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Hyperplastic and Neoplastic Lesions of the Liver

The Digitized Atlas of Mouse Liver Lesions

Bile Duct Hyperplasia - Click on thumbnails to view larger images
While most examples of bile duct hyperplasia consist of a modest duplication of normal appearing bile ducts in portal areas, occasionally more dramatic examples are found in other areas of the hepatic lobule.
Hyperplastic bile ducts lined by low cuboidal epithelium.
Bile Duct Hyperplasia
  
Two local aggregates of proliferating bile ducts within the hepatic lobule.
Bile Duct Hyperplasia
Bile Duct Hyperplasia

 
Higher magnification showing low cuboidal to flattened biliary epithelium forming irregularly shaped bile ducts.
Bile Duct Hyperplasia
  
 
Cholangioma - Click on thumbnails to view larger images
Because their occurrence is rare, morphological characteristics of cholangiomas are not well characterized and must be distinguished from biliary cysts. Cholangiomas are discrete nodular growths in which the proliferating biliary structures are lined by a single layer of relatively uniform cuboidal epithelium. A discrete cholangioma protruding above the natural surface of the liver.
Cholangioma
Cholangioma
 
Neoplasm is comprised of large acini lined by cuboidal epithelium with occasional papillary projections into the lumen.
Cholangioma
  
This cholangioma has connective tissue stroma between acini. Higher magnification shows acinilined by tall cuboidal epithelium. The nuclear crowding and occasional nests of epithelial cells in the stroma suggests progression toward malignancy.
Cholangioma
Cholangioma
 
 
Cholangiocarcinoma & Hepatocholangiocarcinoma - Click on thumbnails to view larger images.
Cholangiocarcinomas consist of proliferation of glandular structures, which are often irregular, lined by single and multiple layers of cuboidal to columnar epithelium, and often associated with an abundant scirrhous reaction. The epithelium may sometimes be pleomorphic and anaplastic, and dilated glands may contain mucinous secretion. Extremely dilated glands are sometimes line in places by attenuated epithelium. Hepatocholangiocarcinomas are rare in mice. They contain neoplastic features of both hepatocellular carcinomas and cholangiocarcinomas.

A discrete cholangiocarcinoma protruding above the natural surface of the liver. Higher magnification shows poorly formed glandular structures and a minimal scirrhous reaction.
cholangiocarcinoma
cholangiocarcinoma
cholangiocarcinoma
A cholangiocarcinoma with a prominent scirrhous reaction.
cholangiocarcinoma
cholangiocarcinoma
cholangiocarcinoma
This hepatocholangiocarcinoma in the liver is comprised of neoplastic hepatocytes and irregularly formed bile ductular structures.
Hepatocholangiocarcinoma
Hepatocholangiocarcinoma
 
This distinct hepatocholangiocarcinoma in the liver is comprised of pleomorphic hepatocytes and poorly formed ductular structures resembling bile ducts. The high magnifications show a disorganized proliferation of hepatocytes and poorly differentiated biliary cells.
hepatocholangiocarcinoma
hepatocholangiocarcinoma
hepatocholangiocarcinoma
hepatocholangiocarcinoma
  
 
Endothelial Hyperplasia - Click on thumbnails to view larger images.
This change was originally diagnosed as endothelial cell proliferation. Based on the H&E stained sections, it is not possible to definitively identify the proliferating sinusoidal lining cells as endothelial cells but some have cytomorphological features consistent with endothelial cells. Low and high magnifications of endothelial cell hyperplasia.
endothelial hyperplasia
endothelial hyperplasia
endothelial hyperplasia
endothelial hyperplasia
endothelial hyperplasia
 
 
Erythroleukemia - Click on thumbnails to view larger images
Erythroleukemia is a spontaneous hematopoietic neoplasm of Tg.AC mice characterized by marked hepatomegaly. The affected liver is infiltrated by metarubricytes and less differentiated erythroid precursors.

Low magnification of erythroleukemic infiltrates in the liver.
erythroleukemic
erythroleukemic
 

A higher magnification of hepatic erythroleukemia.
erythroleukemic
erythroleukemic
 

Examples of erythroleukemia in a Tg.AC mouse.
erythroleukemia
erythroleukemia
erythroleukemia
erythroleukemia
erythroleukemia
erythroleukemia
erythroleukemia
  
 
Foci of Cellular Alteration - Click on thumbnails to view larger images
Foci of cellular alteration represent small to large aggregates of tinctorially distinct hepatocytes within the hepatic parenchyma and are sometimes considered putative preneoplastic lesions. They are frequently classified based upon their phenotypic appearance as basophilic, eosinophilic, clear cell, vacuolated, and mixed foci. Occasionally amphophilic foci are identified by the altered arrangement of the hepatic plates without tinctorial distinction from the surrounding hepatic parenchyma. The distinction between a large focus of cellular alteration and a hepatocellular adenoma is often a difficult judgment. A basophilic focus of cellular alteration with irregular boundaries. Basophilic foci are frequently comprised of hepatocytes that are smaller than the surrounding hepatocytes. The tinctorial properties are a function of closely spaced small nuclei and/or increased cytoplasmic basophilia.
Basophilic foci
Basophilic foci
 

Multiple basophilic foci are prominent in this mouse treated with a neonatal dose of diethylnitrosamine.
Basophilic foci
  

A large eosinophilic focus of cellular alteration that has a well demarcated border. Hepatocytes comprising eosinophilic foci typically have an increased cytoplasm that stains more eosinophilic than the cytoplasm of surrounding hepatocytes. If the hepatocytes within an eosinophilic focus are sufficiently large and numerous, there may be evidence of slight compression of normal hepatic parenchyma along a portion of the border of the focus.
eosinophilic focus
eosinophilic focus
eosinophilic focus

An eosinophilic focus of cellular alteration with slight protrusion above the normal surface contour of the liver.
eosinophilic focus
  

A well delineated small eosinophilic focus comprised of hepatocytes with copious cytoplasm.
eosinophilic focus
eosinophilic focus
 
A small eosinophilic focus of cellular alteration with an irregular border.
eosinophilic focus
  
A large and a small clear cell focus of cellular alteration. Clear cell foci are characterized by relatively clear cytoplasm or cytoplasm with just a hint of very pale eosinophilic staining and wispy strands of cytoplasm making the cytoplasmic vacuoles have an indistinct border. Unlike vacuolated foci, many cells within a clear cell focus have a centrally located nucleus. The clear space is produced when stored glycogen is dissolved out during fixation in aqueous fixatives.
cell focus
cell focus
 
This clear cell focus actually has light pink staining of the cytoplasm.
clear cell focus
  
A vacuolated focus of cellular alteration comprised of a sharply demarcated collection of hepatocytes containing clear spaces. Some pathologists diagnosis this type of lesion as focal fatty change.
vacuolated focus
  
Mixed focus of cellular alteration. While there is a partial rim of basophilic hepatocytes, the central portion of this focus is comprised of a mixture of clear and amphophilic cells.
Mixed focus
Mixed focus
 
A large mixed focus of cellular alteration.
Mixed focus
  
This focal lesion is believed to be associated with stress from the facliform ligament and resembles a focus of cellular alteration. These are examples of tension lipidosis and are not considered pathological changes.
focal lesion
focal lesion
 
 
Foci of Intravascular Hepatocytes - Click on thumbnails to view larger images
In some foci of cellular alteration, primarily basophilic foci, hepatocytes may occasional be seen to protrude into the lumen of hepatic veins. They are usually lined by a layer of flattened endothelial cells. This change has been considered by some to represent a form of microinvasion and such lesions have been diagnosed as hepatocellular carcinomas, possibly motivated by the fact that most are seen within foci induced by treatment with hepatocarcinogens. However, similar changes are occasionally seen in untreated mice and may not necessarily be associated with a focus of cellular alteration. Consequently, we cannot be certain that this change is actually a microcarcinoma. Two clusters of hepatocytes protruding into a large hepatic vein.
Intravascular hepatocytes
Intravascular hepatocytes
Intravascular hepatocytes
Another example of protrusion of hepatocytes into an hepatic vein.
Intravascular hepatocytes
Intravascular hepatocytes
 

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