Multiple myeloma is a cancer of plasma cells that are found in the bone marrow. It is characterized by an overproduction of abnormal plasma cells which produce a monoclonal protein known as M protein. Symptoms include bone pain or fractures, anemia, kidney problems, and infections. Diagnosis involves blood and urine tests to detect the M protein as well as imaging tests and a bone marrow biopsy. Treatment depends on disease severity and transplant eligibility and may include chemotherapy, steroids, and stem cell transplantation.

1. MULTIPLE MYELOMA
Salar Nikmanesh
Medical student at Tabriz
university of medical
sciences

2. WHAT IS MYELOMA?
Multiple Myeloma (also known as Myeloma or Plasma Cell Myeloma)
is a malignancy of plasma cells, which are the white blood cells
responsible for the production of antibodies (proteins).
MM is characterized by a proliferation of malignant plasma cells and
a subsequent overabundance of monoclonal paraprotein (M protein).
When plasma cells become cancerous and grow out of control, they
can produce a tumor called a plasmacytoma. These tumors generally
develop in a bone, but they are also rarely found in other tissues. If
someone has only a single plasma cell tumor, the disease is called
an isolated (or solitary) plasmacytoma. If someone has more than
one plasmacytoma, they have multiple myeloma.

3. WHAT IS MYELOMA?

4. ETIOLOGY
The precise etiology of MM has not yet been established. Roles have
been suggested for a variety of factors, including genetic causes,
environmental or occupational causes, MGUS, radiation, chronic
inflammation, and infection.
.Genetic
.Environmental:agriculture, food, and petrochemical
.MGUS-SMM
.Radiation
.Chronic inflammation
.Infection:Human herpesvirus 8 (HH8) infection of bone marrow
dendritic cells

5. PATHOPHYSIOLOGY AND CLINICAL
PRESENTATION
MM is characterized by neoplastic proliferation of plasma cells
involving more than 10% of the bone marrow and overproduction of
monoclonal immunoglobulin G (IgG), immunoglobulin A (IgA), and/or
light chains, which may be identified with serum protein
electrophoresis (SPEP) or urine protein electrophoresis (UPEP). The
pathophysiologic basis for the clinical sequelae of MM involves the
skeletal, hematologic, renal, and nervous systems.

6. 1.SKELETAL PROCESSES
Plasma-cell proliferation causes extensive skeletal destruction with
osteolytic lesions, anemia, and hypercalcemia. Destruction of bone
and its replacement by tumor may lead to pain, spinal cord
compression, and pathologic fracture.
.Bone pain: Bone pain is the most common presenting symptom in MM.
Most case series report that 70% of patients have bone pain at presentation.
The lumbar spine is one of the most common sites of pain.
.Spinal cord compression:The symptoms that should alert physicians to
consider spinal cord compression are back pain, weakness, numbness, or
dysesthesias in the extremities.
. Hypercalcemia:Confusion, somnolence, bone pain, constipation, nausea,
and thirst are the presenting symptoms of hypercalcemia.

7. 1.SKELETAL PROCESSES
.Pathologic fractures
.Bone lesions

8. 2.HEMATOLOGIC PROCESSES
Bone marrow infiltration by plasma cells results in neutropenia,
anemia, and thrombocytopenia. In terms of bleeding,a patient may
come to medical attention for bleeding resulting from
thrombocytopenia. Rarely, monoclonal protein may absorb clotting
factors and lead to bleeding.
.Anemia:Anemia, which may be quite severe, is the most common cause of
weakness in patients with MM.
.Hyperviscosity:This syndrome is infrequent in MM and occurs with IgG1,
IgG3, or IgA. MM may involve sludging in the capillaries, which results in
purpura, retinal hemorrhage, papilledema, coronary ischemia, or central
nervous system (CNS) symptoms (eg, confusion, vertigo, seizure).
.Cryoglobulinemia:causes Raynaud phenomenon, thrombosis, and
gangrene in the extremities.

9. 3. RENAL PROCESSES
The most common mechanisms of renal injury in MM are direct
tubular injury, amyloidosis, or involvement by plasmacytoma.Renal
conditions that may be observed include hypercalcemic nephropathy,
hyperuricemia due to renal infiltration of plasma cells resulting in
myeloma, light-chain nephropathy,amyloidosis,and
glomerulosclerosis.

10. 3. RENAL PROCESSES
Renal failure and insufficiency are seen in 25% of patients with
MM,including the following manifestations:
.Myeloma kidney syndrome with multiple etiologies
.Amyloidosis with light chains
.Nephrocalcinosis due to hypercalcemia

11. 4. NEUROLOGIC PROCESSES
The nervous system may be involved as a result of radiculopathy
and/or cord compression due to nerve compression and skeletal
destruction (amyloid infiltration of nerves).
Carpal tunnel syndrome is a common complication of myeloma.
Meningitis (especially that resulting from pneumococcal or
meningococcal infection) is more common in patients with MM. Some
peripheral neuropathies have been attributed to MM. Long-term
neurologic function is directly related to the rapidity of the diagnosis
and the institution of appropriate therapy for MM.

12. 5. INFECTION
Abnormal humoral immunity and leukopenia may lead to infection.
Pneumococcal organisms are commonly involved, but shingles (ie,
herpes zoster) and Haemophilus infections are also more common
among patients with MM.

13. PHYSICAL EXAMINATION
.On head, ears, eyes, nose, and throat (HEENT) examination, the eyes may
show exudative macular detachment, retinal hemorrhage, or cotton-wool
spots. Pallor from anemia may be present. Ecchymoses or purpura from
thrombocytopenia may be evident.
.Bony tenderness is not uncommon in MM.
.Neurologic findings may include a sensory level change.
.On evaluation of the abdomen, hepatosplenomegaly may be discovered.
.Amyloidosis may develop in some patients with MM. The characteristic
physical examination findings that suggest amyloidosis include the
following:
Shoulder pad sign
Macroglossia
Typical skin lesions

14. WORKUP
.Blood Studies
.Urine Collection
.Electrophoresis and Immunofixation
.Radiography
.Magnetic Resonance Imaging
.Positron Emission Tomography
.Bone Scan
.Aspiration and Biopsy
.Histologic Findings
.Cytogenetic Analysis

15. DIFFERENTIAL DIAGNOSES

16. MGUS & SMM
Risk factors for progression to MM are as follows:
M protein concentration > 1.5 g/dL
Non-IgG isotype
An abnormal free light chain (FLC) ratio
Risk factors for progression of SMM to MM include any of the
following:
M protein concentration > 3 g/dL
Abnormal FLC ratio
Bone marrow plasma cell concentration > 10%

17. STAGING

18. CHEMOTHERAPY
In patients with symptomatic MM, chemotherapy is required. In
asymptomatic patients with MM, treatment is delayed until disease
clinically progresses or until serum or urine levels of M protein
substantially increase.
The first step before starting therapy in MM is to determine whether a
patient is a candidate for an autologous stem cell transplant.
Eligibility depends primarily on the patient’s age and comorbidities.
Typically an age of 65 years is used as a cut-off point for transplant
eligibility.
Although a single drug may be used to treat multiple myeloma, more
often different kinds of drugs are used in combination. For example:
Melphalan and prednisone (MP), with or without thalidomide or
bortezomib. Vincristine, doxorubicin (Adriamycin), and
dexamethasone (called VAD)

19. E-mail:Salarnikmanesh95@gmail.com
Linkdln:Salar nikmanesh
Call:+0098 914 411 8812