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DOI: 10.1111/vco.12012
Abstract
Keywords
lymph node, metastasis,
sentinel, stage
Current staging of canine mast cell tumours (MCTs) practiced by many veterinarians involves a
minimum of lymph node (LN) assessment, abdominal ultrasound and thoracic radiography.
Historically, some have advocated buffy coat and bone marrow evaluation. Two hundred and twenty
dogs with MCT seen at a referral clinic were staged using LN palpation/cytology, thoracic radiography
and abdominal ultrasound. The utility of each method was evaluated by considering prevalence of
spread and future behaviour. At presentation, 30.9% of dogs had metastases to the local LN; 6.8% of
all the dogs also had distant metastases. No dog had or developed distant metastasis in the absence
of LN metastasis. No dog had convincing evidence of pulmonary metastasis. In this series, the local
LN was sentinel to metastasis and in the absence of local LN metastasis, the utility of further staging
was low. Thoracic radiography was not useful in the staging of canine MCT.
Introduction
Correspondence address:
J. Warland
Queens Veterinary School
Hospital
University of Cambridge
Madingley Road,
Cambridge CB3 0ES, UK
e-mail:
JHW36@CAM.AC.UK
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J. Warland et al.
2012 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, 12, 4, 287298
Ultrasonographic
evidence of visceral
organomegaly accompanied by multiple
hypoechoic nodules or mottled echotexture;
where findings were equivocal, cytology was
used to confirm or refute the presence of
metastatic spread.
Radiological evidence of multiple interstitial
nodules in lung fields consistent with
pulmonary metastasis.
289
Initial presentation
Of the dogs included in the analysis, 123 were female
(101 neutered) and 97 were male (53 neutered).
The mean age was 7.4 years (range 114 years) and
was similar between the sexes. Forty-two different
breeds were represented within the dataset. Five
breeds included more than five cases, which were
Labradors (n = 64), Golden Retrievers (n = 29),
Boxers (n = 22), Staffordshire Bull Terriers (n = 16)
and Jack Russell Terriers (n = 6); there were 23
crossbreed dogs.
The Patnaik system grading4 was recorded for
217 tumours. Twenty-four were considered grade
I, 152 grade II and 20 grade III. Eleven tumours were
graded as III and 10 graded IIIII. The grade was
unavailable in three cases. The grade information is
included in Table 1.
Statistical analysis
Odds ratios (ORs) were calculated, with 95%
confidence intervals (CIs), for different breeds
with respect to the development of metastases
and multiple tumours. These were calculated
using an online calculator (http://www.hutchon.
net/ConfidOR.htm).
The sensitivity and negative predictive values of LN assessment for metastatic spread
were calculated using another online calculator
(http://www.hutchon.net/EPRval.htm).
Logistic regression analysis was used to establish
what factors, including age, breed, sex, neutering
status, grade and tumour location, influence likelihood of metastasis at presentation. A statistical software package (SPSS version 19, IBM, Armonk, NY,
USA) was used to perform the logistic regression.
Results
Two hundred and thirty-four dogs with MCTs were
entered into the oncology database between 1997
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J. Warland et al.
Table 1. Patnaik histological grades for 220 canine skin mast cell tumours
Grade
Breed
All breeds
Labrador Retriever
Golden Retriever
Boxer
Staffordshire Bull Terrier
Jack Russell Terrier
III
II
IIIII
III
Unknown
Total
24
3
5
2
3
0
11
5
2
0
1
0
152
46
16
18
9
5
10
5
2
1
0
0
20
5
3
0
3
1
3
0
1
1
0
0
220
64
29
22
16
6
Breed data
Boxers appeared to be at lower risk of developing LN
metastases (n = 1; OR: 0.095; 95% CI: 0.0120.718).
Golden Retrievers were at increased risk of multiple
tumours (n = 14; OR: 5.96; 95% CI: 2.5813.8)
but not of developing metastasis. No other breeds
showed statistically altered risk of metastasis or
multiple tumours.
Primary site
When site was considered, MCT on the head
(n = 36) appeared to be more likely to metastasize to
the local LN (n = 17; OR: 2.37; 95% CI: 1.144.94)
and distantly (n = 5; OR: 3.93; 95% CI: 1.3111.9).
Fifty-seven percent of dogs had tumours of limbs
(n = 126), but their site, including position on limb,
Other factors
MCT behaviour was not influenced by sex, age
or neutering status, or the presence or absence of
multiple tumours.
When analysed using a backward, stepwise logistic regression, grade (P = 0.018) and breed (Boxer)
(P = 0.033), were both significantly associated with
the presence or absence of metastatic spread.
Higher grade tumours were associated with a
higher risk of metastatic spread, and Boxer breed
with a lower risk of metastasis. Location (head)
appeared significantly associated with metastasis but did not provide any value beyond that
provided by the grade and breed, and so was
removed from the model at the penultimate step
(P = 0.035).
Treatment
A variety of different treatment modalities and combinations were instigated. The treatments given
before and after staging are outlined in Table 4.
Most dogs had undergone surgery at the referring practice. For the purposes of the study,
chemotherapy included corticosteroids, antihistamines or cytotoxic chemotherapeutic agents or
a combination of these. Fourteen dogs received
some form of systemic chemotherapy before their
referral, and this was continued in all these cases.
Radiotherapy used was coarsely fractionated (four
doses at 800850 cGy at weekly intervals; total
dose 3234 Gy), usually on incompletely resected
tumour scars with inclusion of cytologically positive LNs if present. Some dogs with inoperable
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Table 2. Location details of 15 dogs considered to have distant metastasis at the time of initial staging for mast cell tumour
Case
Primary tumour
site
Distant
metastasis
Left elbow
Left prescapular
2
3
Right inguinal
Left submandibular
4
5
6
Right submandibular
Right axillary
Left axillary
7
8
9
10
Left eyebrow
Right axilla
Nose
Scrotum, Lower jaw
Left submandibular
Right axillary
Submandibular
Inguinal, Submandibular
Skin (3)
Prescapular LN, skin
(multiple)
Right prescapular LN
Right prescapular LN
Left prescapular LN,
sternal LN
Left prescapular LN
Right prescapular LN
Prescapular LN
Medial iliac LN
11
Left scapula
Left prescapular
Spleen
12
Right stifle
Popliteal
13
Right submandibular
Spleen
14
Right thigh
Right inguinal
15
Left submandibular
Left prescapular
Follow-up
From the original 220 dogs, follow-up data were
available for 185 dogs. Thirty dogs were considered
lost to follow-up and five dogs were excluded
from follow-up analysis. Two described earlier
had evidence of another incidental but metastatic
tumour found during work up for the MCT. Three
other dogs were excluded as the MCT was an
incidental finding after the dog was presented
Other details
Spleen on ultrasound appearance.
Not sampled because of other
cytologically confirmed
metastases
Cytologically confirmed
Cytologically confirmed
Cytologically confirmed
Cytologically confirmed
Prescapular cytologically
confirmed
Cytologically confirmed
Cytologically confirmed
Cytologically confirmed
Inguinal and submandibular
nodes cytologically confirmed.
Dog died at first consultation
because of mast cell
degranulation. Medial iliac node
significantly enlarged not
sampled because of death
Splenectomy 6 weeks prior to
referral because of rupture.
Considered to be metastatic
although histopathology not
performed
Spleen on ultrasound appearance.
Not sampled because of other
cytologically confirmed
metastases
Splenic nodule aspirated and
cytologically confirmed
Spleen and liver on ultrasound
appearance. Not sampled
because of other metastases
Cytologically confirmed
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Location
Total
number
Number
metastasized
36
20
54
51
16
7
17
4
20
13
7
1
11
1
2
0
Head
Trunk
Upper limb
Lower limb
Foot
Limb (not specified/multiple
same limb)
Inguinal/Scrotal
Tail
for their skin mast cell tumours before and after initial
staging
No
metastasis Metastasis
Prior to referral/staging
No previous surgical treatment
One surgery by referring practice
Multiple surgeries at referring
practice
Chemotherapy (including
steroids)
After referral/staging
No treatment at all (including
prestaging)
No further treatment
Surgical interventions
Further surgery at referral hospital
First surgery at referral hospital
Adjunctive to surgery
Chemotherapy
Radiotherapy
Chemotherapy and radiotherapy
Non-surgical treatments
Radiotherapy (alone)
Chemotherapy (alone)
Radiotherapy and chemotherapy
Cryosurgery
32
108
12
26
38
4
31
5
8
4
6
11
69
10
17
15
7
0
6
14
1
0
9
11
0
2012 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, 12, 4, 287298
Discussion
The main focus of this study was the utility of the
initial staging of MCTs. The key finding was that no
tumours spread distantly without first spreading to
the local LN.
Survival analysis was considered weak because
of the retrospective nature of the study, a lack
of definitive cause of death data (i.e. postmortem
examinations) as well as a huge variety of treatments
and combinations. These factors will invariably act
as confounding factors to the survival analysis,
and therefore in-depth analysis of survival was
considered likely to be flawed and not undertaken.
The follow-up data collected and presented were
used to validate the results of the initial staging. A
small proportion of dogs were lost to follow-up,
but for the majority the follow-up period was of
considerable duration (median 1160 days) and thus
supports the conclusions, although the possibility
of metastasis development beyond the follow-up
period cannot be ruled out.
Because of the limitations of the pathology
reports in this study, the authors did not distinguish
cutaneous and subcutaneous MCTs, and rather
considered them to be skin MCT. Of the 220
tumours, 217 had been assigned a grade by
the pathologist, which should only be used for
cutaneous tumours. However, it is the authors
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Is the Local
Lymph Node
Subcutaneous
No
Yes
Is Local
Lymph
Node
Palpable
?
Ultrasound
assessment of
Local LN +/- FNA
Yes
FNA LN
Is Lymph
Node
Metastasis
present?
No
No
Can
tumour be
excised
with 2cm
margins?
Yes/Suspicious
No
Further Staging
-Abdominal ultrasound
-Further lymph node evaluation
-+/- Blood sample (if appropriate)
Is Distant
Metastasis
Present?
Yes
Yes
Biopsy Primary
Tumour
No
Excise Primary
Tumour (2cm margins)
& Lymph Node for
Histopathology
Figure 1. Summary flow diagram of the authors suggested approach to a newly diagnosed canine skin MCT. Modified
from a previously suggested textbook algorithm.29
grade and evaluation and SLN staging will provide the best information on the extent and likely
behaviour of MCT. We propose the use of the flow
diagram (Fig. 1) to best stage a newly diagnosed
MCT. Further evaluation of the Kiupel et al.10 twotier grading system, immunohistochemical markers
2012 Blackwell Publishing Ltd, Veterinary and Comparative Oncology, 12, 4, 287298
and further studies into the best method of assessment of the SLN are vital to improve our management of MCT. A prospective study using more accurate markers of metastatic MCT spread should be
undertaken to confirm these preliminary findings.
Further to this, investigations into the optimal management strategies, including medical and surgical
treatments, given the SLN status, will drive forward
our treatment of these challenging tumours.
Acknowledgements
The authors would like to thank all the staff at
the Queens Veterinary School Hospital for their
help with the diagnosis and treatment of these dogs
and the referring veterinary practices for providing
vital follow-up information. The authors would
like to thank Tess Hoather for her management
of the Oncology Database. Dr Mark Holmes is
acknowledged for his assistance with the statistical
analyses.
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