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International Congress of
the Italian Association of Companion
Animal Veterinarians
May 19 – 21 2006
Rimini, Italy
Next Congress :
62nd SCIVAC International Congress
&
25th Anniversary of the SCIVAC Foundation
May 29-31, 2009 - Rimini, Italy
Reprinted in IVIS with the permission of the Congress Organizers
94
Cytology of the liver: advanced case examples
Rose E. Raskin
DVM, PhD, Dipl ACVP, West Lafayette, Indiana, USA
In this discussion, we will cover the cytologic aspects of
specific case examples that affect the liver. These will
involve the cytodiagnostic or general classification groups of
hyperplasia, inflammation, hepatic degeneration, response
to tissue injury, and neoplasia.
erate or nondegenerate neutrophils are increased over that
found in peripheral blood. Bacteria may be occasionally
found within neutrophils or extracellularly.
Lymphocytic Cholangiohepatitis
HYPERPLASIA
Nodular Hyperplasia
This condition is common in aged dogs and often presents
with multiple randomly distributed well-defined nodules.
Histologically, these retain a lobular structure in contrast to
neoplastic conditions. The cytologic features of these
enlarged hepatocytes include diffuse or focal vacuolization.
There are discrete vacuoles containing lipid or cytoplasmic
foaminess that is often associated with glycogen deposition.
Regenerative Hyperplasia
Damaged livers respond frequently with hyperplasia
related to exposure to toxins such as drugs, aflatoxins, or
plants. There is significant fibrosis that is not found in
nodular hyperplasia of older dogs and the normal architecture is lost. These may be similar but not identical histologically to hepatocellular adenomas. Cytologic changes
with toxic hepatopathy include an increased nuclear to
cytoplasmic ratio indicating rapid growth. Frequent binucleation is noted along with mild to moderate anisocytosis
of hepatocytes. In addition, the cytoplasm contains more
proteins for proliferation and therefore increased cytoplasmic basophilia. Hepatocytes may display hydropic change
with decreased cytoplasmic staining around the cell
periphery related to organelle swelling. There appears to be
an association between intranuclear crystalline inclusions
and hyperplastic liver conditions although these inclusions
have been noted in some clinically normal patients. With
chronic injury and resulting cirrhosis, fibrocytes and
fibroblasts along with wispy eosinophilic strands of collagen can be found in dense aggregates. This may be accompanied by the presence of bile casts.
INFLAMMATION
Suppurative Hepatitis/Cholangitis
This inflammation is associated with necrosis, bacterial
infection, and feline suppurative cholangiohepatitis. Degen-
The presence of small to intermediate sized lymphocytes
and plasma cells is found in this syndrome in cats often in
association with a mild pancreatitis. Plugged bile canniculi
may be noted in addition on cytology in this syndrome.
Uncommonly, a uniform population of small lymphocytes
may resemble a well-differentiated lymphoma but a mixed
cell population suggests an inflammatory process.
Parasitic Reaction
Reaction to the presence of flukes or their eggs has been
rarely noted on cytology with evidence of an eosinophilic
and neutrophilic inflammatory response along with evidence
of biliary stasis. Fluke eggs have been found on cytology and
appear green, presumably from the bile. Platynosomum
concinnum is a parasite of cats in North America with a life
cycle involving lizards and snails. Amphimerus pseudofelineus is another fluke found in cats.
Cytauxzoonosis
This is a tick-borne disease of cats that occurs in the southern part of the United States. The organism infects organs
such as the liver and can be observed from impression smears
as basophilic intracytoplasmic structures (merozoites)
arranged as schizonts within the swollen macrophages.
HEPATIC DEGENERATION
Glucocorticoid Hepatopathy
Corticosteroids that are administered exogenously or
which occur in increased amounts endogenously produce a
vacuolar change referred to as steroid hepatopathy. The condition can occur in both dogs and cats with similar morphologic effects. The increase in glycogen within the hepatocytes appears similar to hydropic change with indistinct vacuolization of the cytoplasm. It may be diffuse or localized to
the cell periphery. Intranuclear inclusions may be observed
in this condition nonspecifically along with biliary stasis.
95
Feline Hepatic Lipidosis
NEOPLASIA
This common condition occurs as a result of the accumulation of triglycerides within hepatocytes often following
bouts of anorexia. As the disease is diffuse throughout the
parenchyma, fine needle biopsy is often diagnostic. Hepatocytes may have single or multiple clear punctate vacuoles
within the cytoplasm. At times, the vacuoles may become so
numerous as to crowd the nucleus to one side of the cell. The
appearance of these highly vacuolated hepatocytes can be
difficult to distinguish from foamy macrophages. Also present on cytology is biliary stasis with plugged bile canniculi
and increased green granules within hepatocytes. To confirm
the presence of lipid within the vacuoles, one can use equal
amounts of oil-Red-O and new methylene blue on unstained,
unfixed smears. As the lipid is incorporated into the cell, it
is a dull orange color compared to the extracellular bright
orange droplets.
Hepatocellular Adenoma
Copper-Associated Hepatopathy
Certain breeds of dogs such as Bedlington and West Highland White Terriers as well as patients with accumulations of
toxic amounts of copper develop liver failure from the
inflammatory reaction. Pale green refractile granules that are
positive with rubeanic acid are diagnostic for copper. This
may be a primary accumulation that leads to liver disease or
the result of liver disease. Romanowsky staining can produce a similar stain appearance of hepatocytes granules that
are positive for a bilirubin stain and therefore represent bile.
However it has been noted that green granules within hepatocytes without bile casts are most likely lipofuscin. This
pigment occurs with the normal aging of cells and the subsequent degeneration of cellular lipids, the so-called “wear
and tear pigment”.
This uncommon neoplastic condition usually presents as a
solitary lesion in dogs and cats. Clinical signs are generally
minimal so these tumors are generally found incidentally at
necropsy. Histologically, these compressive lesions contain
minimal fibrosis. Hepatocytes are uniform in appearance but
larger than normal containing increased amounts of lipid,
glycogen, or lipofuscin granules within the cytoplasm. There
is mild anisocytosis and anisokaryosis as well as increased
basophilia of the cytoplasm. Nucoleoli are slightly more
prominent than normal. Mitotic figures are not common.
Hepatocellular Carcinoma
It is said that hepatocellular carcinoma is more common
in dogs than cholangiocarcinoma. In the cat, cholangiocarcinoma is considered to occur more frequent than hepatocellular carcinoma. Clinical signs reflect liver disease with
increased activity of several hepatic enzymes. Histologically, hepatic trabeculae appear thick or variable in size
compared with more uniform and thinner trabeculae of
adenoma lesions. Cytologically, hepatocytes may resemble
normal hepatocytes but in poorly differentiated forms,
hepatocytes appear highly pleomorphic making diagnosis
of malignancy easier. In these cases, malignant features of
anisokaryosis, multinucleation, high and variable nuclear
to cytoplasmic ratio, and multiple nucleoli are present.
Mitotic figures are more frequent in the carcinoma compared with the adenoma.
Cholangiocarcinoma
Amyloidosis
This is a relatively uncommon tumor but in cats it may be
the most frequent primary hepatic malignancy according to
some studies. Histologically, there are acinar formations
especially in the more well-differentiated tumors and fibrous
connective tissue may be substantial. A mucinous cystic fluid often fills the lumen. Mitotic figures are often much more
abundant compared with hepatocellular carcinoma. Cytologically, the cells tend to exfoliate in dense clusters. The welldifferentiated tumors have relatively uniform size and
cuboidal shape with scant cytoplasm. More anaplastic
changes such as anisokaryosis, prominent nucleoli, and high
nuclear to cytoplasmic ratio are seen with the poorly-differentiated cholangiocarcinoma.
This is an uncommon condition often related to a chronic
inflammatory disease. Amyloid is identified by the presence
of Congo red positive eosinophilic amorphous material
around hepatocytes. Inflammatory cells such as neutrophils
and lymphocytes are often present in this situation.
Author’s Address for correspondence:
Rose E. Raskin
Professor of Veterinary Clinical Pathology Purdue University,
West Lafayette, Indiana, USA
Hemosiderosis
Animals that undergo chronic breakdown of erythrocytes
or receive supplemental iron develop an overload condition
in which iron accumulates within hepatocytes. This material
appears as blue or blue-green coarse granular material that
stains positive with Prussian blue.
RESPONSE TO TISSUE INJURY
This manuscript is reproduced in the IVIS website with the permission of the Congress Organizing Committee