Multiple Myeloma and MGUS (+some lymphoma) Flashcards
What are lymphomas?
Collection of lymphoid malignancies in which malignant lymphocytes accumulate at LNs and lymphoid tissues; leads to lymphadenopathy, extra nodal disease and constitutional symptoms.
How is Hodgkin distinguished from non-Hodgkin lymphoma?
Presence of Reed Sternberg cells
How are lymphomas staged?
Ann Arbor System (Stage I-IV). Based on LN / extra nodal involvement.
What is the effect and associated neoplasm of t(8;14)?
c-myc activation; Burkitt’s lymphoma.
What is the effect and associated neoplasm of t(14;18)?
bcl-2 activation; Follicular lymphoma
What is the effect and associated neoplasm of t(9;22)?
Philadelphia chr (bcr-abl); CML/ALL in adults (25%)
What is the effect and associated neoplasm of t(11;14)?
Overexertion of cyclin D1 protein.
Mantle cell lymphoma
What is multiple myeloma?
Neoplastic clonal proliferation of plasma cells producing a monoclonal immunoglobulin resulting in end organ dysfunction.
Epidemiology of multiple myeloma?
3/100 000. Most common plasma cell malignancy.
-Increased frequency with age.
Features of end organ damage in multiple myeloma?
CRAB
- Increased Calcium
- Renal failure
- Anemia
- Bony lesions (lytic lesions or osteoporosis felt to be caused by myeloma)
Pathophysiology of multiple myeloma?
Malignant plasma cells secrete monoclonal antibody (95% produce M protein = monoclonal Ig)
Pathogenesis of multiple myeloma?
- Transition of normal plasma cells to precursor disease (monoclonal gammopathy of uncertain significance;MGUS)
- Reflects progression of oncogenic events with acquisition of mutations and cytogenetic abnormalities en route ==> karyotypic instability.
Marrow appearance in multiple myeloma?
Normal marrow
How does the marrow microenvironment facilitate multiple myeloma?
Bone marrow microenvironment promotes proliferation and blocks apoptosis of plasma cells.
- MM cells adhere to ECM proteins of bone marrow through adhesion molecules e.g. VLA4, VCAM1, ICAM1
- Bone marrow homing further facilitated by MM expression of other adhesion molecules e.g. CD138, CD38, CD106
- MM binding induces transcription and secretion of cytokines (e.g. TNFa, IL6, IGF, VEGF), triggering signalling pathways promoting proliferation and preventing apoptosis.
What do normal plasma cells secrete?
Immunoglobulins, composed of heavy chains and light chains. These are polyclonal i.e. different for each plasma cell.
What Ig do MM cells secrete?
CLONAL Ig: intact paraprotein = M protein (or just the light chain component of light chain only MM).
How can light chains be detected in the serum or urine?
Bence Jones protein
What are the features of monoclonal gammopathy of uncertain significance?
-serum M protein
What is asymptomatic (smouldering) myeloma?
-M protein in serum at myeloma levels (>30g/L) AND/OR -10% or more clonal plasma cells in BMA BUT NO CRAB
What are the diagnostic criteria for Multiple Myeloma?
- M PROTEIN in serum or urine: >30g/L of IgG or >25g/L IgA or light chain in urine/serum
- Marrow clonal plasma cells: >10% nucleated cells in marrow
- CRAB (end organ damage)
When should myeloma be suspected?
- # or bone pain w/o precipitating event
- XR shows lytic lesions, severe osteoporosis or crush #
- Unexplained anaemia w/ rouleaux on film and high ESR
- High total protein despite N albumin level
- Unexplained hypercalcemia
- Unexplained renal failure
Ix in ?MM?
- FBE (Anaemia)
- UEC (renal function)
- Calcium (hypercalcemia)
- Serum and urine protein electrophoresis and measurement of free light chains
- B2 microglobulin, serum alb, LDH (prognostic markers)
- BMA
- Imaging: skeletal survey, ?spinal MRI
Bone marrow examination in MM?
- Morphology of aspirate and trephine
- Quantify plasma cells CD138 stain
- Cytogenetics and FISH for chromosomal abnormalities (prognostic info)
Imaging in MM?
- Skeletal survey
- Spinal MRI: severe back pain, ?cord compression, multiple lesions (++sens)
Describe bone lesions in myeloma.
Vast majority purely lytic, sharply defined / punched out with endosteal scalloping when abutting cortex.
-Sclerotic in 3% only
-Osteopenia
-Crush #s of vertebrae
Due to tumour growth and activation of osteoclasts (IL6)
Medical management of hypercalcemia in MM?
Rehydration and IV bisphosphonate
Treatment of underlying disease in MM?
- Chemotherapy
- Judicious transfusions if severely anaemic
- Bisphosphonates for bone disease
Medical emergencies in MM?
- Hypercalcemia
- Spinal cord compression
- Renal failure
- Hypervisocsity (uncommon)
- Infections
Chemotherapy in myeloma treatment?
- Thalidomide based induction in combination with alkylator and steroids (e.g. cyclo/thal/dexa= CTD)
- lenalidomide or bortezomib for relapse
- autologous transplants
Treatment of MGUS?
No treatment! Annual monitoring due to 1-2% risk of progression to myeloma.
DO most patients with MGUS have myeloma?
NO! Look for CRAB features.
Why are skeletal surveys used over bone scans in MM work up?
Variable osteoblastic activity may lead to neg MM bone scan.
Patterns of MM?
- Disseminated: multiple lytic lesions (predom axial)
- Disseminated: diffuse skeletal osteopenia
- Solitary plasmacytoma
- Osteosclerosing myeloma
Components of skeletal survey?
- Lateral skull
- Frontal chest film
- Cervico-thoraco-lumbar spine
- Shoulders
- Pelvis
- Femurs
Main Ddx of MM on imaging?
Widespread bony mets
Features distinguishing bony mets and MM?
Bony mets over MM
- vertebral pedicles affected > bodies
- rarely involve mandible, distal axial skeleton
- bony mets rarely have normal bone scan appearance
