Myeloma

Tumor biology and incidence

• Most common primary malignant tumor of bone (approximately 50% of malignant bone tumors)
• Malignant tumor of plasma cells, characterized by widespread osteolytic bone destruction
• Often associated with refractory anemia, hypercalcemia, renal dysfunction, and decreased resistance to infection
• Less common features: amyloid deposition, derangement of coagulation, cryoglobulinemia, and elevated serum viscosity

Stages

1. Solitary plasmacytoma (single lesion)
2. Multiple sites in bone (myeloma)
3. Multiple sites in bone and organs (myelomatosis)

Age

• Age range: 20 to 80 years
• Average age: 60 years

Gender

M:F = 1:1

Presentation

• Pain is cardinal early symptom
• Pain classically worse during day and with activity
• Patients often treated for other causes of skeletal pain before diagnosis
• Pathologic fracture occurs in 20% of patients
• Fatigue and weakness usually present

Physical findings

Weight loss often evident

Blood work

• Elevation of BUN and creatinine common; poor prognosis
• Anemia and elevated ESR common
• Hypercalcemia frequently present at some stage of disease
• Serum phosphate and alkaline phosphatase generally normal
• Perform serum immune electrophoresis to make diagnosis (monoclonal elevation of IgG, IgA and Bence Jones light chains most common finding)
• Perform peripheral blood smear to detect rouleaux formation
• Check coagulation if surgery is planned

Plain films

Site

• Vertebral bodies, ribs, skull, pelvis, and sternum more commonly affected than femur, tibia, radius, and humerus
• Small bone involvement rare

Size

Variable: Surrounding disease and changes of osteoporosis may be extensive

Tumor effect on bone

• Pure osteolytic destruction of the bone common
• Rarely, focal, or diffuse sclerotic lesions may be seen

Bone response to tumor

No surrounding sclerosis or periosteal reaction

Matrix

None

Cortex

• Slight cortical thinning; can have endosteal scalloping
• Severe osteoporosis often present

Soft tissue mass

Common

Bone scan

Often cold in myeloma, but can be hot

Differential diagnosis

• Osteoporosis
  • May be indistinguishable from osteoporosis in spine; multiple compression fractures
• Metastasis
• Brown tumor
• Giant cell tumor
• Fibrosarcoma
• Malignant fibrous histiocytoma
• Lymphoma
• Osteomyelitis
• Chordoma (in the sacrum)
• Low-grade chondrosarcoma (especially in pelvis)

Pathology

• Gross: Grey-tan or "fish-flesh" type tissue
• Microscopic: Infiltration by atypical plasma cells
• Immunostaining shows monoclonal staining for kappa or lambda light chains

Diagnosis and treatment

• Serum immune electrophoresis generally diagnostic
  • If electrophoresis negative, consider biopsy of remote bone marrow
• Staging system for myeloma used to predict survival by attempting to estimate total body tumor burden
  • Staging based on the values for serum hemoglobin, serum calcium, serum M component, and the extent of skeletal involvement as determined in the radiographic work-up
  • Tumor burden categorized as low (Stage I), intermediate (Stage II), or high (Stage III).
• Patients further divided based on renal function (serum creatinine < 2mg/dl = A, and serum creatinine > 2mg/dl = B).
• Stage and renal function are combined to predict survival.
• Chemotherapy mainstay of treatment
  • Recent randomized trials suggest intensive chemotherapy with autogenous bone marrow transplant will increase length of event-free survival
  • With standard chemotherapy, 15% of patients die within the first 6 months of diagnosis; thereafter, mortality rate approximately 15% per year
  • Results are likely improved with intensive chemotherapy supported by autogenous marrow transplantation
• Pamidronate demonstrated effective in management of hypercalcemia and (in long-term use) in controlling bone symptoms
• Radiation can effectively control localized lesions causing pain or limiting activity
• If radiation not successful, surgery may be required for impending pathologic fracture or spinal compression

Solitary myeloma (plasmacytoma)

• Rare lesion
• Criteria for diagnosis
  • Solitary lesion on skeletal survey
  • Histologic confirmation of plasmacytoma after biopsy of lesion
  • Bone marrow plasmacytosis of 10% or less
  • Negative screening MRI of spine
  • Negative serum immunoelectrophoresis
• May be the sole manifestation of already disseminated process
• Disease may remain localized or progress with time
• Solitary myeloma may be resected or (more commonly) treated locally with irradiation
  

Sclerosing myeloma

• More common in younger males
• Lesions osteolytic, with reactive sclerosis (as opposed to usual, non-sclerosing myeloma)
• Use the mnemonic POEMS
  • Polyneuropathy (in 30-50 %)
  • Organomegaly (liver and spleen)
  • Endocrine (gynecomastia, amenorrhea)
  • Monoclonal Gammopathy
  • Skin hyperpigmentation and hirsutism