Liver neoplasms

Liver metastases at gross.

This article examines liver neoplasms and pre-malignant lesions of the liver. In North America, most malignant liver lesions are metastases.

This article focuses on primary malignancies of the liver, neoplastic liver lesions, and biliary malignancies. It only briefly discusses metastatic lesions. An introduction to liver pathology is in the liver article. Medical liver disease is dealt with in the medical liver disease article.

Overview

Dysplasic lesions of the liver

Types:

• "Large cell dysplasia" (AKA large cell change) - not considered a precursor for HCC, not considered a dysplasia.
• Small liver cell dysplasia (AKA small cell dysplasia).
• Low grade dysplasia.
• High grade dysplasia.

Neoplastic lesions

• Hepatic adenoma.

Malignant lesions of the liver

• Hepatocellular carcinoma (HCC) - most common malignant liver primary in adults.
• Hepatoblastoma - malignant liver primary in children.
• Intrahepatic cholangiocarcinoma (ICC).
• Combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma (CHC).

Lesions that arise in a non-cirrhotic liver

Hepatocellular:

• Hepatic adenoma.
• Fibrolamellar hepatocellular carcinoma.
• Focal nodular hyperplasia.

Other:

• Metastasis.
• Cholangiocarcinoma.
• Liver hemangioma.

Tabular comparison

Precursors

Features of HCC & its precursors - generated from DCHH and STC:

Features	SLCD	Low-grade dysplasia	High-grade dysplasia	HCC
Plate thickness	<3 cells	<=2 cells	<=3 cells, usu. >2 cells	>3 cells
Reticulin (stain)	intact chicken wire	intact chicken wire	intact chicken wire	damaged chicken wire
Nuclear changes	nuc. enlargement, hyperchromasia	+/- atypia (???)	marked atypia	+/- incr. NCR, +/-irreg. nuc. contour
Cytoplasmic change	hyperchromasia, decr. as cell size preserved	none (???)	+/- basophilia	variable (lighter vs. hyperchromasia)
Portal tracts	?	loss of portal tracts	loss of portal tracts	loss of portal tracts
Management	follow ???	follow	ablate	ablate/surgery

Abbreviations:

• SLCD = small liver cell dysplasia.

Notes:

• Large cell dysplasia:
  • Cell size ~ 2x normal, NC ratio ~ normal.
• SLCD:
  • Cell size ~ 1/2x normal, NC ratio - increased.

Hepatic tumours

Benign:

Entity	Gross	Microscopic	IHC/stains	Other	Images
Hepatic hemangioma	similar to normal liver parenchyma, red (hemorrhagic), well-circumscribed	spaces lined by benign endothelial cells	CD31+ (???)	-	gross (rsna.org)
Focal nodular hyperplasia	central scar, large vessels, usu. well-circumscribed	large arteries, unpaired arteries, bile duct proliferation		usu. diagnosed by imaging	gross (rsna.org)
Hepatocellular adenoma	subcapsular, well-circumscribed	loss of portal tracts, nuclear glycogenation	reticulin - liver plate thickness <= 3	background not cirrhotic, assoc. OCP	gross (mda-sy.com)[5]

Malignant:

Entity	Gross	Microscopic	IHC/stains	Other	Images
Liver metastasis	multiple, white lesions	variable, usu. tubular (glandular) with pseudostratified hyperchromatic nuclei	CK7-, CK20+ (colorectal), HepPar-1-, CK19-	colorectal carcinoma most common	Metastases. (WC)
Hepatocellular carcinoma	poorly circumscribed, +/-necrosis, +/-hemorrhage	loss of portal tracts, unpaired arteries, +/-nuclear atypia	reticulin - liver plate thickness > 3	background often cirrhotic	HCC. (WC/Uthman)
Cholangiocarcinoma	cauliflower-like outline, white, classically solitary, no cirrhosis	tubular architecture and mild nuclear atypia (adenocarcinoma), desmoplastic stroma	CK7+, CK19+	background usu. not cirrhotic	Cholangiocarcinoma. (WC)

Dysplasia of the liver

Small liver cell dysplasia

• Abbreviated SLCD.
• AKA small cell dysplasia.

General

• Considered a precursor to HCC.
  • Frequently found in livers with HCC - when compared to livers without HCC.

Microscopic

Features:

• Cells similar in size to normal hepatocytes.
  • Name derived from the fact that there is also an entity that was called large cell dysplasia (AKA large liver cell dysplasia, and large cell change).
• Increased NC ratio - "more blue".
• Mild nuclear and cytoplasmic hyperchromatism.

Notes:

• Normal hepatic architecture (main differentiator from HCC).
• Remember "... blue is bad".

Micrograph:

• Low resolution micrograph of SCD (medscape.com).

Low-grade hepatocellular dysplasia

• Generally referred to as low-grade dysplasia as the context is usually clear.

Microscopic

• Uniform cells - "noticeably different from normal".
  • Changes in nuclear size, irregular nuclear contour and/or changes in cytoplasm staining.
• Loss of portal tracts.
• Irregular margin.

Notes:

• DCHH describes LGD as: "normal hepatocytes in plates [of normal thickness]".

DDx:

• Nodular regenerative hyperplasia - lacks: compressed rim of cells, central portal tract.

High-grade hepatocellular dysplasia

• Generally referred to as high-grade dysplasia as the context is usually clear.

General

• "Bader" version of low-grade dyplasia.

Microscopic

Features - in addition to those of low grade dysplasia:

• Liver plate >2 cells thick.
• Significant nuclear atypia.
• Basophilic cytoplasm.

DDx:

• Low-grade hepatocellular dysplasia.
• Hepatocellular carcinoma.

Image:

• Series of liver micrographs including high grade dysplasia (radiographics.rsna.org).

Benign hepatic neoplasms

Bile duct hamartoma

A. B.
C. D.

Bile duct hamartomas. A. Trichrome shows fibrous spaces with dilated ducts. B. Bizarre, ramifying tubules with dilatations. C. Bland epithelial linings. D. Surrounding tract with tortuous bile ducts & inflammation, likely secondary to hamartomas.

Bile duct adenoma

Should not be confused with bile duct hamartoma.

Main article: Bile duct adenoma

Hepatic adenoma

• AKA hepatocellular adenoma, abbreviated HCA.

Main article: Hepatic adenoma

Hepatobiliary mucinous cystadenoma

• AKA biliary cystadenoma.

General

• Benign neoplasm.
  • May transform into a malignancy.

Microscopic

Features:

• Cystic spaces lined by a mucinous epithelium (simple columnar epithelium with a clear cytoplasm).
• Surrounding dense ovarian like stroma.

DDX: Biliary Intraductal Papillary Neoplasm

• no surrounding ovarian stroma
• Intraductal - connects with the biliary tree lumen.

Note:

• Similar to pancreatic mucinous cystadenoma.

Cavernous hemangioma

A. B.
C. D.

Cavernous hemangioma. A. Fibrous foci with increased spaces, hepatocyte focus with nonspecific fibrotic bridge. B. Cavernous hemangioma with flat, non-atypical endothelium. C. Tortuous bile ductules, not to be considered generalized in presence of mass. D. Tortuous bile ducts, not to be considered generalized in presence of mass.

Malignant hepatic neoplasms

In North America, the most common malignant liver tumour is metastases.

Hepatoblastoma

General

• Most common liver cancer in children.
  • Rare in adolescents and adults.
  • Age of diagnosis usu. ~1 year old; most less than 3 years old.
• Surgical biopsy; core needle biopsy not done as as lesion is vascular.

Associations:

• Beckwith-Wiedemann syndrome.
• Familial adenomatous polyposis.

Clinical:

• Usually present with hepatomegaly.
• High AFP.

Microscopic

Features:

• Small round cell tumour.
• Fetal hepatocytes ~ 1:3 NC ratio, eosinophilic cytoplasm.
• +/-Mesenchymal component
  • Immature fibrous tissue, osteoid or cartilage.

DDx:

• Small round cell tumours.
  • Neuroblastoma.
• Teratoma.
• Hepatocellular carcinoma - separated based on histomorphology alone.

Images

• 

  Hepatoblastoma - very high mag. (WC/Nephron)

• 

  Hepatoblastoma - high mag. (WC/Nephron)

Subtypes

• Six histologic subtypes - that are subdivided into two groups:
  • Epithelial type:
    1. Fetal pattern.
    2. Embryonal and fetal pattern.
    3. Macrotrabecular pattern.
       • May mimic hepatocellular carcinoma histologically.
    4. Small cell undifferentiated pattern.
       • Poor prognosis.
  • Mixed epithelial and mesenchymal type:
    1. With teratoid features.
    2. Without teratoid features.

IHC

• Alpha-fetoprotein +ve.
• Hepatocyte specific antigen +ve esp. in fetal component.
• Beta-catenin +ve (cytoplasmic and nuclear).

Hepatocellular carcinoma

• Abbreviated HCC.

Main article: Hepatocellular carcinoma

Biliary Intraductal Papillary Neoplasm

General

• Rare
• Highest incidence in Far Eastern countries
• Association with hepatolithiasis and clonorchiasis
• Between 50 and 70 years of age
• Slight male predominance
• Intermittent abdominal pain
• Acute cholangitis
• Jaundice

• Biliary counterpart of pancreatic intraductal papillary mucinous neoplasm
• Biliary counterpart of intracholecystic papillary neoplasm (gall bladder)
• Construct consumes some cases of biliary cystadenoma/cystadenocarcinoma, biliary papilloma/papillomatosis, intraductal growth type of cholangiocarcinoma and papillary carcinoma of the extrahepatic bile duct.

Radiology

• Bile duct dilatation
• Intraductal masses

Gross

• Singular, or occasionally multiple, polypoid masses extending into the lumen of a dilated bile duct
• Or multilocular well-defined cystic mass containing mucinous fluid
• Granular or papillary mucosa
• Communication with bile duct may be difficult to confirm

Microscopic

• Papillary or villous growth within the lumen of an intra or extrahepatic bile duct
• Papillary fronds with fine vascular cores
• Epithelium types
  • Pancreatobiliary
  • Intestinal - marked mucin secretion
  • Gastric
  • Oncocytic types
• Dysplasia
  • High or low grade
  • Marked variation in histologic grade between different regions of individual tumors

• Common association with invasive cholangiocarcinoma
  • Tubular adenocarcinoma
  • Mucinous (colloid) carcinoma (often in association with the intestinal type).

DDX

• Biliary Mucinous Cystic Neoplasm
  • • Epithelium is surrounded by a distinct ovarian-like stroma.

Photos

• 

  Bile Ducts - Intraductal Papillary Neoplasm - Low power (SKB)

• 

  Bile Ducts - Intraductal Papillary Neoplasm - Medium power (SKB)

• 

  Bile Ducts - Intraductal Papillary Neoplasm - High power (SKB)

• 

  Bile Ducts - Intraductal Papillary Neoplasm - Low power (SKB)

• 

  Bile Ducts - Intraductal Papillary Neoplasm - High power (SKB)

• 

  Bile Ducts - Intraductal Papillary Neoplasm - High power (SKB)

A. B.
C. D.
E. F.

Intraductal papillary neoplasm of common bile duct with associated invasive carcinoma. A. The papillary tumor comprises mostly variably dilated acini. B. Tumor also shows areas of micropapillae. C. Some areas within the non-invasive tumor showed necrosis, with the black pyknotic nuclei amid red debris. D. Definite invasion was established low power by glands headed in perpendicular directions. E. Embedded in fibroblastic response are non-acinar walls and isolated epithelial groups. F. Also embedded in fibroblastic response are flat glands with nuclei showing loss of polarity (lack of respect for lateral intercellular borders shown by variable orientation to base of gland).

Notes -

• Reflect on the known marked variation in histologic grade between different regions of individual tumors when rendering an opinion on a small biopsy specimen.
• Consider the possibility of an invasive component and submit tissue generously.

See also: PubCan [1]

Cholangiocarcinoma

• AKA bile duct carcinoma.

Main article: Cholangiocarcinoma

Hepatic angiosarcoma

Main article: Angiosarcoma

• AKA angiosarcoma of the liver.

General

• Liver angiosarcomas are associated with vinyl chloride exposure.

Microscopic

Features:

• Atypical endothelial cells - may be subtle.

Hepatic metastasis

Main article: Liver metastasis

• AKA liver metastases.
• AKA metastatic liver disease.

Hematopoietic tumors

A
B
C
D
Plasmacytoma appearing as a tumor mass. A. One liver core was normal. B. A triad with a proliferated bile ductule, otherwise normal. C. The other core showed a mass of tumor mashed against normal liver. D. Tumor cells showed round to ovoid nuclei without pattern and with grey cytoplasm that proved to be CD138 positive.

A.
B.
C.
D.
E.
F.
B cell lymphoma mimicking hepatitis with fibrosis. A. Apparent inflamed fibrous tract with lobular inflammatory collections in adjacent liver. B. Apparent inflamed fibrous band between two relatively hepatocyte regions. C. Apparent piecemeal necrosis with bile ductular proliferation. D. Apparent portal inflammation with unaffected interlobular bile duct. E. Apparent lobular inflammation with collections a bit too large for usual lobular inflammation. F. Proof is at high power. All cells are similar to macrophages but are too closely crowded to be macrophages. The monomorphism (one type of cell) should inspire immunohistochemical stains, which showed the patient had a B cell lymphoma.

Malignant B cell lymphoma, NOS, in a 63 year old man’s liver. No other specimens were available for further classification. A. Tumor expands a triad and occupies parenchymal regions. B. Bounding a bile duct, modestly sized round to reniform lymphoid cells, many without nucleoli, accompany small round lymphocytes. Some of the larger cells have clefts (arrows). C. CD3 stain shows many of the lymphoid cells are intercalated reactive T cells. D. Ki67 shows less than half the tumor cells, mostly the larger ones, are in proliferative phase, arguing against the notion of a high grade B cell lymphoma. E. CD79A establishes B cell phenotype (CD20 was also positive). F. That the tumor cells are BCL2 positive evinces B cell neoplasia. The cells were CD10, BCL6, and cyclin D1 negative, militating against mantle cell lymphoma and CLL, with no follicular origin identified.

High grade B cell lymphoma involving liver in a 77 year old woman. A. A band of cancer abuts fibrotic liver with steatosis. B. Cancer cells show primitive, round to ovoid, variably sized, dark nucleoli and an aberrant mitoses. Cytoplasm is scant. C. Cancer cells are CD79a positive. D. Most cancer cell nuclei were positive for Ki-67, overall about 80%. E. A minority of cancer cells are CD10 positive.

See also

• Pancreas.
• Gastrointestinal pathology.
• Liver pathology.