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.

For more information about Monoclonal gammopathies of undetermined significance click here

Multiple myeloma

Symptomatic multiple myeloma

• People with multiple myeloma with symptoms are categorized to have active multiple myeloma and will exibit any of the following features.
  • M protein in blood or urine
  • Bone marrow plasma cells constitute more than 10% of the blood cells
  • Presence of solitary plasmacytoma in bone
  • ≥1 myeloma-defining event

• • CRAB features ( explained above)
  • Osteolytic lesions on bone x-ray

• Patients with active Multiple myeloma usually require treatment to prevent progression of disease which can lead to death.

Smoldering multiple myeloma

• It is asymptomatic type of multiple myeloma

• Shows presence of M-spike that quantitates > 3 g/dl on protein electrophoresis

• Presence of bone marrow plasma cell burden of > 10% but < 60%

• Absence of end-organ damage such as anemia, hypercalcemia, renal dysfunction, or osseous lesions

• Patients with smoldering (asymptomatic) Multiple myeloma are managed by observation and undergoing follow up tests every 3 to 6 months
• There is high risk of developing active multiple myeloma.

Solitary plasmacytoma of bone

• Plasmacytoma is collection of abnormal plasma cells forming a singl e tumor.
• Solitary plasmacytoma is occurence of single bone tumor made up of myeloma cells.
• Xray shows an osteolytic lesion at the site of the tumor.
• Bone marrow plasma population remains less than 10%
• One third of patients with solitary plasmacytoma will develop multiple myeloma.

Extramedullary plasmacytoma

• It is develped outside the bone marrow in soft tissues of the body
• Most commonly seen in throat,paranasal sinuses, nasal cavity, larynx,GI tract, breast and brain.
• Diagnosis is confirmed by biopsy of the tumor.
• X-rays and bone marrow biopsy is normal.
• Treatment is done with either radiation therapy or surgry.

For more information about Multiple myeloma click here

Waldenstrom macroglobulinemia

• Waldenstrom macroglobulinemia is a cancer involving lymphocytes.
• The main attributing antibody is IgM.
• It is a type of lymphoproliferative disease,
• It shares clinical characteristics with the indolent non-Hodgkin lymphomas.
• Waldenstrom macroglobulinemia represents 1% of all hematological cancers
• Common causes of Waldenström's macroglobulinemia include genetic, environmental, and autoimmune factors.
• Common risk factors in the development of Waldenström's macroglobulinemia are Monoclonal gammopathy of undetermined significance.

For more information about Waldenström's macroglobulinemia click here

Chronic lymphocytic leukemia

• Chronic lymphocytic leukemia arises from pre-follicular center B cells, normally involved in immunoglobulins production.
• Development of chronic lymphocytic leukemia is the result of multiple genetic mutations that promote both malignant leukemic proliferation and apoptotic resistance of mature B cells.
• Chronic lymphocytic leukemia must be differentiated from hairy cell leukaemia, prolymphocytic leukaemia, follicular lymphoma, and mantle cell lymphoma.
• Prognosis is generally good, and the 5-year survival rate of patients with chronic lymphocytic leukemia is approximately 81.7%.
• The mainstay of therapy for symptomatic chronic lymphocytic leukemia patients is immunochemotherapy.

For more information about chronic lymphocytic leukemia click here

Heavy-chain diseases

Heavy chain diseases are plasma cell neoplasias, featuring overproduction of immunoglobulin heavy chains.

γHCD

Gamma chain or IgG heavy chain disease

• Primarily seen in elderly men but can occur in children.
• High levels of IgG with reduction of normal immunoglobulin level
• Lymphadenopathy, hepatosplenomegaly and recurrent infections are common features
• Vincristine, corticosteroids and radiation therapy may produce remission.