Plasma Cell Dyscrasias

Question 1

Most patients start out with MGUS and then progress to ______ before developing _____

Answer 1

Most patients start out with MGUS and then progress to asymptomatic (smoldering) myeloma before developing symptomatic myeloma

Question 2

Multiple myeloma is a monoclonal tumor of _____

Answer 2

plasma cells

Question 3

Multiple myeloma is preceded by a premalignant tumor with which it shares genetic abnormalities, including dysregulation of the _____ pathway

Answer 3

cyclin D / retinoblastoma pathway

Question 4

Malignant plasma cells interact with the bone marrow environment, leading to the activation of ____, suppression of ____, and thus development of ______.

Answer 4

Malignant plasma cells interact with the bone marrow environment, leading to the activation of osteoclasts, suppression of osteoblasts, and thus development of lytic bone disease.

Question 5

The clinical and pathologic findings associated with multiple myeloma are in large part a consquence of: (2)

Answer 5

1. tumor mass effect of the malignant plasma cells proliferating in the bone marrow, or
2. abnormal secretory products from the malignant plasma cells including monoclonal immunoglobulins and cytokines

Question 6

_____ is the presenting symptom of multiple myeloma in 70% of patients

Answer 6

bone pain

(pathologic fractures, associated neurological pain)

Commonly in vertebral column, ribs, skill

Question 7

Findings associated with abnormal immunoglobulins and other factors secreted by malignant plasma cells:

Answer 7

Renal disease

Rouleaux

Amyloid

Hyperviscosity

Cryoglobulins

Coagulation abnormalities

Question 8

What are CRAB symptoms associated with Multiple Myeloma?

Answer 8

hyperCalcemia

Renal disease

Anemia

Bone disease

Question 9

How is Multiple myeloma diagnosed?

Answer 9

1. Clonal bone marrow plasmacytosis of >10%
2. Myeloma-defining event

• CRAB
• Biomarkers
  
  • 60% or more clonal plasma cells in bone marrow
  • MRI bone lesion of greater than 5mm
  • FLC ratio of 100g/dl or greater (involved light chain of at least 100)

Question 10

What is SPEP? What is it used for?

Answer 10

SPEP is Serum Protein ElectroPhoresis, and it is used in conjunction with Immunofixation to look at what immunoglobulins are present in serum.

In normal patients, should see a smear on SPEP and presence of various immunoglobulins composed of various chains.

In Multiple Myeloma, usually see either IgG or IgA, with one particular light chain associated - suggests monoclonality.

Question 11

How is the Bence Jones protein detected via SPEP and Immunofixation? What does this indicate?

Answer 11

The Bence Jones protein is detected via urine SPEP/Immunofixation. Reveals the presence of ONLY a kappa light chain.

These proteins in the urine indicate the potential for renal failure development associated with Multiple Myeloma

Question 12

What test is being run in this image? Are the results normal or abnormal?

Answer 12

This is a bone marrow clonal plasmacytosis study staining for the presence of kappa and lambda.

This is a normal result - see blue staining confirming presence in each test.

(Abnormal result included here)

Question 13

MGUS:

Answer 13

Monoclonal Gammopathy of Undetermined Significance

Characterized by high protein, but below 3

<10% clonal plasma cells in bone marrow

NO end organ damage (no CRAB symptoms)

Question 14

Smoldering (Asymptomatic) Multiple Myeloma characteristics:

Answer 14

>3 g/dl serum monoclonal protein OR >10-60% bone marrow plasma cells OR urinary monoclonal protein

AND

NO myeloma defining events, i.e. no CRAB symptoms

Question 15

Amyloidosis:

Answer 15

Clinical syndrome in which a precursor protein is secreted in a soluble state. The precursor becomes insoluble at some tissue site and compromises organ function.

Question 16

AL amyloidosis is associated with _____ and _____

Answer 16

AL amyloidosis is associated with Multiple Myeloma and abnormal light chains

(many other forms exist, including hereditary forms)

Question 17

What stain is diagnostic for amyloidosis?

Answer 17

Congo red stain

(without Congo Red stain, it looks just like fibrosis on H&E)

Question 18

Amyloidosis is formed by _____ secreted by malignant plasma cells

Answer 18

lambda light chains

Question 19

What organ is most often affected by amyloidosis?

Answer 19

Kidney

Question 20

What is the clinical presentation associated with amyloidosis?

Answer 20

Raccoon eyes

Macroglossia (enlarged tongue)

Can present with many different non-specific symptoms depending on organ affected (kidney is most frequent - proteinuria)

Can also impact liver, heart, peripheral nerves, GI tract, respiratory tract, and coagulation system

Question 21

What population is most commonly affected by Waldenstrom Macroglobulinemia?

Answer 21

Adults (median 63)

Men

Question 22

Waldenstrom Macroglobulinemia is a low grade ____ with a predilection for involving the ____ and _____.

Answer 22

Waldenstrom Macroglobulinemia is a low grade lymphoma with a predilection for involving the bone marrow and spleen.

Question 23

Characteristic cells found on smear of Waldenstrom Macroglobulinemia is ______. These cells have a mature ___ phenotype and are associated with monoclonal _____.

Answer 23

Characteristic cells found on smear of Waldenstrom Macroglobulinemia is lymphoplasmacytic. These cells have a mature B cell phenotype and are associated with monoclonal IgM.

Question 24

Most symptoms associated with Waldenstrom Macroglobulinemia are caused by _____

Answer 24

elevated IgM - leads to hyperviscosity

Question 25

What disease is indicated by this smear?

Answer 25

Waldenstrom Macroglobulinemia

These are plasmacytoid lymphocytes - “look like they’re in between a plasma cell and a lymphocyte”

Question 26

How do patients with Waldenstrom Macroglobulinemia typically present?

Answer 26

With headache, blurred vision

Caused by hyperviscosity

Question 27

What is the diagnostic test for Waldenstrom Macroglobulinemia?

Answer 27

Bone marrow

SPEP showing IgM monoclonal spike

Serum viscosity