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DR KARANU JK

Most common primary malignancy of bone

Itis a plasma cell disorder-


monoclonal neoplasms related to each
other by virtue of their development
from common progenitors in the B
lymphocyte lineage
Thoughtsthat plamacytoma is
simply an early, isolated form of
multiple myeloma

There
are two important variants of
myeloma,
solitary bone plasmacytoma
extramedullary plasmacytoma
Solitarybone 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

Seenmore 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 incidence is in 5th to 7th decades

2:1 male predominance

Blackshave 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
Multiplemyeloma 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
Thecell 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 products-
immunoglobulins, lymphokines

Hosts response to the tumour


Bone pain most common complaint-
precipitated 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

Thespine 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
Neurologicsymptoms
Hyper viscosity, croglobulinemia,
Hypercalcaemia, nerve
compression, POEMS syndrome

Nauseaand 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.

Chestand 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
smallround blue cells
clock face nuclei
abundant cytoplasm
perinuclear clearing or halo

Amyloid production can be abundant and


may be pathognomonic for the disease
Serumimmunoelectrophoresis 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

Theheat 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 2- neither fitting stage 1 or 2

Stage 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
Patientswith 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
Standardtreatment 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, vincristine, doxorubicin,


thalidomide
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

Morethan half of patients who present


with a solitary plasmacytoma eventually
go on to develop multiple myeloma.
Patientsin stage 1A have a median
survival of more than 5 years and those in
3B about 15 months

Themedian overall survival is 5-6 years


with subsets of patients surviving over 10
years.
Themajor 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.
ALIVE DEAD TOTAL
CASES
2008 43 15 58
2009 41 20 61
2010 50 22 72
2011 43 31 74
2012 48 24 72
ALIVE DEAD TOTAL
CASES
2008 2 1 3
2009 2 1 3
2010 1 2 3
2011 4 1 5
2012 1 1 2

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