Myeloma & Plasma Cell Disorders Flashcards
what is multiple myeloma?
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
what population is MM most common in?
elderly patients
what is the clinical presentation of MM?
include bone pain
infections
renal failure
anemia
why do people with MM have bone pain?
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
what’s the pneumonic for the clinical presentation of MM?
CRAB
hyperCalcemia
Renal dysfunction Anemia
Bone pain
what’s the most common cause of death in MM patients?
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
why do MM patients have renal dysfunction?
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:
- directly damage tubular endothelium
- combine with glycoproteins in the urine to form solid casts, which plug up
tubules and cause inflammatio
why do people with MM have anemia?
multifactorial
likely related to renal dysfunction and a resulting decrease in erythropoietin secretion
what is amyloid and how is it related to MM?
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
what’s a key diagnostic test for MM?
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
what does a SPEP of an MM show you?
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
which immunoglobulins are most commonly present in MM?
IgA and IgG
IgG is the most common
what’s another test you can run to test for MM?
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
what do x-rays of MM patients show?
lytic lesions
literally looks like there’s tons of holes in the bones of the patients - like polka dots all over
What are the best first tests to order on a patient that you suspect has myeloma?
SPEP then UPEP
what must be present in the bone marrow to officially diagnose MM?
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
the excessive production of immunoglobulin by the myeloma cells in MM can result in which two strange inclusions within cells?
- Russell bodies
2. Dutcher bodies
what are Russell bodies?
large, eosinophilic, cytoplasmic inclusions thought to represent distended endoplasmic reticulum
looks like a big red/pink circle
what are Dutcher bodies?
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
what is often present in the blood smears of MM patients?
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
What percentage of the marrow must consist of malignant plasma cells in order to make the diagnosis of myeloma?
10%
what is MGUS?
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
what is smoldering myeloma?
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
what is WM?
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
what is LCDD?
LCDD = light chain deposition disease
presents similarly to MM
but in LCDD kidney biopsies will not demonstrate histologic characteristics of amyloidosis seen in MM
what is HCDD?
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
Patients that have < 10 % of their marrow filled with plasma cells and a monoclonal spike on SPEP are diagnosed with what disease?
Monoclonal gammopathy of undetermined significance (MGUS)
what are some other plasma cell disorders other than MM?
- MGUS
- smoldering myeloma
- WM
- LCDD
- HCDD
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?
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
