Axillary Lymphadenopathy in Multiple Myeloma: CT Imaging Findings and Clinical Significance

Axillary lymphadenopathy represents a significant radiological finding that warrants careful clinical correlation, particularly in patients with underlying malignancies such as multiple myeloma. This CT scan demonstrates axillary lymphadenopathy (indicated by the yellow arrow) in a 57-year-old male patient previously diagnosed with multiple myeloma. While multiple myeloma primarily affects the bone marrow and skeletal system, extramedullary manifestations including lymph node involvement can occur in advanced disease. This coronal CT image provides valuable insights into the pattern of disease spread and highlights the importance of comprehensive imaging evaluation in patients with hematological malignancies. Understanding the relationship between axillary lymphadenopathy and multiple myeloma is essential for accurate staging, treatment planning, and prognostic assessment in affected individuals.

Key Labeled Structure in the Image

Axillary Lymphadenopathy (Yellow Arrow): The yellow arrow points to an enlarged lymph node in the right axillary region. This pathologically enlarged lymph node demonstrates increased size compared to normal lymphatic tissue and represents a site of disease involvement in this patient with multiple myeloma. Axillary lymphadenopathy in multiple myeloma patients may indicate extramedullary disease spread or rarely, concurrent lymphoma (a phenomenon known as “collision tumors”).

Understanding Multiple Myeloma and Lymphadenopathy

Pathophysiology of Multiple Myeloma

Multiple myeloma represents a complex hematological malignancy with unique biological characteristics. This plasma cell dyscrasia arises from the abnormal proliferation of clonal plasma cells in the bone marrow microenvironment.

• Multiple myeloma develops from a monoclonal gammopathy of undetermined significance (MGUS) in most cases, progressing through a smoldering phase before becoming symptomatic.
• The malignant plasma cells produce abnormal immunoglobulins (paraproteins) that can be detected in serum and/or urine, serving as important biomarkers for diagnosis and monitoring.
• Genetic abnormalities, including chromosomal translocations (particularly those involving the immunoglobulin heavy chain locus), deletions, and mutations, play crucial roles in disease pathogenesis.
• The interaction between myeloma cells and the bone marrow microenvironment leads to dysregulated cytokine production, promoting tumor growth, angiogenesis, and bone destruction.
• Osteoclast activation and osteoblast inhibition result in characteristic lytic bone lesions, one of the hallmark features of multiple myeloma.

Extramedullary Disease in Multiple Myeloma

The presence of disease outside the bone marrow compartment represents an important aspect of multiple myeloma progression. Extramedullary involvement carries significant clinical implications.

• Extramedullary disease occurs in approximately 7-18% of multiple myeloma patients at diagnosis and up to 20% during disease progression.
• Extramedullary plasmacytomas can develop via direct extension from bone lesions or through hematogenous spread to soft tissues and organs.
• Common sites of extramedullary involvement include the liver, spleen, lymph nodes, kidneys, and central nervous system.
• Molecular mechanisms driving extramedullary spread include decreased expression of adhesion molecules, increased angiogenesis, and acquisition of an invasive phenotype.
• Patients with extramedullary disease typically demonstrate more aggressive disease biology, resistance to conventional treatments, and poorer overall survival.

Lymphadenopathy in Multiple Myeloma

Lymph node involvement in multiple myeloma represents a specific type of extramedullary disease with distinct characteristics and implications.

• Lymphadenopathy occurs in approximately 1-2% of newly diagnosed multiple myeloma cases but is more common in relapsed/refractory disease.
• Axillary lymphadenopathy, as demonstrated in this CT image, may indicate regional spread from bone lesions or part of more widespread lymphatic involvement.
• Histologically, lymph nodes affected by multiple myeloma show infiltration by clonal plasma cells, often with disruption of normal lymph node architecture.
• Differential diagnosis of lymphadenopathy in multiple myeloma patients includes concurrent lymphoma, infections, and inflammatory processes.
• Flow cytometry and immunohistochemistry are essential for confirming the plasma cell origin of lymphadenopathy when tissue sampling is performed.

Imaging Findings in Multiple Myeloma

CT Imaging Characteristics

Computed tomography plays a vital role in the comprehensive evaluation of patients with multiple myeloma. This imaging modality offers detailed anatomical information about disease extent.

• CT scanning provides excellent assessment of both medullary and extramedullary disease components in multiple myeloma.
• Typical bone findings include punched-out lytic lesions without surrounding sclerosis, diffuse osteopenia, and pathological fractures.
• Extramedullary lesions appear as soft tissue masses that may demonstrate moderate enhancement following intravenous contrast administration.
• Lymphadenopathy, as seen in this case, typically manifests as enlarged, rounded lymph nodes that may show homogeneous or heterogeneous enhancement.
• CT is particularly useful for detecting complications such as spinal cord compression, pathological fractures, and soft tissue involvement.

Advanced Imaging Techniques

Modern imaging approaches have significantly enhanced the ability to detect and characterize multiple myeloma manifestations beyond conventional techniques.

• Whole-body low-dose CT has largely replaced conventional radiography for initial skeletal assessment in multiple myeloma.
• PET/CT combines metabolic and anatomical information, particularly valuable for detecting active disease and monitoring treatment response.
• MRI provides superior soft tissue contrast and is especially useful for evaluating bone marrow infiltration patterns and spinal involvement.
• Diffusion-weighted MRI can help distinguish between active and treated lesions based on cellular density and water movement restriction.
• Dual-energy CT techniques allow for improved bone marrow assessment and detection of early marrow infiltration.

Clinical Implications and Management

Prognostic Significance

The presence of axillary lymphadenopathy and other extramedullary manifestations carries important prognostic implications in multiple myeloma patients.

• Extramedullary disease, including lymphadenopathy, is associated with adverse cytogenetics like t(4;14), t(14;16), and del(17p).
• Patients with lymph node involvement typically demonstrate higher lactate dehydrogenase (LDH) levels, elevated β2-microglobulin, and increased proliferation indices.
• The R-ISS (Revised International Staging System) incorporates cytogenetic abnormalities that are often present in patients with extramedullary disease.
• Extramedullary relapse following novel therapies or autologous stem cell transplantation indicates clonal evolution and treatment resistance.
• Serial imaging to monitor lymphadenopathy provides valuable information about treatment efficacy and disease trajectory.

Therapeutic Considerations

Treatment approaches for multiple myeloma with lymphadenopathy require tailored strategies addressing both medullary and extramedullary disease components.

• Proteasome inhibitors (bortezomib, carfilzomib) combined with immunomodulatory drugs (lenalidomide, pomalidomide) form the backbone of therapy for extramedullary disease.
• Monoclonal antibodies (daratumumab, isatuximab) targeting CD38 have shown efficacy against both medullary and extramedullary components.
• High-dose chemotherapy followed by autologous stem cell transplantation remains an important consolidation strategy when feasible.
• Radiation therapy may provide local control for symptomatic extramedullary plasmacytomas or enlarging lymph nodes causing compression symptoms.
• Clinical trials investigating novel agents, including BCMA-targeted therapies and bispecific antibodies, offer promising options for patients with resistant extramedullary disease.

Future Directions and Research

The management of multiple myeloma with extramedullary manifestations continues to evolve with emerging therapies and deeper biological understanding.

• Novel immunotherapeutic approaches, including CAR-T cell therapy, have demonstrated efficacy in heavily pretreated patients with extramedullary disease.
• Improved understanding of the molecular pathways driving extramedullary spread may identify new therapeutic targets.
• Liquid biopsy techniques analyzing circulating tumor DNA and circulating plasma cells may provide less invasive methods for monitoring extramedullary disease.
• Advanced imaging protocols combining functional and anatomical techniques continue to improve detection and characterization of extramedullary lesions.
• Risk-adapted treatment approaches based on the presence of extramedullary disease are being incorporated into clinical practice guidelines.

Conclusion

This CT image highlighting axillary lymphadenopathy in a patient with multiple myeloma provides a valuable teaching point regarding the spectrum of disease manifestations in this complex hematological malignancy. Extramedullary disease, including lymph node involvement, represents a challenging clinical scenario associated with aggressive disease biology and treatment resistance. Comprehensive imaging evaluation using appropriate modalities is essential for accurate staging, treatment planning, and response assessment. As therapeutic options continue to expand, a multidisciplinary approach incorporating advanced imaging, novel therapeutic agents, and supportive care remains the cornerstone of management for multiple myeloma patients with extramedullary manifestations.

1. Extramedullary Disease in Multiple Myeloma: CT Findings of Axillary Lymphadenopathy
2. Multiple Myeloma Beyond Bone: Imaging and Clinical Significance of Axillary Lymphadenopathy
3. CT Imaging Features of Lymph Node Involvement in Multiple Myeloma
4. Advanced Multiple Myeloma: Recognizing and Managing Axillary Lymphadenopathy
5. Radiological Assessment of Extramedullary Multiple Myeloma: Focus on Lymphadenopathy