What is the differential diagnosis for a 49-year-old female with a history of multiple myeloma presenting with a hard, tender lump on the right anterior arm, measuring 4x3 cm?

Differential Diagnosis for Hard, Tender Arm Lump in Multiple Myeloma Patient

The most critical consideration in this patient is an extramedullary plasmacytoma, which represents aggressive disease progression requiring urgent evaluation with tissue biopsy, imaging, and hematologic workup. 1, 2

Primary Differential Considerations

Myeloma-Related Pathology (Highest Priority)

• Extramedullary plasmacytoma is the foremost concern in a patient with known multiple myeloma presenting with a new soft tissue mass 1, 2

  • These represent clonal plasma cell tumors outside the bone marrow and indicate aggressive disease behavior 1, 2
  • Requires biopsy confirmation showing clonal plasma cells with CD138 staining 3, 4
  • Associated with high-risk cytogenetics including del(17p), t(4;14), t(14;16), t(14;20), gain(1q), or p53 mutation 2
  • May necessitate anthracycline-containing combination chemotherapy regimens rather than standard myeloma therapy 1

• Soft tissue extension from underlying bone lesion should be evaluated with imaging 3

  • Lytic bone lesions can erode through cortex and present as palpable soft tissue masses 3, 5
  • MRI of the affected arm is essential to assess bone involvement and soft tissue extent 3, 4

Non-Myeloma Malignant Pathology

• Secondary malignancy must be considered given immunosuppression from myeloma and its treatment 6, 1
  • Soft tissue sarcoma
  • Metastatic disease from occult primary malignancy
  • Lymphoma (particularly in patients on immunomodulatory therapy)

Infectious/Inflammatory Pathology

• Abscess or infected hematoma given the tender nature of the lesion 3

  • Multiple myeloma patients have increased infection risk due to hypogammaglobulinemia and treatment-related immunosuppression 6, 7
  • Recurrent infections are common clinical manifestations 7

• Cellulitis with underlying phlegmon in the setting of immunocompromise 7

Benign Pathology (Lower Priority but Possible)

• Hematoma from minor trauma (patients may have thrombocytopenia or coagulopathy from disease or treatment) 2
• Lipoma or other benign soft tissue tumor (less likely given tenderness and patient's underlying malignancy)

Essential Diagnostic Workup

Immediate Tissue Diagnosis

• Biopsy of the mass is mandatory to establish definitive diagnosis 3, 4
  • Core needle biopsy or excisional biopsy depending on size and location 3
  • Must include CD138 staining if plasmacytoma suspected to accurately quantify plasma cells 3, 4
  • Cytogenetic/FISH studies on tissue for del(17p), t(4;14), t(14;16), t(14;20), gain(1q), p53 mutation 2

Imaging Studies

• MRI of the right arm to assess bone involvement, soft tissue extent, and relationship to neurovascular structures 3, 4
• Whole-body imaging to assess for other extramedullary disease or progression 1, 2
  • PET/CT is more sensitive than skeletal survey for detecting active myeloma 3
  • Full skeletal survey if PET/CT unavailable 4

Laboratory Assessment for Disease Status

• Complete myeloma workup to assess for disease progression 3, 8

  • Serum protein electrophoresis with immunofixation 3, 8
  • 24-hour urine collection (not random sample) for protein electrophoresis with immunofixation 3, 8
  • Serum free light chains with kappa/lambda ratio 3, 8
  • Complete blood count to assess for anemia (hemoglobin <10 g/dL) 3, 8
  • Serum calcium (>11.5 mg/dL indicates hypercalcemia) 3, 8
  • Serum creatinine and creatinine clearance (>2 mg/dL or <40 mL/min indicates renal insufficiency) 3, 8
  • Serum β2-microglobulin and albumin for ISS staging 3, 4

• Bone marrow aspiration and biopsy if not recently performed 3, 8

  • Assess for ≥60% clonal plasma cells (myeloma-defining event) 1, 2
  • Cytogenetic/FISH studies for risk stratification 3, 8

Critical Clinical Pitfalls

• Do not assume benign etiology in a patient with known multiple myeloma—extramedullary disease indicates aggressive biology and requires immediate evaluation 1, 2

• Avoid delay in tissue diagnosis—empiric treatment without histologic confirmation can obscure the diagnosis and delay appropriate therapy 3

• Recognize that extramedullary plasmacytomas may require different treatment approaches than standard myeloma, including consideration of anthracycline-containing regimens 1

• Double-hit or triple-hit myeloma (presence of two or more high-risk cytogenetic features) portends particularly poor prognosis and requires aggressive management 2