Feline lymphoma 1. Principles of diagnosis and management

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In Practice � O C T O B E R 20 06516
PRESENTATION
There are three well-recognised forms of feline lymph-
oma – mediastinal, alimentary and multicentric – and 
the clinical presentation of each reflects the areas of 
involvement. In addition, the disease can arise wherever 
there is lymphoid tissue and this anatomical subdivision 
can be difficult to define and may even be misleading 
when attempting to compare treatment response between 
small subgroups of cats. Importantly, there is also a 
large and disparate group of other sites that can be com-
monly affected. The site of involvement can be related to 
age and feline leukaemia virus (FeLV) status (see table 
below). Unlike dogs, cats infrequently present with gen-
eralised lymphadenopathy and rarely present with para-
neoplastic hypercalcaemia. 
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LYMPHOMA is the most common malignancy in cats and accounts for approximately one-third of all 
feline tumours. Feline lymphoma in its various guises is a relatively frequent diagnosis in UK practice. 
This range of presentations poses a diagnostic challenge for practitioners, and persistence and 
resourcefulness are often needed to obtain a definitive diagnosis. Furthermore, response to treatment 
is not always easy to predict as many cats enjoy sustained remission and even cure with practice-based 
therapy, while other cases respond poorly and thus have a limited life expectancy. Communicating 
the evidence to an owner while presenting a fair and realistic overview of what is to be expected can 
be difficult, but this is necessary to achieve informed consent and owner involvement in therapeutic 
decision-making. This article discusses diagnostic and management principles for feline lymphoma, and 
reviews the current literature on therapy as it pertains to choices in case management in the practice 
setting. Part 2, to be published in the next issue, will focus on specific disease presentations.
Feline lymphoma
1. Principles of diagnosis 
and management ALISON HAYES
In Practice (2006) 
28, 516-524
DIAGNOSIS
In many cases, a compilation of history, signalment, and 
clinical, viral and cytological information can establish 
a working diagnosis. For certain sites (eg, kidney, liver 
and abdominal nodes), cytology can provide a relatively 
non-invasive, inexpensive and rapid diagnosis. However, 
wherever possible, this should be reinforced by histo-
pathology, especially where cytology yields a population 
of small lymphocytes or if findings are inconclusive. 
A Tru-cut style core biopsy device can be safely used 
to obtain tissue for histopathology from larger lym-
phoid masses and mediastinal, renal or gastrointestinal 
Alison Hayes 
graduated from 
Glasgow in 1991 
and spent five years 
in mixed and small 
animal practice in 
north-west England. 
She subsequently 
undertook a 
three-year Blue 
Cross residency in 
oncology at the 
Animal Health Trust 
in Newmarket, 
where she is now a 
clinical oncologist. 
She holds the 
RCVS certificate in 
veterinary radiology 
and an MSc 
in clinical oncology 
from the University 
of Birmingham 
medical school.
PRESENTATIONS OF FELINE LYMPHOMA RELATED TO AGE AND FeLV STATUS
Presentation Age T cell association FeLV status
Relative frequency 
of occurrence
Mediastinal/
thymic
Young High Majority positive 10-20%
Alimentary Older High Minority positive 50-70%
Multicentric Variable Variable Variable 60-70%
Renal Variable Variable Variable 5-10%
Nasal Older Low Minority positive 10%
Others Variable Variable Variable 5-25%
Incidence and aetiology
It is estimated that the incidence of feline lympho-
ma is approximately 200 cases per 100,000 cats, 
which is higher than in other species. The true inci-
dence is difficult to measure, as prevalence and 
anatomical presentation of the disease vary with 
geographical location, but it appears to be reduc-
ing. The variation in incidence has been attrib-
uted to a number of possible factors, although 
differences in FeLV status of the cat population 
are believed to be primarily responsible. For cases 
without viral association, the exact aetiology of 
the disease is unknown. 
This Siamese cat presented as a 10-month-old 
kitten with a prescapular mass measuring 5 x 
3·5 cm. Further investigation revealed a large 
mediastinal mass extending through the 
cervical inlet to the prescapular region, which 
was confluent with the mass found on clinical 
examination. Lymphoma was diagnosed 
following incisional biopsy of the prescapular 
mass. The cat remains well and disease-free 
three years after completing a course of 
combination chemotherapy
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In Practice � O C T O B E R 20 06 519
lesions under ultrasound guidance. Where a peripheral 
lymphadenopathy is present or lymph node sampling is 
required for staging, an excisional biopsy of the node 
is ideal. Nasal biopsy can be difficult and unreward-
ing in the cat; sometimes several attempts are needed 
before a definitive diagnosis is achieved. In the author’s 
experience, forced nasal flushing is often unsatisfac-
tory and contraindicated if the integrity of the cribri-
form plate is compromised. Aspiration techniques using 
a 14 gauge intravenous catheter or 10 French gauge dog 
urinary catheter can be used to obtain a suction biopsy 
via the nostril. The catheter should be premeasured to 
the medial canthus to avoid inadvertent sampling through 
the cribriform plate. Biopsy material should be expelled 
onto a clean swab to absorb blood and secretions, and 
the remainder used to make impression smears or sub-
mitted in formalin for histology. A blind grab biopsy 
technique can also be used, as can retrograde endoscopy 
to visualise and sample lesions. Computed tomography 
and magnetic resonance imaging can assist with identi-
fication of a bony window through which material for 
cytology can be obtained. 
Although immunohistochemistry can be useful in 
aiding definitive diagnosis, especially in cases of gastro-
intestinal lymphoma, it does not appear to offer prognos-
tic information in cats. 
All samples for diagnostic purposes should be taken 
prior to administering chemotherapeutic drugs, including 
glucocorticoids.
CLASSIFICATION AND STAGING
The classification of lymphoma in cats is based on ana-
tomical site and cell morphology. Staging is achieved by 
applying the World Health Organization (WHO) system 
(see table, below left), which sets out various criteria 
and is useful for reporting findings to colleagues, docu-
menting disease progression, and effectively defining 
a study population. The system has been further adapt-
ed for feline lymphoma (Mooney and others 1989) but, 
despite this, remains a generally unsatisfactory way of 
defining the disease in cats. Of 
more importance in the clini-
cal management of a case is 
docu mentation of all areas 
of involvement so that the 
response to treatment canbe 
established accurately – and 
this is the true meaning of 
staging in this context (see box 
on the right). New molecular 
and immunohistochemical tech-
niques are becoming available 
and will enable further, molec-
ular classification in the future, 
but these are not of clinical 
relevance at the present time. 
Tissue samples for definitive histopathology can 
be obtained using needle core (Tru-cut style) biopsy 
devices, which are minimally invasive
Role of viruses in the development of 
feline lymphoma
Approximately 25 per cent of cats persistently infected with FeLV develop lym-
phoma; the remainder will die from other FeLV-related disease. Since the intro-
duction of FeLV vaccination, the incidence of the disease has declined and the 
presentation shifted. Historically, around 70 per cent of cats with lymphoma 
would have been FeLV-positive. In the UK and USA, this figure is now much 
lower. Due to the low incidence of FeLV in some countries, the expectation that 
young FeLV-positive cats develop T cell tumours of mediastinal origin has been 
challenged (Teske and others 2002). While commercially available testing meth-
ods still detect FeLV-positive cats with lymphoma, older cats with negative FeLV 
test results that present with gastrointestinal lymphoma or other extranodal 
lymphomas are becoming more commonplace. However, a bimodal age distri-
bution is still seen in many studies. This may be due to factors other than viral 
status. It is possible that an increase in the numbers of young, FeLV-negative 
Siamese cats developing mediastinal lymphoma may account for a continuing 
bimodal distribution pattern in age at diagnosis. This apparent breed suscepti-
bility in Siamese cats is distinct from a conventional FeLV association.
Another factor that complicates the understanding of FeLV association is 
the method by which viral exposure is determined. Traditional FeLV screening 
by antigen detection in serum is likely to have underestimated the involve-
ment of FeLV in the development of feline lymphoma. Recent PCR detection of 
viral sequences has implicated the virus in cats that are serologically negative 
for FeLV antigen. Feline immunodeficiency virus (FIV) alone may be responsible 
for some FeLV-negative cases of feline lymphoma. However, work with specific 
pathogen-free cats indicates that there are genuine cases where neither FeLV 
nor FIV can be implicated in the development of feline lymphoma.
Viral testing of clinical cases is still recommended and can contribute to suc-
cessful case management. Although prognostic information can be gained in a 
population of cats based on viral status, individual cats should be assessed and 
treated in the same way regardless of their viral status. In other words, viral 
status cannot be relied on as a prognostic indicator on an individual case basis.
While FeLV infection may be decreasing, the accuracy of viral screening is 
improving, and this will hopefully lead to a better understanding of the role 
that viruses play in the aetiology of feline lymphoma.
MODIFIED WORLD HEALTH ORGANIZATION STAGING CRITERIA 
FOR FELINE LYMPHOMA
Anatomic type
A Generalised
B Alimentary
C Thymic
D True leukaemia
E Other
Stage
Stage I Single node or lymphoid tissue in a single 
organ
Stage II Multiple lymph nodes in a region
Stage III Generalised lymph node involvement
Stage IV Liver and/or spleen involvement
Stage V Blood, bone marrow or other organ system 
involvement
Substage a Without systemic signs
Substage b With systemic signs
Staging criteria such as those described above offer little 
prognostic information for an individual case, but do offer 
a means of recording the disease picture
From Owen (1980)
Database for complete staging
Minimum database
� Thoracic radiography
� Abdominal radiography/ultrasonography
� Haematology/biochemistry
� Ocular/fundic examination
� Urinalysis
� FeLV/FIV status
Additional relevant information
� Bone marrow biopsy/aspirates for 
histopathology/cytology
� Cerebrospinal fluid analysis
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In Practice � O C T O B E R 20 06520
TREATMENT
Single versus multimodal treatment
Surgery, radiation therapy and chemotherapy are the three 
main treatment modalities available for the management 
of feline lymphoma. These can be used alone (single 
modality treatment) or in combination (multimodality 
treatment). Lymphoma is generally regarded as a multi-
system disease and, as such, systemically administered 
cytotoxic drug therapy is often required. Careful staging, 
including lymph node sampling, will determine systemic 
involvement at any given time in the course of the dis-
ease. In the absence of systemic disease, radiation therapy 
and/or surgery may be carried out as alternative treatment 
options in selected cases (see Part 2). However, local treat-
ments, such as surgery or radiation therapy alone, may 
be insufficient for long-term control of the disease, and 
chemotherapy will be required following relapse or sys-
temic progression. 
Supportive care
The decision to treat with systemic chemotherapy should 
be constantly reviewed and the cat regularly assessed. 
Additional supportive care may be required to optimise 
an animal’s quality of life during treatment (see box, 
above right).
What is the best chemotherapy protocol? 
The reported response rate to induction chemotherapy 
in cats is between 26 and 79 per cent, with median sur-
vival times of seven to nine months. While this can be 
interpreted as cats doing badly compared with dogs, the 
practitioner should be wary of predicting this for all cats 
treated. Between 30 and 40 per cent of cats achieving 
complete remission will go on to have a durable, com-
plete remission of two years or more. Long-term, main-
tenance chemotherapy can often be stopped following a 
sustained period of remission and many cats subsequent-
ly survive free of disease. Thus, compared with dogs, 
cats will gain remission in lower numbers but, of those 
that do, more cats than dogs will be able to maintain 
durable remission without chemotherapy.
Determining the optimum chemotherapy protocol for 
feline lymphoma is difficult. There are few published 
reports and the number of treated cats in these studies 
is small. Furthermore, reports do not always compare 
like with like, varying in terms of anatomical site of dis-
ease, FeLV status of the cat and the number of clinically 
unwell (substage b) patients, all of which can influence 
outcome in addition to the drug protocol chosen (see 
table on page 521).
While the data are variable, some conclusions can 
be drawn. Multidrug protocols are more effective than 
single agent doxorubicin at inducing first remission, and 
high remission rates have been achieved with cyclophos-
phamide, vincristine (Oncovin; Lilly) and prednisolone 
Prognostic information
Immunophenotype (T cell versus B cell lymphoma) 
does not appear to confer the same prognostic 
information in cats that it does in dogs. Factors 
that have been found to indicate a favourable 
prognosis in terms of overall survival are early pres-
entation, a complete initial response to treatment 
and a clinically well patient (‘substage a’ disease). 
The inclusion of doxorubicin in the treatment pro-
tocol has been shown to influence prognosis in 
certain studies.
Commonly required supportive 
treatments
� High quality, palatable diet
� Appetite stimulation. Cyproheptadine (Periactin; 
MSD) at 1 to 2 mg/cat once or twice daily 
� Antiemetics for ptyalism/anorexia (with or with-
out vomiting). Metoclopromide can be provided at:
– 1 to 2 mg/kg/day via constant rate infusion
– 0·2 to 0·4 mg/kg intramuscularly every eight hours
– 0·4 to 0·6 mg/kg orally every four hours
� Assisted (tube) feeding� Laxatives
� Fluid therapy
� Treatment for:
– Hypercalcaemia
– Azotaemia
– Neutropenia/sepsis
– Pyrexia
� Analgesia
5-Fluorouracil and 
cisplatin are fatally 
toxic to cats and are 
thus contraindicated 
and must not form 
part of lymphoma 
therapy.
MODIFIED UNIVERSITY OF WISCONSIN-MADISON PROTOCOL FOR LYMPHOMA IN CATS
Treatment week
1 2 3 4 5 6 7 8 9 10 11 12 13
Vincristine Once 0·5-0·7 mg/m2 iv • • • • •
Cyclophosphamide Once 200 mg/m2 iv • •
Prednisolone* Once daily 2 mg/kg po • • • • • • • • • • • • •
Doxorubicin Once 25 mg/m2 iv • •
L-asparaginase Once 400 iu/kg sc •
Chlorambucil Once 1·4 mg/kg po •
Methotrexate Once 0·5-0·8 mg/kg iv
*Prednisolone reduces to 1 mg/kg at week 4, given every other day
� If complete remission is achieved at week 9, the protocol continues through to week 25
� If the cat is in complete remission at week 25, some protocols advocate continuing treatment at three-week intervals using 
the same sequence of drugs as weeks 11 to 25, until week 51, and then indefinitely using the sequence at four-week intervals. 
Alternatively, if the cat is in complete remission, treatment can be discontinued at week 25
po Orally, sc Subcutaneously, iv Intravenously
Adapted from Milner and others (2005)
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In Practice � O C T O B E R 20 06 521
(COP) treatments alone (Cotter 1983, Teske and others 
2002). However, a study in the USA reported a response 
rate of only 47 per cent with COP (Moore and others 
1996). More confusingly, the inclusion of doxorubicin in 
the induction phase resulted in lower remission rates and 
lower overall survival (210 days) compared with COP-
based drugs (Milner and others 2005). In another study, 
which was designed to assess the predictive value of 
various biomarkers, the inclusion of doxorubicin in the 
lymphoma protocol was not predictive for the duration 
of first remission or for overall survival in multivariate 
analysis (Vail and others 1998). However, a small study 
comparing the effect of a six-month maintenance proto-
col with either single agent doxorubicin or COP found 
that, for cats successfully induced with the COP proto-
col, the seven animals receiving doxorubicin survived 
longer (281 days) compared with those treated with COP 
alone (83 days), thus suggesting that a short doxorubicin-
based maintenance protocol may be beneficial. Clearly, 
a COP-based protocol resulting in a median survival 
of 266 days and a remission rate of 75 per cent stands 
up well against the potentially more toxic doxorubicin-
containing protocols. Studies relating to feline gastro-
intestinal lymphoma suggest that this group of cats 
may be more refractory to COP regimens (see Part 2). 
Care should be taken when making firm predictions 
about outcome based on control groups from previously 
published reports. In the absence of a large randomised 
control trial that could directly compare COP versus 
doxorubicin-containing protocols for induction and 
maintenance, the question of which protocol gives the 
best results remains unanswered. 
When choosing a protocol, factors such as toxicity, fea-
sibility of administration and expense should all be taken 
into account. The author’s preferred induction regimen 
for cats is a simple low-dose cyclophosphamide, COP-
based protocol (see top table on page 522). Exceptions 
to this approach will be discussed in Part 2. If complete 
remission is sustained over two years, treatment cessa-
tion is achieved as a stepwise withdrawal, omitting first 
vincristine, then cyclophosphamide and, finally, tapering 
the prednisolone dose over the final month, and checking 
for signs of recurrence after the cessation of each drug. 
The published reports listed in the table above include 
300 mg/m2 cyclophosphamide, up to 50 mg/m2 pred-
nisolone once daily and cessation of treatment after one 
year (Cotter 1983, Teske and others 2002) or six months 
of maintenance therapy (Moore and others 1996) if com-
plete remission is maintained. An alternative induction 
protocol, which includes doxorubicin, is described in the 
table on the left. 
When calculating schedules for oral medication, 
tablets and capsules should not be split, crushed or refor-
mulated in the practice, as this will lead to inaccurate dos-
ing and unacceptable exposure to personnel. Interdosing 
PUBLISHED CHEMOTHERAPEUTIC PROTOCOLS FOR FELINE LYMPHOMA
Reference
Number 
of cats Population
Response rate (%) for 
complete remission
Median duration of first 
complete remission
Overall median 
survival time Protocol
Cotter (1983)* 38 USA 79 Not recorded 5 months Cyclophosphamide, vincristine and 
prednisolone
Jeglum and others (1987) 62 USA 52 112 days 56 days Vincristine, cyclophosphamide 
and methotrexate ± prednisolone/
L-asparaginase
Mooney and others (1989) 103 USA 62 210 days Vincristine, cyclophosphamide, 
methotrexate and prednisolone 
± L-asparaginase
Moore and others (1996) 38 USA 47 83 days Cyclophosphamide, vincristine and 
prednisolone
7 USA ** 281 Cyclophosphamide, vincristine and 
prednisolone (plus doxorubicin in 
maintenance)
Peaston and Maddison (1999) 19 Australia 32 Median not reported. 
Four cats had data 
available. Survival was 
4·4, 6, 18 and 44 months
Not reported Doxorubicin
Kristal and others (2001) 19 USA 26 92 days 84 days Doxorubicin
Teske and others (2002) 61 Europe 75·4 266 days Cyclophosphamide, vincristine and 
prednisolone
Milner and others (2005) 38 USA 47 654 days 210 days University of Wisconsin-Madison: 
cyclophosphamide, vincristine, 
prednisolone, doxorubicin, 
L-asparaginase, chlorambucil 
and methotrexate
*Included some cases of leukaemia
**Cats achieving complete remission after cyclophosphamide, vincristine and prednisolone induction were entered into this study
Treatment week
14 15 16 17 18 19 20 21 22 23 24 25
• • •
• • • • • • • • • • • •
•
•
•
� Haematology should be checked before each treatment
� If renal or central nervous system lymphoma is present, 
cytosine arabinoside is given at 150 mg/m2 twice daily, 
for two consecutive days, in place of chlorambucil or 
cyclophosphamide in weeks 7, 13 and 21
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In Practice � O C T O B E R 20 06522
intervals for oral cyclophosphamide can be calculated as 
described in the box below.
Rescue therapy
If remission is lost and treatment failure occurs, subse-
quent attempts to regain remission are termed rescue 
therapy. In vitro work suggests that cats share the same 
multidrug resistant p-glycoprotein gene expression as 
other species, and this is a likely cause of drug resist-
ance in feline patients (Okai and others 2000). 
Irrespective of whether a cat has remained on treat-
ment, the initial induction protocol should be reviewed 
in order to determine whether there is any response to 
one or more drugs in the protocol. If this is the case, 
single agent therapy with that drug using a more intense 
treatment schedule may be rewarding. If the induction 
protocol has been stopped some time previously, the 
induction protocol can be repeated to regain remission 
in some cats. However, a more common scenario is for 
complete treatment failure to occur during the induc-
tion or maintenance phase of the initial protocol. In such 
cases, an alternative protocol using drugs not used in 
previous treatments should be sought. 
� Occasionally, remission can be regained by simply 
substituting an alternative alkylating agent into the ini-
tial protocol. Substituting chlorambucil or melphalan 
for cyclophosphamide may rejuvenate a failing protocol 
without inducing further toxicity. 
� If the protocol did not previously incorporate doxo-
rubicin, thiscan be instituted as single agent therapy at 
either 1 mg/kg intravenously or 20 to 25 mg/m2 intra-
venously once every three weeks, subject to a normal 
blood count. To reduce renal toxicity and promote diu-
resis, cats should be mildly volume loaded with saline at 
5 to 10 ml/kg/hour for three hours. Doxorubicin should 
then be administered over 20 to 30 minutes in a saline 
infusion and fluid therapy continued for a further 60 
minutes after drug administration. 
� If L-asparaginase has not been included in a previous 
regimen, this can be used at 400 iu/kg as a strategic sin-
gle agent therapy to induce remission (repeated dosing is 
likely to become increasingly less effective). 
� The mechlor ethamine hydrochloride, vincristine, pro-
carbazine and prednisolone (MOPP) protocol outlined 
in the table below contains two novel drugs not used in 
other protocols and may be used in the rescue setting, 
although data on its effectiveness is limited. 
� Lomustine has also been used in the treatment 
of feline lymphoma at a dose of 50 to 60 mg/m2, 
MOPP PROTOCOL FOR RESCUE THERAPY 
Treatment week
Drug Frequency Dose Route 1 2 3 4 5 6 7 8
Vincristine Once 0·025 mg/m2 Intravenously • • • •
Mechlorethamine HCl Once 3·0 mg/m2 Intravenously • • • •
Procarbazine Daily 10 mg/cat Orally • • • •
Prednisolone Twice daily 5 mg/cat Orally • • • • • • • •
MOPP Mechlorethamine HCl, vincristine, procarbazine and prednisolone
From G. E. Mauldin, S. C. Mooney and G. N. Mauldin (personal communication). Cycles are repeated on a four-week basis
Calculation of interdosing intervals
� Determine body surface area (BSA) based on bodyweight calculations
� Calculate total weekly dose (TWD)
TWD = BSA x Dose
� Calculate equivalent daily dose (EDD)
EDD = TWD ÷ 7 days
� Calculate interdosing interval (IDI)
IDI = Formulation ÷ EDD
Example
The IDI for 50 mg cyclophosphamide tablets at a dose of 150 mg/m2/week is 
calculated as follows:
� For a cat with a bodyweight of 3·55 kg, BSA = 0·23 m2
� TWD = 0·23 x 150 mg = 34·5 mg
� EDD = 34·5 ÷ 7 = 4·9 mg
� IDI = 50 ÷ 4·9 = 10·1 days
In practice, this cat would receive 50 mg every 10 days, subject to a nor-
mal neutrophil count being recorded between day 8 and day 10. If neu-
tropenia is a problem at day 10, and especially if the cat was sick or had 
severe neutropenia during the treatment period, consider using 25 mg 
tablets (available on licence through the Veterinary Medicines Directorate) 
every five days. If the cat remains well but has mild neutropenia at day 10, 
consider increasing the interdosing interval of 50 mg tablets. Continue to 
monitor the animal haematologically.
LOW-DOSE COP INDUCTION/MAINTENANCE PROTOCOL
Treatment week
Drug Frequency Dose Route 1 2 3 4 5 6 7 8
Vincristine Once 0·75 mg/m2 Intravenously • • • • •
Cyclophosphamide Once 150-200 mg/m2 Orally • • • • • • • •
Prednisolone Once daily 20 mg/m2 Orally • •
Prednisolone Every other day 20 mg/m2 Orally • • • • • •
COP Cyclophosphamide, vincristine and prednisolone
If complete remission is achieved at the end of week 4, the protocol continues through weeks 5 to 8. Weeks 5 to 8 are repeated for 
the duration of the remission, or until two years provided the cat remains in remission
Blood counts are performed weekly, immediately prior to cyclophosphamide treatment. Neutrophil count should be 2·5 x 109/litre or 
above, with a normal platelet count to proceed with the treatment
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In Practice � O C T O B E R 20 06 523
every three to six weeks. Myelosuppressive effects of 
lomustine can be delayed for up to six weeks, which 
preclude other interventions if treatment failure occurs. 
Documenting rising blood counts during weeks 2 to 
4 can be helpful when determining a safe inter dosing 
interval. Restricted availability of 10 mg capsules 
limits the use of this drug, as importation through the 
Veterinary Medicines Directorate is currently required. 
Splitting larger 40 mg capsules is not recommended 
due to unnecessary operator exposure. Commercial 
reconstitution of oral cytotoxic medication is not avail-
able to the veterinary profession in the UK at the time 
of writing. 
Irrespective of the regimen, cats should be moni-
tored closely at weekly intervals to determine treatment 
Haematological monitoring
Regular haematological and biochemical monitor-
ing is recommended during therapy. A full blood 
count and a reliable differential white cell count 
should be determined prior to each treatment. 
Deviation from the chosen protocol should be 
carried out only after consideration of the haema-
tological nadir of the drugs to ensure that over-
lapping toxicities do not develop. The neutrophil 
count should be 2·5 x 109/litre or greater, with an 
adequate (ideally normal) platelet count before 
treatment is given. Sampling too far ahead of treat-
ment may mean that a neutrophil nadir has yet to 
occur. In these circumstances, a normal count will 
underestimate the drug’s effect on bone marrow. 
Treatment with an alkylating agent on a weekly 
dosing schedule such as the COP protocol outlined 
in the top table on page 522, should be monitored 
by analysis of blood taken between days 5 and 7. 
This should ensure that cumulative marrow toxicity 
is avoided. Lomustine is the exception to this rule, 
where a delayed neutrophil nadir of up to 28 days 
can occur, and a six-week interdosing interval is 
recommended unless rising neutrophil and platelet 
counts are recorded (Rassnick and others 2001).
response and assess quality of life. If remission is not 
regained, an alternative treatment can be tried. Although 
long-term second and subsequent remissions are achiev-
able, rescue therapy is seldom more successful than the 
first attempt at treatment. Response rates of 20 to 50 per 
cent with remission durations of one to two months are 
to be expected.
SIDE EFFECTS OF CHEMOTHERAPY
In general, cats tolerate chemotherapy well but some 
side effects can occur:
� ANOREXIA. Gastrointestinal upset often manifests as 
anorexia in cats, with or without other signs. Treatment 
is symptomatic, but antiemetic medication should be 
considered in cats that develop anorexia during chemo-
therapy. In addition, appetite stimulants such as cypro-
heptadine can be used;
� MYELOSUPPRESSION. Haematology should be per-
formed regularly to monitor myelosuppression. A reli-
able differential count should be obtained prior to each 
treatment and at any time that a patient is generally 
unwell with no apparent cause. Antibiotics and marrow 
stimulation may be required (see table below). Most 
cases of mild neutropenia will resolve spontaneously 
within a short period of time;
� RENAL TOXICITY. Doxorubicin can cause renal toxic-
ity and should be administered with fluid therapy. Renal 
insufficiency does not preclude treatment although the 
dose of nephrotoxic drugs (eg, doxorubicin) and drugs 
that reply on renal clearance (eg, cyclophosphamide) 
should be reduced;
� ALOPECIA. Total alopecia is rare in cats treated with 
chemotherapy although loss of whiskers can be expected. 
Generalised hair coat changes such as thinning, dilution of 
the coat colour and loss of coarse hairs are also occasion-
ally seen but are reversible if treatment can be stopped;
� ACUTE TUMOUR LYSIS SYNDROME. This condition 
has been reported in a cat (Calia and others 1996). The 
pathogenesis is poorly understood, but involves rapid 
Predicting disease and treatment 
response
There are no recognised biological markers of dis-
ease that the clinician can use to predict lymphoma 
occurrence or recurrence in cats. Thus, monitoring 
remission is currently only achieved by regular clin-
ical examination and restaging. Similarly, there are 
no effective means of determining whether apar-
ticular cat with lymphoma will respond to treat-
ment and the best guide is still the initial response 
to induction therapy in the individual.
Future studies may determine biological mark-
ers of disease that prove effective in recognis-
ing early lymphoma recurrence. For example, if a 
blood test could determine a biological remission 
before clinical remission was lost, earlier interven-
tion to regain remission when the tumour burden 
was low may ensure a better outcome.
DECISION MAKING IN WELL AND SICK CATS WITH NEUTROPENIA
Neutrophil count Clinical examination Action
>LLRR Normal Administer chemotherapy
1·5 x 109/litre 
to <LLRR
Normal GRADE I NEUTROPENIA. Delay chemotherapy if due, 
monitor at home and maintain daily contact with 
owners. Repeat complete blood cell count in 48 to 
72 hours or on clinical deterioration
1·0-1·49 x 109/litre Normal GRADE II NEUTROPENIA. Delay chemotherapy if due, 
monitor at home and maintain daily contact with 
owners. Repeat complete blood cell count in 48 
to 72 hours or on clinical deterioration. Prescribe 
antibiotics. Consider dose reduction for subsequent 
treatments
<1·0 x 109/litre Normal GRADE III AND IV NEUTROPENIA. Consider hospitalisation 
and institute supportive care. Delay chemotherapy 
if due. Repeat complete blood cell count in 24 hours 
or on clinical deterioration. Prescribe antibiotics 
and consider marrow support such as granulocyte 
colony stimulating factor (Filgastrim Neupogen; 
Amgen). Reduce dose of subsequent treatments
<2·5 x 109/litre Sick, with or without 
febrile response
HOSPITALISATION. Delay chemotherapy if due. Repeat 
complete blood cell count in 24 hours or on clinical 
deterioration. Search for focus of infection and 
alternative causes. Carry out blood cultures. 
Prescribe antibiotics and consider dose reduction 
for subsequent treatments
LLRR Lower laboratory reference range
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In Practice � O C T O B E R 20 06524
release of neoplastic intracellular components lead-
ing to sudden decompensation and electrolyte imbal-
ances. Cats with a large tumour burden, high growth 
fraction and pre-existing renal insufficiency are at risk. 
Hospitalisation, fluid therapy, electrolyte monitoring and 
staged induction are advised for such cats.
SUMMARY
Cats commonly present with lymphoma, but achieving a 
definitive diagnosis and identifying the extent of disease 
can be challenging. Owners may be encouraged to try 
therapy when this is appropriate, as cats tolerate chemo-
therapy well and durable, long-term remissions are not 
uncommon. However, individual response to treatment is 
difficult to predict with any certainty without a therapeu-
tic trial and the initial response to treatment is still one 
of the best prognostic indicators of long-term response 
in cats. Unlike dogs, T cell versus B cell immunopheno-
typing has not been shown to be a significant predictor 
for survival in the limited studies performed to date. 
The question of whether to include doxorubicin in 
the induction protocol remains unanswered. This may 
reflect the diversity of disease presentation in therapeu-
tic analysis thus far, as well as study design or true bio-
logical response. Further work is needed if prognostic 
indicators and optimum chemotherapy protocols are to 
be determined for cats with lymphoma. If the molecular 
characterisation of feline lymphoma is established, the 
biological hallmarks of the different disease entities may 
be elucidated, which, in turn, may permit more specific, 
targeted therapies for the future. 
References
CALIA, C. M., HOHENHAUS, A. E., FOX, P. R. & MELEO, K. A. (1996) 
Acute tumor lysis syndrome in a cat with lymphoma. Journal of 
Veterinary Internal Medicine 10, 409-411
COTTER, S. M. (1983) Treatment of lymphoma and leukemia with 
cyclophosphamide, vincristine, and prednisone. I. Treatment 
of dogs. II. Treatment of cats. Journal of the American Animal 
Hospital Association 19, 159-172
JEGLUM, K. A., WHEREAT, A. & YOUNG, K. (1987) Chemotherapy 
of lymphoma in 75 cats. Journal of the American Veterinary 
Medical Association 190, 174-178
KRISTAL, O., LANA, S. E., OGILVIE, G. K., RAND, W. M., COTTER, 
S. M. & MOORE, A. S. (2001) Single agent chemotherapy with 
doxorubicin for feline lymphoma: a retrospective study 
of 19 cases (1994-1997). Journal of Veterinary Internal 
Medicine 15, 125-130
MILNER, R. J., PEYTON, J., COOKE, K., FOX, L. E., 
GALLAGHER, A., GORDON, P. & HESTER, J. (2005) 
Response rates and survival times for cats with 
lymphoma treated with the University of Wisconsin-
Madison chemotherapy protocol: 38 cases (1996-
2003). Journal of the American Veterinary Medical 
Association 227, 1118-1122
MOONEY, S. C., HAYES, A. A., MacEWEN, E. G., MATUS, 
R. E., GEARY, A. & SHURGOT, B. A. (1989) Treatment 
and prognostic factors in lymphoma in cats: 103 
cases (1977-1981). Journal of the American Veterinary 
Medical Association 194, 696-702
MOORE, A. S., COTTER, S. M., FRIMBERGER, A. E., 
WOOD, C. A., RAND, W. M. & L’HEUREUX, D. A. (1996) 
A comparison of doxorubicin and COP for maintenance 
of remission in cats with lymphoma. Journal of 
Veterinary Internal Medicine 10, 372-375
OKAI, Y., NAKAMURA, N., MATSUSHIRO, H., KATO, 
H., SETOGUCHI, A., YAZAWA, M., OKUDA, M., WATARI, 
T., HASEGAWA, A. & TSUJIMOTO, H. (2000) Molecular 
analysis of multidrug resistance in feline lymphoma 
cells. American Journal of Veterinary Research 61, 
1122-1127
OWEN, L. N. (1980) TNM Classification of Tumours in 
Domestic Animals. Geneva, World Health Organization
PEASTON, A. E. & MADDISON, J. E. (1999) Efficacy 
of doxorubicin as an induction agent for cats with 
lymphosarcoma. Australian Veterinary Journal 77, 
442-444
RASSNICK, K. M., GIEGER, T. L., WILLIAMS, L. E., 
RUSLANDER, D. M., NORTHRUP, N. C., KRISTAL, O., 
MYERS, N. C. & MOORE, A. S. (2001) Phase I evaluation 
of CCNU (lomustine) in tumor-bearing cats. Journal of 
Veterinary Internal Medicine 15, 196-199
TESKE, E., VAN STRATEN, G., VAN NOORT, R. 
& RUTTEMAN, G. R. (2002) Chemotherapy with 
cyclophosphamide, vincristine, and prednisolone (COP) 
in cats with malignant lymphoma: new results with an 
old protocol. Journal of Veterinary Internal Medicine 
16, 179-186
VAIL, D. M., MOORE, A. S., OGILVIE, G. K. & VOLK, 
L. M. (1998) Feline lymphoma (145 cases): proliferation 
indices, cluster of differentiation 3 immunoreactivity, 
and their association with prognosis in 90 cats. Journal 
of Veterinary Internal Medicine 12, 349-354
Further reading
VAIL, D. M. & THAMM, D. H. (2000) Hematopoietic 
tumours. In Textbook of Veterinary Internal Medicine. 
Diseases of the Dog and Cat, 6th edn. Eds S. J. Ettinger 
and E. C. Feldman. Philadelphia, W. B. Saunders. 
pp 732-747
OGILVIE, G. K. & MOORE, A. S. (2001) Feline Oncology. 
A Comprehensive Guide to Compassionate Care. 
Trenton, New Jersey, Veterinary Learning Systems
RICHTER, K. P. (2003) Feline gastrointestinal lymphoma. 
Veterinary Clinics of North America: Small Animal 
Practice 33, 1083-1098
Eight-year-old domestic shorthaired 
cat before (left) and six months after 
(above) the start of chemotherapy for 
feline lymphoma. Loss of the whiskers 
is commonly seen in cats receiving 
chemotherapy. Generalised hair coat 
changes, such as thinning, dilution 
of the colour coat and loss of coarse 
hairs, can also occur
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In Practice � @B V - ? ) - L â , - * - ? ) - L 20 06578
MULTICENTRIC LYMPHOMA
The term multicentric lymphoma is not synonymous with 
multiple lymph node involvement. Although cats are 
often described as having multicentric lymphoma, where 
multiple organ systems are involved, this rarely includes 
the generalised lymphadenopathythat is often seen in 
dogs. This category of lymphoma usually includes cats 
with liver, spleen or peripheral/intra-abdominal lymph 
node involvement. 
Clinical signs range from vague malaise, weight 
loss or anorexia to more acute signs of liver failure. 
Radiography and ultrasound examination of the abdomen 
may indicate changes in the size, shape and echotexture 
of the parenchymal organs, thus prompting needle aspi-
rates in the first instance. It is worth remembering that 
liver infiltration and/or elevated biochemical parameters 
do not equate to liver failure and changes may be revers-
ible with appropriate treatment. Compromised liver 
function will require reductions in cytotoxic drug dos-
ages and careful monitoring for signs of toxicity. 
If generalised lymphadenopathy occurs in cats and 
lymphoma is suspected, definitive histology is required 
to avoid misdiagnosis of healthy, younger cats with non-
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THIS article, the second of two on feline lymphoma, discusses how the disease can present to the 
veterinarian. Lymphoma is a differential diagnosis for a variety of clinical presentations in cats and can 
occur in, or spread to, any anatomical site that contains lymphoid tissue. A regionally localised disease 
must be assumed to have a systemic component unless proved otherwise. Thus, ascribing a disease to a 
particular anatomical form (ie, mediastinal, alimentary or multicentric) can be difficult and may have led 
to inaccuracies in reporting of the disease in the literature. In addition to these commonly recognised 
forms, cutaneous, ocular, central nervous system, tracheal, renal, nasal and pulmonary forms are also 
recognised. These various anatomical presentations of feline lymphoma may come to be regarded as 
specific disease entities in their own right as more is learnt about the pathogenesis and biology of feline 
lymphoid neoplasias, but are currently best considered as manifestations of a disease continuum. Rather 
than struggling to ascribe an individual case to a particular anatomical form, the clinician should be aware 
that the main aim of staging is simply to document all areas of involvement. Initial clinical investigations 
will pertain to the organ system recognised in the presentation of disease, but full staging is always 
required and should include diagnostic investigation of the whole patient wherever possible. This was 
discussed further in Part 1, published in the last issue, which reviewed the principles of diagnosis and 
management in feline lymphoma cases (In Practice, October 2006, volume 28, pp 516-524).
Feline lymphoma
2. Specific disease presentations ALISON HAYES
In Practice (2006) 
28, 578-585
specific immune stimulation. Two studies have alluded 
to this: in the first, lymphadenopathy was reported to 
regress over time in a group of younger cats diagnosed 
with lymphoma and presenting with generalised lym-
phadenopathy (Mooney and others 1987b) and, in the 
Alison Hayes 
graduated from 
Glasgow in 1991 
and spent five years 
in mixed and small 
animal practice in 
north-west England. 
She subsequently 
undertook a 
three-year Blue 
Cross residency in 
oncology at the 
Animal Health Trust 
in Newmarket, 
where she is now a 
clinical oncologist. 
She holds the 
RCVS certificate in 
veterinary radiology 
and an MSc 
in clinical oncology 
from the University 
of Birmingham 
medical school.
Four-year-old female domestic longhaired 
cat, which presented with signs of upper 
respiratory stridor and was FeLV-negative. 
Third eyelid protrusion and reduced 
retropulsion were noted, which were more 
marked on the right side. Nasal biopsy 
confirmed lymphoma and, after complete 
staging, chemotherapy was commenced 
with radiation therapy on relapse. 
Generalised lymphadenopathy is rarely 
a feature of lymphoma in cats
Submandibular lymphadenopathy in a domestic 
shorthaired cat of unknown age. Multicentric lymphomas 
such as this rarely manifest as generalised peripheral 
lymphadenopathy, which is common in dogs. In this cat, 
there was marked, localised, unilateral enlargement of 
the submandibular node (arrow). Picture, Lorraine Fleming
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second, peripheral lymph node enlargement in 14 cats 
led to lymphoma in only one cat, with 13 cats undergo-
ing spontaneous lymph node regression (Moore and oth-
ers 1986). In the latter study, six out of nine cats tested 
had feline leukaemia virus (FeLV) antigen detected in 
the blood and had similar histology findings to kittens 
developing lymphadenopathy following experimental 
FeLV infection. In addition to histology, immunohisto-
chemistry and FeLV antigen detection may be helpful in 
determining a definitive diagnosis. If there is any ambi-
guity, clinical monitoring and re-biopsy is advocated 
before making treatment decisions. 
MEDIASTINAL LYMPHOMA
Mediastinal disease is a common presentation of lym-
phoma. Cats are often dyspnoeic, although sometimes 
this is not recognised by owners. Radiographic changes 
include an anterior thoracic mass effect with or with-
out a pleural effusion. The thymus, mediastinal, pre-
sternal and other intrathoracic lymph nodes may all be 
affected. Lymphadenopathy may be appreciated in the 
thoracic inlet and lower cervical area. Displacement of 
the apex beat and dulled lung sounds will be heard on 
clinical examination. Regurgitation and dysphagia may 
also be reported by owners. Cytology of pleural fluid 
is usually supportive of the diagnosis, although histol-
ogy is advisable wherever possible, especially in older 
cats that are FeLV-negative, in which the disease must 
be differentiated from thymoma, which may be treated 
surgically. 
Ultrasound examination of the thorax facilitates 
guided fine needle aspiration or core biopsy of abnormal 
tissue. The presence of pleural fluid can aid ultrasonog-
raphy, but due care is needed and thoracocentesis may 
be required for initial stabilisation before further inves-
tigation can take place. In cats, the right second to third 
or third to fourth intercostal space is a commonly used 
site for this. Care should be taken to avoid the intercostal 
vessels along the caudal aspect of the rib, while directing 
the needle along the thoracic wall to avoid lung trauma. 
A butterfly catheter or short over-the-needle catheter 
can be used, with or without extension tubing, and 
attached to a three-way tap and syringe for short-term 
drainage. The first fluid that is withdrawn should be 
placed into EDTA and plain tubes for cellular and bio-
chemical analysis.
The mainstay of treatment for mediastinal lymphoma 
is cytotoxic chemotherapy, although low-dose radiation 
therapy to consolidate treatment can lead to durable remis-
sions (Elmsie and others 1991). Young, FeLV-negative, 
Siamese cats may be overrepresented, but can respond 
well to chemotherapy – often achieving complete and 
durable remissions, allowing treatment to be stopped. 
ALIMENTARY LYMPHOMA
Alimentary (or gastrointestinal) lymphoma is frequently 
seen in cats. The small and large intestines, oral cavity, 
oesophagus, stomach, mesenteric nodes, pancreas and 
liver can all be involved. Presenting signs include weight 
loss, anorexia, lethargy and diarrhoea. Vomiting is not 
a consistent feature of the disease in cats. Intestinal 
involvement is generally regarded as a diffuse bowel 
disease, but may initially manifest as a solitary, focal 
mass detectable on abdominal palpation. Alternatively, 
abdominal palpation can reveal diffuse, cord-like bowel 
thickening. Abdominal ultrasonography is essential for 
diagnosis, staging and monitoring, and facilitates guided 
core and needle biopsy. Bowel thickening, loss of motili-
ty and layering, hypoechogenicityand lymphadenopathy 
are characteristic changes seen on ultrasound examina-
tion (Penninck and others 1994). 
When the disease presents as diffuse gastrointestinal 
changes, diagnosis may be achieved by ultrasound-guided 
needle or endoscopic grab biopsies prior to commencing 
chemotherapy. For more solitary masses, fine needle aspi-
ration or needle-core techniques can be used. A surgical 
approach is required if definitive diagnosis is not achieved 
with non-invasive techniques such as Tru-cut style biop-
sies or when there is an immediate need to relieve bowel 
obstruction or intussusception. Superficial grab biopsies 
obtained endoscopically should be interpreted with cau-
tion, as these may underdiagnose lymphoma involving the 
Right lateral recumbent 
(above) and dorsoventral 
(left) projections of 
the thorax showing a 
mediastinal lymphoma 
in a 10-year-old domestic 
shorthaired cat. The 
thoracic air space is 
almost obliterated by 
a homogeneous soft 
tissue opacity which 
obscures the cardiac 
silhouette and displaces 
the trachea dorsally and 
to the right (arrows). Only 
the dorsocaudal part of 
the right lung remains 
aerated. The disease must 
be distinguished from 
thymoma, which may 
be treated surgically. 
Ultrasound-guided 
Tru-cut biopsy can provide 
a definitive diagnosis
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deeper layers and overestimate the importance of inflam-
matory bowel changes seen more superficially. 
Treatment can be surgical, medical or a combination 
of the two. Limitations apply to each form of treatment. 
Chemotherapy can be used as a first-line treatment if a 
definitive diagnosis has already been achieved by non-
invasive means. However, large, focal mass lesions 
treated with chemotherapy can result in a full thick-
ness defect once malignant lymphoid tissue is lost and 
close monitoring is required during the initial induction 
phase. Surgical resection of large areas of bowel does 
not appear to prolong survival compared with cats treat-
ed medically. Chemotherapy is advocated after recovery 
from surgical diagnostic and therapeutic procedures. 
Cats with low-grade gastrointestinal lymphoma have 
been shown to respond well to a combination of pred-
nisolone (10 mg per cat per day) and chlorambucil (15 
mg/m2 daily for four days, repeated every three weeks), 
achieving a median survival time of 22·8 months for the 
67 per cent of animals that achieved complete remission 
(Fondacaro and others 1999). In another study, which 
did not differentiate the grade of disease, 71 per cent of 
cats with gastrointestinal lymphoma achieved complete 
remission with a median survival time of 259 days and 
an overall median survival time for all cats of 201 days 
following treatment with a doxorubicin-based, six-drug 
protocol (Rassnick and others 1999). However, two other 
studies have reported outcomes suggesting that cats with 
gastrointestinal lymphoma may respond less favourably 
to combination protocols than cats with other forms of 
the disease. Zwahlen and others (1998) reported that, 
of 21 cats treated with a doxorubicin-based, six-drug 
protocol, 38 per cent achieved complete remission with 
a median survival time of 291 days, and an overall sur-
vival time of 280 days for all cats. In the second study, 
Mahony and others (1995) reported that, of 27 cats treat-
ed with cyclophosphamide, vincristine and prednisolone 
(COP), 33 per cent achieved complete remission, with a 
median survival time of 213 days for those animals in 
complete remission and an overall survival time of 50 
days. 
As with other forms of the disease, the best chemother-
apy protocol for gastrointestinal lymphoma is probably 
yet to be determined. However, from the limited studies 
to date, it appears that COP alone is probably inadequate 
for the management of gastrointestinal lymphoma.
RENAL LYMPHOMA
Renal lymphoma is the most common renal tumour in 
cats and often presents with acute-onset renal insuffi-
ciency, anorexia, weight loss and polyuria/polydipsia. 
Bilaterally enlarged, and sometimes irregular, kidneys 
can be found on palpation of the abdomen and confirmed 
radiographically. An apparent unilateral presentation can 
be encountered, although the disease is considered to be 
bilateral in all cases. Unsuspected renal involvement 
can be discovered during ultrasound examination if loss 
of corticomedullary definition is seen. This can be due 
to cortical infiltration by neoplastic lymphocytes. The 
diagnosis must be confirmed with fine needle aspira-
tion or Tru-cut style biopsy. There may be an association 
between renal and nasal lymphoma, and also between 
renal and central nervous system lymphoma, but this is 
still unproven. 
Treatment for renal lymphoma is always drug-based 
and can result in a rapid resolution of azotaemia, leav-
ing relatively undamaged, functional kidneys. Surgical 
removal of a kidney for diagnostic purposes should be 
unnecessary and is not warranted from a therapeutic 
Right lateral recumbent 
projection of the abdomen 
of a seven-year-old 
domestic shorthaired cat 
with renal lymphoma. There 
is marked enlargement of 
both kidneys (cranial and 
caudal pole of each kidney 
shown by arrows), which 
has displaced the abdominal 
contents caudoventrally. 
These are typical signs of 
this condition in cats. This 
cat also had disseminated 
signs of disease, suggested 
by the pleural effusion 
Lymphoma or IBD?
If there is a relationship between inflammatory bowel disease and lymphoma, 
it is a contentious one. The pathological classification of feline lymphocytic 
enteric disease has not yet been fully elucidated. Researchers have found that 
epitheliotropic intestinal lymphoma, characterised by infiltration of the super-
ficial layers with small lymphocytes, can only be reliably differentiated from 
inflammatory bowel disease by identifying clonality on immunohistochemistry 
(Carreras and others 2003) and future molecular studies may aid further under-
standing. Currently, it is still unclear whether inflammatory bowel disease is a 
reaction or a precursor to lymphoma. Although it is tempting to regard these 
two diseases as a continuum of each other, this may prove to be inaccurate. 
Cats that show a poor response to inflammatory bowel disease therapy should 
be reviewed, and a diagnosis of lymphoma reinvestigated.
In Practice � @B V - ? ) - L â , - * - ? ) - L 20 06 581
perspective. Survival times can be prolonged for cats 
with renal lymphoma; in one study involving 11 cats 
with disease confined only to the kidneys and treated 
with a multidrug protocol, the median survival time was 
396 days (Mooney and others 1987a). The degree of azo-
taemia should not be regarded as a prognostic indicator 
in cats with renal lymphoma. It is important to realise 
that reported median survival times may be unrepre-
sentative of renal lymphoma per se, due to the possible 
link with central nervous system lymphoma and the 
more guarded prognosis that this carries. 
Supportive care is required in cases of renal lympho-
ma, especially in the early stages of diagnosis and treat-
ment. Cytotoxic drug dose reductions may be necessary 
in sick patients. Drug doses may be increased after the 
initial azotaemia has resolved. Special care should be 
Right lateral recumbent (above) and ventrodorsal (left) 
projections of the abdomen of a nine-year-old domestic 
shorthaired cat with renal lymphoma. Note the 
asymmetry of the left and right renal silhouettes. The 
left kidney is enlarged, with an irregular, globoid shape 
and lies more ventrally than normal (white arrows). 
The right kidney is also enlarged, but retains its normal 
shape and position in the right dorsal abdomen (black 
arrows). Renal involvement is often bilateral, but this 
may not be clinicallyapparent, and enlargement may 
not be symmetrical
Ultrasound image showing a normal feline kidney
(above left) Ultrasound image from a nine-year-old domestic shorthaired cat showing renal lymphoma in the left kidney prior to treatment. The kidney 
is enlarged, measuring 50·91 mm along the long axis (normal range 37 to 44 mm). A hypoechoic rim surrounds the kidney, indicating subcapsular 
fluid and cellular infiltration (white arrows). Poor corticomedullary definition and patchy areas of increased echogenicity give the cortex a mottled 
appearance (black arrows). This loss of corticomedullary definition raises the suspicion of lymphoma and, although marked in this case, a more subtle 
appearance without other renal changes should prompt the clinician to consider a diagnosis of lymphoma. (above right) Ultrasound image from the 
same cat following chemotherapy with cyclophosphamide, vincristine and prednisolone. A marked reduction in renal size can be appreciated, with 
the kidney now measuring about 41 mm in length. There is also a decrease in the amount of subcapsular fluid and almost normal corticomedullary 
definition (arrows), although the mottled appearance of the cortex remains at this stage. Renal lymphoma can respond rapidly to chemotherapy 
without major medical complications; such changes should not necessarily preclude an attempt at induction therapy
In Practice � @B V - ? ) - L â , - * - ? ) - L 20 06582
taken with those drugs that require any degree of renal 
excretion (eg, cyclophosphamide). If used, doxorubicin 
should be administered with pre- and post-treatment 
fluid therapy; extreme care should be taken with cats 
with renal lymphoma, as this drug is nephrotoxic in this 
species.
CENTRAL NERVOUS SYSTEM LYMPHOMA
Lymphoma can affect the brain or spinal cord either as a 
main presenting sign or as a sign of progressive disease 
in cats undergoing treatment. Most cats with central nerv-
ous system involvement will also have lymphoma in sites 
other than the central nervous system. In the past, spinal 
Transverse (left) and dorsal 
(right) T2-weighted magnetic 
resonance images of the 
cervical spine of an 18-year-
old domestic shorthaired cat 
with a three-week history of 
progressive tetraplegia. An 
extradural lymphoma can 
be seen as a roughly ovoid, 
hyperintense, well-defined 
mass within the vertebral 
canal and there is marked 
cord compression. A narrow, 
hyperintense band between the 
mass and the cord corresponds 
to cerebrospinal fluid that is 
located extradurally; this may 
respond to chemotherapy as 
drugs do not have to cross the 
blood–brain barrier to reach 
the target site
Bilaterally enlarged kidneys due to renal lymphoma seen 
at postmortem examination. There are multifocal, nodular 
lymphomatous infiltrates throughout the cortex, which is 
swollen. Picture, Mark Bestbier
Fine needle aspirate cytology from 
a cat with renal lymphoma. Normal 
lymphocytes have a nuclear diameter 
approximately the same size as a red 
blood cell (black arrow). The nucleated 
lymphocytes (white arrows) have 
enlarged nuclei, approximately two 
to four times that of a red blood cell, 
and scant cytoplasm. Magnification X40. 
Picture, Mark Bestbier
Histology of a biopsy sample from a cat with renal 
lymphoma showing an interstitial infiltrate of malignant 
lymphocytes with a moderate variation in nuclear size 
and shape. Loss of function can be reversible with 
prompt treatment. Haematoxylin and eosin, magnification X10. 
Picture, Mark Bestbier
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lymphoma may have occurred more commonly, princi-
pally in FeLV-positive cats, but lymphoma in the brain 
was reported less frequently and in older, FeLV-negative 
cats. Clinical signs of brain involvement include irrita-
bility, seizures, circling, blindness, cranial nerve defi-
cits and nystagmus. With spinal lymphoma, the onset of 
signs can be acute or insidious, and focal hyperaesthesia 
prior to clinical dysfunction has been reported. Paresis 
and ataxia with a rapidly deteriorating clinical course are 
common.
Definitive diagnosis can be difficult to achieve and 
may account for the relative under-reporting of brain 
involvement. Computed tomography or magnetic reso-
nance imaging may detect a focal mass lesion, or a more 
infiltrative or widespread pattern of change. An accu-
rate diagnosis may come from sampling other distant 
sites that are thought to be involved. Cerebrospinal fluid 
analysis may demonstrate malignant cells, but negative 
findings do not rule out lymphoma. The expected high-
er incidence of spinal lymphoma compared with lym-
phomas in the brain was not seen in a recent review of 
cases at the Animal Health Trust. This may reflect the 
changing face of feline lymphoma due to its FeLV/feline 
immunodeficiency virus associations.
Drug-based protocols for brain lymphoma may 
achieve less than expected for other forms of lympho-
ma, as most conventional cytotoxic drugs have minimal 
access across the blood–brain barrier. Protocols con-
taining cytosine arabinoside have been advocated in an 
attempt to access affected areas. However, more success 
is generally achieved with radiation therapy, usually in 
conjunction with chemotherapy. Survival times of up to 
seven months have been reported, but usually the prog-
nosis is regarded as poor. Spinal lymphoma is mainly 
extradural and thus should respond more favourably to 
drug-based therapies, although parenchymal extension 
can occur. Surgical decompression of the spine or adju-
vant, low-dose radiation therapy may be considered on 
an individual case basis. Survival is affected as much by 
disease response to chemotherapy as by the timing of 
decompression, which can cause permanent neurological 
damage. Bone marrow analysis may yield a definitive 
diagnosis without the need for spinal surgery.
OCULAR LYMPHOMA
Ocular lymphoma can be unilateral or bilateral, and can 
precede the onset of systemic disease in many (but not 
all) cats. Any part of the eye and retrobulbar space can 
be affected. The uvea is most commonly affected and 
can show either diffuse or nodular changes. When other, 
systemic sites are thought to be involved, they should be 
sampled to help yield a definitive diagnosis. If an exact 
aetiology cannot be established, symptomatic treatment 
for uveitis can be implemented with regular re-evalua-
tion. If there is a gross tumour within the eye and other 
sites are not involved, enucleation can be performed. In 
Transcorneal ultrasound scan of lymphoma in the 
retrobulbar space of a nine-year-old domestic shorthaired 
cat. An ill-defined, hypoechoic mass in the medial part of 
the orbit causes indentation of the globe (white arrows). 
There is also disruption of the hyperechoic line that 
represents the bony medial wall of the orbit (black arrows). 
Oral examination revealed a mass in the pterygopalatine 
fossa, biopsy of which confirmed lymphoma
Eight-year-old Persian cat with ocular changes associated 
with lymphoma. Diffuse inflammation and thickening of 
the iris was accompanied by miosis and keratic precipitates 
on the corneal endothelium
Ocular changes associated with lymphoma in a cat 
of unknown age. There is localised thickening and 
inflammation of the iris, most marked between 
9 and 12 o’clock
Ocular changes associated with lymphoma in an 
11-year-old domestic shorthaired cat. Diffuse inflammation 
and thickening of the lateral part of the iris can be seen 
together with distortion of the pupil and a cottage cheese-
like deposit in the anterior chamber. Mild corneal oedema 
can also be appreciated. This cat additionally had retinal 
detachment and bilateral panuveitis
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experienced hands, aqueocentesis may yield a diagnosis 
insome cases, thus permitting chemotherapy to be start-
ed without sacrificing the eye. 
As with other forms of feline lymphoma, when ocu-
lar lymphoma is diagnosed, the possibility of systemic 
disease should prompt the use of adjuvant chemotherapy, 
although the clinician should be aware that some long-
term survivors have been reported following enucleation 
alone. 
TRACHEAL LYMPHOMA
Tracheal lymphoma is an uncommon but well recog-
nised form of feline lymphoma. Cats can present with 
dyspnoea, wheezing, cyanosis, coughing and lethargy 
(Brown and others 2003). Lesions can be visualised on 
plain radiography and bronchoscopy will aid collec-
tion of material for cytology. Successful treatment with 
chemotherapy has been reported, although radiation 
therapy can be used as a primary treatment modality, or 
as an adjunct to chemotherapy. As systemic disease can 
be seen at presentation or relapse, it is safest to assume 
that this form of lymphoma is part of a systemic dis-
ease and implement localised treatment as an adjunct to 
systemic therapy.
NASAL LYMPHOMA
Nasal lymphoma is also well recognised in cats. 
Affected animals can present with upper respiratory 
stridor, sneezing, nasal discharge, epiphora, and facial 
pain or deformation. Deviation or poor retropulsion of 
the globe should alert the clinician to the possibility of 
orbital extensions. Although radiographic displacement 
of midline structures, an increase in soft tissue opac-
ity, loss of turbinate detail and bone invasion are all 
more likely to be seen in cases of nasal neoplasia, these 
changes are not specific for cancer versus rhinitis or for 
lymphoma versus any other intranasal neoplasia. As with 
other forms of lymphoma, careful staging is required. 
See Part 1 for a discussion of biopsy techniques. 
Pre- (above) and post-radiotherapy (below) transverse post-
contrast T1-weighted magnetic resonance images of a nasal 
lymphoma in a 10-year-old domestic shorthaired cat at the 
level of the caudal nasal cavity. Prior to treatment, a large 
mass can be seen filling the left nasal cavity, but it does not 
cross the nasal septum or invade the orbit (white arrow). 
Fluid is trapped within the left frontal sinus (black arrow). 
The post-treatment scan shows significant resolution; the 
soft tissue mass is no longer apparent and the trapped fluid 
has been allowed to drain. Radiotherapy can be useful for 
localised disease, as a combined modality treatment or 
rescue therapy
Treatment can involve either chemotherapy or radia-
tion therapy, or a combination of the two modalities. In 
the author’s experience, long-term survival is achiev-
able with radiation therapy alone, and in the absence 
of systemic involvement this is the preferred method 
of treatment when available. This is supported by the 
observations of other authors (Elmsie and others 1991). 
However, systemic disease, even if absent at presenta-
tion, can manifest later in the course of disease and 
ultimately chemotherapy may be required. Conversely, 
relapsing nasal lymphoma treated by chemo therapy in 
the first instance, either due to systemic involvement or 
owner/vet preference, can be successfully rescued with 
radiation therapy. When nasal disease extends to the 
retrobulbar space, radiation of the globe may lead to 
long-term complications necessitating enucleation. A 
combined modality approach using chemotherapy to 
downsize the tumour (neoadjuvant therapy) may allow 
successful radiation therapy without irradiation of 
the globe. Repeated sectional imaging to monitor the 
response to drug-based treatment is essential in such 
cases prior to commencing chemotherapy.
OTHER FORMS OF LYMPHOMA
Other forms of lymphoma can be diagnosed in cats, 
either alone or as part of a multicentric presentation. 
When lymphoma of the lung occurs, it tends to mani-
fest as nodular lesions, which are uncommon in dogs. 
Larnygeal lymphomas can cause respiratory stridor or 
Dorsoventral intraoral projection of nasal lymphoma in 
a nine-year-old domestic shorthaired cat. There is loss of 
turbinate pattern unilaterally, an increase in soft tissue 
opacity (arrow) and occlusion of the nostril. The cribriform 
plate and medial orbital wall are ill-defined (not seen on 
this radiograph). This cat’s orbital ultrasonogram (see page 
583) suggested that the nasal lymphoma had extended 
into the retrobulbar space. A definitive biopsy can often 
be obtained without invasive procedures
In Practice � @B V - ? ) - L â , - * - ? ) - L 20 06 585
Hodgkin’s-like lymphoma
A specific form of feline lymphoma, termed Hodgkin’s-like lymphoma, seems to 
be emerging. As the term suggests, there are pathological and clinical similari-
ties to this specific human form of lymphoma. In people, Hodgkin’s lymphoma 
tends to affect contiguous lymph nodes in the neck and thorax, and the dis-
ease can be slow to progress. Treatment is often based on surgery and radia-
tion, rather than systemic drug therapy, which is more commonly associated 
with non-Hodgkin’s lymphoma. The neoplastic cells (Reed–Sternberg) are in the 
minority and are found among non-neoplastic lymphocytes. 
The feline form of the disease appears to affect older cats, which present 
with unilateral and often focal cervical or mandibular lymphadenopathy. A 
mixed population of lymphocytes is recognised with neoplastic cells seeming to 
be in the minority (Walton and Hendrick 2001). A similar and possibly synony-
mous condition has been described by Day and others (1999) as a T cell rich B 
cell lymphoma. Further work is required to categorise this disease more specifi-
cally and document the clinical outcome. In the author’s experience, neoadju-
vant chemotherapy prior to localised lymph node excision for cervical lymphad-
enopathy has proved rewarding.
dyspnoea. Cutaneous lymphomas can be solitary or dif-
fuse, and composed of T or B cells. Solitary cutaneous 
lymphomas can be cured surgically. In the case of multi-
ple cutaneous lesions, or if surgical treatment is not indi-
cated, treatment with conventional cytotoxic drugs can 
be attempted. Plesiotherapy and external beam radiation 
therapy may be useful as an adjunct to systemic treat-
ment or as single modality therapy in areas that are 
deemed to be non-surgical. 
SUMMARY
Lymphoma can present in many different guises, and the 
clinician should be alert to the possibility of this condi-
tion in any cat regardless of age, breed or viral status. 
Treatment can be rewarding with rapid responses often 
leading to a reversal of life-threatening situations within 
hours or days of commencing appropriate therapy in the 
practice setting. Histological diagnosis and full staging 
are required to tailor treatment choices to the individ-
ual cat. All samples for diagnostic purposes should be 
obtained before commencing therapy, including gluco-
corticoid treatment.
Acknowledgements
The images for this article were compiled with the help of the 
Units of Comparative Ophthalmology and Diagnostic Imaging at 
the Animal Health Trust, with particular thanks to Jane Samson, 
Ruth Dennis and Fraser McConnell.
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Further reading
OGILVIE, G. K. & MOORE, A. S. (2001) Feline Oncology. 
A Comprehensive Guide to Compassionate Care. Trenton, 
New Jersey, Veterinary Learning Systems
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Dog and Cat, 6th edn. Eds S. J. Ettinger and E. C. Feldman. 
Philadelphia, W. B. Saunders. pp 732-747
CORRECTION
Feline lymphoma 1. Principles of diagnosis 
and management (In Practice, October 2006, 
volume 28, pp 516-524)
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