MULTIPLE MYELOMA

It is a cancer of plasma cells, which are type of white blood cells in the bone marrow. Plasma cells are responsible for producing antibodies which help in fighting infections. It is also called Kahler's disease. When plasma cells become cancerous, they proliferate and accumulate in the bone marrow and produce abnormal antibodies which cause complications. It produces osseous as well as extra-osseous manifestations.

                                             

Incidence

• mostly affects elderly individuals(50-60 yrs) and incidence increases with age
• more common in males than females

Etiology

-it can occur due to radiation exposure

-occupational exposure to petroleum products

-mutations

• 13q deletion
• translocation t(11;14)
• overexpression of MYC and RAS growth promoting oncogenes
• mutation in p53 gene(tumor suppressor gene) present on chromosome 17p

Pathogenesis

The neoplastic plasma cells adhere to bone marrow stromal cells(BMSC) with the help of adhesion molecules CD4,VLA4,ICAM-1

                                                                          ↓

Both MM cells and BMSC cells secrete growth factors and anti-apoptotic factors( factors which prevent programmed cell death) like IL-6 ,IGF-1,BCL-2

                                                                           ↓

These secretions mediate tumor cell growth, proliferation, survival, drug resistance and migration

                                                                           ↓

BMSC cells also secrete RANK ligand which bind to RANK receptors on the osteoclasts promoting their differentiation and resorptive activity

                                                                            ↓

                                              This causes lytic lesions of the bone

                                              

                                              

                                                                             

The most common affected bones are vertebrae, skull , ribs and pelvis and long bones of limbs. Radiographically these lesions appear punched out, rounded and 1-2cm in size.

The marrow is hypercellular and the myeloma cells constitute  greater or equal to 10% of marrow cellularity.

                                                                                                                                

Extra osseous lesions include:

• Blood: anemia,neutropenia, inc.↑↑ESR, ↑ serum calcium,↑IL-6
• Myeloma kidney: when the abnormal light chains of the antibodies are excreted in urine they are called Bence Jones proteins which cause renal tubular damage. These proteins combine with Tamm horsfall proteins and form tubular casts in the DCT.
• Myeloma neuropathy
• Systemic amyloidosis
• Liver and spleen involvement

Clinical features include:

• bone pain
• susceptibility to infections( due to neutropenia)
• anemia
• bleeding tendencies (due to thrombocytopenia)
• renal failure
• POEMS syndrome: occurs in 1% of the cases 

                                Polyneuropathy

                                Organomegaly

                                Endocrinopathy

                                Multiple myeloma

                                Skin changes

                                           

Diagnosis

• bone marrow clonal plasmacytosis >10%
• presence of M proteins in serum or urine
• related organ and tissue impairment:

                              C-increased calcium level

                              R-renal insufficiency

                              A-anemia

                              B-bone marrow lesions

• biomarkers-

                               S - 60% or more clonal plasma cells in bone marrow

                               Li- light chains

                               M- MRI