Multiple myeloma differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief:  Hannan Javed, M.D.[2] Haytham Allaham, M.D. [3] Shyam Patel [4]

## Overview

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Multiple myeloma must be differentiated from other causes of bone lesions such as osteoporosis, osteomalacia, scurvy, osteogenesis imperfecta, and homocystinuria. Each condition has unique causes, features, and treatment.

## Differentiating Multiple Myeloma from other Diseases

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* The table below summarizes how to differentiate multiple myeloma from other conditions that have a similar presentation:[1][2][3][4][5][6][7]

Differential Diagnosis | Causes | Features | Therapy

|
|
|

Multiple myeloma |

* Chromosomal aberrations or other genetic insults
* Malignant transformation of plasma cells
* Clonal plasma cell proliferation

* Diffuse bone pain and tenderness with osteolytic lesions
* Renal failure
* Hypercalcemia
* Anemia

* Induction chemotherapy with bortezomib, lenalidomide, and dexamethasone
* Bisphosphonates
* RANK ligand inhibitors (denosumab)
* Autologous stem cell transplantation

Monoclonal gammopathy of undetermined significance (MGUS) |

* Chromosomal aberrations or other genetic insults
* Clonal plasma cell proliferation

* Asymptomatic
* Serum M protein of <30 g/L
* Fewer than 10% plasma cells in the bone marrow
* No evidence of bone or organ damage

| Observation
Asymptomatic Plasma Cell Myeloma

(Smoldering and Indolent plasma cell myeloma)

* Chromosomal aberrations or other genetic insults
* Malignant transformation of plasma cells
* Clonal plasma cell proliferation

* Asymptomatic
* Serum M protein of >30 g/L
* Greater than 10% plasma cells in the bone marrow
* No evidence of bone or organ damage

| Observation
Plasma Cell Leukemia |

* Chromosomal aberrations or other genetic insults
* Malignant transformation of plasma cells

* Renal failure
* Hypercalcemia
* Cytopenias
* No bone lesions

| Chemotherapy
Plasmacytoma |

* Chromosomal aberrations or other genetic insults
* Malignant transformation of plasma cells

* Solitary bone plasmacytoma (bone)
* Extramedullary plasmacytoma (soft tissues)
* Clinical manifestations related to tumor mass and compression symptoms

| Surgery
Osteoporosis |

* Imbalance between bone resorption and bone formation
* Preceded by osteopenia
* Decreased bone mineral density

* Acute musculoskletal pain if fractures develop
* Severe decrease in BMD on dual-energy X-ray absorptiometry (DEXA) test
* T score less than -2.5 on DEXA scan

* Calcium and vitamin D supplementation
* Bisphosphonates
* Weight-bearing exercise
* Teriparatide
* RANK ligand inhibitors (denosumab)

Osteomalacia |

* Inadequate mineralization of bone
* Deficiency of vitamin D calcium, or phosphorus
* Renal tubular acidosis
* Malabsorption

* Diffuse bone pain, fatigue, and fractures
* Low bone mineral density (BMD)
* Hypocalcemia

* Vitamin D3 supplementation

Scurvy |

* Vitamin C deficiency
* Malabsorption
* Hemodialysis

* Gum disease such as gum bleeding
* Loose teeth
* Easy bruising
* Impaired immune response
* Impaired wound healing

* Vitamin C supplementation
* Citrus fruits

Osteogenesis imperfecta |

* Mutations in COL1A1 or COL1A2
* Impaired type I collagen synthesis

* Short stature, scoliosis, and propensity for fractures
* Blue discoloration of sclera

* Bisphosphonates
* Physical therapy
* Surgical fixation of brittle bones
* Genetic counseling for offspring

Homocystinuria |

* Deficiency of cystathionine beta synthase
* Deficiency of folate, vitamin B12, or vitamin B6

* Diffuse bone pain and musculoskeletal symptoms

* High-dose vitamin B6 supplementation
* Betaine supplementation

## References

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1. ↑ "Myeloma - SEER Stat Fact Sheets". Retrieved 17 February 2014.
2. ↑ Zuo QY, Wang H, Li W, Niu XH, Huang YH, Chen J; et al. (2017). "Treatment and outcomes of tumor-induced osteomalacia associated with phosphaturic mesenchymal tumors: retrospective review of 12 patients". BMC Musculoskelet Disord. 18 (1): 403. doi:10.1186/s12891-017-1756-1. PMC 5609032. PMID 28934935.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
3. ↑ Shaker JL, Albert C, Fritz J, Harris G (2015). "Recent developments in osteogenesis imperfecta". F1000Res. 4 (F1000 Faculty Rev): 681. doi:10.12688/f1000research.6398.1. PMC 4566283. PMID 26401268.CS1 maint: Multiple names: authors list (link)
4. ↑ Kumar A, Palfrey HA, Pathak R, Kadowitz PJ, Gettys TW, Murthy SN (2017). "The metabolism and significance of homocysteine in nutrition and health". Nutr Metab (Lond). 14: 78. doi:10.1186/s12986-017-0233-z. PMC 5741875. PMID 29299040.CS1 maint: Multiple names: authors list (link)
5. ↑ Soh KT, Tario JD, Wallace PK (December 2017). "Diagnosis of Plasma Cell Dyscrasias and Monitoring of Minimal Residual Disease by Multiparametric Flow Cytometry". Clin. Lab. Med. 37 (4): 821–853. doi:10.1016/j.cll.2017.08.001. PMC 5804349. PMID 29128071.
6. ↑ Kyle RA, Rajkumar SV (January 2009). "Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma". Leukemia. 23 (1): 3–9. doi:10.1038/leu.2008.291. PMC 2627786. PMID 18971951.
7. ↑ Rajkumar SV, Landgren O, Mateos MV (May 2015). "Smoldering multiple myeloma". Blood. 125 (20): 3069–75. doi:10.1182/blood-2014-09-568899. PMC 4432003. PMID 25838344.