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P - Cytology, Haematology & Clinical Pathology

CYTOLOGY OF EFFUSIONS
Senior Associate Vice President
for Research
Executive Director, Discovery Park
Purdue University
Hovde Hall, Room 332
610 Purdue Mall
West Lafayette, IN 47907-2040
rebar@purdue.edu

Accumulations of excessive uid in the pleural,

peritoneal, or pericardial space represent edema
of these body cavities. As such, the dynamics of
uid accumulation are governed by Starlings law.
In general, pleural, peritoneal, and pericardial
effusions can result from either inammatory
or non-inammatory causes. Non-inammatory
edema results from arterial pressure (a rare
cause in veterinary medicine), venous stasis,
hypoalbuminemia (reduces plasma oncotic
pressure), or lymphatic obstruction. Inammation
causes uid accumulation through vascular
damage and leakage.
Evaluation of abnormal uid accumulation is
based upon integrated assessment of both physical
and cytologic characteristics.
Physical assessment of effusions includes
estimation of total solids (total protein) by
refractometry and determination of total
nucleated cell count with either an automated
particle or manual methods. On the basis of
physical characteristics, effusions are classied
as transudates, modies transudates, or exudates.
As a general rule (there are exceptions which
will be discussed later), transudates are noninammatory in origin while exudates are
the result of inammation. Thus, physical
characteristics of effusions allow classication
according to pathophysiologic mechanism of
uid accumulation but reveal little about specic
disease diagnosis.
Cytologic evaluation of effusions augments
physical
evaluation
by
allowing
the
diagnostician to identify specic etiologic
agents, to follow the progression of a disease
process, and to monitor response to therapy. The
decision of whether or not to culture effusion
uid is based upon cytologic ndings. Through
cytologic examination, inammatory reactions
are classied as to type, hyperplastic responses
of the mesothelial lining can be identied, and
neoplasia is diagnosed.

Rose E. Raskin, DVM, PhD,

Diplomate ACVP
Professor of Veterinary Clinical
Pathology
Dept of Veterinary Pathobiology
Purdue University
School of Veterinary Medicine
725 Harrison Street
West Lafayette, IN 47907
rraskin@purdue.edu

Cytologic Evaluation of Effusions

1) Normal Findings
Cells present in normal pleural, pericardial,
and peritoneal uids include low numbers of
mesothelial cells and occasional inammatory
cells. Mesothelial cells are present in small
clusters or as individuals. If knocked loose from
the cavity lining during the collection process,
mesothelial cells resemble squamous cells with
a low N/C ratio and abundant faintly basophilic
cytoplasm. Cells with this morphology have
historically been referred to as pale mesothelial
cells. Normal mesothelial cells which are present
in the uid prior to collection have rounded up
and are quite basophilic (dark mesothelial
cells). They measure between 25 and 35 in
diameter. Nuclei are centrally located, round,
and uniformly granular. Cytoplasm is abundant.
The most striking characteristic of these cells is
the presence of an eosinophilic peripheral brush
border or skirt.
The inammatory cells present in normal uids
have the morphology of normal peripheral
blood leukocytes. The predominant leukocyte
seen varies with the species. In dogs and horses,
neutrophils are prevalent. In cats and cattle,
lymphocytes predominate.
2) Transudates and Modied Transudates
Cellular morphology in true transudates is similar
to that in normal uid; as emphasized previously,
the principal alteration in transudation is increased
uid volume. The principle cellular constituent of
the modied transudate (even the pseudochylous
effusion) is the reactive mesothelial cell.
Because of the ability of mesothelial cells
to respond to irritation by proliferation, the
presence of increased numbers of mesothelial
cell clusters and rafts is a common nding in
reactivity. Mitoses are increased and occasional
multinucleated reactive mesothelial cells are

2006 World Congress WSAVA/FECAVA/CSAVA

Dr. Alan H. Rebar

659

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2006 World Congress WSAVA/FECAVA/CSAVA

seen. Reactive mesothelial cells in clusters are

capable of imbibing lipid from the effusion uid
and when they do, they take on the characteristics
of secretory cells. In this form they must be
differentiated from metastatic adenocarcinoma or
primary mesothelioma. This is done by critically
evaluating the cell populations for criteria of
malignancy.
Reactive mesothelial cells also may assume
a variety of other morphologies. Individual
mesothelial cells sloughed into effusions
gradually lose their brush border and may develop
phagocytic capabilities, accumulate intracellular
debris, and become indistinguishable from
macrophages.
As modied transudates mature, the proportion
of inammatory cells they contain increases.
In most cases the principle inammatory cell is
the non-degenerate neutrophil, but neutrophils
rarely account for more than 30% of the total cell
population.

660

3) Exudates
Inammatory: Inammatory effusions are
classied according to the standard rules for
inammation as neutrophilic, mixed, or histiocytic.
In neutrophilic reactions, neutrophils (either nondegenerate or degenerate) comprise >70% of the
inammatory cells seen. Mixed reactions are
characterized by a mixture of neutrophils and
macrophages, and in histiocytic inammation,
macrophages are the prevalent cell seen.
Inammatory effusions are by their nature
irritative to the lining of involved body cavities.
Consequently, virtually all inammatory
effusions are characterized by some degree of
reactive mesothelial cell hyperplasia. Because
of the tendency of reactive mesothelial cells
to cytologically merge with the monocyte/
macrophage continuum, they are considered to
be a part of the macrophagic component of any
inammatory effusion.
Most inammatory effusions are cytologically
nonspecic in terms of etiologic diagnosis.
However, as with inammatory responses
elsewhere, cytologic morphology provides
signicant clues as to underlying cause.
Neutrophilic inammatory effusions indicate
severe irritation. If neutrophils are degenerate,
then an effort should be made to identify bacterial
organisms within phagocytes. This is generally
easiest at the featheredge of the smear. If organisms
are not seen, the uid should still be cultured.
Mixed inammatory and macrophagic effusions
reect less severe irritation and are found with
resolving neutrophilic effusions or in association
with less irritating etiologic agents than bacteria
(e.g., fungal organisms or foreign bodies).

Non-Inammatory:
a) Chylous effusions: Chylous effusions are the
result of leakage of lymph into the body cavity
and may involve either the pleural or peritoneal
space. Most commonly, the thoracic cavity is
involved (chylothorax) as a result of trauma to the
thoracic duct.
Cytologically, chylous effusions are characterized by
the presence of large numbers of morphologically
normal small lymphocytes. Lesser numbers of
reactive lymphocytes are also present. Because
these uids are mildly irritating, long-standing
chylous effusions also may contain moderate
numbers of reactive mesothelial cells and other
inammatory cells. We have seen several cases
of chronic chylothorax where signicant numbers
of eosinophils were seen. The presence of lipid
in the background of the slide, visualized as
small unsustained droplets at the periphery of the
nucleated cells, is variable.
It is important to note that in the cat, cardiac
disease results in pleural effusions which
are indistinguishable from chylothorax. The
mechanisms behind these effusions have not been
claried; however, it is well established that heart
failure causes venous and lymphatic stasis with
increases pressure. In the cat it appears that these
circumstances predispose to lymphatic leakage
and result in a secondary chylous effusion.
b) Hemorrhagic effusions: True hemorrhagic
exudates can occur in any of the major body
cavities. Grossly, these effusions are red to
serosanguinous depending upon the age of the
exudate and the extent of the hemorrhage. Physical
evaluation reveals a protein level reective of but
somewhat less than that of peripheral blood. Both
nucleated cell counts and red blood cell counts are
elevated.
Cytology is needed to differentiate true
hemorrhagic exudates from sample contamination
at the time of collection. Hemorrhagic exudates
contain predominantly red blood cells with lesser
numbers of nucleated cells. The most signicant
indicator of true hemorrhage is the presence of
activated macrophages containing phagocytized
red cells (erythrophagocytosis) or hemosiderin.
These cells are best observed at the featheredge
of sediment smears. Erythrophagocytosis is not
seen if hemorrhage is strictly a collection artifact.
A second signicant observation is whether or
not platelets are seen. True hemorrhagic exudates
are devoid of platelets but they are commonly
observed in contaminated samples.
c) Neoplastic effusions: Neoplastic processes,
both primary and metastatic, are relatively
common causes of both abdominal and thoracic
effusions in dogs and cats. They are less frequent
but still represent an important cause of effusion
in the horse.

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Neoplastic effusions may be accompanied by

signicant hemorrhage and/or inammation but
generally they are non-inammatory. Grossly,
the uid may be clear to cloudy and hemorrhagic.
Total protein levels are elevated but nucleated cell
counts are highly variable.
In dogs and cats the common causes of neoplastic
effusions are thymic lymphosarcoma (pleural),

and adenocarcinoma or carcinoma (either pleural

or peritoneal). In horses, squamous cell carcinoma
of the stomach (peritoneal) is by far the most
frequent cause, with lymphosarcoma occurring
only occasionally. Mesothelioma can be a rare
cause of effusion in any species.

P - Cytology, Haematology & Clinical Pathology

CYTOLOGY OF LUMPS AND BUMPS

Professor of Veterinary Clinical

Pathology
Dept of Veterinary Pathobiology
Purdue University
School of Veterinary Medicine
725 Harrison Street
West Lafayette, IN 47907
rraskin@purdue.edu

Follicular Cyst
These cysts are found in a third to a half of the
nonneoplastic
noninammatory
tumor-like
lesions removed in dogs and cats, respectively.
The cyst occurs most frequently in middle to
older aged dogs. They may be single or multiple,
rm to uctuant, with a smooth, round, well
circumscribed appearance. These are often
located on the dorsum and extremities. The cyst
lining arises from well differentiated stratied
squamous epithelium often associated with
adnexal structures. Keratin bars, squames, or
other keratinocytes predominate on cytology.
Degradation of cells within the cyst may lead to the
formation of cholesterol crystals which appear as
negative stained, irregularly notched, rectangular
plates best seen against the amorphous basophilic
cellular debris of the background. The behavior
of these masses is benign, but rupture of the cyst
wall can induce localized pyogranulomatous
cellulitis with evidence of acute and/or chronic
hemorrhage. When this occurs, neutrophils and
macrophages may be frequent.
Mucocele or Sialocele
Duct rupture related to trauma or infection leads to
an accumulation of saliva within the subcutaneous
tissues. The presence of a uctuant mass

Dr. Alan H. Rebar

Senior Associate Vice President
for Research
Executive Director, Discovery Park
Purdue University
Hovde Hall, Room 332
610 Purdue Mall
West Lafayette, IN 47907-2040
rebar@purdue.edu

containing clear to bloody uid with string-like

features suggests a salivary gland duct rupture. The
cytologic specimen often stains uniformly purple
from the high protein content. The background
may contain scattered, pale basophilic, amorphous
material, consistent with saliva. The uid is often
bloody with evidence of both acute and chronic
hemorrhage. Erythrophagocytosis is common
and occasional yellow rhomboid crystals may
be seen. These are termed hematoidin crystals
and are associated with chronic hemorrhage. The
nucleated cell population consists predominately
of highly vacuolated macrophages displaying
active phagocytosis. Distinction between these
cells and secretory glandular tissue may be
difcult, especially when cells are individualized
and nonphagocytic. Nondegenerate neutrophils
are common.
Nodular Panniculitis/Steatitis
This condition may have an infectious or
noninfectious etiology. Causes of noninfectious
panniculitis include trauma, foreign bodies,
vaccination
reactions,
immune-mediated
conditions, drug reactions, pancreatic conditions,
nutritional deciencies, and idiopathic. The
condition appears in the cat and dog as solitary or
multiple, rm to uctuant, raised, well demarcated

2006 World Congress WSAVA/FECAVA/CSAVA

Rose E. Raskin, DVM,

PhD, Diplomate ACVP

661

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lesions. These may ooze an oily yellow-brown
uid. Sites of prevalence involve the dorsal
trunk, neck, and proximal limbs. Cytologically,
nondegenerate neutrophils and macrophages
predominate against a vacuolated background
composed of adipose tissue. Small lymphocytes
and plasma may be numerous, especially in lesions
induced by vaccination reactions. Frequently,
macrophages present with abundant foamy
cytoplasm or as giant multinucleated forms.
When chronic, evidence of brosis is indicated by
the presence of plump fusiform cells with nuclear
immaturity. The brosis may be so extensive as
to suggest a mesenchymal neoplasm. Multiple
lesions are often associated with systemic disease
in young dogs. Dachshunds and poodles may be
predisposed to this form of the disease.

2006 World Congress WSAVA/FECAVA/CSAVA

Dermatophytosis
The lesions vary from alopecia, broken hair
shafts, crusts, scales, and erythema to raised
nodules on the head, feet, and tail of dogs and cats.
Cytologic specimens reveal a pyogranulomatous
inammation with degenerate neutrophils and
large epithelioid macrophages. Arthrospores and
hyphae are associated with hair shafts that are
best visualized using clearing agents with plucked
hairs. Arthrospores are occasionally present as
oval to round lightly basophilic structures having
a thin clear halo and measuring 2 x 2-3 um. They
may be seen extracellularly or within neutrophils
and macrophages and associated with hair or
keratin.

662

Squamous Cell Carcinoma

This is a common tumor occurring as solitary
or multiple proliferative or ulcerative masses.
It is most common on the limbs of dogs and
thinly haired areas of the pinnae or face of cats.
Cytologically, purulent inammation often
accompanies immature or dysplastic squamous
epithelium. Bacterial sepsis may occur if the
surface has eroded. Characteristic tadpole shape
and keratinized blue-green cytoplasm may be
helpful criteria in determining the cell of origin.
Squames and highly keratinized nucleated
squamous epithelium are frequent in welldifferentiated tumors corresponding to the keratin
pearls seen histologically. Cellular and nuclear
pleomorphism is marked. Perinuclear vacuolation
may be present. The neoplastic epithelium may
appear as individual cells or as adherent sheets of
cells.
Basal Cell Tumor
Found commonly in dogs and cats as typically
a single, rm, elevated, well demarcated round
intradermal mass that may be ulcerated or cystic.

Many tumors appear pigmented due to abundant

melanin. Tumors in cats may be cystic. They
are located mostly about the head with frequent
occurrence on the neck and limbs. Cytologically,
basal cells are small cells characterized by high
nuclear to cytoplasmic ratios, monomorphic
nuclei, and deeply basophilic cytoplasm. They
may be arranged as clusters or in row formation.
Perianal Gland Adenoma
The tumor may be single or multiple occurring
generally near the anus, but may also be found
on the tail, perineum, prepuce, thigh, and along
the dorsal or ventral midline. Initially they grossly
appear as smooth, raised round lesions which
become lobulated and ulcerated as they enlarge.
The tumor arises from modied sebaceous gland
epithelium. Cytologically, sheets of mature round
hepatoid cells predominate characterized by
abundant nely granular pinkish-blue cytoplasm.
Nuclei resemble those of normal hepatocytes
appearing round with an often single or multiple,
prominent, nucleolus. A low number of smaller
basophilic reserve cells having a high nuclear to
cytoplasmic ratio may also be present, but these
lack features of cellular pleomorphism.
Fibrosarcoma
In young cats this tumor may be caused by the
feline sarcoma virus and may be multiple. In
older dogs and cats, tumors are solitary with
a predilection for the limbs, trunk, and head.
They are poorly circumscribed and sometimes
ulcerated. Cytologically, brosarcoma consists of
abundant numbers of large plump cells occurring
individualized or in aggregates. Multinucleated
giant cells may be present occasionally. Nuclear
pleomorphism may be marked compared with
the benign counterpart. Cells are less uniform
and generally have high nuclear to cytoplasmic
ratios.
Canine Hemangiopericytoma
This is a common tumor generally considered to
affect dogs only. These are often solitary tumors
with a predilection for the joints of the limbs, but
are found commonly on the thorax and abdomen.
They are rm to soft, multilobulated, and often
well circumscribed. Cytologically, preparations
are moderately cellular. Plump spindle cells
may be individualized or arranged in bundles,
sometimes found adherent to the surface of
capillaries. Nuclei are ovoid, with one or more
prominent central nucleoli. Multinucleated cells
are occasionally seen. Associated with cells
may be a pink amorphous collagenous stroma.
The cytoplasm is basophilic and may contain
numerous small discrete vacuoles. Lymphoid

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Lipoma
This is the most common connective tissue tumor
in dogs. The tumor may be single or multiple,
occurring mostly on the trunk and proximal limbs.
These are dome-shaped, well circumscribed, soft,
often freely moveable masses within the subcutis
which can grow slowly becoming quite large.
Cytologically, unstained slides appear wet with
glistening droplets that do not dry completely.
Lipid may be best demonstrated with watersoluble new methylene blue and a fat stain
(oil-red-O). When stained with alcohol-based
Romanowsky stains, lipid is dissolved leaving
slides often void of cells. When present, intact
adipocytes have abundant clear cytoplasm with a
small compressed nucleus to one side of the cell.
Hemangiosarcoma
This is a malignant inltrative mass of the dermis or
subcutis. Lesions are raised, poorly circumscribed,
ulcerated, and hemorrhagic. Cytologically, slide
preparations are of low cellularity with numerous
blood cells within the background. Evidence of
hemorrhage with hemosiderin-laden macrophages
may be present. Neoplastic cells are pleomorphic
ranging from large spindle to stellate. Cytoplasm
is basophilic, having indistinct cell borders and
occasional punctate vacuolation. Cells have
high nuclear to cytoplasmic ratios, oval nuclei
with coarse chromatin and prominent multiple
nucleoli.
Melanoma
This is a common tumor of dogs and an uncommon
tumor of cats. Older animals are usually affected
as are those with dark skin pigmentation. Gross
features differ for benign and malignant forms.
Benign tumors are mostly dark brown to black,
circumscribed, raised, dome-shaped masses
covered by smooth hairless skin. Malignant tumors
are variably pigmented, inltrative, frequently
ulcerated and inamed. Cytologically, cells are
pleomorphic ranging from epithelioid to fusiform,
or occasionally as discrete round cells. In welldifferentiated tumors, nuclei may be masked by
numerous ne black-green cytoplasmic granules.
Poorly differentiated tumors may contain few or no
cytoplasmic granules. Nuclei in benign forms are
small and uniform compared with characteristics
of anisocytosis, anisokaryosis, coarse chromatin,
and prominent nucleoli seen in the malignant
melanomas. Prognosis depends on tumor site
of origin and histologic characteristics. Benign
skin tumors frequently have a good prognosis.
Malignant forms arise more often from the nail

bed, lip and other oral mucocutaneous junctions

in dogs. The latter forms carry a guarded or poor
prognosis related to frequent recurrence and
metastasis.
Canine Histiocytoma
This is a very common benign rapidly growing
tumor of mostly young dogs. The tumor appears
as a small solitary, well circumscribed, domeshaped, red ulcerated, hairless mass. It occurs
commonly on the head, especially ear pinna,
as well as on the hindlimbs, feet, and trunk.
Cytologically, cells have round to indented nuclei
with ne chromatin and indistinct nucleoli. Cells
exhibit minimal anisocytosis and anisokaryosis.
The cytoplasm is abundant and clear to lightly
basophilic with indistinct cell borders. A variable
number of small well-differentiated lymphocytes
are common in regressing lesions.
Mast Cell Tumor
Tumors in dogs are generally solitary,
nonencapsulated and highly inltrative into
dermis and subcutis. Mast cell tumors in cats
are usually solitary, well circumscribed, dermal
masses that occur on the head, neck, and limbs.
Multiple masses are common in young Siamese
cats. Mast cell tumors in cats are common also in
visceral organs, spleen, and liver. Cytologically,
tumor cells may vary in the degree of granularity
with some cells having numerous distinct
metachromatic stained granules while others
contain moderate numbers of granules or few to no
cytoplasmic granules. In less differentiated forms,
anisokaryosis, coarse chromatin, and prominent
nucleoli may be present along with a poorly
granulated cytoplasm. Giant binucleated cells are
more commonly found in poorly differentiated
forms. Eosinophils are more numerous in canine
tumors than feline tumors.
Plasmacytoma
This tumor is infrequent in dogs and rare in
cats. They present as mostly solitary, well
circumscribed masses often on the digits, ears, and
mouth. Cytologically, aspirates are moderately to
markedly cellular. Individual cells have variable
amounts of basophilic cytoplasm in which borders
are discrete. Anisocytosis and anisokaryosis are
prominent features. Nuclei are round to oval with
ne to moderately coarse chromatin and indistinct
nucleoli. The nuclei are often eccentrically placed
and frequently binucleated. Multinucleated cells
may be present. Amorphous eosinophilic material,
representative of amyloid is seen in less than 10%
of plasmacytomas. Prognosis is generally good,
but local recurrences may be common.

2006 World Congress WSAVA/FECAVA/CSAVA

cells have been found in approximately 10% of

cases.

663

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Cutaneous Lymphoma
The disease may occur primarily in the skin
or rarely as a manifestation of generalized
lymphoma. It is more common in older dogs
and cats. Lesions are solitary to multiple in the
form of nodules, plaques, ulcers, erythroderma,
or exfoliative dermatitis in the form of excessive
scaling. Pruritus may be common. Epitheliotropic
lymphoma is characterized by neoplastic Tlymphocyte inltrates of the epidermis and
adnexa. Focal collections of the neoplastic cells,
termed Pautrier microabscesses, are sometimes
formed within the epidermis. B- or T-lymphocytes
are presumed involved in the inltration of the
dermis and subcutis with nonepitheliotropic
lymphomas. Lymphocytes range in size from
small to large with round, indented, or convoluted
nuclei. Nucleoli may be prominent. Cytoplasm
is scant to moderate and lightly basophilic.
Uniformity of the lymphoid population without

signicant inammation or plasma cell inltration

is suggestive of cutaneous lymphoma. Prognosis
is poor as the disease rapidly progresses
necessitating euthanasia.
Suggested Cytology References
Baker R, Lumsden JH. Colour Atlas of Cytology
of the Dog and Cat: Mosby, St. Louis; 2000
Cowell RL, Tyler RD, Meinkoth JH. Diagnostic
Cytology and Hematology of the Dog and Cat:
Mosby, St. Louis; 2nd Ed. 1999
Radin MJ, Wellman ML. Interpretation of Canine
and Feline Cytology: Ralston Purina Company
Clinical Handbook Series. The Gloyd Group, Inc,
Wilmington, DE; 2001
Raskin RE, Meyer DJ (eds). Atlas of Canine and
Feline Cytology: WB Saunders Co, Philadelphia;
2001

P - Cytology, Haematology & Clinical Pathology

CYTOLOGY OF INTERNAL ORGANS
Rose E. Raskin, DVM,
PhD, Diplomate ACVP

2006 World Congress WSAVA/FECAVA/CSAVA

Professor of Veterinary Clinical

Pathology
Dept of Veterinary Pathobiology
Purdue University
School of Veterinary Medicine
725 Harrison Street
West Lafayette, IN 47907
rraskin@purdue.edu

664

Commonly sampled internal organs include

the liver, spleen, and thyroid gland often by
ultrasound-guided biopsy. Artifacts commonly
encountered involve ultrasound gel that appears
as particulate eosinophilic material similar to
stain precipitate.
Cytodiagnostic Groups for Liver Cytology
1. Normal epithelial cells
2. Cellular degeneration or injury
3. Hyperplasia or adenoma
4. Pigment abnormalities
5. Inammation
6. Malignant neoplasia
7. Hematopoietic tissue
Normal Hepatic Tissue
Hepatocytes consist of clumps or sheets of
large uniform cells. Cells are characterized
by low nuclear to cytoplasmic ratios, lightly
basophilic and granular cytoplasm, centrally

Dr. Alan H. Rebar

Senior Associate Vice President
for Research
Executive Director, Discovery Park
Purdue University
Hovde Hall, Room 332
610 Purdue Mall
West Lafayette, IN 47907-2040
rebar@purdue.edu

placed round nucleus that has stippled chromatin

and a prominent nucleolus. Occasionally cells are
binucleated and nucleoli are multiple.
Biliary epithelium consists of sheets of small
uniform cells with high nuclear to cytoplasmic
ratios. Large biliary ducts are lined by a simple
columnar epithelium. Nucleoli are often
indistinct.
Mast cells and macrophages may be occasionally
found in low numbers.
Hepatocellular Degeneration or Injury
Hydropic change (vacuolar degeneration)
produces a foamy appearance within the
cytoplasm of hepatocytes that is the result of
swelling of endoplasmic reticulum related to
increased intracellular water. This may be seen in
tissue anoxia and toxic hepatopathies.
Fatty change appears as discrete clear vacuoles
within the hepatocyte cytoplasm that is the result
of accumulation of lipids that can freely coalesce.
This appearance is often diagnostic for lipidosis.

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Hepatic Hyperplasia (Regeneration) or Adenoma

are grouped together since they have a similar
cytologic appearance.
Frequent binucleation is noted within
hepatocytes.
Increased nuclear to cytoplasmic ratio indicates
rapid growth.
Mild to moderate anisocytosis and anisokaryosis
is present.
Increased cytoplasmic basophilia may be noted
due to rapid growth.
Increased frequency of intranuclear crystalline
inclusions.
Conditions to consider include nodular
hyperplasia, toxic hepatopathy, hepatocellular
adenoma, bile duct adenoma, and cirrhosis.
Hepatic Pigment Abnormalities are observed
within hepatocytes appearing as shades of blue
and green with routine stains. The etiology of
these pigments may be differentiated by the
cytochemical reactions.
Biliary stasis within canniculi appears as green
casts or granular material between hepatocytes.
Conditions associated with bile pigment changes
include cholangitis, liver ukes, lipidosis,
steroid hepatopathy, toxic hepatopathy, nodular
hyperplasia, and cirrhosis.
Hemosiderosis is an overload condition in
which iron appears as blue or blue-green coarse
granular material that stains positive with
Prussian blue. Chronic hemolysis and excessive
iron supplementation are associated with
hemosiderosis.
Lipofuscin appears as blue-green granules
on Wright-Giemsa stained preparations which
represent degenerated lipids resulting from
cellular aging.
Copper accumulation appears blue-green

material which stains positive with rubeanic acid.

This may be a primary accumulation or secondary
related to liver disease.
Hepatitis/Cholangitis
Neutrophilic (suppurative) inammation is
associated with necrosis, bacterial infection, and
feline suppurative cholangiohepatitis. Degenerate
or nondegenerate neutrophils are increased over
that found in peripheral blood.
Lymphocytic or plasmacytic (nonsuppurative)
inammation is common in feline lymphocytic
cholangiohepatitis. Lymphoid cells are small,
well-differentiated forms associated with chronic
disease that may be difcult to distinguish on
cytology from a small cell lymphoma.
Eosinophilic inammation may be associated
with liver ukes or mast cell tumor occurring
within the liver.
Pyogranulomatous inammation consists of a
mixed population of neutrophils and macrophages.
This is associated with mycobacteriosis,
histoplasmosis, and toxoplasmosis.
Malignant Neoplasms of the Liver
Primary tumors include: hepatocellular carcinoma,
bile duct carcinoma, and hemangiosarcoma
Secondary tumors include: myeloid (nonlymphoid)
leukemias, intestinal carcinomas, and pancreatic
islet cell tumor
Lymphoma and mast cell tumor may be primary
or secondary
Hematopoietic Tissue
Extramedullary hematopoiesis resembles a
mixed bone marrow cell population including
erythroid, granulocytic, and megakaryocytic
precursors. It is often related to a physiologic
need, such as in bone marrow disease or hypoxic
conditions.
Myelolipoma is an uncommon tumor resembling
extramedullary hematopoiesis, but also contains
considerable lipid material. It is benign and often
localized.
SPLEEN
Cytodiagnostic Groups for Spleen Cytology
1. Normal tissue
2. Hyperplasia or reactivity
3. Inammation
4. Malignant neoplasia
5. Hematopoietic tissue
Normal Splenic Tissue
Sheets of normal mesothelium from the splenic
capsular surface are encountered with incisional
and excisional biopsies
Small lymphocytes predominate with occasional

2006 World Congress WSAVA/FECAVA/CSAVA

Glycogen accumulation occurs with altered

glucose metabolism such as seen in steroid
hepatopathy. Cytoplasm appears foamy, similar
to hydropic change. Steroid induced change is
most notable in the dog, but occasionally has been
observed in the cat.
Necrosis may occur as a result of toxicosis,
infectious disease, or neoplasia. Cells appear
indistinct, with loss of cellular detail.
Fibrosis is related to increased connective
tissue reaction to damage, such as that seen in
cirrhosis, post-necrosis hepatopathy, or chronic
inammation.
Amyloid deposition is an uncommon condition
often related to a chronic inammatory disease.
Presence of Congo red positive eosinophilic
amorphous material around hepatocytes is
diagnostic.

665

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medium and large lymphocytes present. A few
macrophages and plasma cells may be seen along
with rare neutrophils and mast cells. Macrophages
may contain small amounts of phagocytized
debris, compatible with hemosiderin.
Small amounts of reticular tissue with
macrophages and stroma in an aggregated
fashion

metastatic neoplasm. Cells are large, individual,

spindle to stellate with indistinct cytoplasmic
borders. The cytoplasm is often vacuolated and
basophilic.
Other mesenchymal neoplasms that occur in the
spleen include brosarcoma, leiomyosarcoma,
and myelolipoma.
THYROID

Splenic hyperplasia or reactive spleen

Small lymphocytes still predominate but there is
an increase in medium and large lymphocytes.
Macrophages and plasma cells are commonly
observed. Associated with the macrophages
may be reticular stroma appearing as basophilic
brillar or spindle shaped elements.
Hemosiderosis may be more noticeable with
large amounts of coarse dark granules.
Increased numbers of mast cells and neutrophils
may be observed.
Hyperplasia may result from antigenic reaction to
infectious agents or presence of blood parasites.

2006 World Congress WSAVA/FECAVA/CSAVA

Splenitis
An inammatory response is likely associated
with splenic hyperplasia.
Macrophages often increase in number to
systemic fungal infections e.g., histoplasmosis,
protozoal infections e.g., cytauxzoonosis, and
leishmaniasis.

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Extramedullary hematopoiesis
This was the most common cytologic abnormality
in one study accounting for 24% of the patients.
While precursors from all three cell lines may
be observed, erythroid cells are the most common
with metarubricytes, rubricytes, and prorubricytes
present. Care must be taken as erythroid precursors
and lymphoid precursors appear very similar.
Conditions associated with extramedullary
hematopoiesis include: chronic hemolytic
anemias, myeloproliferative disorders, and
lymphoproliferative disorders.
Neoplasia (Primary or Metastatic)
In myeloproliferative disorders, expect to nd
immature hematopoietic cell types. Malignant
histiocytosis presents with bizarre and immature
macrophages, often with evidence of marked
erythrophagocytosis.
Lymphoid neoplasia includes lymphoma and
plasmacytoma (extramedullary myeloma). A large
granular cell lymphoma arises primarily from the
spleen to inltrate the blood but not typically the
bone marrow.
Mast cell tumor may be primary or secondary.
Hemangiosarcoma is a common primary or

Thyroid tumor
Thyroid tumors occur most frequently in the
dog, cat, and horse and often present clinically as
a subcutaneous mass on the neck, lateral to the
trachea or near the thoracic inlet. Ectopic thyroid
tumors are occasionally found at the base of the
heart or base of the tongue. Approximately 90%
of the thyroid tumors identied clinically in the
dog are carcinomas. Aspirates from thyroid
carcinomas often contain a large amount of blood
contamination. The epithelial cell clusters appear
as free nuclei embedded in a background of pale
blue cytoplasm with infrequent appearance of
cytoplasmic membranes or borders. Sometimes
seen within the cytoplasm of epithelial cells is
dark blue to black pigment, which is thought
to represent tyrosine-containing granules.
Amorphous pink material representing colloid
may be associated with some clusters.
The nuclei of most endocrine tumors are round
to oval with minimal anaplastic or malignant
features and generally appear of uniform size.
Cytologically, benign and malignant thyroid
tumors appear similar. As most canine thyroid
tumors are malignant, metastasis is common
to the lungs. However, unlike the dog, the vast
majority of tumors in the cat are benign adenomas
or adenomatous hyperplasia.
Suggested Cytology References
Baker R, Lumsden JH. Colour Atlas of Cytology
of the Dog and Cat: Mosby, St. Louis; 2000
Cowell RL, Tyler RD, Meinkoth JH. Diagnostic
Cytology and Hematology of the Dog and Cat:
Mosby, St. Louis; 2nd Ed. 1999
Radin MJ, Wellman ML. Interpretation of Canine
and Feline Cytology: Ralston Purina Company
Clinical Handbook Series. The Gloyd Group, Inc,
Wilmington, DE; 2001
Raskin RE, Meyer DJ (eds). Atlas of Canine and
Feline Cytology: WB Saunders Co, Philadelphia;
2001