DOI: 10.1111/vcp.

12596

CASE REPORT

Mast cell and plasma cell collision tumor in the spleen of a

dog

Valarie A. Pallatto1 | Molly A. Bechtold2

1
ANTECH Diagnostics, Cary, NC, USA
2
Mid-Atlantic Animal specialty Hospital
Abstract
(MASH), Huntington, MD, USA A 9-year-old spayed female English Mastiff was referred for outpatient ultrasound
due to a 3-week history of weight loss, vomiting, and decreased appetite. Abdomi-
Correspondence
V.A. Pallatto, ANTECH Diagnostics, Cary, nal ultrasound showed multiple splenic masses of varying sizes and serum chemistry
NC, USA.
panel showed hyperglobulinemia. Cytologic examination of fine-needle aspirates of
Email: valarie.pallatto@antechmail.com
the splenic masses indicated a mast cell and plasma cell collision tumor. Results of
serum and urine protein electrophoresis and immunofixation indicated the plasma
cell neoplasia was producing IgA immunoglobulins.

KEYWORDS
Collision tumor, mast cell, plasma cell, spleen

1 | CASE PRESENTATION
A 9-year-old spayed female English Mastiff was referred to the Mid-
Atlantic Animal Specialty Hospital (MASH) for an outpatient ultra-
sound due to a 3-week history of weight loss, vomiting, and
decreased appetite. Physical exam revealed splenomegaly and a
recessed vulva; otherwise, the remainder of the exam was unremark-
able.
A CBC revealed mild anemia (Hct-35%; RI: 36%-60%, Hgb-11.7;
RI: 12.1-20.3 g/dL) and mild thrombocytopenia (145 9 103/lL; RI:
170-400 9 10 /lL) as measured by automated platelet count with
3
platelet clumps detected. All other CBC parameters were within ref-
erence limits. Biochemical abnormalities included hyperproteinemia
(9.7 g/dL; RI: 5.0-7.4 g/dL) with hyperglobulinemia (7.2 g/dL; RI:
1.6-3.6 g/dL) and hypoalbuminemia (2.5 g/dL; RI: 2.7-4.4 g/dL). Uri-
nalysis on a voided sample showed a specific gravity of 1.012 (RI:
1.015-1.050), proteinuria (3+; RI: Negative), and blood (trace; RI:
Negative). The urine sediment exam was inactive. The urine protein/
creatinine ratio was 8.7 (RI: ≤0.5) and the urine microalbumin was
>30 mg/dL (RI: <2.5 mg/dL). The IDEXX SNAP 4Dx Plus Test
(IDEXX, Westbrook, ME, USA) for antigen to Dirofilaria immitis and
antibody to Borrelia burgdorferi, Anaplasma phagocytophilum, Ana-
plasma platys, Ehrlichia ewingii, and Ehrlichia canis were all negative.
A FastPanel PCR Canine Tick-borne disease profile performed at
ANTECH Diagnostics (ANTECH Diagnostics, New York, NY, USA)
was negative (Anaplasma phagocytophilum, A platys, Babesia canis,
B gibsoni, Babesia sp. (Coco), Babesia conradae, Bartonella henselae,
B vinsonii, Ehrlichia canis, E chaffeensis, E ewingii, Mycoplasma haemo-
canis, M haematoparvum, Neorickettsia risticii, Rickettsia rickettsii).
Right and left lateral and ventral-dorsal projections of thoracic
radiographs showed no abnormalities and visible skeletal structures
were normal with no lytic bone lesions observed in light of splenic
cytology results.
Multiple splenic masses of varying sizes with mottled echotex-
ture were observed on abdominal ultrasound. The remainder of the
abdominal ultrasound was unremarkable. Ultrasound-guided fine-
needle aspiration of multiple splenic masses was performed, and 1-2
smears were prepared from each site sampled.
Seven smears were stained with a 2-part aqueous Romanowsky
stain (Wescor, Logan, UT, USA) and examined. Smears were of high
cellularity and showed primarily 2 populations of cells occurring in
dense homogeneous sheets and intermingled among one another
(Figures 1 and 2). One population consisted of pleomorphic mast
cells displaying marked anisocytosis, moderate anisokaryosis, round
basophilic nuclei, occasional binucleation, multinucleation, and mod-
erate to abundant cytoplasm containing few to many metachromatic
granules. Some of the mast cells were poorly stained or hypogranu-
lated. Occasional mitotic figures were observed. The second popula-
tion of cells consisted of sheets of plasma cells displaying mild
anisocytosis, round eccentric basophilic nuclei, clumped chromatin,
and abundant blue cytoplasm. Some of the plasma cells contained
discrete round, spherical hyaline bodies (Russell bodies).1 A few

Vet Clin Pathol. 2018;47:303–306. wileyonlinelibrary.com/journal/vcp © 2018 American Society for | 303
Veterinary Clinical Pathology
304 | PALLATTO AND BECHTOLD

plasma cells exhibited flame cell morphology with homogeneous

eosinophilic staining at the cytoplasmic rim. Four of the smears were
predominated by large sheets of plasma cells with presence of fewer
mast cells intermingled individually and in small sheets. Three of the
smears were predominated by large sheets of mast cells with fewer
plasma cells intermingled in small sheets. Few macrophages and rare
nucleated red cells were also present.
Buffy coat evaluation of peripheral blood revealed low numbers
of mast cells and plasma cells (0.4% mast cells and 0.2% plasma
cells/1000 leukocytes). The mast cells and plasma cells were well dif-
ferentiated.
Serum protein electrophoresis revealed a tall monoclonal spike in F I G U R E 2 Photomicrograph of a fine-needle aspirate from the
the gamma region accounting for approximately 54% of the total spleen of the dog with a collision tumor. One sheet of plasma cells
protein (4.9 g/dL; RI: 0.5-1.3 g/dL), and the albumin fraction was (upper right corner) is seen with poorly staining/hypogranulated
decreased (2.4 g/dL; RI: 2.7-4.4 g/dL) (Figure 3). Urine protein elec- mast cells. Two-part aqueous Romanowsky stain, 950 objective
trophoresis revealed high total urine protein (1364.7 mg/dL; RI: 10-
50 mg/dL) and a monoclonal spike in the gamma region accounting
for approximately 40% of the total protein (40.4 g/dL; RI: 0.5-1.3 g/
dL) supporting the presence of Bence Jones proteins (Figure 4).
The patient was treated orally with famotidine (20 mg q
12 hour), diphenhydramine (100 mg q 12 hour), and prednisone
(20 mg q 12 hour for 14 days and then 20 mg q 24 h), and approxi-
mately 1 month later returned for serum and urine immunofixation
testing. Serum protein was measured prior to immunofixation and
was still mildly elevated (4.0 g/dL; RI: 1.6-3.6 g/dL). Immunofixation
electrophoresis results of both serum and urine revealed a restricted
band in the IgA lane supporting an IgA monoclonal gammopathy
(test performed at Colorado State Veterinary Diagnostic Laboratory).
Immunofixation of urine also showed an additional band that was
closer to the albumin band.
Based on splenic cytology (numerous sheets of both atypical
mast cells and mature plasma cells juxtaposed and occasionally inter-
mingled with one another), serum and urine IgA monoclonal gam-
mopathy, and absence of evidence for a vector-borne disease based
on serology and PCR testing, a presumptive diagnosis of mast cell
and plasma cell collision tumor in the spleen was made.

F I G U R E 3 Serum protein electrophoresis showing a monoclonal

gammopathy in the gamma region and a decreased albumin
concentration in the dog with a collision tumor

The owner declined oncology referral and additional diagnostic

testing (ie, histologic biopsy of the spleen, bone marrow exam) and
elected palliative medical therapy.

F I G U R E 1 Photomicrograph of a fine-needle aspirate from the
spleen of the dog with a collision tumor. Hypogranulated/poorly
staining and multinucleated mast cells can be seen. Two-part
aqueous Romanowsky stain, 950 objective
2 | DISCUSSION
The definition of a collision tumor varies depending on the refer-
ence/article. In the majority of articles reviewed, a collision tumor is
defined as the coexistence of 2 or more completely distinct cell
PALLATTO AND BECHTOLD
F I G U R E 4 Urine protein electrophoresis showing a monoclonal
gammopathy in the gamma region in the dog with a collision tumor
types. independent neoplasms adjacent to each other at the same
anatomic site.2-5 The coexistence often results in intermingling of
cellular growth which is described as “collision”.6,7
In other articles, the definition of a collision tumor is described as
2 ‘histologically’ distinct tumor types occurring at the same anatomic
site; morphologically the tumors exhibit a “side-by-side” or “one upon
another” pattern implying the diagnosis of collision tumor requires
histologic evaluation.8,9 Although some definitions imply a diagnosis
of collision tumor requires histopathology, this case provides com-
pelling support that in some instances a collision tumor can be diag-
nosed cytologically. The cytology smears collected from each splenic
mass showed an intimate association, and intermingling of neoplastic
mast cells and plasma cells supporting that 2 distinct neoplasms coex-
isted in the same anatomic location; this meets the definition of colli-
sion tumor described in the majority of articles reviewed.2-5
A collision tumor should be differentiated from a composite/
complex or mixed tumor, which is a tumor arising from one cell type
or clone that differentiates into 2 or more distinct cell lineages (eg,
canine mammary carcinoma-complex type, canine mammary carci-
noma-mixed type).2,5,7,8,10 This is important since this may have an
impact on patient management/treatment.
In this case, the 2 neoplasms arose from 2 distinctly different cell
lineages further fulfilling a requirement of a collision tumor. Mast
cells are myeloid-derived cells that leave the bone marrow as
11
progenitors and mature in tissues. Plasma cells differentiate
| 305
from na€ıve B-cell subsets in bone marrow, spleen, lymph node, and
gut-associated lymphoid tissue.12 In some instances, cytology may
be Collision tumors can also be difficult to diagnose as, for example,
when 2 types of carcinomas in the same anatomic location are indis-
tinguishable from one another cytologically.
The frequency of collision tumors in dogs is unknown. Using
multiple search combinations in 2 databases (PubMed and CAB
[Center for Agriculture and Biosciences International] abstracts) a
total of 5 case reports were retrieved. Three case reports of collision
tumors involved the skin (a hepatoid gland adenoma and a malignant
melanoma; a hemangiosarcoma and a hepatoid cell/circumanal gland
carcinoma; a malignant melanoma and an anaplastic sarcoma), one
was associated with the testicle (a seminoma and a Sertoli cell
tumor), and one was associated with the oral cavity of a dog (a squa-
mous cell carcinoma and a malignant melanoma) were found.3,13-16
Case reports of collision tumors were found in a hamster, rabbit, and
goat.2,4,7
In human medicine, case reports of collision tumors are numer-
ous and described in many anatomic locations (eg, gastrointestinal
tract, liver, thyroid gland, adrenal gland, brain, skin, ovary, prostate,
and lymph node). Interestingly, no case reports were found after a
search for splenic collision tumors in people.
Mast cell neoplasia was diagnosed in this patient based on the
high numbers of mast cells with an abnormal morphologic appear-
ance. While mast cell tumors are the most common cutaneous tumor
in dogs, visceral and specifically splenic mast cell neoplasia is rare.17
In one study, visceral mast cell tumors accounted for 8% of all mast
cell tumors (10/118 mast cell tumors over a 15-year period) and
only 1 reportedly originated in the spleen (0.8%).18
Plasma cell neoplasia was diagnosed based on the large number
of mature plasma cells occurring in dense sheets within the spleen
in conjunction with a monoclonal spike in the gamma region on
both serum and urine protein electrophoresis, and an IgA gammopa-
thy on protein and urine immunofixation with the absence of evi-
dence for a vector-borne disease. The protein and urine
electrophoresis results also supported B-cell lymphoma, but this was
not supported by the cytology results. Bone marrow exam would
have been ideal to differentiate extramedullary plasma cell neoplasia
arising in the spleen and multiple myeloma. The most common site
for extramedullary plasma cell neoplasia is the skin with the spleen
representing <1% of all extramedullary plasma cell neoplasms.17 To
diagnose multiple myeloma in animals, at least 2 of 4 criteria should
be met: (1) bone marrow plasmacytosis with >20% plasma cells, (2)
monoclonal gammopathy on serum protein electrophoresis, (3) oste-
olysis, and (4) light chain (Bence Jones) proteinuria.19 In this case,
criteria 2 and 4 were met, supporting a presumed diagnosis of mul-
tiple myeloma. It is unclear whether the well-differentiated mast
cells and plasma cells in the peripheral blood represented neoplastic
or reactive cell populations. In dogs, circulating mast cells are usually
associated with inflammatory disease, regenerative anemia, neoplasia
other than mast cell neoplasia, trauma, and non-mast cell tumor-
related diseases.20 Thus, circulating mast cells are not diagnostic for
mast cell neoplasia in dogs. Presumably, the circulating plasma cells
306 | PALLATTO
were a component of the neoplastic population. PCR analysis for
antigen receptor gene rearrangements (PARR) may have been help-
ful to further characterize the rare circulating plasma cells provided
sufficient DNA was present.
Additional clinicopathologic abnormalities, in this case, included
mild normocytic, normochromic anemia, which was attributed to ane-
mia of chronic disease. A bone marrow exam would have been useful
to further assess the state of erythropoiesis in light of the probable
multiple myeloma. Mild thrombocytopenia was interpreted as pseu-
dothrombocytopenia since platelet clumps were present in the sam-
ple. Urine proteinuria was primarily attributed to Bence Jones
proteins. However, urine microalbumin was increased, which may
indicate concomitant renal disease or renal insufficiency as a result of
damage secondary to immunoglobulin light chains.21 The urine speci-
fic gravity (USG) was in the isosthenuric range; however, the patient
was not azotemic, and a USG in the isosthenuric range can occasion-
ally occur in animals without kidney disease. Serial USG monitoring
would be indicated to further evaluate the renal concentrating ability
since concomitant kidney disease is possible based on increased urine
microalbumin. The albumin fraction of the serum protein elec-
trophoresis was decreased, most likely due to decreased production
by the liver as a compensatory response to the hyperglobulinemia.
Immunofixation of urine showed a restricted band in the IgA lane
supporting an IgA monoclonal gammopathy. Additionally, there was a
band located closer to the albumin band that may represent differ-
ences in antibody avidity between the whole serum and IgA antibod-
ies used in the assay. Further characterization of this additional
protein band with whole protein mass spectrometry is warranted;
however, due to cost, this was not pursued.
This case was interesting because, to the author’s knowledge, it
is the first report of a collision tumor in the spleen of a dog. Addi-
tionally, this likely represented a rare primary splenic mast cell neo-
plasm since the patient had no visible cutaneous or subcutaneous
masses based on the physical examination by 2 different veterinari-
ans, and the historical absence of previous cutaneous mast cell neo-
plasias as reviewed in medical records from January 2014 and in
conversations with the referring veterinarian. We acknowledge that
medical record review before January 2014 and a necropsy would
have been ideal to completely exclude cutaneous mast cell neoplasia
or mast cell neoplasia at other locations.
In summary, awareness of collision tumors is important for diag-
nosticians. Although collision tumors are rare in dogs, proper diagno-
sis can have critical therapeutic and prognostic implications that will
be helpful for clinician and pet owner decision-making.
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How to cite this article: Pallatto VA, Bechtold MA. Mast cell
and plasma cell collision tumor in the spleen of a dog. Vet
Clin Pathol. 2018;47:303–306. https://doi.org/10.1111/
vcp.12596