What is the appropriate diagnosis and treatment for an older adult with a history of multiple myeloma or other plasma cell disorders presenting with Mott cells?

Diagnosis and Management of Mott Cells in Older Adults with Plasma Cell Disorders

Understanding Mott Cells in Clinical Context

Mott cells represent plasma cells containing multiple cytoplasmic Russell bodies (dilated endoplasmic reticulum filled with immunoglobulin aggregates) and indicate active plasma cell dyscrasia requiring immediate diagnostic workup for multiple myeloma or related disorders. 1, 2

Mott cells are morphologically distinct plasma cells with numerous spherical, faintly blue cytoplasmic inclusions on Wright-Giemsa staining, representing abnormal immunoglobulin synthesis, trafficking, or excretion. 2 These cells can mimic other malignancies (such as Burkitt lymphoma/ALL-L3) due to their vacuolated appearance, making accurate identification critical. 1

Immediate Diagnostic Workup

When Mott cells are identified in an older adult with known or suspected plasma cell disorder, the following evaluation must be performed:

Essential Laboratory Tests

• Serum protein electrophoresis (SPEP) with immunofixation to detect and characterize the monoclonal protein 3, 4
• 24-hour urine protein electrophoresis with immunofixation (not random urine samples, which are insufficient) 4
• Quantification of IgG, IgA, and IgM immunoglobulins by nephelometry 5, 4
• Serum free light chain assay with kappa/lambda ratio 4
• Complete blood count to assess for anemia (hemoglobin <10 g/dL or ≥2 g/dL below normal) 3, 4
• Serum chemistry including creatinine (>2 mg/dL indicates renal involvement), calcium (>11.5 mg/dL indicates hypercalcemia), albumin, LDH, and β2-microglobulin for staging 3, 4

Bone Marrow Examination

• Bone marrow aspiration and biopsy to quantify plasma cell infiltration (≥10% clonal plasma cells required for myeloma diagnosis) 5, 3, 4
• Cytogenetic analysis by FISH to detect high-risk features including del(17p), t(4;14), t(14;16), t(14;20), gain 1q, del 1p, or p53 mutation 3, 4

Imaging Studies

• Full skeletal X-ray survey to detect lytic bone lesions 5, 4
• MRI of spine and pelvis if spinal cord compression is suspected or for superior detection of bone lesions 5, 4

Diagnostic Criteria for Multiple Myeloma

The diagnosis requires ≥10% clonal plasma cells in bone marrow (or biopsy-proven plasmacytoma) PLUS at least one myeloma-defining event: 4

CRAB Criteria (any one confirms symptomatic myeloma):

• Hypercalcemia: serum calcium >11.5 mg/dL 4
• Renal failure: creatinine >2 mg/dL or creatinine clearance <40 mL/min 4
• Anemia: hemoglobin <10 g/dL or ≥2 g/dL below lower limit of normal 4
• Bone lesions: lytic lesions, severe osteopenia, or pathologic fractures 4

Alternative Myeloma-Defining Events:

• ≥60% bone marrow plasma cells 4
• Involved/uninvolved serum free light chain ratio ≥100 4

• 1 focal lesion ≥5mm on MRI 4

Risk Stratification

International Staging System (ISS) classification: 4

• Stage I: β2-microglobulin <3.5 mg/L AND albumin ≥3.5 g/dL
• Stage II: Neither Stage I nor III
• Stage III: β2-microglobulin ≥5.5 mg/L

High-risk cytogenetics (del(17p), t(4;14), t(14;16), t(14;20), gain 1q, del 1p, p53 mutation) fundamentally alter treatment approach and prognosis. 4

Treatment Approach Based on Transplant Eligibility

Transplant-Eligible Patients (Age ≤65, Good Performance Status, No Renal Failure)

Induction therapy with bortezomib, lenalidomide, dexamethasone (VRd) for 3-4 cycles, followed by autologous stem cell transplantation with high-dose melphalan (200 mg/m²). 5, 4, 6

• Bortezomib is FDA-approved for treatment of adult patients with multiple myeloma 6
• High-dose melphalan 200 mg/m² IV should be preferred as the preparative regimen prior to autologous transplantation 5
• Peripheral blood progenitor cells should be used as the source of stem cells rather than bone marrow 5

Transplant-Ineligible Patients (Elderly, Poor Performance Status, Comorbidities)

VRd for 8-12 cycles followed by lenalidomide maintenance, or daratumumab, lenalidomide, dexamethasone (DRd) until progression. 4

Alternative regimens for elderly patients include:

• Bortezomib/melphalan/prednisone (VMP) 5
• Melphalan/prednisone/thalidomide (MPT) 5
• Both are approved by the European Medicines Agency 5

Special Considerations for Patients with Renal Involvement

When Mott cells are present with renal insufficiency (creatinine >2 mg/dL):

Immediate tumor lysis syndrome prophylaxis is mandatory: 3

• Establish IV access and begin normal saline at 150-200 mL/hour to achieve urine output >100 mL/hour 3
• Administer rasburicase 0.2 mg/kg IV as a single dose (or 3-6 mg fixed dose) in high-risk patients 3
• Do not delay chemotherapy for extended periods while attempting conservative measures alone, as this worsens outcomes 3
• Initiate bortezomib-based induction therapy promptly after appropriate prophylaxis 3

Supportive Care

• Long-term bisphosphonates (oral or intravenous) to reduce skeletal events in patients with stage III or relapsed disease 5, 3

Critical Pitfalls to Avoid

• Do not use random urine samples for protein electrophoresis; 24-hour collections are mandatory 4
• Do not overlook cytogenetic testing, as high-risk features fundamentally alter treatment approach 4
• Do not miss spinal cord compression; obtain urgent MRI when clinically indicated 4
• Do not confuse Mott cells with Burkitt lymphoma cells (ALL-L3) due to their vacuolated appearance; proper immunophenotyping and serum electrophoresis will distinguish plasma cell disorders 1
• Do not delay treatment in symptomatic patients meeting CRAB criteria, as immediate therapy is indicated 5, 3

Follow-Up Monitoring

For patients in remission after treatment: 7

• Every 3-6 months: CBC, serum chemistry (creatinine, albumin, calcium, LDH, β2-microglobulin), quantitative immunoglobulins, SPEP with immunofixation, serum free light chain assay 7
• Annually or as clinically indicated: bone survey or appropriate imaging (MRI/CT/PET-CT) 7
• Bone marrow assessment when disease progression is suspected 7