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]; 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 BM examination; serum involved:uninvolved FLC ratio of ≥100; >1 focal lesion on MRI ≥5 mm

CRAB features: elevated calcium (>11 mg/dL), renal insufficiency (serum creatinine >2 mg/dL or creatinine clearance <40 mL/min), anemia (Hb <10 g/dL or 2 g/dL < normal), 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.