extramedullary involvement (or extramedullary disease, EMD) in multiple myeloma (MM)

Last edited 06/2023 and last reviewed 06/2023

Extramedullary involvement (or extramedullary disease, EMD) in multiple myeloma

  • multiple myeloma (MM)
    • is a mature B-cell neoplasm defined by the presence of >=10% of clonal plasma cells (PCs) in the bone marrow (or plasmacytoma confirmed by biopsy) and by evidence of end-organ damage (hypercalcemia, renal insufficiency, anemia, bone lesions) caused by the PC disorder
      • PC proliferation is restricted to bone marrow in most patients with MM, a subset develops soft-tissue plasmacytomas, whereby clonal PCs escape and are found outside the bone marrow

  • extramedullary involvement (or extramedullary disease, EMD)
    • represents an aggressive form of multiple myeloma (MM), characterized by the ability of a clone and/or subclone to thrive and grow independent of the bone marrow microenvironment
    • defined by the presence of extraskeletal (i.e. soft tissue or visceral) clonal plasma cells infiltrates
      • can be present either at the time of initial diagnosis (primary EMD) or at the time of relapse (secondary EMD)
    • can be either:
      • a) tumor mass adjacent to bone and extending into soft tissues;
      • b) soft tissue or visceral tumor that is not connected to the bone; or
      • c) diffuse infiltration of organs by plasma cells without any obvious focal lesion
    • most common sites of EMD occurrence at diagnosis were skin/muscle (24%), pleura (12%), lymph nodes (10%), liver (9%), and CNS (6%) (1)
    • presence of soft-tissue plasmacytomas represents an aggressive form of MM, which can be found at the time of MM diagnosis or at relapse
    • study evidence (2)
      • found evidence of EMD in 24% (55 of 226) of evaluable relapsed MM patients
        • in 14% (32 of 226) of these patients, the lesions were not adjacent to bone and thus were classified as EMD-S (soft tissue), while EMD-B (bone) was documented in 10% (23 of 226) of cases
          • in the EMD-S group, the most common site of EMD was skin and subcutaneous tissue (69%), while extramedullary masses extending from vertebrae (78%) were most common in the EMD-B group.
      • patients with soft tissue-related extramedullary relapse had significantly poorer overall survival compared to bone-related extramedullary relapse patients
      • overall survival from diagnosis was as low as five months for soft tissue-related extramedullary relapse patients when compared to 12 months overall survival for bone-related extramedullary relapse

Reference:

  1. Blade J, Beksac M, Caers J, Jurczyszyn A, von Lilienfeld-Toal M, Moreau P, Rasche L, Rosiñol L, Usmani SZ, Zamagni E, Richardson P. Extramedullary disease in multiple myeloma: a systematic literature review. Blood Cancer J. 2022 Mar 21;12(3):45. doi: 10.1038/s41408-022-00643-3. PMID: 35314675; PMCID: PMC8938478
  2. Pour L, Sevcikova S, Greslikova H, Kupska R, Majkova P, Zahradova L, Sandecka V, Adam Z, Krejci M, Kuglik P, Hajek R. Soft-tissue extramedullary multiple myeloma prognosis is significantly worse in comparison to bone-related extramedullary relapse. Haematologica. 2014 Feb;99(2):360-4. doi: 10.3324/haematol.2013.094409. Epub 2013 Sep 13. PMID: 24038024; PMCID: PMC3912968.