Hepatocellular carcinoma

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Author: Mikael Häggström [note 1]


Hepatocellular carcinoma is the most common diagnosis for liver tumors.:[1]

Microscopic evaluation

Hepatocellular carcinoma typically displays:[2]

  • Trabecular pattern surrounded by layer of flattened endothelial cells.
  • Presence of sinusoidal vessels surrounding tumor cells
  • Scant stroma, and minimal desmoplasia
  • Polygonal cells with distinct cell membranes
  • Abundant granular eosinophilic cytoplasm
  • Nuclei with increased N/C ratio, round nuclei with coarse chromatin and thickened nuclear membrane, and may have prominent nucleoli.

Hepatocellular adenoma versus carcinoma

Histopathology of inflammatory hepatocellular adenoma, with inflammatory cells and minor atypia.[3]

A hepatocellular adenoma, in contrast to a carcinoma, has a well-defined border between the lesion and background liver, and is composed of hepatocytes with less significant cytologic atypia.[4]

Both hepatocellular adenoma and well-differentiated hepatocellular carcinoma may display:

  • Steatosis: A steatotic hepatocellular carcinoma is a common variant, found most commonly in small, well-differentiated tumors.[5]
  • Portal triads, which commonly persist in well-differentiated hepatocellular carcinomas.[6]


Differentiations of hepatocellular carcinoma are:[2]

  • Well differentiated:
  • Thin plates (1 - 3 hepatocytes thick)
  • Hepatocytes are smaller than normal
  • Abnormal reticulin network
  • Minimal nuclear atypia
  • Nuclear density of 2x compared to normal liver
  • Moderately differentiated:
  • Trabecular pattern at least 4 cells thick
  • Larger cells with more eosinophilic cytoplasm
  • Distinct nucleoli
  • Pseudoglands
  • Poorly differentiated:
  • Large tumor cells with hyperchromatic nuclei in compact growth pattern
  • Rare trabeculae or bile
  • Prominent pleomorphism
  • May have spindle cell or small cell areas


For cancers, generally include a synoptic report, such as per College of American Pathologists (CAP) protocols at cap.org/protocols-and-guidelines.

  See also: General notes on reporting


  1. For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.

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  1. Table 37.2 in: Sternberg, Stephen (2012). Sternberg's diagnostic surgical pathology . Place of publication not identified: LWW. ISBN 978-1-4511-5289-0. OCLC 953861627. 
  2. 2.0 2.1 Deepali Jain. Liver & intrahepatic bile ducts - Hepatocellular carcinoma - Hepatocellular carcinoma overview. PathologyOutlines. Topic Completed: 1 February 2012. Minor changes: 30 September 2020
  3. Bioulac-Sage, Paulette; Sempoux, Christine; Possenti, Laurent; Frulio, Nora; Laumonier, Hervé; Laurent, Christophe; Chiche, Laurence; Frédéric Blanc, Jean; et al. (2013). "Pathological Diagnosis of Hepatocellular Cellular Adenoma according to the Clinical Context ". International Journal of Hepatology 2013: 1–13. doi:10.1155/2013/253261. ISSN 2090-3448. 
  4. Author: Avani Pendse, M.D., Ph.D.. Liver & intrahepatic bile ducts - Benign / nonneoplastic - Hepatocellular adenoma. Pathology Outlines. Topic Completed: 1 October 2018. Minor changes: 30 September 2020
  5. Chan, Anthony W H; Yu, Shuangni; Yu, Yau-Hei; Tong, Joanna H M; Wang, Lei; Tin, Edith K Y; Chong, Charing C N; Chan, Stephen L; et al. (2016). "Steatotic hepatocellular carcinoma: a variant associated with metabolic factors and late tumour relapse ". Histopathology 69 (6): 971–984. doi:10.1111/his.13029. ISSN 03090167. 
  6. Motohashi, Ikuko; Okudaira, Masahiko; Takai, Tomoko; Kaneko, Satoshi; Ikeda, Noriaki (1992). "Morphological differences between hepatocellular carcinoma and hepatocellular carcinomalike lesions ". Hepatology 16 (1): 118–126. doi:10.1002/hep.1840160120. ISSN 02709139. 

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