Patho - 4th Assessment - Plasma Cell Neoplasms - 28 Jan 2007

Plasma Cell Neoplasms

Plasma Cell Neoplasms AGENDA Definition Classification

Plasma Cell Neoplasms Definition - Immuno-secretory disorders resulting from expansion of a single clone (monoclonal) of immunoglobulin secreting terminally differentiated, end-stage B cells (plasma cells). - Secretion of a monoclonal homogenous immunoglobulin product (M-component).

Plasma Cell Neoplasms Pro-T Lymphocyte

Pre-T Lymphocyte Cytotoxic T Lymphocyte

Helper T Lymphocyte Lymphoid Stem Cell

Pre-B Lymphocyte

B Lymphocyte

Plasma Cell

Plasma Cell Neoplasms Classification • •

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Plasma Cell Myeloma Monoclonal Gammopathy of Undetermined Significance (MGUS) Plasmacytoma Primary Amyloidosis

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Plasma Cell Myeloma - Definition - Epidemiology - Diagnosis

Plasma Cell Neoplasms • Plasma Cell Myeloma Definition - Bone marrow-based multifocal monoclonal plasma cell proliferation characterized by serum Mcomponent and osteolytic lesions. - Spectrum of severity (indolent- to-aggressive)

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Plasma Cell Myeloma Epidemiology - ~ 15% of hematological malignancies. - Disease of elderly (6th – 7th decade).

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Plasma Cell Myeloma Diagnosis A) Clinical Features B) Radiological Features C) Laboratory Features

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Plasma Cell Myeloma Diagnosis (cont’d) A) Clinical Features - Extensive skeletal destruction: bone pain, pathological fractures

- Excessive monoclonal immunoglobulin production: hyperviscosity syndrome

- Depressed normal immunoglobulin production: recurrent infections

- Bone marrow replacement: anemia, thrombocytopenia (late)

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Plasma Cell Myeloma Diagnosis (cont’d) B) Radiological Features - Lytic bone lesions

Plasma Cell Neoplasms

Plasma Cell Neoplasms

Plasma Cell Neoplasms

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Plasma Cell Myeloma Diagnosis (cont’d) C) Laboratory Features - Hematology CBC, PBS examination, BM examination

- Serum Protein Electrophoresis (SPE) Monoclonal band (IgG, IgA), hypogammaglobulinemia

- Urine Protein Electrophoresis Bence-Jones Protein

- Others hypercalcemia, renal impairment

PBS

BM

BM

Plasma Cell Neoplasms

Polyclonal vs. Monoclonal Ig Production

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Plasma Cell Myeloma Diagnostic Criteria Major Criteria

Marrow plasmacytosis (30%) (10-30%) Plasmacytoma on biopsy M-component (serum or urine) Serum IgG > 35g/L, IgA > 20g/L Urine > 1g/24hrs of BJ protein

Minor Criteria Marrow plasmacytosis M-component Lytic bone lesions Hypogammaglobulinemia

Plasma Cell Neoplasms • MGUS - The presence of M-component in persons without evidence of plasma cell neoplasm. - ~ 25% will develop plasma cell neoplasm (~ 10years). - Follow up is essential.

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MGUS (cont’d) Diagnostic Criteria - M-component - Marrow plasmacytosis (< 10%) - No lytic bone lesions - No myeloma-related symptoms

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Plasmacytoma - Clonal proliferations of plasma cells that are identical to plasma cell myeloma but manifest a localized osseous or extraosseous growth pattern.

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Primary Amyloidosis - Plasma cell neoplasm that secretes an abnormal immunoglobulin, which deposits in various tissues and forms fibrillary protein (Amyloid). - Systemic deposition involving heart, liver, kidneys, GIT, tongue, nerves. - Binds Congo red stain to produce characteristic birefringence. - M-component in 80% of patients. - 20% have plasma cell myeloma.

Congo red