asymptomatic hyperglobulinemia

Volume 7 | Issue 7 | July 2015
Clinical Consults
What’s Your Diagnosis?
PATIENT HISTORY
SIGNALMENT: “Trooper” is a 9 year old MC
American Staffordshire Terrier owned by a
receptionist at VCA East Penn Animal
Hospital. Weight 63.7 lb/29 kg/0.94 m2.
PERTINENT PAST HISTORY: “Trooper” has
generally been a very healthy dog. He
sustained an unwitnessed traumatic injury
as a puppy which necessitated amputation
of his left pelvic limb. Over time, “Trooper”
has developed moderate degenerative joint
disease in the right coxofemoral joint and
experiences intermittent lameness. To
address his orthopedic issues, he receives
chiropractic care once every 3 months,
Adequan® injections monthly, and
Dasuquin® and omega 3 fatty acids once
daily. “Trooper” has a history of atopic
dermatitis which is generally well controlled
with occasional seasonal flare-ups.
“Trooper” is current on all recommended
vaccinations and receives monthly
heartworm and flea/tick preventatives as
directed by Dr. Payne.
CURRENT HISTORY: In November 2014
“Trooper” presented for a senior wellness
examination. His owner expressed no
concerns other than a worsening of his
allergies with a relapse of pruritus and skin
irritation at that time. “Trooper’s” owner also
reported increased drinking and urination
over the past 1 month. Otherwise “Trooper”
exhibited no evidence of systemic illness.
On physical examination “Trooper” was
noted to have a small intradermal nodule at
the left pelvic limb amputation incision site.
The owner reported the nodule had been
present for several years and had been
previously aspirated as fat. “Trooper” also
ASYMPTOMATIC
HYPERGLOBULINEMIA—
is it significant?
Donna J. Spector, DVM, DACVIM, Internal Medicine
Case materials and images contributed by Dr. Douglas Payne, VMD, VCA East Penn
Animal Hospital, Emmaus, PA
CURRENT HISTORY CONTINUED:
had evidence of moderate pruritus. His paws were erythematous and he had mild diffuse
superficial pyoderma. Blood was obtained for a minimum database including a complete blood
count, chemistry panel, T4 measurement, and Accuplex 4. A mid-stream urine sample was
submitted for urinalysis. A cefovecin (Convenia®) injection was administered to address his
pyoderma.
Moderate hyperglobulinemia (5.4 g/dL; ref. range: 1.6-3.6 g/dL) was noted and attributed to the
current exacerbation of allergic skin disease and mild pyoderma. There was 1+ proteinuria and
4-10 WBC/hpf noted on the free-catch urinalysis. Since “Trooper” had received cefovecin, a urine
culture was not performed and a follow-up cystocentesis was recommended to monitor for
resolution of possible infection and proteinuria.
Recheck urinalyses two months later (1/2015) and 4 months later (3/2015) both revealed 2+
proteinuria with inactive sediment. A urine protein:creatinine (UPC) ratio performed in 3/2015
was mildly elevated at 0.8. A urine culture was obtained on this same sample and had positive
growth of E. coli which was thought to be falsely elevating the UPC value. “Trooper” was started
on marbofloxacin (150 mg PO q day x 21 days) to address both the urinary tract infection and the
persistent pododermatitis present on physical examination. Clinical Note: Bacteria present in
the urine without active inflammatory sediment or clinical signs of urinary tract infection is
called asymptomatic bacteriuria and treatment is generally not recommended. “Trooper”
returned one month later (4/2015)—9 days after completion of his antibiotics—for follow-up
bloodwork, urinalysis and urine culture. The urinalysis revealed more dilute urine with urine
specific gravity of 1.016 and 2+ proteinuria. The urine sediment was inactive and culture was
negative. A UPC was performed to more fully evaluate the persistent proteinuria and was elevated
at 1.6.
Dr. Payne contacted Antech for an internal medicine consultation to discuss “Trooper’s” persistent
proteinuria and the remainder of his bloodwork. See Table 1 for “Trooper’s” laboratory
abnormalities and trends.
TABLE 1.
“TROOPER’S” LABORATORY ABNORMALITIES AND TRENDS
6/2014
11/2014
WBC (ref. range: 4,000-15,500/uL
5,700
7,100
1/2015
3/2015
4/2015
3,600
Neutrophils (ref. range: 2,060-10,600/uL)
3,306
4,189
1,908
Lymphocytes (ref. range: 690-4,500/uL)
1,995
2,272
1,296
RBC (ref. range: 4.8-9.3 million/uL)
6.3
6.3
5.8
Total protein (ref. range: 5.0-7.4 g/dL)
7.0
8.5
10.3
Albumin (ref. range: 2.7-4.4 g/dL)
3.4
3.1
1.9
Globulin (ref. range: 1.6-3.6 g/dL)
3.6
5.4
8.4
Calcium (ref. range: 8.9-11.4 mg/dL)
Urine specific gravity
Proteinuria/UPC
N/A
10.7
1.023
1.049
negative
Of concern was “Trooper’s” markedly elevated
total protein (10.3 g/dL) characterized by a
significant hypoalbuminemia (1.9 g/dL) and
hyperglobulinemia (8.4 g/dL). A mild
hypercalcemia (11.9 mg/dL) was noted when
corrected for hypoalbuminemia. Clinical Note:
An ionized calcium would have been required
to determine if a pathologic ionized
hypercalcemia was present. Mild leukopenia
characterized as mild neutropenia was present
and was notably different than historical white
blood cell values in “Trooper.”
ADDITIONAL DIAGNOSTICS AND
ASSESSMENT
Dr. Payne expressed concern about “Trooper’s”
underlying allergic skin disease and whether it
could lead to hyperglobulinemia and
progressive proteinuria. Clinical Note: Dogs
with atopy can indeed develop protein losing
10.3/11.9 corr
1.050
1+/4-10 WBC 2+/no sed
1.031
1.016
2+/0.8
2+/1.6
nephropathies (i.e. glomerulonephritis)
associated with immune complex deposition,
subsequent complement activation and
significant inflammatory reaction within the
glomerular capillaries. While Dr. Payne had
very valid concerns, after discussion of
“Trooper’s” history, it was determined his
allergic skin disease did not seem severe
enough to cause a hyperglobulinemia of this
magnitude. A serum protein electrophoresis
(SPE) was recommended to more fully
characterize “Trooper’s” hyperglobulinemia as
either a monoclonal or polyclonal gammopathy
to shed more light on the potential etiology.
Polyclonal gammopathies are most commonly
identified in dogs affected by chronic
inflammatory, allergic or infectious diseases.
Monoclonal gammopathies are most often
associated with neoplasia. In a 2011
retrospective study, an underlying neoplastic
disorder was identified in all cases in which a
TABLE 2.
“TROOPER’S” SERUM PROTEIN ELECTROPHORESIS RESULTS
Total Protein (ref. range: 5.0-7.4 g/dL)
10.7
Albumin (ref. range: 2.7-4.4 g/dL)
3.5
Globulin (ref. range: 1.6-3.6 g/dL)
7.2
• Alpha-1 (ref. range: 0.2-0.5 g/dL)
0.3
• Alpha-2 (ref. range: 0.3-1.1 g/dL)
0.7
• Beta (ref. range: 0.7-1.3 g/dL)
0.6
• Gamma (ref. range: 0.5-1.3 g/dL)
5.6—markedly elevated!
INTERPRETATION: The gamma globulin fraction is elevated and is characterized by a narrow
monoclonal spike, resulting from a single clone of secretory immunoglobulin cells
producing one type of protein. The most common potential causes include lymphoma,
multiple myeloma, macroglobulinemia and canine ehrlichiosis.
monoclonal gammopathy was present. While it
is possible for chronic ehrlichiosis or
bartonellosis to present with monoclonal
gammopathy, it generally arises from a broad
polyclonal band. See Table 2 for “Trooper’s”
SPE results.
Due to the presence of a monoclonal
gammopathy, a search for underlying neoplasia
was indicated and three-view THORACIC
RADIOGRAPHS and two-view ABDOMINAL
RADIOGRAPHS were advised. Radiographs
of the EXTREMITIES were also recommended
in order to identify potential osteolytic lesions
which can be present with multiple myeloma.
The thoracic radiographs—including extrathoracic structures—were unremarkable. The
abdominal radiographs revealed moderate
splenomegaly (see Figure 1). The left pelvic
limb was noted to have been amputated
mid-femur and remodeling of the right femoral
head, femoral neck and acetabulum were
noted. No abnormalities were noted on
radiographs of the extremities.
A urine protein electrophoresis (UPE) was
performed and confirmed the presence of
albuminuria but there was no monoclonal
spike which would infer the presence of Bence
Jones proteinuria.
As plasma cell neoplasia will sometimes
present as a cutaneous mass(es), a thorough
examination with fine needle aspiration of any
lesion was recommended. Four cutaneous
masses were identified on examination.
Although most had been present for over 1
year, all masses were aspirated. One mass
was a keratin-filled cyst and two others were
aspirated as lipomas. The aspirate of the
cutaneous mass located over the previous
amputation incision was consistent with a mast
cell tumor.
FIGURE 1.
To more completely define the splenomegaly and as further identification of underlying neoplasia,
“Trooper” was referred for an ABDOMINAL ULTRASOUND and SPLENIC FINE NEEDLE
ASPIRATION. The ultrasound revealed mild iliac lymphadenopathy on the left side (note: same
side as the cutaneous mast cell tumor) and generalized splenomegaly. The remainder of the
examination was unremarkable.
DIAGNOSIS
Multiple myeloma—
asymptomatic
The results of the splenic fine needle aspiration are found in Table 3.
Cutaneous mast cell tumor
TABLE 3.
Protein-losing nephropathy
“TROOPER’S” SPLENIC ASPIRATION CYTOLOGY
Description: The slides are moderately cellular and consist of few aggregates of splenic stroma
and a nucleated cell population predominated by hematopoietic precursors of various lineage and
stages of maturation. Also present are an increased number of plasma cells. These plasma cells
are well differentiated but do exhibit a mild degree of anisokaryosis and anisocytosis with rare
binucleation. No mast cells are identified.
Cytologic interpretation: Given the mild morphologic changes to these plasma cells in addition
to the laboratory findings of monoclonal gammopathy, multiple myeloma seems very likely.
Recommend bone marrow aspiration.
Clinical Note: It is of critical importance to provide an adequate patient
history and associated laboratory or imaging abnormalities to your pathologist
in order to glean as much pertinent information as possible from cytologic
samples.
A bone marrow aspiration was performed and results can be found in Table 4.
TABLE 4.
“TROOPER’S” BONE MARROW CYTOLOGY
Description: Bone marrow smears are highly cellular with large amounts of blood present. There
were moderate numbers of mature megakaryocytes and moderate amounts of hemosiderin.
Nucleated cells were predominantly a mixture of atypical plasma cells and hematopoietic
precursors. Plasma cells were round to oval with moderate to large amounts of moderate to deep
blue cytoplasm with variably sized central cytoplasmic clear zones. This population had moderate
to marked anisocytosis and moderate anisokaryosis. Nuclei were centrally to eccentrically located
and were round to oval with clumped, irregular clumped or stippled chromatin and rarely 1-2
small, round, variably prominent nucleoli. Few binucleate plasma cells were present. The myeloid
to erythroid ratio appeared to be 1-2:1 and both lineages appeared to have orderly and complete
maturation. No inflammation or infectious agents were detected.
Cytologic Interpretation: Plasma cell neoplasia. Although there were no overt abnormalities
within the hematopoietic lineages, the hematopoietic populations could not be interpreted
without a recent complete blood count.
Clinical Note: It is imperative to provide a CBC with a bone marrow evaluation
in order to obtain the most meaningful information.
Based on the presence of monoclonal gammopathy together with splenic and bone marrow
infiltration with plasma cells, “Trooper” was diagnosed with multiple myeloma.
Atopy
DISCUSSION
A detailed discussion of multiple myeloma is
beyond the scope of this article and the
reader is referred to the listed references.
Multiple Myeloma
Multiple myeloma is a neoplastic proliferation
of plasma cells and their precursors within the
bone marrow. The etiology of multiple
myeloma is unknown but chronic antigenic
stimulation is suspected. As neoplastic plasma
cells are released into peripheral circulation
they can infiltrate any organ; but have
predilection for lymph nodes, spleen, kidney,
liver and the skeleton. Plasmacytomas
associated with multiple myeloma can occur in
other organs and a 2012 report described a
highly malignant anaplastic cutaneous version.
Malignant plasma cells may produce an
excessive amount of a single type of
immunoglobulin such as IgA, IgG or IgM.
Alternatively, these cells may produce an
excessive amount of a portion of the
immunoglobulin such as the light chain (called
Bence Jones protein) or the heavy chain.
Regardless of the type of immunoglobulin
produced, affected dogs will usually exhibit a
monoclonal (or sometimes biclonal)
gammopathy.
Clinical Signs and Physical Examination
Findings
The clinical signs of dogs affected by multiple
myeloma are often vague and non-specific.
Due to potential multi-organ involvement,
affected dogs may present with a wide variety
of pathologic abnormalities and clinical
syndromes. Polyuria, polydipsia, lethargy,
inappetence and bone pain are common.
Several specific syndromes have been
described in dogs affected by multiple
myeloma and are outlined in Table 5.
TABLE 5.
CLINICAL SYNDROMES ASSOCIATED WITH MULTIPLE MYELOMA IN DOGS
Immunodeficiency
Dogs affected by multiple myeloma produce excessive amounts of a
single immunoglobulin which inhibits production of normal levels of all
other immunoglobulin. Leukopenia and neutropenia are common
findings. Together these features predispose affected dogs to infection.
Hyperviscosity
syndrome
Approximately 20% of dogs affected by multiple myeloma exhibit
clinical signs resulting from high concentrations of plasma proteins.
Clinical signs are caused by reduced blood flow through small vessels,
high plasma volume (i.e., hypervolemia), and/or associated
coagulopathies. Neurologic signs (e.g., ataxia, mentation alterations,
seizures, etc.), ocular abnormalities (e.g., decreased vision, blindness,
hyphema, etc.) and/or cardiopulmonary failure have all been described
as a result of hyperviscosity.
Cardiac failure
The etiology of heart failure in dogs affected by multiple myeloma is
likely multifactorial. Anemia, myocardial hypoxia and myocardial
infiltration by neoplastic plasma cells may all play a role. Additionally,
hyperviscosity associated with multiple myeloma leads to hypervolemia
and necessitates increased perfusion pressure to maintain vascular
flow. These features may result in heart failure due to increased
cardiac workload.
Cytopenias
Most dogs with multiple myeloma (>60%) exhibit some form of
cytopenia. The most common hematologic abnormality is normocytic,
normochromic, non-regenerative anemia. Thrombocytopenia and
leukopenia are also identified in approximately 30% of dogs.
Cytopenias may result from myelophthisis, chronic disease, chronic
blood loss associated with concurrent coagulopathies, immune
mediated hemolysis and even RBC destruction related to hyperviscosity.
Bleeding tendencies
The etiology of bleeding tendencies is multifactorial in dogs affected by
multiple myeloma. Increased immunoglobulin levels may result in
thrombocytopathy due to interference with platelet activity, aggregation
and normal clotting. Hyperviscosity and overt thrombocytopenia may
also result in coagulation abnormalities resulting in clinical bleeding.
Epistaxis, gingival bleeding, hematuria, and hyphema are common
findings.
Hypercalcemia
Hypercalcemia is found in approximately 15-20% of dogs affected by
multiple myeloma. It results from the production of osteoclastactivating factor or other cytokines produced by neoplastic plasma
cells. Excessive osteoclast activity in the skeleton may lead to bony
lysis and pathologic fractures. If pathologic fractures affect vertebral
bodies, spinal cord compression with resultant paralysis can be seen.
Renal disease
Renal disease is diagnosed in 30-50% of dogs affected by multiple
myeloma and may be attributed to hypercalcemia, infiltration of the
kidneys by neoplastic cells, decreased renal perfusion due to
hyperviscosity, ascending pyelonephritis or related to renal tubular
toxicity from Bence Jones proteins.
Diagnosis
The diagnosis of multiple myeloma involves
demonstration of 2 of the following 4 criteria:
1
Monoclonal gammopathy. The majority of
dogs affected by multiple myeloma will
exhibit a monoclonal gammopathy on serum
protein electrophoresis (SPE). The monoclonal
spike is expected to be present in the gamma
protein region as it results from production of a
single immunoglobulin by a clone of neoplastic
plasma cells. Occasionally, a biclonal spike will
be identified and this must be differentiated from
a polyclonal gammopathy. Other causes of a
monoclonal gammopathy include lymphoma,
chronic
lymphocytic
leukemia,
acute
lymphoblastic leukemia and less commonly,
chronic ehrlichiosis. Monoclonal gammopathies
have also been reported in association with
Bartonella species infections in dogs.
2
Osteolytic lesions on radiographs OR
other organ infiltration by plasma cells.
Multiple myeloma associated bone lesions
include lytic or “punched-out” areas,
generalized osteopenia and/or pathologic
fractures. 25-50% of affected dogs will exhibit
some radiographic evidence of multiple
myeloma. Clinical Note: Special attention
should be given to the vertebral column and
ribs as osteolytic lesions are frequently noted
in these areas. Many times, neoplastic plasma
cells are more readily demonstrated in other
organs (e.g., liver, spleen, kidneys, etc.)
compared to the bone. Demonstration of
visceral organ infiltration is supportive of a
diagnosis of multiple myeloma.
3
Bence Jones proteinuria OR monoclonal
gammopathy on urine protein electrophoresis
(UPE). Bence Jones proteinuria can be
demonstrated in 25-40% of dogs affected by
multiple myeloma and are usually associated with
a serum monoclonal gammopathy. Urine normally
contains no intact immunoglobulin to obscure
Bence Jones proteins and these light chains
readily enter the glomerular ultrafiltrate and
become concentrated. Clinical Note: Bence
Jones proteins DO NOT register on normal urine
dipsticks because dipsticks are designed to
detect albumin. There is a Bence Jones protein
assay which relies on heat precipitation and can
be used, however, the UPE has largely replaced
this assay due to its higher sensitivity.
The presence of a monoclonal gammopathy on
UPE infers the presence of Bence Jones proteins.
A positive test is not absolute proof of multiple
myeloma as chronic ehrlichiosis may also cause a
positive result. Clinical Note: It is clear that
chronic Ehrlichiosis is a main differential for the
presence of monoclonal serum and urine
gammopathies as well as the clinical signs
commonly exhibited by dogs affected by multiple
myeloma. If a dog has an appropriate tick
exposure history, a thorough Ehrlichia evaluation
is imperative before a diagnosis of multiple
myeloma can be made.
4
Plasma cell infiltration of the bone marrow.
Greater than 20% infiltration of the bone
marrow by plasma cells supports a diagnosis
of multiple myeloma. Other causes of chronic
antigenic stimulation such as atopy, tick-borne
disease, leishmania, and heartworm disease may
also have similar bone marrow results, therefore
adequate history taking and testing are necessary.
Treatment and Prognosis
Initial treatment of multiple myeloma must not
only include definitive chemotherapy, but must
also address any associated organ dysfunction.
For example, if renal disease and/or
hypercalcemia are present, fluid diuresis may
be necessary. If a patient has pain from
associated bone lesions, pamidronate may be
considered for pain control until the lesions
improve with chemotherapy (see Table 6). If
severe complications from hyperviscosity exist,
plasmapheresis can be considered to alleviate
the signs quite rapidly but it has limited
availability.
TABLE 7.
MELPHALAN CHEMOTHERAPY PROTOCOLS FOR MULTIPLE MYELOMA
Option A
0.1 mg/kg PO q day x 10
days and
0.05 mg/kg PO q 48 hours
thereafter
Option B
0.25 mg/kg PO q day x 4
days and
2-4 mg/day PO q day
thereafter
uncomplicated multiple myeloma. Clinical
Note: Cyclophosphamide is sometimes used
at the time of initial diagnosis in complicated
cases of multiple myeloma as it is a faster
alkylating agent and may be superior for
alleviating hypercalcemia, bone pain or other
more severe systemic clinical signs. Several
melphalan protocols have been described (see
Table 7) and can be tailored to the needs of
each individual patient. Clinical Note: It is
always advised to consult with an oncologist
in your area when managing multiple
myeloma or other cancer patients to discuss
their preferred protocols. This allows your
local oncologist to best help you manage your
patients and to support them if there are
unexpected outcomes or complications.
Melphalan is highly effective at decreasing
myeloma cells and serum immunoglobulin
levels as well as relieving bone pain. Typically,
clinical improvement is seen within 2 to 4
weeks of starting chemotherapy and laboratory
improvement (decreased serum
immunoglobulins and/or Bence Jones
proteinuria) often occurs within 3 to 8 weeks.
Radiographic improvement of bony lesions can
take months and sometimes resolution is only
Option C
7 mg/m PO q 24 hours x 5 days once every 21 days
Clinical Note: This is considered pulse
therapy and is used in dogs where
myelosuppression limits more
conventional continuous low-dosing
therapy
2
partial. A good response to treatment is
defined as a reduction in measured values to
at least 50% of pre-treatment values.
Chemotherapy can be expected to extend
both the quality and length of most dogs’
lives. The short term prognosis for multiple
myeloma is quite good with a reported median
survival time of 540 days. In a study of 60
dogs with multiple myeloma, 43% achieved
complete remission (with normalized serum
immunoglobulins), 49% achieved partial
remission (immunoglobulins less than 50% of
pre-treatment values) and only 8% did not
respond to chemotherapy. Clinical Note:
Bence Jones proteinuria, hypercalcemia and
extensive bony lysis are known negative
prognostic indicators in dogs. An anaplastic
variant of myeloma with cutaneous involvement
has been described and appears to have a much
more malignant biologic course.
In dogs affected by severe hypercalcemia and/or pain associated with bony lysis, pamidronate can help
alleviate clinical signs until chemotherapy becomes effective.
Chemotherapy treatment with melphalan is
continued long term—usually until a dog
experiences relapse of disease. Several rescue
chemotherapy protocols have been described
for progressive disease and can be attempted
at that time. Even if a dog responds to initial
and rescue chemotherapy, complete
elimination of the neoplastic cells is rarely
achieved, therefore the long term prognosis for
cure is poor, and recurrence is expected.
Mechanism of action: Pamidronate is a bisphosphonate compound that lowers serum calcium
concentration through inhibition of osteoclastic bone resorption. A single dose often decreases serum
calcium concentrations to normal within 48 hours and will last for up to one week.
“TROOPER’S” TREATMENT AND
UPDATE
Chemotherapy with the slow alkylating agent,
melphalan, together with prednisone is
considered the treatment of choice for
TABLE 6
PAMIDRONATE IN DOGS WITH MULTIPLE MYELOMA
Dosage: 1.5-2.0 mg/kg IV infused over 2 hours in 250 mls of saline q 28 days.
Monitoring: Perform renal panel and urinalysis before each administration as renal tubular injury may
occur.
Due to “Trooper’s” initial level of
myelosuppression related to multiple myeloma,
melphalan chemotherapy was started using a
pulse protocol at a dosage of 7 mg PO q day
for 5 consecutive days administered every 3
weeks. Prednisone was not started as
“Trooper” was asymptomatic for illness.
A CBC was repeated immediately after 5 days
of melphalan chemotherapy and no further
indication of bone marrow suppression was
identified. Another CBC and chemistry panel
were performed on 6/2/2015 which was 3
weeks after the first melphalan treatment and
right before the next cycle.
After just one single melphalan treatment,
“Trooper’s” globulin had decreased from 8.4 to
6.2 g/dL. The hypercalcemia had improved
with the total calcium within the normal
reference range at 11.4 mg/dL. “Trooper’s”
neutrophil count had increased into the low
normal range at 2,300/uL.
“Trooper” remains completely asymptomatic
and has experienced no adverse effects of
chemotherapy. The current plan is to resect
his cutaneous mast cell tumor (and monitor
the left iliac lymphadenopathy) as the MCT has
the potential to develop into a higher grade
malignancy over time.
Dr. Payne, Trooper and his owner
REFERENCES
Vail, David M. Hematopoietic Tumors, Chapter 324. The Textbook of Veterinary Internal Medicine, Ettinger and Feldman editors, 7th edition, Elsevier,
St. Louis, 2014.
Fukumoto, Shinya, K Hanazono, N Kawasaki, et al. Anaplastic atypical myeloma with extensive cutaneous involvement in a dog. J Vet Med Sci. January
2012; 74(1): 111-5.
Tappin, SW, SS Taylor, S Tasker et al. Serum protein electrophoresis in 147 dogs. Vet Rec. April 2011; 168(17): 456.
CLINICAL ASSESSMENT
1
Hyperglobulinemia detected in an older
asymptomatic dog always warrants further
evaluation with serum protein electrophoresis.
True or False?
2
Which of the following criteria is NOT
consistent with multiple myeloma in the dog?
a.Biclonal gammopathy
b.Punched out vertebral body lesion
c.Plasma cell infiltration in liver
d.Polyclonal gammopathy
3
The absence of Bence Jones proteinuria
or radiographic bony lesions rules out a
diagnosis of multiple myeloma in the dog.
True or False?
4
Monoclonal gammopathies may be associated
with all the following EXCEPT:
6
a.Lymphoma
b.Chronic lymphocytic leukemia
c.Heartworm disease
d.Ehrlichiosis
e.Bartonellosis
7
5
Which of the following is NOT a recognized
clinical syndrome associated with multiple
myeloma?
a.Hyperviscosity syndrome
b.Anemia
c.Hypoglycemia
d.Coagulopathy
e.Hypercalcemia
If a urine dipstick is negative for protein,
Bence Jones proteinuria is not present.
True or False?
Most dogs affected by multiple myeloma have
cytopenias and anemia is the most common.
True or False?
8
Multiple myeloma is the only disorder which
will result in plasma cell infiltration in the bone
marrow. True or False?
9
Cyclophosphamide is the treatment of choice
for
multiple
myeloma
in
dogs.
True or False?
10
The treatment expectation for a dog affected
by multiple myeloma is lifelong continuation
of chemotherapy. True or False?
CLINICAL ASSESSMENT ANSWERS:
1.
True. Hyperglobulinemia detected in any older asymptomatic dog warrants further evaluation with serum protein electrophoresis as multiple myeloma
often has a slow, insidious onset and many dogs—like “Trooper”—will be asymptomatic.
2.
d) Polyclonal gammopathy. The diagnosis of multiple myeloma involves demonstration of 2 out of the following 4 criteria: 1) monoclonal gammopathy
(which is sometimes a biclonal gammopathy), 2) osteolytic lesions OR organ infiltration by plasma cells, 3) Bence Jones proteinuria OR monoclonal
gammopathy on urine protein electrophoresis, and/or 4) bone marrow infiltration by plasma cells.
3.
False. Only 25-40% of dogs affected by multiple myeloma have Bence Jones proteinuria and 25-50% have radiographic bony lesions. The absence of
these findings DOES NOT rule out multiple myeloma.
4.
c) Heartworm disease. Heartworm disease would generally result in a polyclonal gammopathy.
5.
c) Hypoglycemia. While hypoglycemia is a well-recognized paraneoplastic syndrome, it is not commonly associated with multiple myeloma.
6.
False. Bence Jones proteins will not be identified on urine dipsticks for protein as these dipsticks are designed to detect albumin. Bence Jones proteins
will only be identified on a heat precipitation assay or preferably, on the more sensitive urine protein electrophoresis.
7.
True. Most dogs with multiple myeloma (>60%) exhibit some form of cytopenia. The most common hematologic abnormality is normocytic, normochromic,
non-regenerative anemia. Thrombocytopenia and leukopenia are also commonly identified. Cytopenias may result from myelophthisis, chronic disease,
chronic blood loss associated with concurrent coagulopathies, immune mediated hemolysis and even RBC destruction related to hyperviscosity.
8.
False. While >20% bone marrow infiltration is supportive of a diagnosis of multiple myeloma, other causes of chronic antigenic stimulation (such as
atopy, Ehrlichia and other tick-borne diseases, leishmania, heartworm disease, etc.) may result in some bone marrow plasma cell infiltration.
9.
False. Melphalan with prednisone is the treatment of choice in most canine multiple myeloma cases. Melphalan is highly effective at decreasing
myeloma cells and immunoglobulin levels. Cyclophosphamide is sometimes used at the time of initial diagnosis in more advanced or complicated cases,
especially if severe hypercalcemia or bone pain is present.
10. True. Chemotherapy treatment with melphalan is continued long term—until a dog experiences clinical relapse (at which time a rescue protocol is
started) or until drug-associated myelosuppression necessitates a change in therapy. Complete elimination of neoplastic cells is rarely achieved so the
long term prognosis for cure is poor. The median survival time for multiple myeloma is good at 540 days.