What is the next best step in management for a patient with an indeterminate expansile lytic lesion in the inferior right occipital bone, impaired renal function, and elevated total bilirubin, considering the blood work and imaging results?

Diagnostic Assessment: Expansile Lytic Occipital Bone Lesion with Impaired Renal Function and Elevated Bilirubin

This clinical presentation most likely represents multiple myeloma with skull involvement, given the combination of an expansile lytic bone lesion, impaired renal function, and elevated bilirubin—all consistent with CRAB criteria (hypercalcemia, renal insufficiency, anemia, bone lesions) that define symptomatic multiple myeloma. 1

Immediate Diagnostic Workup Required

Essential Laboratory Tests

• Obtain serum protein electrophoresis with immunofixation, serum free light chain assay, complete blood count, serum calcium, creatinine, and albumin immediately to evaluate for plasma cell dyscrasia 1, 2
• Fractionate the total bilirubin into direct and indirect components to determine if the elevation represents conjugated (>35% direct) or unconjugated hyperbilirubinemia, as this guides the differential diagnosis 3
• Check comprehensive liver function tests including ALT, AST, alkaline phosphatase, GGT, and INR/PT to assess for hepatocellular injury versus cholestasis 3

Mandatory Imaging Studies

• MRI of the skull with gadolinium contrast is the gold standard for characterizing this occipital bone lesion, assessing bone marrow involvement, soft tissue extension, and potential intracranial complications 2
• CT of the skull with bone windows should be performed concurrently to evaluate cortical bone detail and identify the full extent of lytic destruction 2, 4
• Whole-body low-dose CT or skeletal survey is mandatory to determine whether this is a solitary lesion or part of systemic multiple myeloma, as this fundamentally changes diagnosis and management 1, 2, 4

Tissue Diagnosis

• Bone marrow aspiration and biopsy with flow cytometry is mandatory if multiple myeloma is suspected, as ≥10% clonal plasma cells on bone marrow examination confirms multiple myeloma rather than solitary plasmacytoma 1, 2
• Flow cytometry can detect occult bone marrow disease in 49-68% of patients with apparent solitary plasmacytoma, and these patients have dramatically higher progression rates to multiple myeloma (71-72% versus 8-12.5%) 2

Differential Diagnosis Framework

Most Likely: Multiple Myeloma

• The combination of lytic skull lesion + renal insufficiency + elevated bilirubin strongly suggests multiple myeloma with end-organ damage meeting CRAB criteria 1
• Multiple myeloma characteristically presents with numerous, well-circumscribed, punched-out lytic bone lesions in the skull without reactive bone formation 4
• Renal insufficiency (creatinine >1.73 μmol/L or >2 mg/dl) is one of the defining CRAB criteria for symptomatic multiple myeloma requiring treatment 1
• Whole-body low-dose CT can detect lesions with less than 5% trabecular bone destruction and is the first-line diagnostic imaging procedure for lytic bone disease in multiple myeloma 4

Alternative: Solitary Plasmacytoma

• Solitary plasmacytoma presents as mixed lytic-sclerotic lesions in two-thirds of cases, with preferential replacement of trabecular bone while cortical bone remains partly conserved 2
• However, bone marrow plasmacytosis >10% excludes solitary plasmacytoma and confirms multiple myeloma 2
• The presence of renal impairment and elevated bilirubin suggests systemic disease rather than a solitary lesion 1

Less Likely: Aneurysmal Bone Cyst

• Aneurysmal bone cysts are benign, expansile, lytic bone lesions that can occur in the skull 5, 6, 7
• MRI would show characteristic fluid-fluid levels if this were an aneurysmal bone cyst 5
• This diagnosis does not explain the renal impairment or elevated bilirubin, making it unlikely in this clinical context 5, 8, 6

Addressing the Renal Impairment

Relationship to Bone Lesion

• Renal insufficiency in multiple myeloma results from light chain cast nephropathy, hypercalcemia, dehydration, or direct tubular toxicity from monoclonal proteins 1
• The presence of renal insufficiency with a lytic bone lesion fulfills CRAB criteria for symptomatic multiple myeloma requiring immediate treatment 1

Addressing the Elevated Bilirubin

Initial Bilirubin Evaluation

• Determine if hyperbilirubinemia is conjugated (direct >35% of total) or unconjugated (<20-30% of total) to guide the diagnostic pathway 3
• If unconjugated hyperbilirubinemia with otherwise normal liver tests, consider Gilbert's syndrome, hemolysis, or medication-induced causes 3
• If conjugated hyperbilirubinemia, obtain abdominal ultrasound within 24-48 hours to exclude biliary obstruction and evaluate liver parenchyma, as ultrasound has 98% positive predictive value for liver parenchymal disease 9, 3

Relationship to Systemic Disease

• Elevated bilirubin in multiple myeloma may result from hepatic infiltration by plasma cells, biliary obstruction from lymphadenopathy, or concurrent liver disease 1
• If ultrasound shows biliary dilation or clinical suspicion remains high, proceed to MRCP, which achieves 85-100% sensitivity and 90% specificity for detecting biliary obstruction 9

Critical Diagnostic Algorithm

1. Immediately order: Serum protein electrophoresis with immunofixation, serum free light chain assay, CBC, calcium, creatinine, albumin, fractionated bilirubin, comprehensive liver function tests 1, 3, 2

2. Imaging sequence: MRI skull with gadolinium + CT skull with bone windows + whole-body low-dose CT or skeletal survey 2, 4

3. Abdominal ultrasound within 24-48 hours to evaluate elevated bilirubin and exclude biliary obstruction 9, 3

4. Bone marrow aspiration and biopsy with flow cytometry if laboratory studies suggest plasma cell dyscrasia 1, 2

5. If bone marrow shows ≥10% clonal plasma cells + lytic bone lesion + renal insufficiency = symptomatic multiple myeloma requiring immediate treatment 1

Critical Pitfalls to Avoid

• Do not rely solely on plain radiographs, as they detect lytic lesions only when >30% of cortical bone is destroyed 2
• Do not skip bone marrow evaluation—occult marrow involvement detected by flow cytometry dramatically changes prognosis and management 2
• Do not miss soft tissue extension: obtain MRI with gadolinium to identify any intracranial extension or spinal cord compression 2
• Do not delay abdominal ultrasound for conjugated hyperbilirubinemia, as biliary obstruction requires urgent intervention 9, 3
• Do not attribute elevated bilirubin to Gilbert's syndrome without first excluding conjugated hyperbilirubinemia and systemic disease 3