Clinical and epidemiological profile
The disease predominantly affects the axial skeleton and the proximal ends of long tubular bones. The main clinical symptoms include fever, severe fatigue, as well as persistent bone and back pain.
Approximately 20% of patients additionally present with concurrent amyloidosis. Disease manifestation is often incidental (based on blood tests or radiographs ordered for another reason). However, in a third of cases, the disease debuts acutely with a severe pathological fracture, typically in the axial skeleton region.
Radiography and computed tomography
The classic radiographic appearance of multiple myeloma is well-circumscribed lytic bone defects known as "punched-out lesions" (punched-out lesions). This sign is particularly striking on skull radiographs. Less common are permeative destruction or a "moth-eaten" pattern of bone destruction (moth-eaten).
An important sign is diffuse osteopenia, which affects the spine and leads to multiple compression fractures. Sclerotic or mixed lesions without prior treatment are atypical; an exclusively sclerotic form is associated with the rare POEMS syndrome.
CT and PET/CT Low-dose whole-body CT (Low-dose whole-body CT) and PET/CT significantly outperform conventional radiography in sensitivity.
- On CT, foci in the bone marrow are visualized as areas of soft-tissue attenuation.
- Disease progression is accompanied by endosteal scalloping (endosteal scalloping), destruction of the cortical layer, and breakthrough of tumor masses into the surrounding tissue.
- It is important to remember that diffuse osteopenia in myeloma can be visually indistinguishable from routine osteoporosis on CT.
MRI diagnostics and bone marrow patterns
Whole-body magnetic resonance imaging (WB-MRI) is the most sensitive imaging method for detecting bone marrow infiltration. There are 5 main MRI patterns:
- Normal pattern — occurs with a low grade of malignancy of plasma cell infiltration.
- Focal (18–50%) — areas greater than 5 mm with low signal intensity on T1-weighted images and high signal intensity on T2-weighted and STIR images.
- Diffuse (25–43%) — generalized reduction in bone marrow signal intensity on T1-weighted images. The intervertebral discs appear brighter (hyperintense) than the vertebral bodies themselves. This pattern indicates a high tumor burden and a worse prognosis.
- Combined — a combination of diffuse changes with distinct large foci.
- Variegated (1–5%) — multiple tiny foci against a background of healthy bone marrow, typical of early stages.
MRI is the modality of choice for the differential diagnosis of vertebral collapse: it accurately differentiates benign osteoporotic fractures (~66%) from malignant infiltrative ones (~33%). MRI findings are integrated into the modern Durie and Salmon PLUS staging system.
Assessment of treatment response
Radiological assessment of treatment efficacy is based on changes in bone marrow signal characteristics:
- Good response: complete normalization of signal intensity on MRI.
- Partial response: transition of the diffuse pattern to a focal or variegated pattern.
- Residual non-viable foci: persist on MRI but acquire cystic/fluid characteristics. They do not enhance with contrast (or show only peripheral rim enhancement) and may develop a "fatty halo" (fatty halo) around them.
Functional imaging is also widely used. Diffusion-weighted imaging (DWI) shows an increase in the apparent diffusion coefficient (ADC) upon effective treatment, while PET/CT registers a decrease in radiopharmaceutical (FDG) uptake.
Plasma cell dyscrasias and systemic mastocytosis
Multiple myeloma is just one nosology within the spectrum of plasma cell dyscrasias. This group also includes monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma, and solitary plasmacytoma (radiologically appearing as an expansile lytic lesion with a soft-tissue component).
The differential diagnosis of bone marrow lesions should also include systemic mastocytosis. This is a myeloproliferative disorder that involves the bone marrow in 90% of cases and manifests with back pain. It presents predominantly in older adults (5th–8th decades of life) and is classified into indolent, smoldering, and aggressive forms.
Briefly: answers to topical questions
What are the components of the CRAB diagnostic criteria in multiple myeloma?
The CRAB diagnostic criteria include the following end-organ damage markers:
- C (Calcium) — hypercalcemia (serum calcium > 2.75 mmol/L);
- R (Renal) — renal impairment attributable to myeloma;
- A (Anemia) — anemia (hemoglobin < 100 g/L);
- B (Bone) — bone lesions (lytic lesions or osteoporosis with compression fractures).
How does multiple myeloma differ from osteolytic metastases on radiographs?
On radiographs, multiple myeloma differs from osteolytic metastases in the character and size of the destructive lesions. Multiple myeloma is more specifically characterized by multiple small (up to 20 mm), well-circumscribed round or oval lytic lesions known as "punched-out lesions" (punched-out lesions). Metastatic disease is the primary differential diagnosis in this age group.
What are the radiological signs characteristic of solitary bone plasmacytoma?
Solitary bone plasmacytoma is characterized by an expansile lytic lesion associated with a soft-tissue component.
- Radiography — an expansile bone lesion with thickened trabeculae and a multilocular appearance ("soap bubble" appearance — soap bubble).
- CT — "hollow vertebral body or pedicle" sign (hollow vertebral body or pedicle).
- MRI — low signal on T1-weighted images, high signal on T2-weighted images, homogeneous intense contrast enhancement.
- Specific sign — "mini-brain appearance" (mini-brain appearance) on CT and MRI, caused by thickened peripheral trabeculae protruding into the bone marrow cavity.
What radiological criteria are used in the Durie-Salmon PLUS staging system for multiple myeloma?
The Durie-Salmon PLUS staging system incorporates whole-body magnetic resonance imaging (Whole-body MRI) and/or positron emission tomography-computed tomography (PET-CT) data. The primary radiological criterion that directly determines the assigned disease stage is the number of detected bone lesions.
The "punched-out" lesion sign is easy to remember as marks from a standard office hole puncher on the skull bones, as the lytic lesions appear so smooth and well-defined on radiographs.
Class and exam questions
How does multiple myeloma differ from bone metastases on X-ray?
Unlike metastases, multiple small (up to 20 mm), very well-defined round or oval lytic lesions are more specific for myeloma.
Why do vertebrae frequently fracture in myeloma?
Fractures occur against the background of pronounced diffuse osteopenia, as well as due to direct malignant infiltration of vertebral bodies by tumor cells.
What is the advantage of MRI over PET/CT in staging?
Whole-body MRI is more sensitive to bone marrow involvement patterns. PET/CT may miss areas of diffuse bone marrow involvement that are clearly visible on MRI.
What else to study on this topic
- Solitary plasmacytoma and monoclonal gammopathy of undetermined significance (MGUS)
- Durie and Salmon PLUS myeloma staging system
- Sclerotic myeloma and POEMS syndrome
- Classification and imaging findings of systemic mastocytosis
- Use of DWI sequences to assess tumor response to treatment
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