Plasma cell disorder

Plasma cell disorders
Overview
Classification Monoclonal gammopathy of undetermined significance (MGUS) Malignant monoclonal gammopathies Multiple myeloma Malignant lymphoproliferative disorders Chronic lymphocytic leukemia Heavy-chain diseases Cryoglobulinemia Primary amyloidosis
Differentiating Plasma Cell Disorder

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Nazia Fuad M.D.

Overview

Plasma cell disorders are a diverse type of blood disorders characterized by the presence of a monoclonal paraprotein in the serum or urine. Monoclonal plasma cells are present in the bone marrow or, rarely, in other tissues. Plasma cell disorders include monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM), lymphoplasmacytic lymphoma/ Waldenstrom macroglobulinemia (LPL/WM), lymphoproliferative disorders, smoldering multiple myeloma (SMM); solitary or extramedullary plasmacytoma, amyloidosis, and POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, and Skin changes).The plasma-cell disorders are characterized by the proliferation of a single clone of plasma cells that produces a homogeneous monoclonal (M) protein. these disorders have been defined by the International Myeloma Working Group.1 In 2006.

Classification

Monoclonal gammopathies of undetermined significance (MGUS)

• Benign (IgG, IgA, IgD, IgM, and, rarely, free light chains)
• Associated neoplasms or other diseases not known to produce monoclonal proteins
• Biclonal and triclonal gammopathies
• Idiopathic (Bence Jones proteinuria)

Malignant monoclonal gammopathies

• Multiple myeloma (IgG, IgA, IgD, IgE, and free light chains)
  • Symptomatic multiple myeloma
  • Smoldering multiple myeloma
  • Plasma-cell leukemia
  • Non-secretory myeloma
  • IgD myeloma
  • POEMS syndrome: polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (osteosclerotic myeloma)
  • Solitary plasmacytoma of bone
  • Extramedullary plasmacytoma
• Malignant lymphoproliferative disorders
  • Waldenstrom macroglobulinemia
  • Malignant lymphoma

Heavy-chain diseases (HCDs)

• • γHCD
  • αHCD
  • μHCD

Differential Diagnosis

Disease	IgM	IgG	IgA	IgE	IgD	Monoclonal Ig level	SFLC	Bone marrow plasma cells	Other criteria
IgM MGUS	+	−	−	−	−	< 3gm/dl	N/A	<10%	No end-organ damage
Non igM MGUS	+	−	+	−	−	< 3gm/dl	N/A	<10%	No end-organ damage
Smoldering MM	−	+	+	−	−	> 3gm/dl	N/A	10-60%	No myeloma-defining event No CRAB features
Light chain MGUS	−	−	−	−	−	<500 mg/24 hrs (urine)	Free kappa or lambda light chain Abnormal ratio (<0.26 or >1.65) Increase in involved light chain concentration	<10%	No end-organ damage
Active symptomatic Multiple myeloma	−	+	+	+	+	>3gm/dl	>100	>60%	≥1 myeloma-defining event CRAB features
Waldenstrom macroglobulinemia	+	−	−	−	−	Variable	N/A	>10%	Evidence of organ/tissue damage. Anemia, Hepatosplenomegaly
Solitary Plasmacytoma	+	−	−	−	−	<3mg/dl	Abnormal in 47% cases	Normal	Solitory bone lesion due to plasma cell tumor Preserved levels of uninvolved immunoglobulins No anemia, hypercalcemia or renal disease
Primary amyloidosis	−	−	−	−	−	<3md/dl	Light chains of immunoglobulines	<10%	No bone lesions, Nephrotic syndrome Restrictive cardiomyopathy Peripheral neuropathy Hepatomegaly with elevated liver enzymes Macroglossia Purpura and an unexplained bleeding diathesis

Myeloma defining events: >60% clonal plasma cells on B.M exam; serum involved:uninvolved FLC ratio >100; >1 focal lesion on MRI >5mm

CRAB features: elevated calcium >11mg/dl, renal insufficiency, anemia Hb <10 g/dL , bone disease ≥1 lytic lesions on skeletal radiography, CT, or PET-CT , SFLC: serum free light chains, kappa and lambda immunoglobulin light chains.

The normal κ:λ ratio is 0.26 to 1.65 (17,18). A κ:λ ratio of <0.26 strongly suggests the presence of a of plasma cells that are producing clonal λ free light chains. Ratio >1.65 suggests production of clonal κ free light chains.

Plasma cell disorders

Monoclonal gammopathies of undetermined significance (MGUS)

Monoclonal gammopathy of undetermined significance is a condition in which a low or non-quantifiable level of a monoclonal paraprotein is detected in the blood by means of protein electrophoresis. In addition, some patients develop a polyneuropathy (damage to peripheral nerves) or other problems related to the secreted antibody. MGUS is distinct from multiple myeloma. Pathologically, the lesion in Monoclonal gammopathy of undetermined significance is in fact very similar to that in multiple myeloma.

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