What is the most likely diagnosis for a patient with a lytic lesion in the inferior right occipital bone, normal laboratory results, and no significant past medical history?

Most Likely Diagnosis: Solitary Bone Plasmacytoma

The most likely diagnosis for a patient with a solitary lytic lesion in the inferior right occipital bone and normal laboratory results is solitary bone plasmacytoma, which must be distinguished from multiple myeloma through comprehensive workup including bone marrow evaluation and whole-body imaging. 1

Immediate Diagnostic Workup Required

Despite "normal" laboratory results, the following tests are mandatory to confirm the diagnosis and exclude systemic disease:

Essential Imaging Studies

• MRI with gadolinium contrast of the skull and spine is the gold standard for characterizing skull base abnormalities, assessing bone marrow involvement, soft tissue extension, and excluding additional focal lesions 2, 1
• Whole-body low-dose CT (WBLD-CT) must be obtained to determine whether this is truly a solitary lesion or part of systemic multiple myeloma, as WBLD-CT detects 60% more relevant findings than conventional X-rays 1
• CT with bone windows should be performed concurrently to evaluate cortical bone detail and identify small lytic areas that plain radiographs may miss 2

Critical Laboratory Evaluation

Even with reportedly "normal" labs, the following specific tests are mandatory 1:

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

Bone Marrow Examination

Bone marrow aspiration and biopsy with flow cytometry is mandatory for diagnosing solitary plasmacytoma, as flow cytometry can detect occult bone marrow disease in 49-68% of patients with apparent solitary plasmacytoma 1. These patients with occult marrow involvement have dramatically higher progression rates to multiple myeloma (71-72% versus 8-12.5%) 2, 1. Bone marrow plasmacytosis >10% excludes solitary plasmacytoma and confirms multiple myeloma 2, 1.

Why Solitary Bone Plasmacytoma is Most Likely

Characteristic Features

• Solitary bone plasmacytoma presents as mixed lytic-sclerotic lesions in two-thirds of cases, with preferential replacement of trabecular bone while cortical bone remains partly conserved or sclerotic 2
• The skull (including occipital bone) is a common site for solitary bone plasmacytoma 3, 4
• Normal laboratory results do not exclude solitary plasmacytoma, as laboratory findings may be absent or minimal in truly solitary disease 4

Key Distinguishing Features from Multiple Myeloma

Solitary bone plasmacytoma differs from multiple myeloma by 5:

• Absence of CRAB criteria (hypercalcemia, renal insufficiency, anemia, bone lesions attributable to plasma cell disorder)
• <10% clonal plasma cells on bone marrow examination
• Absence of additional lytic lesions on whole-body imaging
• Serum monoclonal protein <3 g/dL (if present at all)

Critical Diagnostic Pitfalls to Avoid

Do Not Rely on "Normal" Labs Alone

• Standard laboratory panels may appear normal in solitary plasmacytoma, but specialized testing (SPEP, SIFE, FLC assay) is required to detect subtle monoclonal proteins 1
• Small M-proteins or light chain-only disease may be missed without immunofixation and FLC assay 5

Do Not Skip Bone Marrow Evaluation

• Occult marrow involvement detected by flow cytometry dramatically changes prognosis and indicates progression to multiple myeloma rather than true solitary disease 2, 1
• Unilateral bone marrow aspiration and trephine biopsy with immunophenotyping using flow cytometry or kappa/lambda labeling is mandatory 2

Do Not Miss Additional Lesions

• Plain radiographs detect lytic lesions only when >30% of cortical bone is destroyed 2
• MRI may reveal more than one focal lesion, which characterizes symptomatic multiple myeloma requiring systemic therapy even without visible lytic lesions on X-ray 1
• The presence of more than 1 focal lesion on MRI excludes solitary plasmacytoma 1

Alternative Diagnoses to Consider

While solitary bone plasmacytoma is most likely, the differential diagnosis includes:

Multiple Myeloma

• Would require ≥10% clonal bone marrow plasma cells AND evidence of end-organ damage (CRAB criteria) 5
• Present in approximately 80-90% of multiple myeloma patients at diagnosis with lytic lesions 1
• Excluded if bone marrow shows <10% plasma cells and no additional lesions on whole-body imaging

Smoldering Multiple Myeloma

• Requires serum monoclonal protein ≥3 g/dL and/or clonal bone marrow plasma cells ≥10% 5
• Absence of end-organ damage (no CRAB criteria) 5
• Less likely given single lytic lesion and normal labs

Other Bone Lesions

• Giant cell tumor of bone can present as expansile lytic lesion but typically occurs in long bones 2
• Metastatic disease from other primary malignancies should be considered but is less common in occipital bone without known primary cancer 6

Prognosis and Natural History

Solitary bone plasmacytoma has a high rate of progression to multiple myeloma (approximately 50% of patients), with most progression occurring within 3 years 3, 7. The median time to progression ranges from 2-3 years 5. Overall survival and progression-free survival of solitary bone plasmacytoma are poorer than solitary extramedullary plasmacytoma due to higher rates of evolution to multiple myeloma 3.