Multiple Myeloma

 

Multiple MyelomaMyeloma pelvis

 

Definition

 

Hematological disease

- uncontrolled proliferation of single clone of plasma cells

- secrete monoclonal immunoglobulins

 

Epidemiology

 

10% of all hemotological diseases - cecond most common hemotological diease

Most common primary bone cancer

 

Median age 65 - 70

 

Twice as common in African Americans as in Caucasians

 

Pathology

 

Plasma cell malignancies

 

Genetically complex disease

- collection of several different cytogenetically distinct malignancies

- usually bone marrow of entire skeleton involved

 

Associated with abnormality of protein synthesis

- monoclonal M proteins (IgG,M,A,D,E) - cause hyperviscosity

- monoclonal free light chain proteins (Bence Jone proteins) - damage kidney

 

Morbidity due to end organ destruction

 

Predisease

 

Monoclonal Gammopathy of Unknown Significance (MGUS)

- 3% of white population > 50

- 6% of African-American population > 50

- risk of progression to multiple myeloma is 1% per year

 

Two Forms

 

1.  Multiple Myeloma 95% 

- disseminated disease

 

2.  Plasmacytoma 5% 

- solitary bone or soft tissue lesion

- usually axial skeleton

- usually disseminates to multiple myeloma in 5 - 10 years

 

International Myeloma Working Group Diagnostic Criteria

 

Plasmacytoma 

1.  Biopsy proven single osseous lesion

2.  Normal bone marrow with no evidence of clonal plasma cells

3.  Normal skeletal survey and MRI (or CT) of spine and pelvis

4.  No end-organ damage such as hypercalcemia / renal insufficiency / anemia, or bone lesions (CRAB)

     secondary to a lympho-plasma cell proliferative disorder

 

Multiple myeloma

Any one or more of:

1. 60% or greater clonal plasma cells on marrow examination

2. Serum involved/uninvolved free light chain ratio of 100 or greater AND involved light chains > 100mg/L

3. More than one focal lesion on MRI > 5mm in size

 

Location

 

Always spine

 

Common in skull, ribs, sternum and pelvis

 

History

 

Bone pain

- back / long bones / skull / pelvis

 

Low back pain

- worse at night

- worse supine

- resistant to simple analgesia

 

Fatigue / fever / night sweats

Infections

Peripheral neuropathy

 

Laboratory

 

Pancytopenia

Elevated ESR > 100

Hypercalcaemia

Chronic Renal Failure

 

Bence Jones Proteins in urine

- 24 hour urinalysis

- urine electrophoresis

 

Serum electrophoresis

- monoclonal antibody band/ M protein

- most sensitive

 

Bone Marrow Biopsy

 

Definitive diagnosis

 

Plasmocytoma Nephron GNU Free Documentation License Version 1.3

 

Sheets of plasma cells

- clock-faced eccentric nuclei

- perinuclear clear area

- increased rER on electron microscopy

- no background stroma

 

Cellular atypia not prognostic

 

May see amyloid

 

X-ray

 

1.  Punched out lytic lesions

- axial and appendical skeleton

- widely disseminated

- soap bubble appearance

- no sclerotic reaction

 

Multiple Myeloma Pelvis0001Multiple Myeloma Pelvis0002

 

MM 1MM 3

 

Myeloma Humerus

 

2.  Diffuse osteopenia

- in 15% to 25% of patients, no discrete lysis occurs

- diffuse osteopenia and osteoporosis are the only skeletal manifestations

 

Multiple Myeloma Diffuse Osteopenia

 

3.  Vertebrae Plana

 

Spine Multiple Myeloma

 

4.  Pathological Fracture

 

MM 2

 

5.  Pepper pot skull

 

Bone Scan

 

25% negative - no malignant or reactive bone formation

 

Skeletal survey

 

Xray

- skull / spine / humerus / femurs / pelvis / chest & ribs

- low sensitivity

- only detect lesions with > 30% cortical destruction

 

Low dose whole body CT

- detects lesions < 5 mm

 

Whole body MRI

 

PET / CT

 

CT MM RCT MM MRI MM

 

Management Multiple Myeloma

 

Systemic Problems

 

Anaemia - erythropoietin

Acute / chronic renal failure - dialysis

Hypercalcaemia

Coagulation defects - systemic anticoagulation

Amyloidosis

Gout

Bone fragility - bisphosphonates

Infection - frequent cause of death in elderly

 

Algorithm

 

Chemotherapy

Allogenic stem cell transplantation

Maintenance therapy

 

+/- immunotherapy / monoclonal antibody therapy (lenalidomide / daratumumab)

 

Orthopedic Management

 

1. To confirm diagnosis - biopsy isolated lesions

2. To treat impending or actual pathological fracture

3. Rarely to excise solitary lesions

 

MM HumerusMM Humerus post op

 

MM 2MM 4

 

Prognosis

 

Survival has doubled recently in younger patients

- new medications / immunotherapy + stem cell transplantation

 

Almost all patients eventually relapse

 

Munshi et al JAMA Oncol 2017

- meta-analysis of minimal residual disease after chemotherapy

- associated with increased long term survival

- mean disease free survival 54 months with minimal residual disease versus 26 months

- mean overall survival 98 months with minimal residual disease versus 82 months

 

Plasmacytoma 

 

Definition

 

Single mass of plasma cells

- no plasmacytosis

- no other symptoms

 

Solitary bone lesion or Extra-medullary / soft tissue

 

50% with solitary bone lesion develop multiple myeloma within 10 years

 

Diagnosis

 

Exclude multiple myeloma

- bone marrow biopsy

- whole body PET / CT / MRI

 

Clinical

 

Tend to be younger and have better prognosis

- usually long bone or vertebrae

- in spine commonly present with rapidly progressive paraplegia

- this is more common in plasmacytoma then multiple myeloma

 

Management

 

Highly sensitive to radiotherapy

 

Chemotherapy iindicated for persistent disease after radiotherapy

 

Surgery

- pathological fractures

- stabilization of spinal lesions

 

Monitor for progression to multiple myeloma

 

Prognosis

 

Ozsahin et al Int J Radiat Oncol Biol Phys 2006

- 206 solitary bone plasmacytoma

- treated with radiotherapy

- 5 year overall survival 74%

- 5 year probability of progression to multiple myeloma 45% at mean of 21 months

 

Paiva et al Blood 2014

- bone marrow evaluation for plasma cell infiltration

- 70% of plasmacytoma progressed to multiple myeloma if bone marrow biopsy positive

- 8% progressed to multiple myeloma if bone marrow biopsy negative