What is the workup for a lytic bone lesion?

From the Guidelines

The workup for a lytic bone lesion should begin with a thorough history and physical examination, focusing on pain characteristics, duration of symptoms, and risk factors for malignancy, and should include a full skeleton X-ray survey, with optional magnetic resonance imaging (MRI) for greater detail, particularly if spinal cord compression is suspected, as recommended by the most recent guidelines 1. The initial evaluation should also include laboratory tests such as complete blood count, comprehensive metabolic panel, calcium, phosphorus, alkaline phosphatase, and erythrocyte sedimentation rate.

• Additional specific tests may include serum protein electrophoresis and urine protein electrophoresis to evaluate for multiple myeloma, particularly in patients over 40 years old.
• Advanced imaging is typically necessary and should include CT scan of the affected area to better characterize the lesion and assess cortical involvement, and MRI to evaluate soft tissue extension and marrow involvement.
• A whole-body bone scan can identify additional lesions, and for lesions suspicious for malignancy, a CT chest/abdomen/pelvis should be performed to search for a primary tumor. The use of FDG-PET-CT imaging is also recommended for assessing treatment response of hypermetabolic bone metastasis, as it allows for quantitative assessment of FDG uptake immediately before, during, and after therapy, with partial response requiring a drop of 30% of the most active bone (or other) lesion, according to the PERCIST criteria 1. Ultimately, a biopsy is often required for definitive diagnosis, either through CT-guided needle biopsy or open biopsy depending on lesion location and suspected diagnosis, and should be carefully planned with input from the surgeon who will perform any potential definitive resection to avoid contaminating tissue planes, as this systematic approach helps differentiate between benign conditions like bone cysts or fibrous dysplasia and malignant processes such as metastatic disease, multiple myeloma, or primary bone tumors.

From the Research

Lytic Bone Lesion Workup

• Lytic bone lesions can have various differential diagnoses, including bone metastasis of cancer, multiple myeloma, primary bone cancers, and infections 2
• Diagnosing lytic bone lesions with either multiple myeloma or tumor metastasis can be challenging, despite the development of several imaging modalities such as magnetic resonance imaging and positron emission tomography/computed tomography 2
• Urinalysis can be a useful noninvasive diagnostic method, and physicians should evaluate urine protein levels when lytic bone lesions are observed 2

Diagnostic Techniques

• Ultrasonically guided fine-needle aspiration biopsy (US-FNAB) can be a useful technique to obtain a pathological diagnosis in cases of lytic bone lesions that can be visualized with ultrasound, with a sensitivity of 93% 3
• Computed tomography (CT)-guided percutaneous bone biopsies of lytic bone lesions can provide a diagnosis of certainty in all cases, with a yield of 100% for pathological analysis and 94.6% for molecular testing 4
• CT-guided percutaneous biopsies of lytic bone lesions are associated with a very low complication rate of 2% 4

Treatment and Prognosis

• Bone remineralization of lytic lesions in multiple myeloma can occur in 72% of patients, with 36% achieving at least 25% of bone remineralization 5
• Factors such as serum alkaline phosphatase, high levels of RUNX2 and SOX4 gene expression, and patient baseline bone-related factors can correlate with increasing extent of bone remineralization 5
• Female patients and those with high-risk disease defined by gene expression profile signature (GEP70 ≥ 0.66) may be more likely to experience bone remineralization 5

Clinical Considerations

• When photon-deficient lesions are demonstrated on bone scans of patients in the cancer age group, metastatic disease should be the first consideration, especially in the presence of a lytic bone lesion 6
• Bronchogenic and breast carcinomas are the most common primaries, and a negative physical examination and normal CEA levels do not exclude the possibility of metastatic breast cancer 6