Plasma Cell Tumors and MM

Question 1

You perform a bone marrow aspirate as part of your work-up of a dog suspected to have multiple myeloma. Which of the following is considered the threshold for diagnosis of canine bone marrow plasmacytosis?

a. >5% plasma cells
b. >10% plasma cells
c. >20% plasma cells
d. >30% plasma cells

Answer 1

c.

Normal marrow is

Question 2

Extramedullary plasmacytomas may occur in a variety of anatomic locations, including oral mucus membranes, skin/cutaneous, colon/rectum, and spleen. Which of the following correctly lists the sites in order from most common to least common site of EMP?

a. skin/cutaneous, oral mucus membranes, colon/rectum, spleen
b. spleen, skin/cutaneous, oral mucus membranes, colon/rectum
c. oral mucus membranes, skin/cutaneous, colon/rectum, spleen
d. skin/cutaneous, spleen, oral mucus membranes, colon/rectum

Answer 2

a.

skin/cutaneous make up 86% of EMPs; oral mucus membranes 9%, colon/rectum 4%, and spleen

Question 3

Which of the following are likely potential causes of bleeding diathesis in a patient with multiple myeloma?

i. inhibition of the release of platelet factor-3
ii. adsorption of clotting proteins
iii. abnormal fibrin polymerization
iv. decreased thrombopoeitin leading to thrombocytopenia

a. i, ii, and iv
b. i, ii, iii, and iv
c. ii and iii
d. i, ii, and iii

Answer 3

d.

all but decreased TPO are proposed as possible mechanisms. Although MM can cause hypercalcemia, decreases in functional calcium levels are also a proposed mechanism of bleeding.

Question 4

Bence Jones proteinuria occurs in approximately what percentage of dogs diagnosed with Multiple myeloma?
A. 90-100%
B. 25-40%
C. 5-10%
D. 75-80%
E. 0-5%

Answer 4

b.

Question 5

What percentage of canine patients with MM are reported to be hypercalcemic?
A. 35-50%
B. 90-100%
C. 15-20%
D. 75-80%
E. 0-5%

Answer 5

c.

Question 6

What is the most clinically significant toxicity of melphalan?

A.	Hair loss
B.	Vomiting
C.	Anaphylaxis
D.	Thrombocytopenia
E.	Pancreatitis

Answer 6

d.
The vast majority of dogs on melphalan and prednisone combination therapy tolerate the regimen well. The most clinically significant toxicity of melphalan is myelosupression, in particular a delayed thrombocytopenia.

Question 7

BCR-ABL chromosomal translocation has been reported in both humans and dogs with chronic myelogenous leukemia. What two chromosomes are involved in this mutation in dogs?

i. Chromosome 5
ii. Chromosome 9
iii. Chromosome 12
iv. Chromosome 22
v. Chromosome 26

a. i, iii
b. ii, iv
c. iii, iv
d. ii, v
e. iii, v

Answer 7

B.
BCR-ABL mutations are common in humans with CML, and occur between chromosomes 9 and 22. This mutation has been reported in 3 dogs and occurs between chromosomes 9 and 26.

Question 8

A patient presents for pancytopenia. A bone marrow core is performed, revealing the following: hypercellular bone marrow elements, M:E of 1.2, blast cells accounting for 10% of all nucleated cells. What is your diagnosis?

a. M6
b. MDS-EB
c. MDS-RC
d. MDS-ER
e. M6ER

Answer 8

b.
MDS-EB is characterized by M:E>1 and blast percentages greater than 5% but less than 20%. Progression to AML may occur. MDS-RC has blast percentages

Question 9

You are treating a dog with chronic myelogenous leukemia. After inducing with hydroxyurea (20mg/kg twice daily), what hematologic parameter is used to guide your dose reduction?

a. Fine needle aspirates documenting absence of visceral disease
b. Neutrophil counts less than 15k/uL
c. Less than 30% blast cells within the bone marrow
d. Leukocyte counts less than 30k/uL
e. Leukocyte counts less than 20k/uL

Answer 9

e.

After the leukocyte count falls to 15-20k/uL, dose reduce by 50% on a daily basis or to 50mg/kg biweekly or triweekly.

Question 10

Hyperviscosity syndrome is most common with what subtype of multiple myeloma?

a. IgA
b. IgG
c. IgM
d. Pure light chain
e. MGUS

Answer 10

c.
IgM, or Waldenstrom’s macroglobulinemia, has a higher molecular weight than the other subtypes, thus making HVS more common. In general, HVS occurs in 20-30% of dogs with MM.

Question 11

What is the median survival time of dogs with multiple myeloma treated with melphalan and prednisone?

a. 11 months
b. 15 months
c. 18 months
d. 21 months
e. 23 months

Answer 11

c.
Matus et al reports a MST of 540 days (18 months) for 37 dogs with MM that received melphalan, cyclophosphamide and prednisone. The overall response rate was 92%.

Question 12

What chemotherapeutic agent, when administered to dogs with IgM macroglobulinemia, is associated with a median survival time of 11 months?

a. Melphalan
b. Cyclophosphamide
c. Chlorambucil
d. Lomustine
e. Pulse-dosing of melphalan

Answer 12

c.

In 9 dogs treated with chlorambucil (0.2mg/kg PO once daily), there was a 77% response rate with a MST of 11 months.

Question 13

What type of M component do you expect to find in the cat diagnosed with multiple myeloma?

a. IgE
b. IgG
c. IgM
d. IgA
e. IgD

Answer 13

b.

Question 14

Which of the following is the primary factor that has been associated with the development of hypercalcemia in multiple myeloma?

a. IL-12
b. IL-6
c. TGF-β
d. osteoclast activating factor (IL-1 alpha)
e. PTH-rp

Answer 14

d.

although all of these have been associated with hypercalcemia from MM, this is the primary mechanism

Question 15

Which of the following have been associated with a poor prognosis in cats diagnosed with multiple myeloma?

i. azotemia
ii. hypocalcemia
iii. Bence-Jones proteinuria
iv. bone marrow involvement
v. partial clinical improvement of serum protein levels after 8 weeks

a. i, ii, iii, iv
b. i, iii, iv, v
c. ii, iii, iv, v
d. i, ii, iii, v
e. ii, iii, iv

Answer 15

d.
cats with these criteria have MST of 5 days compared to cats with the “less aggressive form” which MST = 387. Based on Hanna F; Multiple myeloma in cats. J Feline Med Surg 7: 275-287, 2005.

Question 16

What is thought to be the primary cause of hypercalcemia in dogs with multiple myeloma?
A. IL-1alpha
B. PTH-rp
C. receptor activator of NF-Kappa B (RANK) ligand
D. diffuse osteolysis

Answer 16

a.
Other name for IL-1β is osteoclast-activating factor (OAF). Hypercalcemia is observed in 15-20% of dogs with MM. Other factor that are thought to contribute to hypercalcemia with MM in humans are TNF, IL-1, IL-6. Serum elevations in PTHrP have also been observed in two dogs with MM.

Question 17

A 6 year old male neutered boxer presents with a pink, well circumscribed, 2cm mass caudal to the maxillary canine tooth on the left side. A biopsy is performed and histopathology describes an expansile mass composed of round cells with moderate to marked anisocytosis and anisokaryosis. There are frequent binucleated and multinucleated cells. The primary differential is a plasmacytic tumor, but special stains are recommended to differentiate the tumor from other round cell tumors. Positive staining with which of the following would support the diagnosis of a plasmacytic tumor?

i. thioflavin T
ii. CD4
iii. MUM1/Interferon regulatory factor-4
iv. CD3

A. i, ii
B. i, ii, iii
C. i, iii
D. iii, iv

Answer 17

c.

may also be CD18 positive?

Question 18

A dog is diagnosed with a plasma cell tumor based on positive staining for appropriate markers. What is the next best step?
A. CT to plan for mass removal
B. Mass removal
C. Melphalan and prednisone administration
D. Thoracic radiographs and abdominal ultrasound

Answer 18

d.
It is important to thoroughly stage dogs with plasmacytomas (TXR, AUS, liver and spleen aspirates, globulin level +/- protein electrophoresis, BM, etc). Most important with SOP and GI EMP due to their relatively high metastatic rate and progression to MM. Less important with cutaneous, oral, and colorectal plasmacytomas because of their more typical benign behavior.