Visceral Mast Cell Tumor
with Metastasis in a Sevenyear-old Boston Terrier
Michelle White
DVM Class of 2014
College of Veterinary Medicine
Cornell University
April 2nd, 2014
Clinical Advisor: Dr. Kelly Hume
Pre-Clinical Advisor: Dr. Tracy Stokol
Abstract
Case Description – A seven-year-old, female, spayed Boston Terrier was presented with
a one day history of lethargy and tachycardia and history of abdominal discomfort
immediately prior to presentation.
Clinical Findings - On presentation, the patient was euthermic, tachycardic, tachypneic,
and overconditioned. Initial physical examination revealed a tense, painful abdomen and
a mid-abdominal mass but no other abnormalities. Focused Assessment with Sonography
in Trauma (FAST) imaging revealed pleural and peritoneal effusion. A hemogram
revealed an inflammatory leukogram with moderate mast cells throughout the smear.
Abdominal ultrasonographic examination revealed a large, multilobular, hypo-echoic
mass in the right caudal abdomen adjacent to a jejunal lymph node. Many abdominal
lymph nodes were enlarged. Three-view thoracic radiographs confirmed moderate pleural
fluid and revealed atelectasis of the right middle lung lobe. Cytologic examination of
Wright’s-stained smears of fine needle aspirates (FNA) of the splenic lymph node and
abdominal mass were diagnostic for a mast cell tumor (MCT). A relative lack of
lymphocytes in the splenic lymph node sample suggested effacement of the node. Mast
cells were also seen on examination of the pleural fluid.
Treatment and Outcome - Due to the poor prognosis, the owner elected humane
euthanasia.
Clinical Relevance – Visceral mast cell tumors are much less common in the dog
compared to cutaneous and subcutaneous MCT. Their biologic behavior tends to be
highly aggressive with rapid metastasis. There is a relative lack of peer-reviewed
literature involving canine visceral MCT as compared to cutaneous MCT.
1
Case History
A seven-year-old, spayed, female Boston Terrier was presented to the Cornell
University Hospital for Animals (CUHA) Emergency and Critical Care Service with a
one day history of lethargy and tachycardia. The owner had also noticed abdominal
discomfort immediately prior to presentation. The patient had previously been apparently
healthy.
Clinical Findings
Physical Examination
On presentation, the patient was euthermic (101.3°F), tachycardic (180 beats per
minute), tachypneic (36 breaths per minute) and overconditioned with a body condition
score of 7/9. Initial physical examination revealed a tense, painful abdomen but no other
abnormalities. Pain medication (5 ug/kg of Fentanyl) was administered intravenously to
allow more thorough abdominal palpation and a large mid-abdominal mass was detected.
Initial Diagnostic Tests
Focused Assessment with Sonography in Trauma (FAST) imaging of the thorax
and abdomen was performed to gather more information about the potential cause of the
tachycardia, tachypnea, and abdominal abnormalities. The purpose of a FAST
examination is to find free fluid in the pericardial, pleural, or peritoneal spaces. FAST
examination provides a rapid, accurate, non-invasive means of prioritizing potentially
life-saving treatments in emergent cases1. Pleural and peritoneal effusions were detected
in the patient. Therapeutic thoracocentesis was not deemed necessary because the fluid
accumulation was not severe and the patient was not in respiratory distress. Causes of
ascites that would require emergency intervention such as a ruptured hemangiosarcoma
2
or traumatic internal hemorrhage were considered less likely because the dog had a
normal packed cell volume as measured via quick assessment tests.
After physical examination and initial diagnostic testing, the patient’s problem list
included:

Lethargy

Tachycardia

Tachypnea

Pain on abdominal palpation

Mid-abdominal mass

Bicavitary effusion
Differential Diagnosis
With fentanyl administration, the patient’s pain seemed effectively controlled and her
heart and respiratory rates normalized. With these problems managed, the focus for
further diagnostic testing was placed on further characterization of the abdominal mass.
Differential diagnoses that were considered for the patient’s mid-abdominal mass
included neoplasia of an abdominal organ (including the liver, spleen, and
gastrointestinal tract), lymph node, or other tissue; reactive mesenteric lymphadenopathy
due to a non-neoplastic cause such as inflammatory bowel disease or an infection within
the gastrointestinal tract; and non-neoplastic causes of gastrointestinal obstruction such as
a foreign body or intussusception.
Neoplasia was prioritized as the most likely differential diagnosis because of the
associated pleural and peritoneal effusions and the patient’s age. Non-neoplastic causes
of mesenteric lymphadenopathy were considered less likely due to lack of commonly
3
associated signs such as vomiting and diarrhea. For these same reasons, gastrointestinal
obstruction was also considered less likely. Additionally, the patient had no history of
dietary indiscretion. The patient was hospitalized overnight, given intravenous fluids and
a constant rate intravenous infusion of fentanyl, and then transferred to the Oncology
Service the following morning for continued evaluation and care.
Additional Diagnostic Testing
Upon transfer to the Oncology service, blood was taken for a hemogram and
chemistry panel. The hemogram revealed an inflammatory leukogram with a stress
component and moderate mast cells throughout the smear (suggesting the presence of a
MCT). Hematocrit and platelet count were within reference intervals, decreasing
concerns for potential complications if fine needle aspirates were to be performed.
Hemogram
Test
White Blood Cells (thou/uL)
Segmented Neutrophils (thou/uL)
Band Neutrophils (thou/uL)
Lymphocytes (thou/uL)
Monocytes (thou/uL)
Eosinophils (thou/uL)
Result
17.3
14.3
0.2
0.5
2.2
0.0
Change






Reference Interval
5.7-14.2
2.7-9.4
0-0.1
0.9-4.7
0.1-1.3
0.1-2.1
The chemistry panel showed a mild hypocalcemia, hypoproteinemia due to
hypoalbuminemia, and hypocholesterolemia. The hypocalcemia was attributed to the
hypoalbuminemia due to a decrease in the protein-bound component of calcium.
Prioritized differential diagnoses for hypoalbuminemia included a negative acute phase
response and malabsorption due to inflammation in the gastrointestinal tract.
Inflammation, malabsorption or tumor consumption are potential causes for the
hypocholesterolemia.
4
Chemistry Profile
Test
Calcium (mg/dL)
Total Protein (g/dL)
Albumin (g/dL)
Cholesterol (mg/dL)
Result
9.0
5.0
2.9
128
Change




Reference Interval
9.3-11.4
5.3-7.0
3.1-4.2
138-332
For further characterization of the mid-abdominal mass, including potential
associations with abdominal organs or other tissues, an ultrasonographic examination was
done. This revealed a 6.8 x 4.8 x 8.7 cm multilobular, mostly hypoechoic mass in the
right caudal abdomen in the region of jejunal lymph nodes, thus possibly representing (or
being continuous with) one of these nodes. Many other abdominal lymph nodes were also
enlarged, including the splenic (up to 1.7 x 2.6 cm), medial iliac (left node 1.0 x 1.5 x 2.6
cm; right node 1.0 x 1.0 x 2.0 cm), right renal (1.5 x 1.6 x 2.0 cm), and portal (up to 0.8 x
1.2 cm with probable cyst) lymph nodes. Moderate amounts of anechoic pleural and
peritoneal fluid were seen. The spleen, liver, gastrointestinal tract, pancreas, adrenal
glands and kidneys appeared morphologically normal. Fine needle aspirates of the pleural
fluid, splenic lymph node, and right caudal abdominal mass were obtained.
Due to the suspicion of neoplasia and moderate pleural fluid detected via FAST,
three-view thoracic radiographs were performed. These radiographs confirmed moderate
pleural fluid accumulation that displaced the lung margins from the body wall and
created interlobar fissures. The right middle lung lobe appeared small with increased
opacity and obscured the margins of the cardiac silhouette, suggesting atelectasis of this
lobe. Macroscopic pulmonary metastasis and thoracic lymph node enlargement were not
detected.
5
Initial slides of the fine needle aspirates and pleural fluid had been stained with
Diff-Quik stain that was absorbed poorly by the mast cell granules, leaving some of the
tumor cells with an appearance consistent with either a mast cell tumor or a lymphoma of
granular lymphocytes. For this reason, additional staining (Wright’s) was performed to
confirm the diagnosis. Cytologic examination of Wright’s-stained smears of the FNA
samples of the splenic lymph node, mass, and pleural fluid were diagnostic for a mast cell
tumor. The mast cells displayed many criteria of malignancy, including moderate to
marked anisokaryosis and anisocytosis, prominent nucleoli, and variable granulation.
Several binucleate cells and mitotic figures were seen. A relative lack of lymphocytes in
the sample from the splenic lymph node suggested effacement of the node. Though the
remaining enlarged lymph nodes were not sampled, all were considered affected by
metastasis given their ultrasonographic appearance combined with the severity of the
findings in the splenic lymph node.
In one study of 152 dogs with MCT, effacement of a regional lymph node by the
mast cell tumor, as identified on cytologic examination of fine needle aspirates (i.e.
“certain metastasis”), was a negative prognostic indicator, regardless of the anatomic
location of the primary tumor2. Dogs with lymph node effacement had the shortest
median survival time (MST) (0.8 years). Unfortunately, the anatomic location of the
primary tumor was not provided in this study and it is not known how many of the MCT
were primary cutaneous tumors or primary visceral tumors.
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Interpretation
Description
Normal
Reactive lymphoid
hyperplasia
No mast cells seen
Greater than 50% small lymphocytes,
mixed leukocyte population, rare
individual mast cells
On at least one slide, two to three
incidences of mast cells in aggregates of
two to three cells
On at least one slide, greater than three
foci of mast cells in aggregates of two to
three cells and/or two to five aggregates
of more than three mast cells
On at least one slide, effacement of
lymphoid tissue by mast cells, and/or the
presence of aggregated, poorly
differentiated mast cells with
pleomorphism, and/or greater than five
aggregates of more than three mast cells
Possible metastasis
Probable metastasis
Certain metastasis
MST of group
(years; 95% CI)
6.3 (4.1-7.3)
6.2 (5.3-10.2)
5.2 (5.2-8.3)
2.9 (0.4-4.6)
0.8 (0.4-1.9)
Table adapted from Krick et. al 2009
The presence of mast cells in the pleural fluid in this case was also a negative
prognostic indicator because it confirmed spread of the tumor from the presumptive
primary site (the abdomen) into the thorax. The presence of mast cells on the blood smear
from the hemogram also suggested diffuse metastasis with possible bone marrow
involvement.
Shortly after fine needle aspirates were performed, the patient regurgitated and
had an episode of diarrhea. This was assumed to be secondary to mast cell degranulation
after manipulation and fine needle aspiration of the mass, so corticosteroids
(dexamethasone, 0.1 mg/kg, intramuscular) and antihistamines (diphenhydramine, 2
mg/kg, intramuscular and famotidine, 0.5 mg/kg, intravenous) were administered.
Outcome
Due to the poor prognosis, the owner elected humane euthanasia.
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Discussion
Mast Cells
Mast cells are leukocytes found in most tissues of the body with increased
concentrations in areas with greatest exposure to the environment, including the skin,
respiratory tract, and gastrointestinal tract. They play an important role in connecting
innate and adaptive immune responses when fighting pathogens3. Mast cells are released
from the bone marrow and circulate as immature cells. Upon migration into vascularized
tissue, they are exposed to cytokines released by endothelial cells and fibroblasts that
drive them to fully differentiate and mature. When stimulated, mast cells can immediately
release granules from the cytoplasm that contain several inflammatory mediators
including histamine, heparin, tryptase, chymase, and tumor necrosis factor alpha.
Following degranulation, mast cells can produce and release prostaglandins and
leukotrienes. Later, within hours of degranulation, the cells can up-regulate the
production of cytokines and chemokines for further mediation of inflammation. Any or
all of these responses may occur depending on the stimulus.
Mast Cell Tumors
The clinical presentation, frequency, and biologic behavior of MCT vary widely
between species. In dogs in the United States, MCT comprise 16 to 21% of all skin
tumors and 11 to 27% of all malignant skin tumors4. In dogs, most MCT arise from the
dermis and subcutaneous tissues, where they can present as raised, ulcerated, haired or
hairless, soft or firm, single or multiple masses. Mast cell tumors also vary in biologic
behavior, with the most important prognostic factor being histologic grade. Though
diagnosis can be made from a fine needle aspirate, histologic grading requires a surgical
8
biopsy and histopathologic assessment. Low-grade tumors are associated with median
survival times of 2-5 years, while high-grade tumors are associated with median survival
times of several months to less than one year. The most widely used grading scheme for
cutaneous MCT was developed by Patnaik:
Grade
Description
MCT confined to the dermis and interfollicular spaces. Cells are monomorphic with ample
1
cytoplasm with distinct boundaries and medium-sized intracytoplasmic granules. There are no
mitoses and minimal edema and necrosis.
MCT infiltrating or replacing the lower dermal or subcutaneous tissue. Cells are moderately
2
pleomorphic with scattered spindle and giant cells. Cytoplasm is mostly but not always distinct
with fine or occasionally large intracytoplasmic granules. Mitoses rare (0-2 per high-power
field). Areas of diffuse edema and necrosis are present.
MCT replacing the subcutaneous and deep tissues. Cells are pleomorphic with many binucleate,
3
giant, and multinucleated cells. Cytoplasm is indistinct with fine or absent intracytoplasmic
granules. Mitoses are common (3-6 per high-power field). Hemorrhage, edema, and necrosis are
common.
Table adapted from North and Banks 20095.
The primary treatment for cutaneous MCT is surgical excision with wide margins
(2-3 cm laterally and one fascial plane deep). Radiation therapy is effective in controlling
residual local microscopic disease. Chemotherapy is recommended if systemic or
metastatic disease is detected, in cases of high-grade tumors with increased risk of
metastasis, to reduce the tumor burden prior to surgical resection, or when there has been
incomplete surgical excision but repeat surgery and/or radiation are not possible.
Chemotherapeutic drugs commonly used to treat MCT include prednisone, vinblastine,
CCNU, and tyrosine kinase inhibitors (such as toceranib mesylate).
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Common metastatic sites for cutaneous MCT include lymph nodes, liver, spleen,
and bone marrow. In this patient, the liver and spleen appeared normal in size, shape, and
echogenicity during abdominal ultrasound. However, this finding does not rule out
metastasis to either organ. A 2011 study by Book et. al reported that, in 19 dogs
diagnosed with high grade MCT, the sensitivity of ultrasonographic examination for
detecting mast cell infiltration was 43% for the spleen and 0% for the liver6. This study
suggests that fine needle aspirates should be performed of both the spleen and liver
regardless of findings on abdominal ultrasonographic examination when there is
suspicion of a mast cell tumor in order to provide the most informed treatment plan and
prognosis. In this case, aspiration of the spleen and liver was not deemed necessary for
prognostication purposes due to the indication of metastasis beyond the abdomen
indicated by the presence of mast cells in the pleural fluid and blood smear.
Visceral Mast Cell Tumors
Disseminated mastocytosis occurs rarely and is almost always secondary to a
primary cutaneous tumor. In rare cases, MCT of primary visceral origin have been
diagnosed in the dog. A retrospective study in 2000 by Takahashi, et. al4 examined 10
cases of visceral mast cell tumor as defined by the presence of histologically confirmed
MCT (by biopsies obtained through exploratory laparotomy or at necropsy, cytologic
examination of blood smears, or fine needle aspirates of the mass) without a history of a
cutaneous MCT. All patients received prednisolone intravenously (IV) or by mouth (PO)
at a dose of 1-2 mg/kg. Three dogs died immediately after exploratory laparotomy.
Chemotherapy was initiated in two dogs with vincristine sulfate (0.5 mg/m2, IV) and/or
cyclophosphamide (50 mg/m2, 3 times/wk, PO). Though medical intervention initially
10
improved the severity of clinical signs in the other seven dogs, the signs then worsened
gradually until death. Median survival time from diagnosis was 16 days with a range
extending from 2 to 48 days. Immediate causes of death in the non-surgical group
included pulmonary edema and perforation of the gastrointestinal tract. The authors
suggest several reasons for the poor prognosis with canine visceral MCT, including a
potentially more aggressive biological behavior and decreased drug sensitivity compared
to cutaneous MCT, lack of specific clinical signs early in the disease leading to a delay in
diagnosis, rapid progression of clinical signs, and difficulty in diagnosis due to the rarity
of visceral MCT and less accessible location of the primary tumor for diagnostic
sampling.
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References
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Sonography for Trauma, Triage, and Monitoring in Small Animals." Journal of
Veterinary Emergency and Critical Care 21.2 (2011): 104-22.
2. Krick, E. L., A. P. Billings, F. S. Shofer, S. Watanabe, and K. U. Sorenmo.
"Cytological Lymph Node Evaluation in Dogs with Mast Cell Tumours:
Association with Grade and Survival." Veterinary and Comparative Oncology 7.2
(2009): 130-38.
3. Urb, Mirjam, and Donald C. Sheppard. "The Role of Mast Cells in the Defence
against Pathogens." Ed. Joseph Heitman. PLoS Pathogens 8.4 (2012):
E1002619.
4. Takahashi, Tomoko, Tsuyoshi Kadosawa, Masayuki Nagase, Satoru Matsunaga,
Manabu Mochizuki, Ryohei Nishimura, and Nobuo Sasaki. "Visceral Mast Cell
Tumors in Dogs: 10 Cases (1982-1997)." Journal of the American Veterinary
Medical Association 216.2 (2000): 222-26.
5. North, Susan M., and Tania A. Banks. "Mast Cell Tumours." Small Animal Oncology:
An Introduction. Edinburgh: Saunders/Elsevier, 2009. 183-96.
6. Book, Alison P., Janean Fidel, Tamara Wills, Jeffrey Bryan, Rance Sellon, and John
Mattoon. "Correlation Of Ultrasound Findings, Liver And Spleen Cytology, And
Prognosis In The Clinical Staging Of High Metastatic Risk Canine Mast Cell
Tumors." Veterinary Radiology & Ultrasound 52.5 (2011): 548-54.
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