What is the next best step in managing a likely adult patient with a history of head pain, visual disturbances, and headaches, who has an indeterminate expansile lytic lesion in the inferior right occipital bone, with differential considerations including multiple myeloma, metastatic disease, and lymphoproliferative disorders, after undergoing CT (Computed Tomography) and MRI (Magnetic Resonance Imaging) scans?

Next Best Step: PET/CT for Systemic Evaluation and Tissue Diagnosis

The next best step is to obtain PET/CT for systemic evaluation followed by comprehensive laboratory workup for plasma cell dyscrasia and bone marrow biopsy, as this lytic skull lesion requires both characterization of systemic disease burden and definitive tissue diagnosis to guide treatment. 1, 2

Immediate Imaging: PET/CT Whole Body

PET/CT is the recommended next imaging modality because the MRI has already characterized the local lesion, and you now need to determine whether this is solitary or part of systemic disease. 3, 1

• PET/CT is superior to conventional radiography in detecting lytic disease and is particularly valuable for evaluating extramedullary disease, which is critical given the differential includes multiple myeloma, metastatic disease, and lymphoproliferative disorders. 3
• The European Myeloma Network guidelines specifically recommend PET/CT for better definition of disease extent and for detecting additional lesions that would change management from solitary plasmacytoma to multiple myeloma. 3
• Ensure the CT component has imaging quality equivalent to whole-body low-dose CT (WBLD-CT), not just for attenuation correction, as WBLD-CT detects 60% more relevant findings than conventional skeletal surveys. 1, 4

Concurrent Laboratory Workup: Rule Out Plasma Cell Dyscrasia

Order the complete myeloma workup immediately while arranging PET/CT, as multiple myeloma and solitary plasmacytoma are leading differential diagnoses for skull lytic lesions. 1, 2

Required Laboratory Tests:

• Serum protein electrophoresis (SPEP) with immunofixation electrophoresis (SIFE) 1, 2
• Serum free light chain (FLC) assay 1, 2
• Complete blood count, serum calcium, creatinine, and albumin 1, 2
• Quantitative immunoglobulin levels (IgG, IgA, IgM) 1
• 24-hour urine for total protein with urine protein electrophoresis (UPEP) and urine immunofixation electrophoresis (UIFE) 1

Clinical reasoning: Multiple myeloma presents with lytic bone lesions in approximately 80-90% of patients at diagnosis, and the skull is a common site. 1, 2 The presence of more than 1 focal lesion on MRI characterizes symptomatic disease requiring therapy. 3, 1

Bone Marrow Evaluation: Mandatory for Diagnosis

Bone marrow aspiration and biopsy with flow cytometry is mandatory if imaging or laboratory findings suggest plasma cell dyscrasia. 1, 2

• Flow cytometry can detect occult bone marrow disease in 49-68% of patients with apparent solitary plasmacytoma, and these patients have significantly higher progression rates to multiple myeloma (71-72% versus 8-12.5%). 1, 2
• Bone marrow plasmacytosis >10% excludes solitary plasmacytoma and confirms multiple myeloma. 1, 2
• This is the definitive diagnostic step that will determine whether the patient has solitary plasmacytoma (potentially curable with radiation) versus multiple myeloma (requiring systemic therapy). 1, 2, 5

Critical Differential Diagnoses to Consider

Multiple Myeloma/Solitary Plasmacytoma (Most Likely):

• Presents as mixed lytic-sclerotic lesions in two-thirds of cases, with preferential replacement of trabecular bone while cortical bone remains partly conserved. 1, 2
• The MRI findings of T1 and T2 hyperintensity with moderate contrast enhancement are consistent with plasma cell infiltration. 1, 2

Metastatic Disease:

• Requires PET/CT to identify primary malignancy and additional metastatic sites. 3
• Common primaries metastasizing to skull include breast, lung, kidney, thyroid, and prostate. 6

Lymphoproliferative Disorders:

• Langerhans cell histiocytosis can present as expansile lytic skull lesions. 1
• Lymphoma requires tissue diagnosis and systemic staging. 3, 7

Key Pitfalls to Avoid

Do not skip bone marrow evaluation: Occult marrow involvement detected by flow cytometry dramatically changes prognosis and treatment approach in apparent solitary plasmacytoma. 1, 2

Do not rely on imaging alone: The MRI appearance is not specific enough to differentiate between the differential diagnoses without tissue confirmation and systemic evaluation. 3, 6

Do not miss soft tissue extension: The MRI shows minimal dural thickening near the hypoglossal canal, which requires careful monitoring as progression could cause cranial nerve XII palsy. 1, 2

Do not delay systemic evaluation: If this represents multiple myeloma rather than solitary plasmacytoma, the patient requires systemic therapy, not just local radiation. 5

Management Algorithm Summary

1. Order PET/CT whole body to determine solitary versus systemic disease 3, 1
2. Obtain complete myeloma laboratory workup (SPEP/SIFE, FLC, CBC, calcium, creatinine, albumin, immunoglobulins, 24-hour urine) 1, 2
3. Perform bone marrow aspiration and biopsy with flow cytometry if plasma cell dyscrasia is suspected 1, 2
4. Consider biopsy of the skull lesion if bone marrow and laboratory workup are negative or inconclusive, as tissue diagnosis is ultimately required 3, 1

The combination of PET/CT, laboratory evaluation, and bone marrow assessment will definitively establish whether this is solitary plasmacytoma (treated with radiation), multiple myeloma (requiring systemic therapy), metastatic disease (requiring identification of primary), or another lymphoproliferative disorder. 3, 1, 2, 5