Plasma Cell Neoplasm Pathology

Question 1

Multiple Myeloma is a clonal neoplastic proliferation of ______.

Answer 1

mature plasma cells

Question 2

Answer 2

Question 3

Each clone of MM produces a single Ig, which are typically

Answer 3

1. IgG
2. IgA
3. Bence-Jones proteins (free light chains)

Question 4

_____ (cytokines) → increases plasma cell proliferation

Answer 4

IL-6

Question 5

How does renal insufficiency develop in MM?

Answer 5

Bence-jones proteins are renally excreted → proteinuria/light chain toxicity

(some light chains also predispose to amyloidosis)

Question 6

Russell bodies (cytoplasmic) or Dutcher bodies (nuclear)

(PAS+)

… are found in which 2 neoplasms?

Answer 6

1. MM
2. Waldenstrom

Question 7

Mott cell

Answer 7

cell w/many Russel Bodies

(found in MM; note clock-faced nucleus)

Question 8

Flame cells are due to _____ at the periphery

Answer 8

Ig

(found in MM)

Question 9

MM flow cytometry markers (3)

Answer 9

CD38+, CD138+, CD19+

(contrast w/B cell CD20+, CD19+)

Question 10

MM is due to a _____ (2) deletion or ____ duplication or _____ translocation.

Answer 10

• 13q or 17p → LOF p53
• 1q
• t(4;14)(p16;q32)

Question 11

Genetic pathway affected by MM

Answer 11

MAPK → RAS → c-myc activation (the event that transforms it into MM)

Question 12

MM clinical presentation (6)

Answer 12

1. anemia (normocytic, normochromic)
2. bone pain + fatigue
3. Elevated Creatinine
4. hematologic malignancy sx: fever, wt. loss, fatigue
5. peripheral neuropathy
6. renal insufficiency

Question 13

_____ (lab finding) that confirms MM.

Answer 13

M-spike: dense band on electrophoresis → shine a light through it and it gives you this graph

(albumin is the band to the left; Igs are in the gamma band)

Question 14

Once you find the M-spike, what is the next step?

Answer 14

immunofixation to detect the isotype

(IgG & lambda present in the example)

Question 15

Diagnostic criteria for MM includes > 10% clonal plasma, CRAB criteria. What is the CRAB mn?

(the opposite of MGUS which has <10% & NO CRAB sx)

Answer 15

C: increased calcium

R: renal insufficiency

A: Anemia

B: bone pain (osteoporotic)

Question 16

Most sensitive imaging for “punched out lesions” of MM

Answer 16

MRI

Question 17

Staging of MM is based on _____(4).

Answer 17

1. kidney function
2. beta-2 microglobulin
3. LDH
4. cytogenetics

Question 18

MC cause of death in MM

Answer 18

1. infection
2. kidney failure

Question 19

prognosis of MM

Answer 19

50% at 5 years

Question 20

Clinical course of MM w/non-BMT tx

Answer 20

Question 21

Monoclonal gammopathy of Undetermined Significance (MGUS) is a production of low-levels of _____.

Answer 21

Igs

(clonal plasma cells in BM; plasma cell dyscrasia)

Question 22

MGUS affects 1 in _____ people of 50 years old

Answer 22

100! (mostly asymptomatic)

(african americans and white males)

Question 23

Answer 23

Right: could be due to inflammation

Question 24

________ has >10% BM cells and NO light chain restriction.

Answer 24

Reactive Plasmacytosis (aka polyclonal plasmacytosis)

Question 25

25% of ______ transforms into MM

Answer 25

Reactive Plasmacytosis (aka polyclonal plasmacytosis) (tx: observation only)

Question 26

Smoldering myeloma is the middle ground between ______ (2 diseases)

Answer 26

MGUS & MM (no CRAB manifestations)

Question 27

elevated plasma cells, elevated IgM, and an asymptomatic presentation is likely \_\_\_\_\_\_

Answer 27

smoldering myeloma | (tx: observation only)

Question 28

Monoclonal IgM (M-protein), malignant lymphoplasmacytic cell infiltration of BM, hepatosplenomegaly and lymphadenopathy, hyperviscosity indicate ________ (dx)

Answer 28

Waldenstrom Macroglobulinemia (aka lymphoplasmacytic lymphoma)

Question 29

Waldenstrom Macroglobulinemia (aka Lymphoplasmacytic Lymphoma) is a _____ - grade lymphoma.

Answer 29

low

Question 30

Waldenstrom Macroglobulinemia (aka lymphoplasmacytic lymphoma) risk factors (3)

Answer 30

1. Hep C (viral) 2. Autoimmune (i.e. Sjogren's) 3. White Elderly Caucasian

Question 31

**MD88** activation on gene at 3p22.2 loci, CD20+, CD38+, CD138(-) → \_\_\_\_\_\_

Answer 31

Waldenstrom Macroglobulinemia (aka lymphoplasmacytic lymphoma) (translocations rare)

Question 32

\_\_\_\_\_\_ is a distinguishing laboratory finding of Waldenstrom and likely the reason it remains asymptomatic

Answer 32

elevated serum Igs | (hypergammaglobulinemia)

Question 33

Sequelae of Waldenstrom Macroglobulinemia (4)

Answer 33

1. DLBCL (Richter) 2. amyloidosis 3. stroke 4. cold agglutinin diz 5. CHF

Question 34

Tx for waldenstrome

Answer 34

1. observe 2. chemo 3. BMT

Question 35

Amyloidosis

Answer 35

accumulation of EC tissue deposition of fibrils (low molecular weight proteins (Ig light chains) in tissue

Question 36

Amyloidosis may lead to ______ (4).

Answer 36

1. nephrotic syndrome 2. heart failure 3. hepatomegaly 4. neuropathy (\<10% of MM is a/w amyloidosis)