What is the next best step in managing a 30-year-old female patient with an indeterminate expansile lytic lesion in the inferior right occipital bone, slightly elevated creatinine (Impaired renal function), and elevated total bilirubin (Hyperbilirubinemia), with differential considerations including multiple myeloma, metastatic disease, and lymphoproliferative disorder?

Management of Indeterminate Lytic Occipital Bone Lesion

The next best step is to obtain whole-body low-dose CT (WBLD-CT) for systemic evaluation and complete the multiple myeloma laboratory workup including serum protein electrophoresis with immunofixation, serum free light chain assay, and bone marrow biopsy with flow cytometry. 1

Immediate Imaging Requirements

You must obtain WBLD-CT immediately to determine whether this is a solitary lesion or part of systemic disease, as WBLD-CT detects 60% more relevant findings than conventional X-rays and is the gold standard for detecting lytic lesions (grade 1A recommendation). 1, 2 The MRI has already been completed and shows the characteristic features of the lesion, but whole-body imaging is mandatory to exclude multiple sites of disease. 1

Why WBLD-CT Over PET/CT Initially

• WBLD-CT is the novel standard procedure for diagnosis of lytic disease in myeloma patients (grade 1A). 3
• While PET/CT was recommended in the radiology report, WBLD-CT provides superior evaluation of cortical bone detail and areas at risk of fracture. 1
• PET/CT has limited utility for identifying unknown primary cancers in skeletal metastases (failed to identify primary in 12 of 13 patients in one study), though it may be useful for staging if a primary is identified. 4

Mandatory Laboratory Workup

Order the complete myeloma panel immediately, which includes: 1

• Serum protein electrophoresis (SPEP) with immunofixation electrophoresis (SIFE)
• Serum free light chain (FLC) assay
• Complete blood count (already done—normal)
• Serum calcium (already done—normal at 9.0 mg/dL)
• Creatinine (already done—mildly elevated at 1.04 mg/dL)
• Albumin (already done—normal at 4.8 g/dL)
• Quantitative immunoglobulin levels (IgG, IgA, IgM)
• 24-hour urine for total protein with urine protein electrophoresis (UPEP) and urine immunofixation electrophoresis (UIFE)

Key Laboratory Findings Already Present

Your patient's labs show mostly normal values, which is reassuring but does not exclude myeloma. 5 The slightly elevated creatinine (1.04 mg/dL) and normal calcium argue against advanced myeloma with "myeloma kidney" or hypercalcemia, which are present in 25% of myeloma patients at diagnosis. 5 However, 98% of myeloma patients have an M-protein detectable in serum or urine, so the protein studies are essential. 5

Bone Marrow Evaluation

Proceed with bone marrow aspiration and biopsy with flow cytometry if imaging or laboratory findings suggest plasma cell dyscrasia. 1 This is mandatory because:

• Flow cytometry can detect occult bone marrow disease in 49-68% of patients with apparent solitary plasmacytoma. 1
• Patients with occult marrow involvement have significantly higher progression rates to multiple myeloma (71-72% versus 8-12.5%). 1
• Bone marrow plasmacytosis >10% would exclude solitary plasmacytoma and confirm multiple myeloma. 1

Differential Diagnosis Considerations

The imaging characteristics favor multiple myeloma/solitary plasmacytoma as the leading diagnosis: 1, 2

• Lytic lesions are present in 80-90% of myeloma patients at diagnosis. 2, 6
• Multiple myeloma classically presents as "punched out" lytic lesions. 6
• The lesion shows moderate contrast enhancement and hyperintensity on T1 and T2, consistent with marrow replacement. 1

Metastatic disease remains in the differential, as metastases are the most frequent cause of skull lesions in adults (most commonly from breast cancer). 6 However, the patient's age (30 years) and lack of known primary malignancy make this less likely.

Langerhans cell histiocytosis should be considered, as eosinophilic granuloma presents as an osteolytic lesion with bevelled edges in younger patients. 6

Management Algorithm Summary

1. Order WBLD-CT immediately to assess for systemic disease. 3, 1
2. Complete myeloma laboratory workup (SPEP/SIFE, FLC, immunoglobulins, UPEP/UIFE). 1
3. Perform bone marrow biopsy with flow cytometry if myeloma workup is positive or if WBLD-CT shows additional lesions. 1
4. Consider PET/CT for staging if a primary malignancy is identified or if initial workup is inconclusive. 1

Critical Pitfalls to Avoid

Do not delay the workup based on normal CBC and calcium. 5 Approximately 20% of myeloma patients have normal skeletal radiographs at diagnosis, and early disease may present with isolated lesions. 5

Do not assume this is a benign lesion based on the patient's young age—while metastases are more common in patients over 40, myeloma and lymphoproliferative disorders can occur in younger patients. 4

Address the renal impairment carefully. The mildly elevated creatinine (1.04 mg/dL, eGFR 74) requires attention, as contrast-enhanced imaging may be needed and myeloma can cause progressive renal dysfunction. 5 Ensure adequate hydration if additional contrast studies are required.