA stain shows a canalicular pattern. Immunohistochemical stains for CK7 and CK20 are nonreactive. The morphologic and immunohistochemical profile supports the diagnosis of moderately differentiated hepatocellular carcinoma.
Differential diagnosis of well and moderately differentiated HCC
Differential diagnosis of poorly differentiated HCC
Board review style question #1

Which of the following serum markers has the highest diagnostic accuracy for the condition shown in the above smear obtained from a liver fine needle aspiration?

  1. AFP
  2. CA125
  3. CA19-9
  4. CEA
  5. PSA
Board review style answer #1

Comment here

Reference: HCC - cytology
Board review style question #2
Which of the following is the most common neoplasm in the liver?

  1. Cholangiocarcinoma
  2. Hepatocellular adenoma
  3. Hepatocellular carcinoma
  4. Lymphoma
  5. Metastatic carcinoma
Board review style answer #2
E. Metastatic carcinoma

Comment here

Reference: HCC - cytology
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