DR KARANU JK
 Most
 It
common primary malignancy of bone
is a plasma cell disorder monoclonal neoplasms related to each
other by virtue of their development
from common progenitors in the B
lymphocyte lineage
 Thoughts
that plamacytoma is
simply an early, isolated form of
multiple myeloma
 There
are two important variants of
myeloma,
solitary bone plasmacytoma
extramedullary plasmacytoma

 Solitary
bone plasmacytoma is a
single lytic bone lesion without
marrow plasmacytosis
 Extramedullary
plasmacytomas
usually involve the submuscosal
lymphoid tissue of the nasopharynx
or paranasal sinuses without marrow
plasmacytosis.
 The
cause of myeloma is not known
 Incresed
frequency in those exposed
to radiation
 Seen
more frequently among
farmers, wood workers, leather
workers and those exposed to
petroleum products
 Chromosomal
alterations identified:
13q14 deletions
17p13 deletions
11q abnormalities
 Common
translocations
t(11;14)(q13;q32) and
t(4;14)(p16;q32)
Overexpression
of myc or ras
genes has been noted in some
cases
Mutations
in p53 and Rb1 have
also been described
No common molecular
pathogenesis has yet
emerged
 Represents
more than 40% of primary
bone cancers
 Peak
 2:1
incidence is in 5th to 7th decades
male predominance
 Blacks
have nearly twice the incidence
of whites.
 Yearly
incidence is around 4 per 100000
Knh
multiple myeloma 337 cases
in 5 years, average of 67 per
year
Plasmacytoma
16 cases in 5
years, average of 3 per year
 Multiple
myeloma cells bind via cell
surface adhesion molecules to bone
marrow stromal cells and
extracellular matrix.
 This
triggers multiple myeloma cell
growth, survival, drug resistance and
migration in the bone marrow milieu
 The
cell effect is due to direct
multiple myeloma and bone marrow
stromal cell interaction , as well as
induction of cytokines
 Cytokines
involved include
IL6,
insulin like growth factor 1,
vascular endothelial growth factor
stromal cell derived growth factor

Growth, drug resistance and
migration are mediated via
Ras/Raf/mitogen- activated protein
kinase, PI3-K/Akt and protein kinase
c signaling cascades
The
clinical manifestation of all
the plasma cell disorders relate
to
expansion
of the neoplastic cells
secretion
of cell productsimmunoglobulins, lymphokines
Host’s
response to the tumour
 Bone
pain most common complaintprecipitated my movement
 Weakness
 Weight loss
 Anaemia and thrombocytopenia
 Peripheral neuropathy
 Hypercalcaemia
 Renal failure
 Pathological
fractures
 Symptoms
are usually of short
duration because of the aggressive
nature of the disease
 The
spine is the most common
location followed by the ribs and
pelvis.
 Hypercalcaemia,
osteoporosis,
pathological fracture, lytic bone
lesions, bone pain
Tumor expansion, osteoclast
activating factor, osteoblast
inhibitory factors
 Renal failureHypercalcaemia, light chain
deposition, urate nephropathy,
drugs
Easy
fatigue- anaemia
 Bone marrow infiltration,
haemolysis, decreased
erythropoietin levels
Recurrent
infections
 Hypogammaglobulinaemia, low cd4
count, decreased neutrophil
migration
 Neurologic
symptoms
Hyper viscosity, croglobulinemia,
Hypercalcaemia, nerve
compression, POEMS syndrome
 Nausea
and vomiting
Renal failure, Hypercalcaemia
The classic triad of myeloma is
i. Marrow plasmacytosis
(>10%)- CD138+, monoclonal
ii. Lytic bone lesions
iii. Serum and/ or urine M
component
Monoclonal gammopathies of
uncertain significance
 1% go on to develop myeloma
 M protein in serum<30g/l
 Bone marrow clonal plasma
cells<10%
 No evidence of other B cell
proliferative disorder
 Clinical
evaluation of patients with
myeloma includes a careful physical
examination searching for tender
bones and masses.
 Chest
and bone radiographs may
reveal lytic lesions or diffuse
osteopenia
Multiple ‘punched out’ sharply
demarcated, purely lytic lesions
without any surrounding reactive
sclerosis
The lack of reactive bone
formation is shown by the fact
that most lesions are negative
on bone scan
MRI offers a sensitive means to
document extent of bone marrow
infiltration and cord or root
compression in patients with pain
syndromes

Histologically multiple myeloma appears as
sheets of plasma cells

These are
 small
round blue cells
 clock face nuclei
 abundant cytoplasm
 perinuclear clearing or halo

Amyloid production can be abundant and
may be pathognomonic for the disease
 Serum
immunoelectrophoresis shows
monoclonal gammopathy
A
24 hr urine specimen
quantitate protein excretion
concentrated aliquot is used for
electrophoresis and immunologic
typing of any M component

 The
serum M component will be IgG
in 53%, IgA in 25%, and IgD in 1%.
 20%
of patients will have only light
chains in serum and urine.
 Fewer
than 1% of patients will have
no identifiable M component
 The
heat test for detecting Bence
Jones proteins is falsely negative in
50% of patients with light chain
myeloma
 Complete
blood count with
differential may reveal anaemia
 ESR
is elavated
 Serum
chemistries calcium, urea,
nitrogen, creatinine and uric acid
levels may be elevated.
Solitary plasmacytoma pathological
differentials may include chronic
osteomyelitis with abundant plasma
cells
 Plasmcytoma
has monoclonal light
chains whereas in COM they are
polyclonal
 Myeloma cells stain positive for natural
killer antigen CD56, whereas reactive
cells do not
In poorly differentiated cases
lymphoma could be a differential
Lymphoma
cells usually stain
positive for CD45 (leukocyte
common antigen)

and CD20 ( a B cell marker),
Stage
1
 Hb>10g/dl,
 serum calcium <3 mmol/l,
 normal bone xray or solitary lesion,
 low M component production
Stage
Stage
2- neither fitting stage 1 or 2
3- one or more of the
following:
 Hb <8.5g/dl
 Serum calcium >3 mmol/l
 Advanced lytic bone lesion
 High M component production
 10%
of patients will have an indolent
course- slow progression
 These
patients only require antitumor
therapy when the disease becomes
symptomatic
 anaemia, hypercalcaemia, progressive
lytic bone lesions, progressive rise in
serum myeloma protein levels or
recurrent infections.
 Primary
treatment of multiple myeloma is
chemotherapy
 Symptomatic
bone lesions usually respond
rapidly to radiation treatment 40 Gy
 Treatment
of impending or actual
pathological fractures of the spine,
acetabulum, proximal femur or proximal
humerus
 Patients
with symptomatic and/ or
progressive myeloma require therapeutic
intervention
2
sorts of such therapy
 Systemic therapy to control the
progression of myeloma
 Symptomatic supportive care to prevent
serious morbidity from the
complications of the disease
 Standard
treatment for newly diagnosed
cases depends on whether the patient is a
candidate for high dose chemotherapy
with autologous stem cell transplant
 Transplant
candidates avoid alkylating
agents such as melphalan
 Glucorticoids,
thalidomide
vincristine, doxorubicin,
 Supportive
care directed at the
anticipated complications
 Hypercalcaemia-bisphosphonates,
glucocorticoids,hydration, natriuresis
 Prophylactic
IV gamma globulin in
recurrent serious infections
 Anaemia-
erythropoietin, along with
haematinics
 Short
life expectancy in these patients
operations aimed to earliest resumption
of full activity
 Tumor debulking
 Internal
fixation augmented with
methacrylate
 Cemented
total joint arthroplasty or
hemiarthroplasty
In most patients local radiation
treatment should be instituted
approximately 3 weeks after surgery
or when the wound appears to be
healed.
 No
conclusive evidence on the
corelation
 Aggressive course and worse
prognosis in HIV
 Multiple myeloma can accelerate
progression of HIV infection
 HIV plays a major role in the
evolution of malignant plasma cell
tumors
 Patients
with solitary plasmacytoma
without evidence of systemic involvement
have a better prognosis
 More
than half of patients who present
with a solitary plasmacytoma eventually
go on to develop multiple myeloma.
 Patients
in stage 1A have a median
survival of more than 5 years and those in
3B about 15 months
 The
median overall survival is 5-6 years
with subsets of patients surviving over 10
years.
 The
major causes of death are
progressive myeloma,renal failure,
sepsis or therapy related acute
leukaemia or myelodysplasia.
 Nearly
a quarter die of myocardial
infarction, chronic lung disease,
diabetes or stroke.
2008
2009
2010
2011
2012
ALIVE
DEAD
43
41
50
43
48
15
20
22
31
24
TOTAL
CASES
58
61
72
74
72
ALIVE DEAD
2008
2009
2010
2011
2012
2
2
1
4
1
1
1
2
1
1
TOTAL
CASES
3
3
3
5
2