COMPANION ANIMAL PRACTICE Dog showing extensive bruising

and oedema associated with

degranulation of a mast cell
tumour, which metastasised
to the inguinal lymph nodes

Skin neoplasia in small animals

1. Principles of diagnosis and
management SUE MURPHY

SKIN cancers are very common in cats and dogs. The fact that skin cancer is often reported is not too
surprising as lesions are often readily visible to the owner. The skin is a large, complex organ, the barrier
between the body and its environment, and is continuously being bombarded by carcinogens. It is an
area of rapid cell turnover, increasing the chance of DNA mutations and allowing cancer to arise. This
article, the first in a series of three, discusses the general approach to the diagnosis and management of
a suspected neoplastic mass in the skin or subcutis of dogs and cats. Articles in the June and July/August
issues of In Practice will concentrate on feline and canine cutaneous neoplasms, respectively.

Sue Murphy
graduated from
SKIN ANATOMY layers. Melanocytes are found in the basal layer of
Edinburgh in 1986 pigmented tissue. The epidermis interdigitates with the
and spent 10 years dermis, which is the vascular layer feeding the epidermis.
Knowledge of the normal anatomy of the skin is impor-
in general practice
before undertaking a tant and can help in differentiating between those The dermis consists mostly of connective tissue and blood
residency in oncology tumours that arise in a particular tissue and those that or lymphatic vessels. The basement membrane separates
at the Animal Health
Trust (AHT). Since are more likely to have arisen as a result of metastatic the epidermis from the dermis, below which is the hypo-
2001, she has worked disease. dermis where fat accumulates. Sebaceous glands, sweat
as a clinician at the
AHT, where she The skin is broadly divided into three layers – the glands and hair follicles form the adnexal structures run-
currently runs the epidermis, dermis and hypodermis. The epidermis is the ning through the dermis and epidermis. Other cells found
oncology unit. She
holds an MSc in
outer, non-vascular layer, which comprises the basal in the skin that can form tumours include mast cells,
clinical oncology. (mitotically active), spinous, granular, clear and cornified lymphocytes, plasma cells and histiocytes.

Epidermis

Basal layer

Dermis

Adnexal structures

In Practice (2006) Low-power photomicrograph showing

28, 266-271 the normal structure of canine skin

266 In Practice ● MAY 2006

APPROACH TO A LESION CUTANEOUS TUMOURS AND THEIR ORIGIN

Origin Benign Malignant

HISTORY
A complete and detailed history should be taken to Epidermis Basal cell tumour Squamous cell carcinoma
assess the presenting problem as well as any concurrent Dermis
Blood vessels Haemangioma Haemangiosarcoma
disease that may influence treatment options. This Pericytes Haemangiopericytoma
should provide some clues about the potential stage Connective tissue Fibroma, lipoma, etc Soft tissue sarcoma
(extent) of disease and also determine whether there is Adnexa
any evidence of paraneoplastic syndromes (eg, vomiting Hair follicles Pilomatricoma
Trichoepithelioma
and melaena in the case of mast cell disease). In particu- Sebaceous gland Adenoma Adenocarcinoma
lar, it is important to establish how long the lesion has Sweat gland Adenocarcinoma
Anal sac Adenocarcinoma
been present, whether it is increasing or decreasing in
Other
size, and at what rate, whether other cutaneous or non- Lymphoid Lymphoma
cutaneous lesions have been or are present and, if these Plasmacytoma
were sampled, what the findings were. Mast cells Compact mast cell tumour* Diffuse mast cell tumour*
Histiocytic mast cell tumour*
Melanocytes Malignant melanoma
CLINICAL EXAMINATION *These are recognised subgroups of mast cell tumours in cats. In dogs, all mast cell tumours are
A thorough clinical examination should be carried out considered to be potentially malignant
and should attempt to answer a number of questions.
This will help to differentiate between suspicious lesions
and those that are more likely to be benign, although as can inflammation around the tumour itself. Metastatic
cytology or histopathology is almost always needed to disease can be appreciated on palpation as a more irregu-
provide an accurate diagnosis. lar hard node that can be fixed to underlying tissues. It
should be noted that early tumour invasion of a lymph
The lesion node cannot be assessed accurately by clinical examina-
■ Where is it? tion alone, and requires cytological or histopathological
■ How large is it? evaluation.
■ Is it well circumscribed and freely movable, or is it
fixed to adjacent tissues? Other abnormalities
Benign tumours are usually freely movable and well ■ Are there any abnormalities associated with other
circumscribed with little inflammation around them. organs, such as splenomegaly or dyspnoea?
Malignant tumours, meanwhile, are invasive and will Abnormalities could suggest distant metastatic dis-
therefore fix to adjacent tissues and have a less obvious ease. However, it should be noted that animals with lung
margin. It should be borne in mind that, although most metastases often have no overt clinical signs.
skin lesions are primary tumours, some can be secondary
metastases with primary tumours occurring elsewhere.
DIAGNOSIS
The drainage lymph node
■ Is it enlarged? A number of proliferative or ulcerative skin conditions
■ Is it soft and symmetrically enlarged or hard and can mimic neoplasia. Tumours are better managed
knobbly? sooner rather than later as surgery is the mainstay of
■ Is it fixed to adjacent tissues? treatment for most skin neoplasms. Therefore, prompt
Local inflammation (eg, in cases of dental disease) diagnosis by fine needle aspiration (FNA) or surgical
can cause draining lymph nodes to become hyperplastic, biopsy of any suspicious lesion is warranted.

FINE NEEDLE ASPIRATION

FNA can be carried out cheaply and easily on a con-
scious patient and will often provide a diagnosis or at

Multiple subcutaneous masses (arrows) on the forelimb of

a labrador. Histopathology revealed a poorly differentiated This lesion on the tail of a Staffordshire bull terrier was
round cell malignancy. Cutaneous B cell lymphoma was initially thought to be a lipoma, but fine needle aspiration
subsequently diagnosed by immunohistochemistry identified a mast cell tumour

In Practice ● MAY 2006 267

 Fine needle aspiration of a
cutaneous lesion using the
core technique

least some indication of neoplastic involvement. It can

be performed using one of two methods:
■ Core technique;
■ Aspiration technique.
For both procedures, care should be taken to choose Cytological sample from a soft tissue sarcoma showing
an approach that will allow the needle tract to be excised the spindle-shaped cells’ cytoplasm. Magnification x1000,
at surgery. The needle should not be poked through the Giemsa stain

lesion into the normal tissue beyond. Different areas of

the lesion should be sampled. The centre of a lesion is
frequently necrotic and this area should be avoided. It
should be ensured that all slides are prepared and the
syringe ready prior to sample collection. Smears should
be made gently to minimise cell damage.
Core technique
■ Hold the lesion gently between finger and thumb and
insert a 23 gauge needle into the lesion, angling the nee-
dle into different areas of the mass.
■ Once the sample has been obtained, attach a 5 ml
syringe of air to the needle hub and vigorously expel the
contents onto a slide and make a smear.
There is less chance of blood contamination using the
core technique than the aspiration technique, but it may
yield a lower cell harvest.
■ Once removed from the lesion, disconnect the syringe
from the needle, fill it full of air, reconnect it, expel the
sample onto a slide and make a smear.
EXCISIONAL BIOPSY
Removing small lesions with a narrow margin of
‘normal’ tissue will cure benign and some low-grade,
less infiltrative malignancies. All the untrimmed tissue
should be sent to a histopathologist for analysis, which
should identify the lesion, the grade of the tumour, if
appropriate, and provide an assessment of whether the
entire tumour has been removed (ie, the margins).
For more infiltrative tumours, the rule that ‘the first
surgery is the best surgery’ means that excisional biopsy
should only be carried out if removing a tumour with no
margin of normal tissue will not affect the outcome.

Aspiration technique INCISIONAL BIOPSY

■ Hold the lesion gently between finger and thumb. If excisional biopsy is not appropriate, an incisional
■ Attach a needle to a syringe and insert the needle into biopsy, ideally including part of the lesion’s margin, can
the lesion. Pull back on the syringe, angling the needle
into different areas of the mass. Release the pressure prior
to removing the needle from the lesion to minimise the
risk of spreading neoplastic cells along the needle tract.

Fine needle aspiration: general considerations

and limitations
Ideally, following FNA, one slide should be stained in-house to assess the quality
of the sample. This will establish, for example, whether the cells are recognisable,
whether they are thinly spread and whether there is a good harvest of cells. If not,
the technique can be repeated while the animal is still in the clinic. The author
usually performs the core technique to minimise blood contamination, stains a
representative slide and, if the cell harvest is poor, uses the aspiration technique
to try to get a better cell harvest.
FNA has some limitations. For instance, not all cell types are shed easily, so the
sample may not be representative or diagnostic. Also, it provides no information
about tissue architecture and, hence, the grade of the tumour. All FNA diagnoses
of primary tumours should be confirmed by histopathology. As well as providing a
definitive diagnosis, histopathology can indicate how aggressive a tumour is and
also allows the margins of the tumour to be assessed to ensure that it has been Tools that can be used for obtaining an incisional biopsy.
completely excised. (from left to right) Dermal punch, ‘Tru-Cut’ biopsy needle
and scalpel blade

268 In Practice ● MAY 2006

be taken from a representative area (avoiding obvious
areas of inflammation or necrosis) that is unlikely to
compromise a definitive surgery. As with FNA, any
follow-up surgery should remove all tissue disturbed by
the biopsy as this is regarded as contaminated with
tumour cells. Tissue should be handled gently to avoid
crush artefacts. Diathermy should only be used to control
bleeding after the biopsy has been taken, to avoid dam-
age to the biopsied tissue.
Incisional biopsies can be performed using a dermal
punch, ‘Tru-Cut’ or Vet-Core instrument, or a scalpel
blade.
IMMUNOHISTOCHEMISTRY
For a significant number of tumours, the specific tissue of
origin cannot be readily identified using light microscopy
alone. Sometimes, the tumour cells are so poorly differ-
entiated that they do not exhibit the normal histological
characteristics of their cell or tissue type. For example,
mast cell tumours may lose their typical metachromati-
cally staining granules, metastatic melanomas may be
amelanotic and have very pleomorphic cells, and cuta-
neous histiocytomas can occasionally resemble cutaneous
lymphomas. Immunohistochemistry can help to distin-
guish between different tumour types that would require
very different treatments and would have different clini-
cal outcomes.
Immunohistochemistry detects tissue antigens and, in
this context, can be used to detect antigens that are specif-
ic to certain cell types, which, in turn, can help to predict
the cell type of origin. During the staining process, tissue
sections are incubated with the antibodies specific to the
target antigen. Binding of the antibody to its target anti-
gen within the section is detected using a second antibody
layer in the presence of an enzyme catalyst and a chroma-
gen. This reaction generates a brown precipitate at the
original antigen/antibody binding site, which can then be
seen on the section through the microscope.
Information gained by this technique can be extremely
useful, but the limitations should be understood. Immuno-
histochemistry will not differentiate between the same
antigen expressed on neoplastic and normal cells. It is
also possible for a cell to be so poorly differentiated that
it fails to express its ‘normal’ tissue antigens (false nega-
tives) or even expresses antigens that would not normally
be expressed by its tissue of origin (false positives). It is
therefore most appropriate to use a panel of antibodies
to try to identify a lesion rather than rely on a single anti-
body to make the diagnosis. Most antibodies that are
routinely used for tumour diagnosis can be used on for-
malin-fixed tissue, but some require fresh tissue samples.
It is sensible to discuss the exact requirements with a
pathologist offering this service before deciding on what
panel of antibodies would be useful in any particular case,
and indeed whether immunohistochemistry is appropriate.
When sending samples to a pathologist, it is impor-
tant also to send a clinical history to aid interpretation. If
the pathologist’s report says ‘inflammation’ and the vet-
erinary surgeon suspects ‘tumour’, it may be that an area
of peritumoral inflammation has been sampled and
another biopsy is needed. If the clinical and pathological
pictures are at odds with each other, discuss the case
with the pathologist. Sometimes, a second opinion can
be useful. In the author’s experience, pathologists are
only too happy to discuss an individual case and to
arrange for a second opinion, if required.
In Practice ● MAY 2006
Epitheliotropic lymphoma with cells positive for CD3
(T lymphocyte marker) staining brown
STAGING
An assessment of the extent of tumour spread is referred
to as staging. Different tumour types have different pat-
terns of spread and likelihood of metastasis. For most
lesions, therefore, staging occurs after a diagnosis has
been reached. For lesions strongly suspected of being a
particular type of cancer (eg, most mammary masses in
cats are malignant) or where it is obvious that a tumour
has spread, staging may take place prior to surgical biop-
sy. Metastases are most often found in the local drainage
lymph nodes and the lung parenchyma. However, for
some tumours, such as mast cell tumours, common sites
of metastasis include the liver and spleen. Recent work
has suggested that normal sized lymph nodes in the dog
can harbour metastatic disease. It would therefore seem
sensible to carry out FNA on accessible drainage lymph
nodes of tumours with a high risk of metastasis prior to
STAGING OF CANINE OR FELINE TUMOURS OF EPIDERMAL OR DERMAL ORIGIN* ACCORDING
TO THE WORLD HEALTH ORGANIZATION CLASSIFICATION SYSTEM
Stage Clinical description
Tumours
Tis Pre-invasive carcinoma (carcinoma in situ)†
T0 No evidence of tumour
T1 Tumour is no more than 2 cm in diameter, and is superficial or exophytic
T2 Tumour is no more than 2 to 5 cm in diameter, or shows minimal invasion,
irrespective of size
T3 Tumour is over 5 cm in diameter, or shows invasion of the subcutis,
irrespective of size
T4 Tumour is invading other structures, such as fascia, muscle, bone or
cartilage
Regional lymph nodes
N0 No evidence of regional lymph node involvement
N1 Movable ipsilateral nodes
a Nodes not considered to contain growth‡
b Nodes considered to contain growth‡
N2 Movable contralateral or bilateral nodes
a Nodes not considered to contain growth‡
b Nodes considered to contain growth‡
N3 Fixed nodes
Distant metastasis
M0 No evidence of distant metastasis
M1 Distant metastasis detected at specific site(s) (including lymph nodes
beyond the region in which the primary tumour is situated)
*Excluding lymphoma or mast cell tumours, †Carcinoma in situ describes a very superficial tumour
not breaching the basement membrane, ‡Histologically negative/positive, as appropriate
269
definitive local treatment, if feasible. It is also worth APPROACH TO TREATMENT
noting that not all lesions drain into the expected local
lymph node, so any other enlarged lymph nodes in the It goes without saying that all animals should be treated
vicinity should be treated with suspicion. Chest radiogra- as a whole, with concurrent disease, owners’ wishes and
phy should always include at least two inflated views of finances being taken into consideration when formulating
all lung fields to ensure no abnormalities are missed. a plan of action. However, a diagnosis of ‘cancer’ is a very
Tumours should be staged to: emotive one. One in three humans will develop cancer.
■ Assess the value of any treatment plan (there is often Many clients have strong opinions as to how their animal
no point embarking on a course of treatment that only should be treated, often based on their own immediate
addresses the primary disease if there is evidence of experience. Cancer is still the most curable chronic disease
metastasis); and veterinary surgeons need to be aware of their own and
■ Provide a baseline from which to assess a tumour’s their clients’ prejudices when dealing with a pet with can-
response to treatment; cer. If there is any doubt about appropriate treatment, a
■ Allow like-for-like comparison with reports in the veterinary oncologist should be consulted (see box, below
literature to help make treatment decisions and to give an left).
idea of prognosis. There are three main treatment modalities for cancer:
All information from the clinical examination and surgery, radiotherapy and chemotherapy. Increasingly,
staging should be recorded. a multimodality approach is being employed in many
cases. Having said that, surgery alone, with wide enough
margins of normal tissue taken to ensure complete inci-
sion of the tumour, will cure most cutaneous lesions.
When to refer Often, lesions that do not appear to be amenable to surgi-
Most tumours of the skin and subcutis can be cured
cal management to the general practitioner may carry a
by surgery and therefore a prompt diagnosis fol-
better prognosis if assessed by an experienced soft tissue
lowed by the right ‘dose’ of surgery (depending on
surgeon. For some cutaneous tumours cytotoxic drugs
the tumour type) is the best way forward.
are not appropriate therapy. There are species differences
Occasionally, advanced reconstructive techniques
between cats, dogs and humans that should be appreciat-
may be required to achieve complete removal of all
ed prior to pursuing any protocol. Cytotoxic drugs are
neoplastic tissue. In such cases, it is better to consid-
not licensed for use in companion animals, so signed
er referral of an animal to a soft tissue surgeon
consent forms should be obtained from clients to ensure
straightaway rather than attempt a conservative
that they understand the implications of treating their
surgery and then refer later. An attempted defini-
animals with unlicensed drugs. Clients should also be
tive surgery with some tumour left in the scar will
given handouts on the potential side effects that may
require a second surgery to remove not only the scar
occur and when to seek veterinary advice. Information
but, as the scar may potentially contain contaminat-
on how to minimise human exposure to cytotoxic drugs
ed tumour cells, also the margins of seemingly nor-
should also be provided.
mal tissue around the scar. Also, the position of the
scar may compromise the use of skin flaps, and the Further reading
fascial planes around the tumour may have been LASCELLES, D. & DOBSON, J. M. (Eds) (2003) Manual of Feline and
Canine Oncology, 2nd edn. Gloucester, BSAVA
disrupted, making the surgical procedure more diffi- MORRIS, J. & DOBSON, J. (Eds) (2001) Small Animal Oncology.
cult. Furthermore, if the second surgeon cannot Oxford, Blackwell Publishing
OGILVIE, G. & MOORE, A. S. (Eds) (2001) Feline Oncology. Trenton,
accurately identify the site of the original tumour, New Jersey, Learning Systems
the chances of appropriate surgery are compro- WITHROW, S. J. & McEWAN, E. G. (Eds) (2001) Small Animal Clinical
Oncology, 3rd edn. Philadelphia, W. B. Saunders
mised. Generally, therefore, a second surgery is less
successful at controlling disease.
Radiotherapy can be used as an adjunct to sur-
gical debulking on the extremities. External beam
radiotherapy is best used for tumours where there
is a low risk of metastasis as it only kills neoplastic
cells in the radiation field. Radiotherapy is most
effective for cutaneous tumours where the tumour
has been reduced to microscopic disease. If radia-
tion is likely to be an option, it is sensible to contact
an oncologist before surgery is undertaken, as
there may be a preferred surgical approach to opti-
mise the chances of radiotherapy being feasible
and effective.
Cytotoxic drugs should be used appropriately.
Veterinarians have a duty to ensure that they are
fully conversant with any side effects that animals
may experience and also the steps that should be
taken to protect people from exposure to these
teratogenic and carcinogenic agents. It is appropri-
ate to refer cases where any of these issues cannot
adequately be addressed in practice.

In Practice ● MAY 2006 271