Feline Renal Lymphoma Incidence Study
Feline Renal Lymphoma Incidence Study
Original Article
Abstract
Objectives Lymphoma is the most common feline hematopoietic malignancy. Incidence of renal lymphoma has
not been reported as a subset of a large population of feline lymphoma cases. Previous studies have reported
renal lymphoma as both a singular entity as well as a component of multicentric disease. The clinical presentation,
diagnostic evaluation, therapy and outcomes related to renal lymphoma have not been reported since Mooney et al
in 1987. This retrospective study aimed to describe the incidence of renal lymphoma, clinical signs, treatment and
survival.
Methods Using a database of cats diagnosed with lymphoma between January 2008 and October 2017, cats
with renal lymphoma were selected for further analysis. Cases were retrospectively staged according to Mooney
et al (1987) and Gabor et al (1998). Data collected included age, clinical signs, clinicopathologic data, diagnostic
imaging findings, lymphoma diagnostic method(s), treatment protocol(s) and survival time. Analyses comparing
median survival based on therapy administered, renal lymphoma vs multicentric lymphoma, central nervous system
involvement, presence of azotemia, anemia and International Renal Interest Society (IRIS) stage at diagnosis were
performed.
Results From a population of 740 cats with lymphoma, 27 cats had renal lymphoma (incidence, 3.6%), and 14 of
those cats had multicentric lymphoma. Fewer stage IV and V cases were identified in this data set compared with
Mooney et al; however, not all cats were completely staged. Median survival (range) for cats receiving corticosteroids
alone compared with those receiving an L-CHOP (L-asparaginase, vincristine, cyclophosphamide, doxorubicin,
prednisolone)-based protocol was 50 days (20–1027 days) in the corticosteroid group and 203 days (44–2364
days) for the L-CHOP group (P = 0.753) for cats that died secondary to lymphoma.
Conclusions and relevance Neither clinical stage nor other factors were predictive of survival. Prospective studies
are required to determine the optimal chemotherapy protocol.
Introduction
Lymphoma is the most common hematopoietic malig- The goals of this study were to retrospectively apply
nancy in cats and is the most common neoplasm reported two staging systems for renal lymphoma in cats to this
in the kidney of cats.1 The incidence of renal lymphoma population of cats and to describe the incidence, clinical
has been reported to range from 7–30% in studies of signs, treatment and outcomes in cats with renal lym-
approximately 100 cats each.2–5 The clinical presentation, phoma. The secondary aim was to evaluate prognostic
results of a diagnostic work-up, therapy and outcomes
related specifically to renal lymphoma have not been
reported since Mooney et al in 1987.1 Since that time, 1The Cancer Institute, Animal Medical Center, New York, NY, USA
advances in diagnostics, such as the widespread use 2Lamb Statistical Consulting, West St Paul, MN, USA
of abdominal ultrasound, have improved the ability to
Corresponding author:
detect changes concerning for neoplastic infiltration and Ashlyn G Williams, DVM, Animal Cancer Care Clinic, 1122 NE 4th
may have resulted in stage migration in feline lymphoma, Avenue, Fort Lauderdale, FL 33304, USA
as has been reported in canine multicentric lymphoma.6 Email: [email protected]
2 Journal of Feline Medicine and Surgery
factors in renal lymphoma including International Renal Table 1 Animal Medical Center staging system1
Interest Society (IRIS) stage, presence of azotemia and
anemia at diagnosis and evidence of multicentric disease Stage Organ/tissue involvement
at diagnosis. I Single tumor (extranodal) or anatomic area
Our primary hypothesis was that renal lymphoma (nodal)
occurs both as a singular entity within the kidneys and II Two tumors (extranodal), two or more nodal
also as a component of multicentric disease. Our sec- areas on same side of the diaphragm, primary
ondary hypothesis was that the presence of azotemia or resectable gastrointestinal tumor
anemia, diagnosis of multicentric disease, stage of dis- III Two tumors (extranodal) on opposite sides of
ease and type of treatment pursued would significantly the diaphragm, unresectable intra-abdominal
disease, paraspinal or epidural tumors
impact survival. The authors also hypothesized that
IV Stage I–III with liver or spleen involvement
the decrease in the prevalence of feline leukemia virus
V Stage I–IV with central nervous system or bone
(FeLV)-positive cats since 1987 would have an impact on marrow involvement
response to therapy and survival.
Figure 2 Feline lymphoma diagnoses from the Animal Medical Center between January 2008 and October 2017
illustrates the AMC staging system from Mooney et al1 treated with chemotherapy received steroids orally for
compared with the current study. the duration of their chemotherapy protocol. The most
Each patient was staged according to clinical find- common chemotherapy protocol was a combination
ings using the previously described staging systems.1,2 of L–CHOP, which was administered to nine cats. The
Twenty-four cats were placed in the abdominal stage and L-CHOP protocol utilized is outlined below in Table 6. The
three in the mixed stage based on the Gabor staging sys- cat with large granular lymphocyte lymphoma received
tem. Table 5 compares the staging of cats in the present cytosine arabinoside as a single agent. Five cats received
study and the prior study using the AMC staging system. chemotherapy but had an unknown treatment protocol
Twenty-four cats underwent treatment for lymphoma. owing to incomplete medical records. Nine cats were
Fifteen cats were treated with chemotherapy. All cats treated with corticosteroids alone. Radiation therapy was
Williams et al 5
grade 3 or 4 toxicities were reported. Gastrointestinal data set appears to identify an increase in the incidence
signs were commonly mild and managed at home with of renal lymphoma in the AMC feline population over the
supportive medications (maropitant [Cerenia; Zoetis], past three decades.5
ondansetron, metronidazole). Stage has had variable impact on survival and response
Cats with renal lymphoma as a singular entity within to therapy in the literature on feline lymphoma. 1,4,13
the kidneys had a median survival of 50 days. The dif- Neither staging system evaluated predicted outcome in
ference between the two groups was not statistically this group of cats, potentially owing to the small number
significant (P = 0.8428). Azotemia at diagnosis was not of cases or lack of complete staging in the cats included
found to have a significant impact on survival (median in this and previous studies; however, the authors also
75 days in azotemic cats, 47 days in non-azotemic believe there are likely inherent problems with the two
cats, P = 0.4100). Anemia at diagnosis also had no sig- staging systems. Tumor staging serves the purpose of
nificant impact on survival (median 44 days in anemic identifying patients with increasing tumor burden and
cats, 86 days in non-anemic cats, P = 0.1735). Cats with determining prognosis from that information. The Gabor
stage II disease had a median survival of 97 days and staging system provides an anatomic description of
cats with stage III disease had a median survival of tumor location, which would not be expected to correlate
45 days, which was not statistically different (P = 0.6595). with tumor burden.2 The AMC staging system attempts
A median survival could not be calculated for the cats to define increasing tumor burden with increasing stage
in the remaining stages due to low case numbers. Cats by having higher stages correlate with disease identified
within the abdominal stage had a median survival of in an increasing number of anatomic sites.1 Despite the
50 days and cats in the mixed stage had a median sur- cats included in this study not receiving full staging, the
vival of 114.5 days, which was not statistically significant authors feel that the staging that was performed is reflec-
(P = 0.9586). tive of the typical clinical staging performed in cats with
The primary cause of death in 22 of the 27 cats was lymphoma. The cats included in the Mooney et al1 manu-
lymphoma. Four cats died of causes other than lym- script had no abdominal ultrasounds performed and only
phoma. The first cat died of a second malignancy, oral eight of 28 cats had bone marrow aspirates performed.
squamous cell carcinoma, 2639 days post diagnosis. This The cats included in Gabor et al2 only had thoracic radio-
cat was treated with an L-CHOP chemotherapy protocol. graphs performed if dyspneic or if the heart was in an
The second cat was euthanized secondary to neurologic abnormal location based on physical examination find-
disease with no evidence of recurrent lymphoma based ings. Abdominal ultrasound was also not performed in
on complete blood count (CBC), biochemical profile, tho- all cats in Gabor et al.2
racic radiographs, abdominal ultrasound and MRI 2363 Since the routine use of abdominal ultrasound became
days post diagnosis. This cat was treated with an L-CHOP commonplace at the AMC after 1984, we hypothesized
chemotherapy protocol. The third cat was euthanized for that the three decades between Mooney et al1 and this
an unknown cause but had no evidence of lymphoma on data set would result in stage migration. Stage migration
physical examination, CBC, biochemical profile, thoracic is defined as the addition of newer and more sensitive
radiographs, or abdominal ultrasound 1026 days post- staging tests, which can identify previously undetectable
diagnosis after treatment with steroids alone. The fourth lesions resulting in ‘migration’ into higher stages.6 Stage
cat had a complete necropsy performed by a board-certi- migration has been documented in humans, dogs and
fied pathologist, which revealed no evidence of recurrent cats.6,14–16 Our data showed that there were fewer stage
lymphoma on histopathology examination 666 days post- IV and stage V cases, an increased number of stage III
diagnosis. This cat received an L-CHOP chemotherapy cases and similar numbers of stage I and II according to
protocol as well as rescue protocols including radiation the AMC staging system, although no bone marrow aspi-
therapy to the brain and spinal cord, a MOPP chemother- ration cytology was performed in any cats in this study,
apy protocol and single-agent cytarabine arabinoside. which may have resulted in underestimation of stage.
One cat was lost to follow-up and censored from survival Our data suggests, but cannot confirm, the presence of
data 1 day post-diagnosis. reverse stage migration. Reverse stage migration has
been previously documented in men with prostate can-
Discussion cer after the implementation of prostate-specific antigen
This study reports an incidence of renal lymphoma of testing.17 Our hypothesis to explain the potential reverse
3.6% in a population of 740 cats diagnosed with lym- stage migration observed in our patient population is that
phoma and a 22.3% incidence in a population of 121 cats routine use of advanced diagnostics with greater sensi-
with large cell lymphoma. Others reported a similar renal tivity provides a more accurate assessment of internal
lymphoma incidence of 2.2–3.9%.11,12 However, renal organs than palpation and less sensitive imaging tech-
large cell lymphoma was reported to have an incidence niques such as radiography, which was used previously.1
of 15%, which is lower than reported here.5 The current However, since neither the current data set nor the data
Williams et al 7
sets in Mooney et al1 or Gabor et al2 had complete stag- Mooney et al1 since FeLV infection has been shown to
ing data on all cats, reverse stage migration in feline renal confer a shorter median survival time.4 The median sur-
lymphoma remains speculative. vival time of cats in Mooney et al1 is difficult to determine
Clinical staging of feline cancer patients is inherently but 17/28 cats had a complete response with a reported
imprecise because samples are not typically collected median survival of 169 days, which does not appear to
from normal-appearing tissues that might harbor lym- differ from the median survival reported in this study.
phoma. In many studies, costs associated with testing, This finding was unexpected.
risks of adverse outcomes from testing and the fact that Lymphoma of the CNS appears to be less common
complete staging is not required for successful treatment in this study than in Mooney et al.1 We speculate the
limit the number of cats undergoing an extensive staging decrease in CNS lymphoma may be related to a decrease
evaluation. It is likely that nearly all reports of clinical in FeLV infection.1 The median survival in the present
staging of feline lymphoma patients over- or underesti- study is comparable to Mooney et al1, yet only one cat
mate stage to some degree. developed CNS lymphoma during treatment compared
The authors acknowledge that this study may under- with eight cats in the previous report. The low number
estimate stage because 19/27 cats had thoracic radio- of cases with CNS involvement in this case series calls
graphs and no cats underwent bone marrow aspiration. into question the recommendation to include cytosine
In the previous study, only 8/28 cats underwent bone arabinoside in the treatment protocol for renal lymphoma
marrow aspiration, and no abdominal ultrasounds or as previously described.1 Cytosine arabinoside has been
MRIs were performed. Stage may have been over- and recommended as prophylaxis for CNS lymphoma due
underestimated in that group of cats.1 However, given to its ability to cross the blood–barrier and cats treated
that similar limitations exist in all publications reporting with a protocol containing this chemotherapy agent were
feline lymphoma stage, there may still be value in com- reported to have a lower rate of CNS lymphoma than cats
paring staging in different studies even though none of not treated with cytosine arabinoside.1 Prospective stud-
those studies are perfect. ies are indicated to determine the optimal chemotherapy
The presence of azotemia and anemia at diagnosis is protocol for renal lymphoma in cats and if CNS prophy-
considered of potential prognostic significance in renal laxis with cytosine arabinoside or any drug is indicated.
lymphoma. Based on Boyd et al,18 we hypothesized severe Another difference between this study and the prior
azotemia would result in poorer responses to chemother- one is the use of L-CHOP chemotherapy in nine cats. The
apy and shorter survival times. Previously, in cats with chemotherapy protocol used previously to treat renal
chronic kidney disease, IRIS stage at diagnosis has been lymphoma did not include doxorubicin.1 Doxorubicin
shown to predict outcome.18 Boyd et al18 also reported a was added to the chemotherapy protocol used in some
short median survival time in patients with chronic kid- cats in this study with the expectation that the addition
ney disease and anemia requiring treatment. Our study of this drug would improve survival, though statistical
did not identify azotemia or anemia as prognostic factors analysis did not confirm this outcome. Prior reports of
for survival, but anemia is one difference that might have the efficacy of doxorubicin in feline lymphoma have been
influenced survival between the cats previously reported mixed. Some studies report long survival times using
and these cats. In this study, a greater number of cats protocols without doxorubicin, some report no difference
(17/27) were anemic compared with Mooney et al,1 where in survival times between protocols with and without
14/28 cats were anemic. In at least one study of canine doxorubicin and single-agent doxorubicin chemotherapy
lymphoma, anemia was a predictor of survival.19 Dogs has not been as successful in the cat as in the dog.1,3,9,10,21–28
diagnosed with anemia and lymphoma had a median Three of the four long-term survivors (and cats poten-
hematocrit 10% lower than dogs with lymphoma with- tially ‘cured’ of renal lymphoma) were initially treated
out anemia. Both remission duration and survival were with the L-CHOP protocol, suggesting the addition of
shorter in dogs with anemia compared with dogs without doxorubicin to the treatment protocol of some cats with
anemia. This study may have been too small to identify renal lymphoma is beneficial. The infrequent occurrence
anemia as a prognostic factor for survival but the subject of renal lymphoma in this population of over 700 cats
warrants further investigation. results in a small number of cases, causing a challenge
The decrease in FeLV infections and the decrease in in detecting differences between groups. Thus, we can-
its role in lymphomagenesis has made FeLV infection not conclusively say the addition of doxorubicin is not
uncommon in cats with lymphoma.20 FeLV infection is of benefit in at least some cats with renal lymphoma.
uncommon in our patient population and thus testing Cats included within the current study treated with an
is no longer routine, as evidenced by the small number L-CHOP protocol had a treatment duration of 25 weeks,
of cats tested. Because the cats in this study likely had a unless there was evidence of progressive disease requir-
low prevalence of FeLV infection, we hypothesized the ing a change in protocol prior to that time. Cats included
survival would be longer in these cats compared with in Mooney et al1 were treated with chemotherapy for
8 Journal of Feline Medicine and Surgery
several years. Considering the median survival time in practice’) of individual veterinary clinical patient care were
Mooney et al1 was not longer when compared with the followed. Ethical approval from a committee was therefore not
current data set, prolonged maintenance chemotherapy necessarily required.
treatment may not have clinical benefit. The efficacy of
prolonged maintenance chemotherapy has been ques- Informed consent Informed consent (either verbal or writ-
tioned in canine lymphoma.29 An interesting and unex- ten) was obtained from the owner or legal custodian of all
plainable finding regarding survival time observed in animal(s) described in this work (either experimental or non-
experimental animals) for the procedure(s) undertaken (either
both this study and Mooney et al1 is the report of a few
prospective or retrospective studies). No animals or humans
cats with very long survival times. In Mooney et al,1 at
are identifiable within this publication, and therefore addi-
least three cats survived >1 year and in the present study, tional informed consent for publication was not required.
four cats survived >1 year. The prolonged survival in the
four cats ‘cured’ of renal lymphoma in the present study
suggests prolonged maintenance chemotherapy is not ORCID iD Ashlyn G Williams https://orcid.org/0000-
0001-6100-7052
required in at least a subset of cats with renal lymphoma.
In Australian2 and Dutch cats,28 a predilection for
lymphoma in young, purebred cats, specifically Oriental References
breeds, has been reported. Young Siamese cats treated for 1 Mooney SC, Hayes AA and Matus RE. Renal lymphoma
in cats: 28 cases (1977–1984). J Am Vet Med Assoc 1987; 191:
lymphoma may have a prolonged disease-free interval.10
1473–1477.
The inclusion of two Abyssinian cats, a Siamese and a
2 Gabor LJ and Canfield PJ. Clinical and anatomical features
Burmese cat may have had an impact on survival in the of lymphosarcoma in 118 cats. Aust Vet J 1998; 76: 725–732.
prior study and explain in part why the cats in the present 3 Taylor SS, Goodfellow MR and Browne WJ. Feline extra
study, which included no young, Oriental cats, have a nodal lymphoma: response to chemotherapy and survival
similar survival time to Mooney et al, despite there being in 110 cats. J Small Anim Pract 2009; 50: 584–592.
fewer FeLV-positive cats in this study.1 The two purebred 4 Vail DM, Moore AS and Ogilvie GK. Feline lymphoma
cats in this study were both older, 13 and 17 years of age. (145 cases): proliferation indices, cluster of differentiation
3 immunoreactivity, and their association with prognosis
in 90 cats. J Vet Intern Med 1998; 12: 349–354.
Conclusions
5 Mooney SC and Hayes AA. Lymphoma in the cat: an
This study reports an incidence of 3.6% for renal lym-
approach to diagnosis and management. Semin Vet Med
phoma in a population of 740 cats diagnosed with lym- Surg 1986; 1: 51–57.
phoma and a 22.3% incidence in 121 cats with large cell 6 Flory AB, Rassnick KM and Stokol T. Stage migration in
lymphoma. The survival time in this group of cats was dogs with lymphoma. J Vet Intern Med 2007; 21: 1041–1047.
unexpectedly and disappointingly short, although some 7 Veterinary Co-operative Oncology Group (VCOG). Com
cats appeared to be ‘cured’. The cause of the short sur- mon terminology criteria for adverse events (VCOG
vival time is elusive. The cats’ FeLV status, chemotherapy – CTCAE) following chemotherapy or biological antineo
protocol and known prognostic factors do not appear plastic therapy in dogs and cats v1.0. Vet Comp Oncol 2004;
to explain the outcome in this group of cats. This study 2: 195–213.
suggests CNS prophylaxis may not be necessary in cats 8 Finotello R, Vasconi ME and Sabattini S. Feline large gran
ular lymphocyte lymphoma: an Italian Society of Veteri
with renal lymphoma as has previously been suggested.
nary Oncology (SIONCOV) retrospective study. Vet Comp
Prospective studies are required to determine the optimal
Oncol 2018; 16: 159–166.
chemotherapy protocol for cats with renal lymphoma. 9 Roccabianca P, Vernau W, Caniatti M, et al. Feline large
granular lymphocyte (LGL) lymphoma with secondary
Acknowledgements The authors thank Drs KZ Wright and leukemia: primary intestinal origin with predominance
AM Verrilli and Ms S Vaughan-Wasser for use of their feline of a CD3/CD8 (alpha) (alpha) phenotype. Vet Pathol 2006;
lymphoma database. 43: 15–28.
10 Krick EL, Little L, Patel R, et al. Description of clinical and
Conflict of interest The authors declared no potential pathological findings, treatment and outcome of feline
conflicts of interest with respect to the research, authorship, large granular lymphocyte lymphoma (1996–2004). Vet
and/or publication of this article. Comp Oncol 2008; 6: 102–110.
11 Chino J, Fujino Y, Kobayashia T, et al. Cytomorphological
Funding The authors received no financial support for the and immunological classification of feline lymphomas:
research, authorship, and/or publication of this article. clinicopathological features of 76 cases. J Vet Med Sci 2013;
75: 701–707.
Ethical approval This work involved the use of non- 12 Graf R, Gruntzig K, Hassig M, et al. Swiss Feline Can
experimental animals only (including owned or unowned cer Registry: a retrospective study of the occurrence of
animals and data from prospective or retrospective studies). tumours in cats in Switzerland from 1965 to 2008. J Comp
Established internationally recognized high standards (‘best Pathol 2015; 153: 266–277.
Williams et al 9
13 Mooney SC, Hayes AA, MacEwen EG, et al. Treatment of 22 Kristal O, Lana SE, Ogilvie GK, et al. Single agent chemo
prognostic factors in lymphoma in cats: 103 cases (1977– therapy with doxorubicin for feline lymphoma: a retro
1981). J Am Vet Med Assoc 1989; 194: 696–699. spective study of 19 cases (1994–1997). J Vet Intern Med
14 Nerschbach V, Eule JC, Eberle N, et al. Ocular manifes 2001; 15: 125–130.
tation of lymphoma in newly diagnosed cats. Vet Comp 23 Hadden AG, Cotter SM and Rand W. Efficacy and toxi
Oncol 2016; 14: 58–66. cosis of VELCAP-C treatment of lymphoma in cats. J Vet
15 Nerschbach V, Eberle N and Joetzke AE. Splenic and Intern Med 2008; 22: 153–157.
hepatic ultrasound and cytology in canine lymphoma: 24 Moore AS, Cotter SM and Frimberger AE. A comparison
effects of findings on stage migration and assessment of of doxorubicin and COP for maintenance of remission in
prognosis. Vet Comp Oncol 2016; 14: 82–94. cats with lymphoma. J Vet Intern Med 1996; 10: 372–375.
16 Koshy M, Fairchild A and Son CH. Improved survival 25 Simon D, Eberle N and Laacke-Singer L. Combination
time trends in Hodgkin’s lymphoma. Cancer Med 2016; 5: chemotherapy in feline lymphoma: treatment outcome,
997–1003. tolerability, and duration in 23 cats. J Vet Intern Med 2008;
17 Wallis CJD and Klaassen Z. “Reverse stage migration”: what 22: 394–400.
can population-based data tell us about trends in prostate 26 Collette SA, Allstadt SD and Chon EM. Treatment of feline
cancer presentation? Eur Urol Oncol 2018; 1: 321–322. intermediate-to high-grade lymphoma with a modified
18 Boyd LM, Langston C and Zivin K. Survival in cats with university of Wisconsin–Madison protocol: 119 cases
naturally occurring chronic kidney disease (2000–2002). (2004–2012). Vet Comp Oncol 2016; 14: 136–146.
J Vet Intern Med 2008; 2: 1111–1117. 27 Waite AHK, Jackson K, Gregor T, et al. Lymphoma in cats
19 Miller AG, Morley PS, Rao S, et al. Anemia is associated treated with a weekly cyclophosphamide-, vincristine-,
with decreased survival time in dogs with lymphoma. and prednisone-based protocol: 114 cases (1998–2008).
J Vet Intern Med 2009; 22: 116–122. J Am Vet Med Assoc 2013; 242: 1104–1109.
20 Louwerens M, London CA and Pedersen NC. Feline lym 28 Teske E, Van Straten G, Van Noort R, et al. Chemotherapy
phoma in the post-feline leukemia virus era. J Vet Intern with cyclophosphamide, vincristine and prednisolone
Med 2005; 19: 329–335. (COP) in cats with malignant lymphoma: new results
21 Gouldin ED, Mullin C and Morges M. Feline discrete high- with an old protocol. J Vet Intern Med 2002; 16: 179–186.
grade gastrointestinal lymphoma treated with surgical 29 Hahn KA, Richardson RC and Teclaw RF. Is maintenance
resection and adjuvant CHOP-based chemotherapy: retro chemotherapy appropriate for the management of canine
spective study of 20 cases. Vet Comp Oncol 2017; 15: 328–335. malignant lymphoma? J Vet Intern Med 1992; 6: 3–10.