MULTIPLE MYELOMA AND PLASMACYTOMA
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Transcript MULTIPLE MYELOMA AND PLASMACYTOMA
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 failureHypercalcaemia, 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