plasma cell neoplasms: Flashcards
plasma cell dyscrasia:
* Neoplastic proliferation of plasma cells which secrete – intact immunoglobulin – or – (– chain)
classifications of plasma cell neoplasm ( dyscrasia):
monoclonal
Ig
ig fragments
free light chain
classifications:
I. Multiple myeloma
II. Smoldering multiple myeloma
III. Solitary myeloma (plasmacytoma)
IV. Monoclonal gammopathy of undetermined significance
V. Lymphoplasmacytic lymphoma (Waldenstrom’s macro-
globulinaemia)
VI. Other rare entities
—- is multifocal bone marrow disease characterised by malignant
proliferation of plasma cells with skeletal destruction
– Monoclonal B cells produce a – type of –
* Most common primary malignancy of–
* Accounts for 15% of haematological malignancies
* Causes 1% of cancer death
* Adults- usually >50 years
– M:F —
– More common in Africans and African Americans
* – > – (2:1)
multiple myeloma
single type of Ig
bone
3:1
blacks> whites
pathogenesis of mutable myeloma:
* Previous exposure to –
* Exposure to — , – products, rubber and – products
* Human –
* – (multiple and variable)
* No common — pathogenies known
* — cells (i.e. malignant plasma cells) bind to —- cells via cell surface adhesion molecules –> myeloma cell — , survival, drug resistance and migration in the bone marrow milieu
* Myeloma cells produce — (eg. IL6)
– Growth of — cells
– Interaction with bone marrow stromal cells —> — activation ( —receptors) and— inhibition
irradiation
asbestos petroleum plastic
human herpes virus 8
cytogenetic
molecular
myeloma cella
bone marrow stromal cells
growth
cytokines
myeloma
osteoclast
rank
osteoblast
multiple myeloma:
* – cells produce intact –
– Present in – ( – component)
– – molecular weight (not present in urine without glomerular
disease)
– – 55%, – 25%, – chain only 15%
– IgD, IgE, IgM uncommon
* Plasma cells produce –
– With complete –
– Or – chain only (15%)
– Excreted in the – (Bence-Jones protein)
* Non secretory myeloma rare <1%
plasma
monoclonal Ig
plasma
m component
high
igg iga and light chain
light chain
igs
light chain
urine
diagnosis of multiple myeloma:
* –
* — examination
* – and – electrophoresis and–
levels
radiology
bone marrow
serum n urine
immunoglobulin levels
- Multifocal destructive lesions
– Axial skeleton - Vertebrae, ribs and skull, pelvis and femur, clavicle and scapula
– Punched out lytic lesions/ Soap-bubble appearance
these are known as –
skeletal lesions
1-bone marrow examination:
* Plasma cells are –
* Perinuclear clearing and eccentric nucleus
* Atypical cells with bi-nucleated, tri-nucleated or multinucleated forms
* Immature blasts
* Intra-cytoplasmic inclusions (Russell bodies)
* Mott cells
* Intra-nuclear inclusions (Dutcher bodies)
* Immunohistochemistry- a single type of Ig (Monoclonal,eg IgG only) and a single type of light chain (either
kappa or lambda)
2- serum and urine analysis:
* Serum
– Monoclonal globulin – on serum electrophoresis
– (– spike) most commonly –or –
– >3g/dL for IgG
* Urine
– Proteinuria ( – chain)
– Either Kappa or lambda light chain
* The absence of – or its components from blood or — does not exclude myeloma
increased
spike
m spike
IgG n IgA
light chain
ig or urine
- clinical features - common tetra of multiple myeloma is–
- clinical features of bone lesions: * Proliferation of – cells which infiltrate the bone
- Production of – and – activating factor
- Presentation:
– – pain
– lytic–
– Pathologic –
– Diffuse –
– — (confusion, weakness, lethargy, abdominal pain
constipation, polyuria, depression, renal stones)
– The — are one of the most common sites of pain –>spinal cord –
CRAB:
– Calcium (elevated)
– Renal (kidney) failure
– Anaemia
– Bone lesions
tumour
IL-6
osteoclast
bone pain
lesion
fractures
osteoprosis
hypercalcaemia
lumbar vertebrae
compression
- clinical features - bone marrow involvement:
- Tumour cells – the bone marrow –> – , – and —
- clinical features - anemia:
- Anaemia: – and —
- Due to:
A- replacement of – by tumour cells
B- — of normal red blood cell production by—
C- — in erythropoietin production
Note: Decrease– of red blood cells
(Rouleaux formation on blood smear) - clinical features - bleeding:
– Monoclonal immune proteins interfere with normal—
– Infiltration of the bone marrow – > –
replace
Anaemia, thrombocytopenia and leucopenia
normocytic or normochromic
normal bone marrow
inhibition
cytokines
decrease
charge
coagulate
thrombocytopenia
- clinical features of hypersensitivity :
- – volume of monoclonal protein –> blood —- increases –> complications such as – , — , —- ( see hypervisioty syndrome )
- clinical features of sepsis :
- Recurrent –
– The most common cause of –
– – production of normal Ig – > recurrent — (Encapsulated organisms, eg. – , – , – infections)
– –
high
viscosity
stroke , mycordaial ischiema n infarction
infection
death
decreased
bacterial infection
staph strep e coli
leucopenia
clinical features of renal failure;
* Occurs in up to — of patients
* — most common cause of death
* —
– Myeloma – = myeloma cast –
* Bence-Jones toxic to renal tubular epithelial cells
– Amyloidosis- AL type
– Light chain nephropathy
– Hypercalcaemia and hyperuricaemia
– Pyelonephritis
– Drug induced
50%
2nd
mutlifactorial
kidney = nephropathy
clinical features of amyloidosis:
* — deposition of – type (derived from — )
– – : Nephrotic syndrome
– — : Restrictive cardiomyopathy
– Tongue – (macroglossia)
* Requires – (subcutaneous/GI
tract/bone marrow/other)
* Congo – staining with apple green
birefringence under –
* Treatment includes –
systemic
AL
light chain
kindney
heart
elargement
tissue biosy
red
polarised light
chemotherapy
( everything in here is soo examinable material )
- clinical features of neurological symotoms: —- , — , —
- prognosis of mutable myeloma:
- — if untreated
- Median survival —
- Causes of death
– —
– — - treatment of multiple myeloma :
- Currently —
- New therapies ( — , —
inhibitors, — antibodies) - — transplantation:
–> –
–> – (rarely used)
Hyperviscosity, hypercalcaemia, nerve compression
6-12 months
4-7 years
infection n renal failure
not curable
immunomodulatory, proteasome
inhibitors, monoclonal antibodies
biophosphonates
bone marrow
autologous
allogenic
smouldering multiple myeloma:
* Patients are—
* Plasma cells make up – of bone marrow
* M protein > – g/dL
* – progress to multiple myeloma
solitary plasmacytoma:
* Solitary –
– Osseous ( – )
– Extra-osseous (extra-medullary) (– )
* Serum immunoglobulin concentrations are usually within – limits
- solitary plasmacytoma of bone:
* Patients are – than patients with multiple myeloma
* Involves –, – and –
* A – area of bone destruction
* Progression to multiple myeloma in – years
asymtpomatic
10-60%
3
75%
lesions
bone
soft tissue
normal
younger
spine pelvis femur
single symptomatic
10-20
extramdeullary plasmacytoma:
* Involves –, – and —
* Extra-osseous lesions can be cured by — or —
* Progression to multiple myeloma is – common
lung, oronasopharynx and nasal sinuses
local resection or radiotherapy
less
