How to investigate a patient with incidental pathological fractures at T6 and L3 and leptomeningeal enhancement on MRI (Magnetic Resonance Imaging) whole spine with contrast, presenting with bilateral foot numbness?

Investigation of Pathological Fractures at T6 and L3 with Leptomeningeal Enhancement

Immediate Priority: Rule Out Malignancy

The presence of pathological fractures at two non-contiguous spinal levels (T6 and L3) combined with leptomeningeal enhancement demands urgent investigation for metastatic disease or primary malignancy, as this constellation of findings is highly suspicious for cancer with leptomeningeal spread. 1

Systematic Diagnostic Approach

Step 1: Obtain Comprehensive Imaging

• CT chest/abdomen/pelvis with contrast is essential to identify a primary malignancy, as spindle cell sarcomas and metastatic disease commonly present with pathological fractures in older patients 1
• Whole-body PET-CT should be considered if initial CT is negative, as it can identify occult primary tumors and assess for systemic metastatic disease 1
• The existing MRI spine with contrast already provides critical information about the extent of spinal involvement and leptomeningeal disease 1

Step 2: Cerebrospinal Fluid Analysis

• Lumbar puncture with optimized CSF analysis must be performed as part of the diagnostic work-up for suspected leptomeningeal metastasis 1
• CSF studies should include: cytology for malignant cells, cell count, protein, glucose, and flow cytometry 1
• If initial CSF cytology is negative but clinical suspicion remains high, one repeat lumbar puncture should be performed with optimized analysis conditions 1
• CSF flow studies should be considered if there is evidence of hydrocephalus or large nodules potentially reducing CSF circulation on MRI 1

Step 3: Tissue Diagnosis

• Biopsy of the pathological fracture site is mandatory before any surgical fixation, as adequate imaging including MRI should be performed followed by biopsy 1
• Critical pitfall to avoid: Internal fixation is contraindicated before tissue diagnosis, as it disseminates tumor cells into bone and soft tissues, increasing local recurrence risk 1
• External splintage is recommended for fracture stabilization while awaiting biopsy results 1
• If leptomeningeal disease is confirmed but primary site remains unclear, consider brain or spinal cord biopsy of an accessible leptomeningeal lesion 1

Step 4: Laboratory Evaluation

• Serum markers: LDH, calcium, alkaline phosphatase, complete blood count, and serum protein electrophoresis 1
• Bone marrow biopsy may be indicated if hematologic malignancy is suspected 1
• Inflammatory markers (ESR, CRP) to help differentiate infectious from neoplastic processes 1

Addressing the Bilateral Feet Numbness

The bilateral foot numbness likely represents:

• Spinal cord compression from the pathological fractures at T6 and/or L3, requiring urgent neurological assessment 1
• Leptomeningeal involvement affecting nerve roots, which correlates with the MRI findings 1
• Perform detailed neurological examination documenting motor strength, sensory deficits, reflexes, and gait 1

Differential Diagnosis Considerations

While malignancy is the primary concern, the leptomeningeal enhancement could represent:

• Leptomeningeal metastasis from solid tumors (most likely given pathological fractures) 1
• Primary CNS vasculitis with leptomeningeal involvement, though less likely with pathological fractures 2
• Infectious meningitis (tuberculosis, fungal), though typically presents with fever and systemic symptoms 1
• Primary bone sarcoma with leptomeningeal spread 1, 3

Monitoring and Follow-up Protocol

• Detailed neurological examination every 2-3 months using a standard evaluation form, or sooner if new symptoms develop 1
• Repeat cerebrospinal MRI every 2-3 months or at any instance of suspected clinical progression 1
• Serial CSF studies every 2-3 months if undergoing intra-CSF pharmacotherapy 1

Critical Management Principles

• Do not perform internal fixation until tissue diagnosis is established, as this significantly increases local recurrence risk 1
• External splintage with appropriate pain control is the recommended approach for fracture management during diagnostic work-up 1
• If malignancy is confirmed, neoadjuvant chemotherapy may allow fracture hematoma contraction and facilitate subsequent tumor resection 1
• Treatment should be coordinated through reference centers or reference networks experienced in managing rare bone tumors and leptomeningeal disease 1

Expected Timeline

• CSF analysis and initial staging imaging should be completed within 72 hours of presentation 1
• Biopsy should be performed urgently, ideally within 1 week, given the high suspicion for malignancy 1
• Treatment decisions should be made within a multidisciplinary tumor board once tissue diagnosis is available 1