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). Plasma-cell disorders are characterized by 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

Plasma cell disorder

Monoclonal gammopathy of undetermined significance (MGUS)

Malignant monoclonal gammopathy

Chronic lymphocytic leukemia

Heavy chain diseases (γHCD αHCD μHCD)

Cryoglobulinemia

Primary amyloidosis

Multiple myeloma

Malignant lymphoproliferative disorders

Waldenstrom macroglobulinemia

Malignant lymphoma

Symptomatic multiple myeloma

Smoldering multiple myeloma

Plasma-cell leukemia

Non-secretory myeloma

Solitary plasmacytoma of bone

Osteosclerotic myeloma

Extramedullary plasmacytoma

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 sugnificance may be further classified into:
  • 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)
• 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 polyneuropathyor other problems related to the secreted antibody.
• MGUS is a premalignant condition and 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

Malignant monoclonal gammopathies

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.

Plasma-cell leukemia

• Charecterized by large number of plasma cells circulating in the blood
• Rare condition, can develop in to most aggressive form of multiple myeloma.
• Treatment options for plasma cell leukemia is chemotherapy or stem cell transplant.

Non-secretory myeloma

• Type of multiple myeloma with less amount of M proteins secretion in blood or urine.
• M protein is not detected by serum protein electrophoresis
• Bone marrow exibit myeloma cells.
• Osteolytic bone lesions are seen on xrays.

IgD myeloma

• IgD type constitues 2% of multiple myeloma
• IgD multiple myeloma has similar signs and symptoms as other types of multiple myeloma.

• IgD myeloma mostly affect people of younger age.

Osteosclerotic myeloma

• It is a rare disorder affecting multiple systems of the body

• It is called POEMS syndrome: polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes
• Treatment option for osteoclastic myeloma include:
  • Chemotherapy
  • Radiation therapy
  • Stem cell transplant

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 surgery.

For more information about Multiple myeloma click here

Malignant lymphoproliferative disorders

• 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

Malignant lymphoma

• Type of cancer that originates in lymphocytes
• Also called hematological neoplasms.
• Main types are Hodgkin lymphoma and Non-Hodgkin lymphoma

For more information about lymphoma 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.

αHCD

• Alpha chain or IgA heavy chain

• • Appears between age 10-30 as an immune response to a microorganism
  • Patients present with diffuse abdominal lymphoma and malabsorption.
  • Course is variable, some patients die in 1-2 yrs, others go in to remission lasting for many years.
  • Serum protein electrophoresis detect increased α & β fraction.
  • Treatment is corticosteroids, cytotoxic drugs and broadspectrum antibiotics

μHCD

• MU chain or IGM heavy chain disease

• • Mainly affects individuals > 50 yrs
  • Spleen, liver and abdominal lymph nodes involvement is more common than peripheral lymphadenopathy
  • Serum protein electrophoresis exibit hypogammaglobulinemia.
  • Vacuolated plasma cells are pathognomic on bone marrow exam.
  • Treatment consists of alkylating agents and corticosteroids.

Cryoglobulinemia

• Cryoglobulinemia is the presence of high amount of heavy globulins (e.g. IgM) in the bloodstream which thicken on exposure to cold.
• Cryoglobulins are circulating immunoglobulins or proteins that become insoluble at less than 4 degrees Celsius.
• Cryoglobulinemia can lead to a medium-sized vessel vasculitis due to vascular deposition of circulating immune complexes.
• This leads to the triad of palpable purpura, arthralgias and peripheral neuropathy
• Common causes ofCryoglobulinemia are primarily hematologic, oncologic, and rheumatic

For more information on Cryoglobulinemia click here

AL Primary amyloidosis

• The "AL" refers to amyloid light chain.

• • AL amyloidosis is the most common form of systemic amyloidosis in the US.
  • Occurs in 5 to 15% of people with multiple myeloma.
  • Treatment can involve application of chemotherapy similar to that used in multiple myeloma

For more information on amyloidosis click here