CASE STUDY MARCH 2012

CASE STUDY
MARCH 2012
Signalment:
10 year old FS Domestic Longhair – 4.8#
History:
Dolly, an indoor only cat in a multi-cat household was
diagnosed with hyperthyroidism six months prior to referral
and was being managed on methimazole. She was current on
her vaccinations and received routine monthly heartworm
prevention. She was continuing to lose weight with intermittent
vomiting and diarrhea despite her normalized T4. Blood work
Laboratory Data
Table 1
Biochemistry Profile
Examination:
09/27/2011
Tests
Results
Reference Range
Total Protein
7.5 g/dL
5.2-8.8 g/dL
Albumin
3.3 g/dL
2.5-3.9 g/dL
Globulin
4.2 g/dL
2.3-5.3 g/dL
AST (SGOT)
104 IU/L (High)
10-100 IU/L
ALT (SGPT)
571 IU/L (High)
10-100 IU/L
Alkaline Phosphatase
158 (High)
6-102
GGT
2 IU/L
1-10 IU/L
Total Bilirubin
0.1 mg/dL
0.1-0.4 mg/dL
BUN
14 mg/dL
14-36 mg/dL
Creatinine
0.6 mg/dL
0.5-1.6 mg/dL
BUN/Creatinine Ratio
28
4-33
Phosphorus
4.2 mg/dL
2.4-802 mg/dL
Glucose
95 mg/dL
64-170 mg/dL
Calcium
9.3 mg/dL
8.2-10.8 mg/dL
Magnesium
1.6 mEq/L
1.5-2.5 mEq/L
Sodium
154 mEq/L
145-158 mEq/L
Potassium
3.8 mEq/L
3.4-5.6 mEq/L
Na/K Ratio
41
32-41
Chloride
117 mEq/L
104-128 mEq/L
Cholesterol
104 mg/dL
75-220 mg/dL
Triglyceride
32 mg/dL
25-160 mg/dL
Amylase
10 days prior to referral revealed a bicytopenia with a
normocytic, normochromic, non-regenerative anemia (HCT
20.8%) with a leukopenia (WBC 2,150) and neutropenia (170).
A feline leukemia SNAP test was a weak positive, and her most
recent T4 was 0.9ug/dL. Thoracic radiographs taken by the
referring veterinarian revealed a normal cardiac silhouette
with no evidence of pulmonary parenchyma changes or
lymphadenopathy with normal thoracic skeletal structures.
The owners had stopped her methimazole several days prior
to presentation because they felt it was making her sick. She
was referred for additional diagnostics for her weight loss
and bicytopenia.
1414 IU/L (High) 100-1200 IU/L
Lipase
87 IU/L
0-205 IU/L
CPK
456 IU/L
56-529 IU/L
T=102.9, P=280, R=32. The patient was severely muscle
wasted with a BCS1 of 1.5/5. She had a grade II/VI holosystic
murmur with thready pulses. Doppler blood pressure
measured 130mm Hg. She had a pronounced 1cm X 2cm
goiter. On abdominal palpation, a mid-abdominal mass effect
measuring 1cm X 1.5cm was detected. She had a dull and
poor hair coat. Her mucous membranes were pale pink and
moist. The patient was admitted for additional laboratory
testing and an abdominal ultrasound.
Table 2
CBC
09/27/2011
Tests
Results
Reference Range
3
WBC
9.6 X 10 /µL
3.5-16.0 X 103/µL
4
RBC
6.0 X 10 /µL
5.92-9.93 X 104/µL
HGB
9.3 g/dL
9.3-15.9 g/dL
HCT
27% (Low)
29-48 %
MCV
46 fL
37-61 fL
MCH
15.5
11.21 pg
MCHC
34 pg
30-38 g/dL
Platelet Count
69 103/µL (Low)
200-500 103/µL
Platelet Estimate
Adequate
-Differential
Absolute
Normal
Neutrophils
5376 µL
2500-8500/µL
Lymphocytes
3360 µL
1200-8000/µL
Monocytes
768 µL (High)
0-600/µL
Eosinophils
96 µL
0-1000/µL
Basophils
0 µL
0-150/µL
T4
23.4 µg/dl (High)
0.8-0.4 µg/dl
FeLV Antigen (ELISA)
Negative
-FIV Antibody
Negative
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Abdominal Ultrasound
Abdominal ultrasound revealed a mild diffuse
hyperechogenicity to the hepatic parenchyma. The left
kidney was atrophied and irregular measuring 2.63cm
X 1.94cm with decreased corticomedullary definition and
an irregular, blunted cranial pole. The right kidney was
mildly hypertrophied measuring 4.06cm X 1.99cm with
decreased corticomedullary definition. No evidence of
pyelectasia or mineralization was seen to either kidney. An
abdominal mixed echogenic focal area measuring 0.52cm
thought to represent bowel or lymph node was observed
in the caudal abdomen. The remainder of the abdominal
ultrasound was unremarkable.
Ultrasound guided needle aspirates were taken from the
abdominal lesion (Fig. 1), and a GI panel was ordered
(Table 1). A cardiac ultrasound was recommended but was
declined by the owner.
Figure 1
Table 1
GI Panel
Tests
Cobalamin
Folate
Spec fPL
09/27/2011
Results
Reference Range
1488 ng/L
276-1425 ng/L
13.5 µf/L
8.9-19.9 µg/L
2.0 µg/L
<2.5 µg/L
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Figure 1
Cytology Of Abdominal Mass:
A mixed population of primarily small lymphocytes exhibiting
occasional cleaved nuclei was noted. Intermediate
lymphocytes and lymphoblasts of varied morphology were
present in increased, but lesser numbers with infrequent
plasma cells. No etiologic agents were seen. Findings were
most consistent with reactive lymphoid hyperplasia.
Treatment:
The patient was started on Atenolol at 6.25mg by mouth every
24 hours for her severe tachycardia and was admitted for
radioactive iodine therapy (I-131) for her uncontrolled
hyperthyroidism. Dolly received 5 mCi of I-131 subcutaneously
and was hospitalized for 72 hours prior to discharge to her
owners for continued isolation for two weeks.
Recheck Evaluation:
The patient presented one week after discharge from
radioactive iodine treatment for evaluation of an acute 2cm X
1cm swelling on her left carpus characterized as a red, raised,
and ulcerated mass (Fig. 2).
Cytology of the mass was performed and she was discharged
on antibiotic pending cytology results. She re-presented a
couple of days later for evaluation of a new mass that had
appeared in the left axilla measuring 2cm X 2cm. The new
mass was irregular, indiscreet, and poorly marginated. The
primary mass remained static in size and shape. Cytology of
the new mass was taken and submitted for evaluation.
Figure 2
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Carpal Mass
Cytopathology Of Carpal And Axillary Masses: Questions:
Carpal Mass – Cytologic evaluation revealed sheets and
clusters of cells with round and abundant cytoplasm with
variable amounts of metachromatic granulation consistent
with mast cell tumor.
1. How was the bicytopenia related to the continued
weight loss, increased liver enzymes, and gastrointestinal
signs? Should the weak positive FeLV test be considered a
false positive, or not?
Axillary Mass – Cytologic evaluation revealed a moderate
to marked infiltrate of mast cells with poor metachromatic
granulation arranged in variably sized clusters mixed within
a heterogenous lymphoid population of primarily small to
intermediate lymphocytes. Findings consistent with
metastatic mast cell tumor.
2. Should additional causes for weight loss have been
pursued in light of the very elevated T4 of 23.4 ug/dL?
3. How would you approach Dolly’s mast cell tumor now?
What is her prognosis?
Axillary Mass
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Part Two
Treatment:
Dolly was initially started on Prednisolone at 5mg by mouth
every 24 hours. After one week, there was no appreciable
shrinkage of the mast cell tumor so the patient was given
Lomustine (CCNU) at 50mg/m2 by mouth and was scheduled
for surgery one week later. Upon her return for surgery Dolly’s
weight had increased to 5.8 pounds and she was reported to
be feeling very well. Her mass and lymph node were reduced
in size by 30%-50%. A T4 and pre-anesthetic panel were done
prior to surgery.
Table 1
Tests
T4
BUN
HCT
WBC
Results
1.2 µg/dL
35 mg/dL
35%
4560 /µL
ReferenceRange
0.8-0.4 µg/dL
15-34 mg/dL
29-48%
5.5-19.5 K/µL
Surgery:
Surgery was performed to resect both masses with minimal
margins attained. An advancement flap was used to cover
the large carpal defect. Both tissues were submitted for
histopathology. Surgery was uneventful and Dolly was
discharged the following day on Clavamox drops (40mg
PO BID), Prednisolone (5mg PO q 24 hr), and Buprenex
(0.04mg sublingually BID-TID).
Histopathology:
Sections of the submitted tissue consisted of sheets of discrete
round cells with an abundant amount of cytoplasm that was
faintly granular with pleomorphic, round nuclei exhibiting
prominent nucleoli. Mitoses were infrequent at 1-2 per high
power field with some binuleated cells present. Aggregates of
eosinophils and lymphocytes were present as well. The tumor
was invasive deeply and there were clumps of cells separate
from the main mass that were present at the edge of the
section. Findings were consistent with mast cell tumor.
Sections of the submitted axillary lymph node were partially
replaced by mast cells with aggregates extensively within
sinuses consistent with metastatic mast cell tumor.
Outcome:
Dolly is five months post I131 and MCT treatment and has gained
weight to 8.0 pounds. She is reported to be doing extremely well
at home with no evidence of recurrence of her mast cell tumor.
Dolly has received 3 rounds of Lomustine and though her white
cell count drops with each treatment, she has normalized by six
weeks post treatment and has handled each dose without
incident. We will continue treating for six rounds of chemotherapy
and re-stage her before discontinuing her treatment.
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Discussion:
On initial presentation, Dolly’s laboratory work revealed multiple
abnormalities, many of which could be attributed to unregulated
hyperthyroidism. More than 75% of hyperthyroid cats exhibit
elevations in ALT or Alk Phosphatase Hepatic enzyme increases
may be due to malnutrition, congestive heart failure, infection,
direct toxic effects of thyroid hormones on hepatic parenchyma, or
hepatic hypoxia due to increased splanchnic oxygen consumption.
Serum Alkaline Phosphatase (SAP) elevations may be attributed to
hepatic lipidosis due to weight loss or possible increased bone
isoenzymes due to altered bone metabolism and loss of bone
density. The pre-referral bicytopenia was thought to be attributed
to a methimazole reaction. Anemia, thrombocytopenia, and
leukopenia are well recognized side effects of methimazole
therapy and her CBC improved immediately with cessation of the
methimazole, and the FeLV testing came back normal. Since bone
marrow cytology was not performed one cannot rule out the
possibility of laboratory error or other disease.
Mast cell tumors (MCT) account for approximately 20% of
cutaneous tumors in the cat. Well differentiated MCTs which
account for approximately 50%-90% of cutaneous mast cell
tumors are generally considered to behave in a more benign
manner with the majority of cats being affected in the head and
cervical region. Dolly’s case is representative of another subset of
cats that develop diffuse or anaplastic MCTs which are less discrete,
more infiltrative and show more anisocytosis, multinucleated cells
and esoinophilic infiltrate. These turmors are more frequently
associated with metastasis or disseminated disease.
Little published data exists in the literature on chemotherapy
treatmentofmastcelltumorsinthecatandtreatmentmodalitieshave
often been replicated from the canine literature anecdotally. In 2008,
one study in JAVMA (JAVMA, April 2008; 232 (8); 1200-5) reported
the use of Lomustine in the treatment of mast cell tumor in the cat in
38 cases. The study reported an overall response rate of 50% with a
median response duration of 168 days (range, 25-727 days), with
cutaneous disease in cats faring better than cats with visceral MCTs.
Studies are underway looking at the new Tyrosine kinase inhibitors
(TKIs), like toceranib and masitinib, and these drugs may prove useful
in our arsenal against aggressive mast cell tumors in the cat.
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