Hematologic neoplasms
Myeloma of bone

Author: Sheren Younes, M.D. (see Authors page)

Revised: 28 October 2016, last major update April 2014

Copyright: (c) 2003-2016,, Inc.

PubMed search: myeloma [title] bone

Related topics: Indolent myeloma, multilobated nuclei, nonsecretory myeloma, osteosclerotic myeloma, plasma cell leukemia (primary), smoldering myeloma

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Cite this page: Myeloma of bone. website. Accessed December 18th, 2018.
Definition / general
  • Multiple myeloma (MM) is a neoplastic proliferation of terminally differentiated plasma cells with multifocal skeletal involvement and organ dysfunction
  • Characterized by clonal plasma cells and production of a monoclonal immunoglobulin or its fragment
  • The neoplastic plasma cells can produce:
    • Any of the five immunoglobulin subtypes
    • Production and secretion of light chain only (κ or λ type)
    • Nonsecretory MM
  • Most common bone neoplasm (40% of total bone neoplasms, 50% of malignancies), usually diagnosed by marrow aspiration and biopsy
  • 50 - 80 years
  • Males > females
  • African Americans > Whites
  • Multifocal involving vertebral column, ribs, skull, pelvis, sternum
  • Begins in medulla, then erodes cortical bone
  • Can spread to skin, lymph nodes
  • Myeloma cells interact with bone marrow stromal cells, leading to local cytokine production and signaling changes
  • Cytokines include IL6, insulin like growth factor 1 (IGF1), VEGF, tumor necrosis factor 1 (TNF1), transforming growth factor-B (TGF-B), IL17, IL21, CXC chemokine ligand 12 (CXCL12), and others (Nat Rev Cancer 2007;7:585)
  • Myeloma symptoms are caused by marrow infiltration, bone involvement, organ dysfunction, cytokine production, Ig deposition in tissue and therapy effect (chemotherapy and pain killers)
Clinical features
  • Usually older patients (rare before 40 years), 2 / 3 male, with widespread skeletal lytic lesions, pathologic fractures and back pain
  • Also weakness, normochromic normocytic anemia with rouleux formation, pallor, hepatosplenomegaly, hypercalcemia, primary amyloidosis (AL type) and renal insufficiency due to toxicity of light chains (Bence Jones proteins) to renal epithelium
  • Causes 1% of cancer deaths in Western countries
  • Infections common (due to impaired humoral immunity) with Streptococcus pneumoniae, Staphylococcus aureus, E coli
  • Cellular immunity is normal
  • Hyperviscosity syndrome present in 7%, usually due to IgA or IgG3
  • Most patients have elevated serum levels of IL6
  • History and examination
  • Lab investigations
  • Peripheral blood smear
  • Bone marrow examination, aspirate and trephine, immunophenotyping, cytogenetics
  • Radiologic investigations
  • WHO Diagnostic criteria for MM
    • M protein in serum or Urine
    • Bone marrow (clonal) plasma cells or plasmacytoma
    • Related organ or tissue impairment (end organ damage, including bone lesions)
  • CBC
  • Differential leukocytic count
  • Serum calcium
  • Serum protein electrophoresis to detect clonality, mostly associated with IgG, followed by IgA, light chains only and other Ig types
  • Kidney function tests
  • β2 microglobulin
  • Lactate dehydrogenase
  • C reactive protein
  • 24 hour Bence-Jones proteins in urine
Serum protein electrophoresis images
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Monoclonal gammopathy

Serum protein immunofixation images
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IgD lambda myeloma in 68 year old woman

  • In 20% of cases, only monoclonal light chains (Kappa or Lambda) are present, usually in urine
  • Rouleux formation in peripheral smear (erythrocytes resemble stacked coins) is due to protein present, parallels erythrocyte sedimentation rate
Radiology description
  • Disseminated MM has two common radiological appearances,
    • Numerous, well circumscribed lytic bone lesions (more common) - punched out lucencies without sclerosis (pepperpot skull or raindrop skull with endosteal scalloping)
    • Generalized osteopenia (less common), often associated with vertebral compression fractures
Radiology images
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Skull xray - contributed by Dr. Mark R. Wick

Tibia xray - contributed by Dr. Mark R. Wick

Plasma cell myeloma

Solitary plasma cell myeloma

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Prominent skull defect

Prognostic factors
  • Overall poor prognosis; < 1 year if multiple lesions and no treatment; many years if indolent
    • See Staging
    • Median survival is 3 years with chemotherapy; 10% survive 10 years
    • Poorer prognosis if plasmablastic morphology, CD10+ , IgA myeloma, β microglobulin, more than 3 lytic bone lesions, hypercalcemia, high IL6
    • Unfavorable cytogenetics: t(4;14), t(14;16), t(14;20), del 17p13, hypoploidy, del 13 or aneuploidy
    • Patient related factors include age, performance status, renal failure
Case reports
  • Alkylating agent chemotherapy, bone marrow transplantation, anti topoisomerase II alpha agents
Gross description
  • Multiple masses of soft, red, currant jelly-like material throughout skeletal system; may resemble lymphoma
  • Generalized osteoporosis
Gross images
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Plasma cell myeloma

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Vertebrae with myeloma lesions

Microscopic (histologic) description
  • Bone marrow trephine biopsy shows focal, interstitial or diffuse infiltrate, with variable percentage of involvement
  • Bone marrow biopsies should have > 10% plasma cells to diagnose myeloma
  • Variable degree of plasmacytic maturation, from plasmablastic to plasma cells
  • Cells have large nuclei, may be multinucleated
  • Often with prominent nucleoli, perinuclear hof (due to prominent Golgi apparatus), Mott Cells (blue grapelike inclusions), Russell bodies (cytoplasmic crystalline rods), Dutcher bodies (intranuclear crystalline rods), hyaline inclusions, vacuoles or granules
  • Reticulin deposition, graulomas, decreased hematopoiesis, increased marrow vascularity may be seen
  • 10% have amyloid in vessel walls or as masses
Microscopic (histologic) images
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Bone marrow - high power

With amyloid production - contributed by Dr. Mark R. Wick

Contributed by Dr. Mark R. Wick

Kappa light chain, contributed by Dr. Mark R. Wick

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Bone marrow - low power

Bone marrow - high power

Bone marrow smear

Flame cell

Plasma cells forming rosettes

Prominent kappa staining

Prominent lambda staining

Sarcoidosis and myeloma

Cytology description
  • Variable percentage of involvement
  • Variable morphology of plasma cells: mature, immature, intermediate and plasmablastic
  • Mature plasma cells have eccentric nucleus, condensed chromatin and perinuclear hof
  • Dysplastic forms exist showing nucleocytoplasmic asynchrony with mature cytoplasm compared to nuclei showing diffuse chromatin and nucleli, pleomorphism, high N / C ratio, multilobated and convoluted nuclei, multinuclearity, and mitotic figures
  • Cytoplasm may show basophilia, eosinophilia and flaming crystalline inclusions, Russel body type inclusions, Dutcher body type inclusions
  • Mott cells may be seen
Peripheral blood images
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Plasma cell

Plasma cells with blastic features

Positive stains
  • Kappa or lambda light chains (usually one markedly more than the other), CD38 (plasma cells), CD79a, CD138
  • Variable EMA, variable CD10, may be positive for CD56, CD117, CD52
Negative stains
Flow cytometry images
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Prominent monotypic pattern

Molecular / cytogenetics description
  • del 17p, del 13 or 13q
  • t(4;14)(p16.3;q32) in 25% of cases, causing increased expression of FGFR3 (fibroblast growth factor receptor 3) and IgH
  • t(11;14)(q13;q32) [cyclin D1]:
    • Usually part of complex karyotype
    • May be missed by routine cytogenetics, particularly if the proliferative rate is low (Am J Clin Pathol 2000;113:831)
  • Hyperdiploidy and hypoploidy
Differential diagnosis