Diagnosing Leg Swelling from Leukemia Infiltration
To diagnose leg swelling from leukemia infiltration, obtain tissue biopsy of the affected muscle with comprehensive pathologic evaluation including morphology, flow cytometry, cytogenetics, and molecular studies—the same ancillary testing required for bone marrow specimens.
Clinical Presentation
Leukemic muscle infiltration typically manifests as:
- Focal pain and swelling in the affected extremity 1
- Muscle weakness 1
- Palpable mass or diffuse muscle enlargement 1
The lower extremities are involved in 44% of intramuscular leukemic cases, making leg swelling a recognized presentation 1.
Diagnostic Approach
Initial Assessment
When leukemia infiltration is suspected as the cause of leg swelling, document:
- Duration of swelling and associated symptoms (pain, weakness) 2
- Known leukemia diagnosis and treatment history 2
- Recent growth factor therapy or transfusions that might confound findings 2
Physical examination should specifically assess for:
- Asymmetric leg swelling suggesting focal infiltration 2
- Presence of other extramedullary masses or organomegaly 2
- Cutaneous lesions that may indicate leukemic involvement 3
Laboratory Studies
Obtain peripheral blood evaluation including:
- Complete blood count with differential 2, 4
- Peripheral blood smear review to assess for circulating blasts 2, 4
- Lactate dehydrogenase, comprehensive metabolic panel 2, 4
If peripheral blood shows sufficient blasts, perform flow cytometry, FISH, and molecular studies on blood specimens 2, 4.
Imaging Studies
MRI is the preferred imaging modality for evaluating suspected leukemic muscle infiltration 1. Characteristic findings include:
- Diffuse muscle infiltration (most common pattern) 1
- Hypointense to isointense signal on T1-weighted images 1
- Hyperintense signal on T2-weighted images 1
- Homogeneous enhancement with contrast 1
CT imaging can also demonstrate muscle infiltration with homogeneous enhancement 1.
FDG-PET/CT may be valuable for detecting extramedullary leukemic infiltrates and can identify occult lesions not apparent on physical examination 5. This modality is particularly useful given the high frequency of extramedullary involvement in leukemia 2.
Definitive Diagnosis: Tissue Biopsy
When extramedullary disease presents without bone marrow or blood involvement, tissue biopsy of the affected muscle is mandatory 2. The pathologist must process the specimen for:
- Morphologic examination with adequate tissue for evaluation 2, 6
- Flow cytometry immunophenotyping to confirm leukemic lineage 2
- Conventional cytogenetic analysis (karyotype) 2
- Molecular genetic studies appropriate to the suspected leukemia subtype 2
This comprehensive ancillary testing mirrors the requirements for bone marrow specimens and is essential for definitive diagnosis 2, 6.
Bone Marrow Evaluation
Even when extramedullary infiltration is confirmed, obtain bone marrow aspirate and biopsy to:
- Assess for concurrent marrow involvement 2, 4
- Establish baseline disease burden 4
- Guide treatment decisions 2
Fresh bone marrow aspirate should be processed for morphology, flow cytometry, cytogenetics, and molecular studies 2, 4.
Common Pitfalls
Do not rely solely on imaging to diagnose leukemic infiltration—tissue confirmation is required 2, 6. While MRI and PET/CT can identify suspicious lesions, they cannot definitively distinguish leukemic infiltration from other causes of muscle pathology.
Avoid delaying biopsy when extramedullary disease is suspected, as isolated extramedullary relapse can occur even with bone marrow in complete remission 5.
Ensure adequate tissue sampling for all required ancillary studies, as immunophenotyping and genetic analysis are essential for proper classification and treatment planning 2.
Leukemia Subtypes
Acute myeloid leukemia is the most common subtype associated with intramuscular infiltration 1. However, any leukemia type can present with extramedullary involvement, necessitating comprehensive diagnostic evaluation regardless of suspected subtype 1, 3.