Can lymphoma be missed on Computed Tomography (CT) and ultrasound?

Lymphoma Can Be Missed on CT and Ultrasound

Yes, lymphoma can be missed on both CT and ultrasound imaging, which is why PET-CT is now considered the gold standard for staging and assessment of FDG-avid lymphomas. 1

Limitations of CT and Ultrasound in Lymphoma Detection

CT Limitations

• CT alone may miss small lymphomatous lesions, particularly those less than 1.5 cm in diameter
• Cannot reliably distinguish between benign and malignant lymph nodes based solely on size criteria
• Limited ability to detect bone marrow involvement, which can be present with normal-appearing CT
• May miss diffuse organ infiltration without discrete nodules, especially in liver and spleen

Ultrasound Limitations

• Operator-dependent with variable sensitivity
• Limited field of view compared to cross-sectional imaging
• Cannot reliably assess deep structures (mediastinum, retroperitoneum)
• May detect abnormal nodes but cannot definitively characterize them as lymphomatous
• Limited utility for staging compared to CT and PET-CT

Why PET-CT is Superior

PET-CT has become the imaging modality of choice for most lymphoma types because:

1. It combines anatomical information (CT) with functional/metabolic information (PET)
2. Can detect lymphomatous involvement in normal-sized lymph nodes
3. More sensitive for bone marrow involvement than CT alone or even bone marrow biopsy in some lymphoma types 1
4. Can distinguish between viable tumor and fibrosis in residual masses after treatment 1

The Lugano classification (2014) specifically recommends PET-CT as "the gold standard" for staging FDG-avid nodal lymphomas, which includes most common lymphoma types except:

• Chronic lymphocytic leukemia/small lymphocytic lymphoma
• Lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia
• Mycosis fungoides
• Marginal zone NHLs (unless transformation is suspected) 1

Specific Scenarios Where Lymphoma May Be Missed

1. Bone marrow involvement:

   • CT and ultrasound have poor sensitivity
   • Even PET-CT can miss low-volume diffuse involvement (10-20%) in DLBCL 1
   • Bone marrow biopsy remains necessary for many lymphoma types

2. Small nodal disease:

   • Nodes <1.5 cm may not be considered pathologic on CT alone
   • Ultrasound may detect small nodes but cannot characterize them definitively

3. Extranodal sites:

   • Diffuse organ infiltration may be subtle on CT
   • Splenic involvement may be missed if there are no focal lesions
   • Liver involvement may be difficult to detect without discrete lesions

4. Post-treatment assessment:

   • CT cannot reliably distinguish between residual fibrotic masses and active disease
   • Ultrasound has even greater limitations in this setting

Recommendations for Optimal Imaging

For accurate lymphoma detection and staging:

1. Use PET-CT as the primary imaging modality for FDG-avid lymphomas 1
2. Include contrast-enhanced CT when needed for:
   • More accurate nodal measurements
   • Better distinction between bowel and lymphadenopathy
   • Assessment of vascular compression/thrombosis
   • Radiation planning 1
3. Consider bone marrow biopsy based on lymphoma type and PET-CT findings
4. For non-FDG-avid lymphomas, use contrast-enhanced CT as the primary imaging modality

Conclusion

While CT and ultrasound remain valuable tools in lymphoma management, they have significant limitations that can result in missed disease. The integration of PET with CT has dramatically improved the accuracy of lymphoma detection and staging, making PET-CT the current standard of care for most lymphoma types.