Myeloma

Classification

In hematopathology, plasma cell neoplasms are classified into:

  • Non IgM Monoclonal Gammopathy of Undetermined Significance (MGUS - precursor)

  • Monoclonal immunoglobulin deposition disease

    • Systemic light chain deposition disease

    • Primary amyloidosis

  • Plasma cell myeloma (Multiple myeloma)

    • Smouldering myeloma

    • Plasma cell leukemia

    • Non secretary myeloma

  • Plasmacytoma

    • Solitary plasmacytoma of bone

    • Extraosseous plasmacytoma

Plasma cell myeloma

Epidemiology

Primary bone malignancies are rare. (1%)

Predisposition to Old aged (>50years) and males.

Criteria

Plasma cell Myeloma

  • Clonal bone marrow plasma cells ≥ 10% of all plasma cells.
    OR
    Biopsy proven 'Plasmacytoma'

  • ≥1 from the following myeloma defining events

    • CRAB criteria for End organ damage

      1. Serum Calcium > 11mg/dL

      2. Renal insufficiency denoted by
        Serum Creatinine >2mg/dL

      3. Anemia, Hb < 10g/dL

      4. Bone shows ≥ 1 osteolytic lesions


    • Positive biomarkers for malignancy:

      1. Clonal bone marrow plasma cells ≥ 60%.

      2. Involved light chains >100 times of uninvolved.

      3. MRI shows >1 focal lesions.

Smouldering Myeloma

  • Serum M protein >30g/dL; urinary M protein > 500mg/24hr.

  • Clonal BM plasma cells 10 - 60% of all plasma cells.

  • No myeloma defining events / amyloid.

Clinical features and investigations

  • Pallor

  • Bleeding due to thrombocytopenia

  • Bone

    • Mass

    • Lytic lesion

    • Osteoporosis

    • Pathological fracture

    • Compression fracture of vertebrae

    • Involvement: Vertebrae > Ribs > Skull > Pectoral and Pelvic girdles > Long bones

  • Tumor mass in extramedullary involvement - Can cause spinal compression or peripheral neuropathy

  • End organ damage leads to components of CRAB criteria

  • Diminished normal plasma cell immunoglobulin secretion leads to infections

  • Skin may have plasma cell infiltration and purpura.

  • M Protein

    • 97% of PCMs secrete abnormal light chain or heavy chain of one type of immunoglobulin (IgG > IgA > IgD > IgE > IgM)

    • If IgG, it will be >30g/dL. And if TgA, it will be >20g/dL.

    • 3% of PCM won't secrete this. [ Non secretary myeloma ]

  • Hyperuricemia and hypoalbuminemia

Gross

Soft gelatinous fish flesh hemorrhagic tissue

Peripheral smear

Rouleaux formation

Leukoerythroblastic blood picture

If clonal plasma cells are seen in peripheral blood as >20% of total WBC (absolute counts >2000/microL), it is Plasma cell leukaemia.

Bone Marrow Aspirate

  • Total plasma cells > 90% of nucleated cells

  • In which, clonal plasma cells are ≥ 10% of all plasma cells.

  • Forms:

    • Mature plasmacytes

      • Oval with abundant basophilic cytoplasm

      • Round eccentric nucleus.

      • Clock-face chromatin

      • Perinuclear hof due to ribosomes

    • Immature plasma cells

    • Plasmablasts

    • Pleomorphic cells

    • Cells with endoplasmic reticulum containing crystalline clonal immunoglobulins (May be seen in reactive conditions also).

      • Mott cells / Morula cells - Pale blue cells with bunch of grape like cytoplasm

      • Russel bodies - Cherry red refractile round bodies in cytoplasm

      • Flame cells - Glycogen rich IgA in cytoplasm

      • Pseudo-Gaucher cells - fibrils in cytoplasm

      • Thesaurocytes - similar to pseudogaucher cells

The major limitation of aspirates is that, focal distribution of plasma cell clusters may lead to inadequate findings. Plasma cells in aspirate may be <10% if aspiration missed the clusters. Hence biopsy is recommended.

Bone Marrow Biopsy

The tumour mass may be biopsied by the surgeon from bone without any accompanied blood studies.

Plasma cells constitute 30% of the volume of marrow

Involvement may be singly scattered cells to focal interstitial clusters. Advanced diseases will have diffuse involvement.

Small cell variant mimics a Mantle cell lymphoma.

Mature plasma cell

Mott cell / Morula cell

Mature and Immature plasma cells