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Yr 3 cancer > multiple myeloma > Flashcards

multiple myeloma Flashcards

1
Q

definition of multiple myeloma

A

Haematological malignancy characterized by proliferation of plasma cells resulting in bone lesions and production of a monoclonal immunoglobulin (paraprotein, usually IgG or IgA).

plasma cells are the effector cells of the specific humoral immune response

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2
Q

aetiology of multiple myeloma

A

unknown

postulated viral trigger

Chromosomal aberrations are frequent, certain cytokines (e.g. IL-6) act as potent growth factors for plasma cell proliferation.

Associated with ionizing radiation, agricultural work or occupational chemical exposures (benzene).

transformation is because of genetic aberrations that accumulate from a pre-malignant condition - monoclonal gammopathy undetermined significance - always

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3
Q

epidemiology of multiple myeloma

A

2nd most common haematological malignancy

Annual incidence is 4 in 100,000,

prevalence is increasing

70yrs - incidence increase with age

men more

Afro-Caribbeans>white people>Asians.

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4
Q

sx of multiple myeloma

A

may be asymptomatic

bone pain

  • in back/ribs/pelvic (prox skeleton)
  • sudden and severe if caused by pathological fracture or vertebral collapse

infections - often recurrent - from immunoparesis and neutropenia from disease and chemo

general

  • tiredness
  • thirst
  • polyuria
  • nausea
  • constipation
  • mental change - from hypercalcaemia

hyperviscocity

  • bleeding
  • headaches
  • visual disturbance

sx of hypercalcaemia - fatigue, constipation, confusion

sx of anaemia

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5
Q

signs of multiple myeloma

A

pallor

tachycardia

flow murmur

signs of HF

dehydration

purpura

hepatosplenomegaly - not according to lecture

macroglossia

carpal tunnel syndrome

peripheral neuropathies

renal impairment

cachexia

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6
Q

Ix for multiple myeloma

A

blood

blood film

bone marrow aspirate and trephine

chest, pelvic or vertebral XR

skeletal imaging, whole body MRI, skeletal survey

possible renal biospy

screening:

  • serum or urine electrophoresis (do for all >50 with new back pain)
  • B2 microglobin - prognostic
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7
Q

blood results in multiple myeloma

A

FBC - normochromic, normocytic anaemia

thrombocytopenia

neutropenia

high ESR CRP (can have normal CRP) because a lot of Ig

normal AlkPhos

high urea and creatinine

high Ca

serum Ig, serum free light chains - can have light chain only myeloma so need to look for SFLC or bence jones proteins

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8
Q

blood film in multiple myeloma

A

rouleaux formation with bluish background because of increased protein

pancytopenia

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9
Q

serum or urine electrophoresis

A

Serum paraprotein - ie monoclonal immunoglobin (two-thirds IgG, one-third IgA)

If IgG – increase in IgG and suppression of normal Ig – immune paresis

serum free light chains

Bence–Jones protein - free light chains in urine - k or y in 70% cases

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10
Q

bone marrow aspirate and trephine in multiple myeloma

A

increased plasma cells (large cells with a perinuclear halo, eccentric nuclei, blue cytoplasm) - usually >20%

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11
Q

chest, pelvic or vertebral XR in multiple myeloma

A

osteolytic punched out lesions without surrounding sclerosis eg pepper pot skull - from increased osteoclast activation from signalling by myeloma cells

pathological fractures

vertebral collapse

fractures

osteoporosis, osteopenia

(CT/MRI to detect lesions not seen on XR)

in pic - plasmocytoma in sternum

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12
Q

what is a plasma cell dyscrasia

A

eg myeloma

abnormal proliferation of single clone of plasma or lymphoplasmacytic cells = secretion of Ig or an Ig fragment = dysfunction of many organs especially the klidneys

Ig is seen as a monoclonal band, or paraprotein, on serum or urine electrophoresis

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13
Q

classification of plasma cell dyscrasias

A

based on Ig

  • IgG in 2/3
  • IgA in 1/3
  • few IgM or IgD

other Ig levels are low - immunoparesis = increased suseptibility to infection

in 2/3 urine contains Bence Jones proteins - free Ig light chains of kappa or lambda, filtered by the kidney

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14
Q

how does myeloma cause renal impairment

A

light chain deposition

light chains have toxic and inflammatory effect on the proximal tubule cells

damage is mainly caused by the precipitation of light chains in teh distal loop of henle

deposits may be AL-amyloid = nephrotic syndrome

monoclonal immunoglobulins also disrupt glomeruli

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15
Q

diagnostic criteria for myeloma

A

have high index of suspicion

eg in bone pain, or back pain that isnt improving

check blood film and electrophoresis

criteria:

  1. monoclonal protein band in serum or urine elctrophoresis
  2. increased plasma cells on marrow biopsy
  3. evidence of end-organ damage from myeloma
    • hypercalcaemia
    • renal insufficiency
    • anaemia
  4. bone lesions - XR of spine, chest, skull, pelvis, +- Tc-99m MIBI and PET
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16
Q

complications of myeloma

A

bone disease

renal failure form large-scale If secretion

17
Q

RF for multiple myeloma

A

obesity

age

genetics:

  • incidence in black population,
  • sporadic cases of familiar myeloma
18
Q

pathophysiology of multiple myeloma

A

myeloma plasma cells:

  • infiltrate bone marrow
  • form bone expansile or soft tussue tumours - plasmacytomas
  • produce serum monoclonal IgG or IgA: paraprotein or M-spike
  • produce excess monoclonal (k or lambda) serum free light chains
  • bence jones protein - urine monoclonal free light chains

In bone marrow – cells accumulate and form plasmacytomas – damage bone

BM infiltration – anaemia (most common), pancytopenia

IgA can give you increased plasma viscosity

Free light chains more damaging than Ig

Free light chains pass through the GBM – in loop of henle ph change – light chains ppte = cast nephropathy = acute renal failure

19
Q

key features of myeloma

A

monoclonal plasma cells

paraprotein

osteolytic lesions

anaemia

infections

kidney failure

20
Q

dx of MM

A

CRAB:

  • calcium high
  • renal impairment
  • anaemia
  • bone lesions

+ monoclonal protein

back pain

abnormality on routine test

fatigue

acute renal failure

pneumonia

paralysis - cord compression

21
Q

why do you get bone lesions in multiple myeloma

A

plasma cells reside in axial skeleton/proximal bone marrow

secrete soluble factors that activate osteoclasts

no osteoblastic reaction

=punched out lesions on plain XR

22
Q

cord compression in multiple myeloma

A

vertebral body collapses and compress cord - acute or gradual

dx and mx in 24hr

MRI scan

Ig and FLC studies +/- biopsy

dexamethasone, radiotherapy

neurosurgery rarely needed

stabalise spine

23
Q

hypercalcaemia and mx

A

sx - drowsiness, constipation, fatigue, muscle weakness, AKI

Mx - fluids, steroids, zolendronic acid

24
Q

myeloma kidney disease

A

serum creatinine >177umol/L or eGFR <40ml/mon

AKI and result of muelomia

cause:

  • cast nephropathy by serum free light chains and Bence Jones proteinuria
  • hypercalcaemia, diuretics, infection, dehydration

Yr 3 cancer (12 decks)

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