MULTIPLE MYELOMA

Quick and dirty- what is it

Incidence: morbidity/mortality
Etiology
Pathophysiology
Signs and Symptoms
Diagnosis
Prognosis
Describe Casts
 EPIDEMIOLOGY

Plasma cell dyscrasia that causes plasma cells to

overproduce immunoglobulin/immunoglobulin
fragments and invade and destroy adjacent bone
tissue
2nd most common hematological malignancy
Generally between the 4th and 7th decades of life
mean age is 65
Higher incidence in Black, Pacific Islanders, and Maori
Incidence is 2-4/100,000 (in US) 4-6/100,000 in
Europe
Mortality 4.1/100,000
 ETIOLOGY

No one knows
As they arise from post germinal cells in the
lymph node, with Ig gene rearrangement,
extensive somatic hypermutation, and class
switching of IgH genes- they have undergone
antigen selection
Risk Factors
Most significant is age- 96% of diagnoses cases occur in
individuals>45 years, more than 63% of cases are those
older than 65 years
Agricultural occupations, petroleum workers, leather
industries, cosmetologists
 PATHOPHYSIOLOGY

B cell becomes Plasma cell

Damage
Chromosomal abnormalities involving 14q32 (IgH gene)
Chromosome 13 deletions
IgH translocations
MMSET and FGFR3 (15%) t(4p16;14)
Cyclin D3 (3%)6p21
Cyclin D1 (15%) 11q13
C-maf (5%) 16q23
MAFB (2%) 20q11
Then they express homing molecules and adhesion to Bone Marrow
stromal cells
This binding stimulates BMSCs to screte IL-6 and ILGF-1 which help
MM cells survive
Osteoclastogenesis is stimulated thru cytokines- causes osteolytic
bone disease and hypercalcemia
 CLASSIFICATION

Monoclonal Gammopathy of unknown significange

M protein <30g/L, clonal cells in BM <10%
Smouldering Myeloma
M protein in serum >30g/L and/or bone marrow clonal cells
>10% BUT no organ or tissue impairment, and no symptoms
Active Myeloma
M-protein in serum >30g/L, Bmclonal cells >10%
AND at least 1 of the following
Calcium elevation (>10.5mg/dL)
Renal insufficiency (CR>2mg/dL/173mmol/L)
Anemia (Hb <100g/L)
Bone disease- lytic or osteopenic
 RENAL INSUFFICIENCY
PATHOPHYSIOLOGY
Light-Chain Cast Nephropathy
Occurs in 50% of patients with
multiply myeloma
Bence Jones Proteinuria and cast
nephropathy
1- light chains can be directly toxic to
the epithelial cells
2- Bence Jones proetins combine with
urinary glycoprotein (tamm-horsfall) in
acidic urine to form large tubular casts
that obstruct lumens and induce
inflammatory reaction
Amyloidosis- AL type (lambda
chain) in 6-24%
Light chain deoposition disease
(kappa type)
Hypercalcemia and hyperuricemia
RENAL BIOPSY
 HISTORY & PHYSICAL FINDINGS

Anemia
Bone Pain
MGUS
Infections
Fatigue
Renal Failure
 SUSPECT? INVESTIGATIONS

Serum/urine
electrophoresis
Skeletal Survey-
Xray
Whole body CT
Serum free light
chain assay
Serum calcium
CBC
Creatinine-serum
Beta2-microglobulin
Albumin
BONE MARROW BIOPSY

Histological
classifications
Low grade
Marshalko type
Small type
Intermeadiate grade
Cleaved type
Polymorphous type
Asynchronous type
High grade
Blastic type
 DIFFERENTIAL DIAGNOSIS

MGUS
Solitary Plasmacytoma
Waldenstrom macroglobulinemia
Amyloidosis
 URINARY CASTS

Cylindrical
structures
formed in distal
convoluted
tubule and
collecting ducts
of nephrons
Dislodge and
pass into urine
In acidic
environment,
with Tamm-
Horsfall
mucoprotein-
precipitate
 CASTS

Acellular
Hyaline
Granular
Cellular
Waxy
RBC
Fatty
WBC
Pigment
Bacterial
crystal
Epithelial cell
 HYALINE CASTS

Solidified Tamm-
horsfall mucoprotein
secreted from tubular
epithelial cells
Cylindrical and clear,
low refractivity
Low urine flow
Concentrated urine
Acidic urine
 GRANULAR

Breakdown of
cellular casts
Inclusion of protein
aggregates
(albumin or
immunoglobulin)
Muddy brown cast-
acute tubular
necrosis
 WAXY CASTS

Larger than hyaline

casts
Suggest
longstanding
kidney disease
(renal failure)
 FATTY CASTS

High urinary
protein nephrotic
syndrome
 PIGMENT CASTS

Hemoglobin
Myoglobin
Bilirubin
Drugs
 CRYSTAL CASTS

Oxalates
Urates
Sulfonamides
Ketanaline cast
 RBC CASTS

SLE
Post-streptococcal
glomerulonephritis
Goodpastures
Nephritic
syndromes
 WBC CASTS

Pyelonephritis
Allergic interstitial
nephritis
 EPITHELIAL CASTS

Acute tubular
necrosis
Toxin ingestion:
Mercury
Diethylene glycol
salicylate