Myeloma & Plasma Cell Disorders

Question 1

what is multiple myeloma?

Answer 1

a malignant proliferation of plasma cells in the bone marrow

the tumor cells almost always remain localized to the marrow (“myelo-“), and tend to grow in distinct tumorous masses (“-oma”), of which there are many (“multiple”)

malignant plasma cells all arise from a single malignant plasma cell, so they all express the same kind of immunoglobulin as that original cell = M spike

Question 2

what population is MM most common in?

Answer 2

elderly patients

Question 3

what is the clinical presentation of MM?

Answer 3

include bone pain

infections

renal failure

anemia

Question 4

why do people with MM have bone pain?

Answer 4

can result directly from the collections of malignant plasma cells in the bones, or from the resulting weakening of the bones, which may sometimes lead to pathologic fractures

Question 5

what’s the pneumonic for the clinical presentation of MM?

Answer 5

CRAB

hyperCalcemia
Renal dysfunction Anemia
Bone pain

Question 6

what’s the most common cause of death in MM patients?

Answer 6

infection

the malignant plasma cells inhibit the formation of normal, polyclonal immunoglobulin by benign plasma cells, rendering the patient more susceptible to infections, particularly those caused by bacterial organisms

Question 7

why do MM patients have renal dysfunction?

Answer 7

kidney problems in myeloma have multiple contributing factors

the majority of the damage is due to Bence-Jones (light-chain) proteins, which do two things:

1. directly damage tubular endothelium
2. combine with glycoproteins in the urine to form solid casts, which plug up
   tubules and cause inflammatio

Question 8

why do people with MM have anemia?

Answer 8

multifactorial

likely related to renal dysfunction and a resulting decrease in erythropoietin secretion

Question 9

what is amyloid and how is it related to MM?

Answer 9

amyloid = pink, glassy substance that gets deposited in the kidneys or other organs in MM patients

in MM, it’s formed from immunoglobulins

amyloid may be abundant enough to worsen kidney function, and interfere with the normal functions of other organs, such as the heart and the liver

Question 10

what’s a key diagnostic test for MM?

Answer 10

serum protein electrophoresis (SPEP)

in an SPEP an electrical field separates the proteins in the serum based on size, shape, and charge

go look at what the chart produced looks like

Question 11

what does a SPEP of an MM show you?

Answer 11

an M spike

“M” stands for monoclonal, and monoclonal refers to the monoclonal immunoglobulins that are secreted in myeloma

**the amount of monoclonal immunoglobulin present is closely correlated to the amount of tumor mass present

Question 12

which immunoglobulins are most commonly present in MM?

Answer 12

IgA and IgG

IgG is the most common

Question 13

what’s another test you can run to test for MM?

Answer 13

sometimes there’s no M spike in the SPEP so you can do a urine protein electrophoresis (UPEP)

UPEP will show that there’s a monoclonal protein

in these cases, the monoclonal immunoglobulin produced consists only the light chain portion, which is small enough to be filtered into the urine = Bence-Jones proteins

Question 14

what do x-rays of MM patients show?

Answer 14

lytic lesions

literally looks like there’s tons of holes in the bones of the patients - like polka dots all over

Question 15

What are the best first tests to order on a patient that you suspect has myeloma?

Answer 15

SPEP then UPEP

Question 16

what must be present in the bone marrow to officially diagnose MM?

Answer 16

bone marrow must contain at least 10 % plasma cells

most times, there are malignant cells that are larger than normal plasma cells, but still retain the eccentric nucleus and perinuclear clearing that are characteristic of plasma cells

Question 17

the excessive production of immunoglobulin by the myeloma cells in MM can result in which two strange inclusions within cells?

Answer 17

1. Russell bodies

2. Dutcher bodies

Question 18

what are Russell bodies?

Answer 18

large, eosinophilic, cytoplasmic inclusions thought to represent distended endoplasmic reticulum

looks like a big red/pink circle

Question 19

what are Dutcher bodies?

Answer 19

appear to be intranuclear inclusions, but are really composed of excess cytoplasmic immunoglobulin invaginating into the nucleus creating a pseudo-inclusion

go look at a picture

Question 20

what is often present in the blood smears of MM patients?

Answer 20

rouleaux formation in RBCs

this occurs because the increased amount of immunoglobulin in the patient’s serum interferes with the normal repellant force that pushes red cells apart from each other, allowing the red cells to stack upon each other

literally look like stacked up RBCs

go look at a picture

Question 21

What percentage of the marrow must consist of malignant plasma cells in order to make the diagnosis of myeloma?

Answer 21

10%

Question 22

what is MGUS?

Answer 22

MGUS = monoclonal gammopathy of undetermined significance

there is less than 10% of monoclonal plasma cells found within the bone marrow and a small monoclonal spike on SPEP or UPEP

MGUS patients have small, but increased risk of developing MM later

**patients that have MGUS lack lytic bone lesions, anemia, and kidney dysfunction aka the only finding that these patients have is an M spike on SPEP or UPEP

Question 23

what is smoldering myeloma?

Answer 23

patients have an M spike

they have tons of plasma cells (»10%) to diagnose myeloma

higher risk to develop MM than MGUS

but they don’t have any MM defining events - there’s no end organ damage or biopsy proven amyloidosis

Question 24

what is WM?

Answer 24

WM = Waldenstrom macroglobulinemia

typically occurs in a lymphoma called lymphoplasmacytic lymphoma

patient has a monocloncal gammopathy – but the immunoglobulin in this case is IgM, NOT IgG

IgM is a pentamer, so it can easily clump RBCs together in the serum

so patients may present with symptoms of “sludgy” serum like visual difficulties due to sluggish flow in retinal veins; or even stroke

Question 25

what is LCDD?

Answer 25

LCDD = light chain deposition disease

presents similarly to MM

but in LCDD kidney biopsies will not demonstrate histologic characteristics of amyloidosis seen in MM

Question 26

what is HCDD?

Answer 26

HCDD = heavy chain deposition disease

a population of plasma cells produce both light and heavy immunoglobulin chains which are deposited as granules in tissues

these heavy and light chains are unable to form amyloid fibrils, so again they do not demonstrate hallmark histologic features of amyloidosis, but rather are identified via immunofluorescence

Question 27

Patients that have < 10 % of their marrow filled with plasma cells and a monoclonal spike on SPEP are diagnosed with what disease?

Answer 27

Monoclonal gammopathy of undetermined significance (MGUS)

Question 28

what are some other plasma cell disorders other than MM?

Answer 28

1. MGUS
2. smoldering myeloma
3. WM
4. LCDD
5. HCDD

Question 29

You are seeing a patient in the clinic who has been diagnosed with multiple myeloma (MM) two years ago. He wonders why his urine looks foamy and he has lower extremity edema. You inform him that the most likely reason is because he has which of the following?

Answer 29

protein-losing nephropathy

this patient has developed end organ damage related to his MM

the antibody that is secreted by the cancer is ultimately deposited in the kidney which can cause glomerular damage leading to the loss of protein as the charge on the basement membrane is lost from antibody deposition

bilateral lower extremity edema is commonly seen in nephrotic syndrome (protein-losing nephropathy) as the albumin that is lost in the urine is necessary to maintain the oncotic pressure in the blood