Pathogenesis and Molecular Mechanisms
The disease is rooted in the clonal expansion of a single plasma cell clone that synthesizes identical heavy and light chains of immunoglobulins, known as the M-component (monoclonal protein). Tumor cell proliferation is actively supported by the cytokine IL-6, which is produced by fibroblasts and macrophages of the bone marrow stroma.
At the genetic level, frequent alterations include chromosomal translocations involving the IgG locus on chromosome 14, as well as chromosome 4 aberrations with mutations in the fibroblast growth factor receptor 3 gene (FGFR3). The tumor grows outward from the medullary cavity toward the cortical bone, and the secretion of specific factors activates osteoclasts, causing massive bone resorption.
Clinical and Morphological Manifestations
Skeletal involvement predominantly affects the spine, ribs, and flat bones of the skull. Radiographically, destruction lesions appear as 'punched-out' holes, which carry a high risk of pathological fractures and vertebral collapse.
Blood tests reveal a markedly elevated ESR (erythrocyte sedimentation rate; notably, it is not elevated in light-chain myeloma), formation of rouleaux (stacks of red blood cells), and hyperviscosity syndrome. Replacement of the bone marrow by tumor masses leads to normochromic normocytic anemia, neutropenia, and thrombocytopenia, rendering patients highly susceptible to infections.
Renal involvement develops due to hypercalcemia, nephrocalcinosis, and the filtration of low-molecular-weight Bence Jones proteins, leading to uremia.
Laboratory Diagnostics and Cytology
To confirm the diagnosis, serum protein electrophoresis is used, where paraproteins are visualized as dense bands in the globulin region, alongside confirmatory methods such as immunoelectrophoresis.
Cytological examination of bone marrow aspirates reveals a predominance of plasmablasts, mature plasma cells, and intermediate forms showing signs of atypia (such as multinucleation). A characteristic morphological feature is the presence of intracellular protein aggregates known as Russell bodies. Normally, plasma cells account for less than 10% of the bone marrow cellularity, whereas in myeloma, this proportion is significantly elevated.