synthesize excess L or H chains or complete homogenous immunoglobulins
Monoclonal plasma cells
When is the peak incidence of plasma cell disorders?
In a plasma cell disorder, how much of bone marrow consists of neoplastic cells?
Describe pathological features of plasma cell disorders
Osteolytic lesions in ribs,skull, sternum, vertebrae
Bone marrow patchy, can have fibrosis
Morphology of plasma cells varies
Describe malignant plasma cells
eccentricalyl located nucleus
chromatin is clumped like clock faced chromatin
perinuclear huff and pail area
In multiple myeloma, describe bone destruction
Begins in medullary cavity and works its way outword
Pathology fx and punched out lesions occur and occasionally produce diffuse demineralization of the bone
soft, red, gelatinous masses
perinuclear clearing due to prominent Golgi apparatus, eccentrically placed nucleus
neoplastic plasma cell associated with MM
Dysregulated synthesis and secretion of immunoglobulin can lead to accumulation of intact or partially degraded Ig
Fiery red cytoplasm
Flame cell associated with MM
multiple blue grapelike cytoplasmic droplets
Mott cell associated with MM
Russell and Dutcher bodies
Russell: cytoplasmic inclusions
Dutcher bodies: nuclear inclusions
Associated with MM
What happens as MM progresses?
Invades soft organs: kidneys, lung, lymph nodes
Describe cells you might see in MM
Peripheral red blood smears may cause rouleaux formation from high levels of M protein
Neoplastic plasma cells may be seen in peripheral blood (making it look a little like leukemia)
Myeloma kidney MOA
Bence Jones proteins injure the kidney as some light chains are directly toxic to epithelial cells AND/OR BJ proteins combine with a urinary protein to produce tubular casts that obstruct the tubular luminal and induce an inflammatory reaction around the casts
Clinical features of myeloma kidney
Hypercalcemia and hyperuricemia
Light chain deposition dz
Formation of concentric laminated casts which obstruct tubular lumen (By BJ proteins)
What infections is a MM pt prone to?
Strep pneumo, staph aureus, and e coli
What type of anemia is associated with MM and why?
normocytic normochromic as plasma cells crowd out RBC precursors
What is the M component and where is it found?
Monoclonal immunoglobulin in blood
Comes from same clone
Have high molecular weights
Restricted to plasma and extracellular fluid because of
Not typically in urine if the glomerulus is uninjured
Light chains exreted in urine due to small size
BJ proteins (will be high in blood in cases of renal failure or if kidneys can't excrete fast enough)
Most common symptomatic monoclonal gammopathy
Multiple nodules composed of abnormal plasma cells
What is significant abuot IL-6 in MM
IL-6 leads to proliferation and increased survival of plasma cells, therefore high levels are associated with a poor prognosis
Which factors in MM are produce by neoplastic plasma cells? What do they do?
MIP-1 and RANKL
They activate osteoclasts, resorb the bone and break it down, giving rise to osteolytic lesions
They contribute to increased calcium in the blood
Calcium is ultimately filtered in the kidney
What are karyotopic abnormalities with MM? What do they lead to?
Deletions of 13q
Translocation involving heavy IgH chain locus on 14
Cyclin D1: a cell regulatory gene on chromosome 11q13
Cyclin D3: on chromosome 6p21
cMAF: gene for transcription factor on chromosome 16q23
MUM1/IRF4: a gene for
an interferon regulatory factor
They lead to cell being transcribed more rapidly, going through the cell cycle more rapidly, and proliferating more rapidly
Plasma cell disorder not associated with skeletal lesions but with diffuse infiltratesof neoplastic cells into various tissues
Plasma cell disorder not associated with lytic lesions but with diffuse infiltratesof neoplastic cells into various tissues
heavy chain dz
What do you need with the criteria to dx MM?
1 major or 3 minor
What are the major criteria for MM?
Marrow plasmacytosis >30%
Plasmacytoma on bx
M component, serum IgG >3.5; IgA >2, Urine >1 g/24 of BJ protein
What are the minor criteria for MM?
Marrow plasmacytosis of 10-30%
M component present but less than in major criteria
Lytic bone lesions
Reduced nl serum Igs (<50% of nl)
What are the four features of a localize plasmacytoma?
skeletal lesions (can be readily bx)
may have masses in the upper respiratory tract
extra osseous lesions rarely disseminate
Plasma cell disorder involving multiple organs with progressive demyelinating polyneuropathy
POEMS (osteosclerotic myeloma)
What are clinical features of osterosclerotic myeloma?
What are the three major differences between MM and POEMS?
POEMs has sclerotic, not lytic lesions, and there is neurological involvement.
Onset is much younger than MM (51 opposed to 70s)
Megakaryocytes may be large with hyperlobulated nuclei
What is a plasmacytoma and how is it related to MM?
It is a solitary myeloma (single lesion of bone or soft tissue) associated with modest increase of proteins in the blood or urine
Can be osseous or extraosseous, but the osseous variety commonly progresses to MM (extraosseous less likely to progress)
Sheets of abnl neoplastic plasma cells that are extremely heterogenous
no evidence of plasma cell dyscraise and minimal to no Bence JOnes protein in the urine
Monoclonal protein <3g
NO bone lesion, renal impairment, or hypercalcemia
Bone marrow might be nl or have a slight increase in nl plasma cells
What do you need to be careful of MGUS?
It can smolder and lead to MM, therefore have periodic assessment of B-J proteins and serum M component spikes
AKA Waldenstrom’s macroglobulinemia
B cell lymphoma of primarily males 60-70 yo
Tumor cells undergo terminal differentiation to plasma cells
H-S megaly with lymphadenopathy
Russell and Dutcher bodies
Inclusions associated with lymphoplasmacytic lymphoma
Visual abnormalities due to hyperviscosity of RBCs (problems perfusing eyes and brain); neurologic abnl (HA, dizziness, stupor)
Bleeding problems due to complexes between macroglobulins and platelets
Plasma cell disorder involving BM, LN, liver and spleen but WITHOUT bony erosions
Hemolysis by cold agglutinins : IgM Abs binding to RBC at temperatures below 37C
Raynau'd phenomenon and cold urticaria
BM sparse with plasma cells, lymphocytes, and plasmacytoid lymphocytes
Hyperplasia of mast cells
Prognosis of someone with Lymphoplasmacytic lymphoma
Incurable progressive, median surviva is 4 years
What is the difference between IgG and IgA in heavy chain dz?
IgG: diffuse, lymphadenopathy with h-s megaly
IgA: prediliction for SI, respiratory tract
Monoclonal group of plasma cells secrete free L chains
L chains pressed and deposited as amyloid that can be deposited in a lot of different organs