Plasma Cell Dyscrasia

Definition

Plasma cell dyscrasia is a medical condition, in which the plasma cells are affected. The abnormal proliferation of the plasma cells leads to the appearance of plasma cell dyscrasia, with the monoclonal population of cells secreting immunoglobulin or fragments of immunoglobulin (these fragments are known as paraprotein or M protein). There are a wide range of medical conditions that can be classified as plasma cell dyscrasias, as you will have the opportunity to discover below.

Classification

These are the most common plasma cell dyscrasias:

• Cryoglobulinemia
  • Medical condition in which high quantities of cryoglobulins (immunoglobulins) are found in the blood
  • This condition can be found in association with multiple myeloma or Waldenström’s macroglobulinemia (type I); it is also found in patients who are infected with the hepatic virus C (type II and III)
  • Can also appear in patients who have been infected with the hepatic virus B or HIV
• Heavy chain disease
  • Form of paraproteinemia, in which the cells that produce the immunoglobulin heavy chains proliferate
  • There are four main forms – alpha chain disease (Seligman’s disease), gamma chain disease (Franklin’s disease), mu chain disease and delta chain disease
• Monoclonal gammopathy of undetermined significance
  • Medical condition, in which paraprotein is identified in the blood
  • The condition resembles with one of multiple myeloma – differences: lower levels of antibodies, lower number of plasma cells at the level of the bone marrow
  • No symptoms are present, no treatment required (regular follow-up is recommended)
• Multiple myeloma
  • Cancer of the plasma cells
  • Abnormal plasma cells accumulate at the level of the bone marrow
  • Paraproteins are also produced, affecting the health of the kidneys
  • The patients suffer from lesions at the levels of the bones, with high levels of calcium
  • The methods of diagnosis include: blood testing, examination of the bone marrow, electrophoresis of the urine and X-ray investigations (bone assessment)
  • Treatment solutions include: corticosteroids, chemotherapy, administration of proteasome inhibitors, immunomodulatory drugs (thalidomide, lenalidomide), stem cell transplants, radiation therapy
• Plasmacytoma
  • Malignant tumor of the plasma cells
  • It can affect the soft tissues or the axial skeleton
  • Three main types – solitary plasmacytoma of bone, extramedullary plasmacytoma and multiple plasmacytomas (primary or recurrent)
• Plasma cell leukemia
  • Lymphoproliferative disorder, rare type of cancer involving the plasma cells
  • Considered as one of the most aggressive types of cancer
  • The condition can appear on its own or it can derive from multiple myeloma
  • Main treatment solutions – chemotherapy and supportive care (poor survival rate)
• POEMS syndrome
  • The acronym stands for: polyneuropathy (the peripheral nerves become damaged), organomegaly (the internal organs become abnormally enlarged), endocrinopathy (the glands that produce hormones are damaged) or edema (inflammation in different tissues of the body), M-protein (one of the immunoglobulins that are abnormal), skin abnormalities (such as the excessive pigmentation or the increase hair growth on the skin)
• Primary amyloidosis (immunoglobulin light chain amyloidosis)
  • Medical condition, in which the cells that should produce antibodies do not function in an adequate manner
  • These cells produce abnormal protein fibers, which are known as light chains
  • It can affect different organs of the body, leading to organ failure in the end
• Waldenström’s macroglobulinemia
  • Type of cancer, affecting primarily the B cells
  • Lymphoproliferative disease, affecting the white cells (B) that are formed at the level of the bone marrow and the lymph nodes
  • Many of the characteristics that are encountered in this condition are also seen in those diagnosed with non-Hodgkin lymphomas.

The testing for plasma cell dyscrasia is indicated in the following situations:

• Bone pain
• Recurrent infection
• Anemia
• Lytic bone lesions

Diagnosis

The methods used for the diagnosis of plasma cell dyscrasia include:

• Laboratory testing
  • Complete blood count (CBC) – may reveal anemia, platelet disturbances (thrombocytopenia, thrombocytosis – rare), leukocytosis, plasma cells over 20% on smear (confirmation of plasma cell leukemia)
  • Electrolytes – blood urea nitrogen, calcium, lactate dehydrogenase, proteins, albumins
  • Viscosity measurement – in serum or whole blood
  • Serum protein electrophoresis
  • Urine protein electrophoresis
• Morphology and cytogenetics
  • Morphology can be used to confirm the diagnosis of multiple myeloma
  • Cytogenetics – useful in determining genetic mutations that might have caused the mutations in the first place
• Imaging studies
  • X-rays – identification of lytic lesions (common in multiple myeloma and in Waldenström’s macroglobulinemia)
  • MRI (magnetic resonance imaging), PET (positron emission tomography) or computed tomography (CT) – recommended for a better visualization of the suspected lesions

The differential diagnosis of plasma cell dyscrasia is made with the following conditions: autoimmune disorders (connective tissue disease), malignancy (metastatic bone disease, non-Hodgkin lymphoma), Paget disease, infection, rheumatoid arthritis, protein-losing disorders, chronic disease (affecting either the liver or the kidneys), genetic or metabolic disorders, deficiency of vitamin D and polymyalgia rheumatica.

In adults, the usage of sensitive electrophoretic methods has been shown to reduce the incidence of these conditions. As you have had the opportunity to read, some of these plasma cell dyscrasias can transform into cancerous conditions, leading to bone lesions (such as myelomas, for which the bone lesions are characteristic). It is quite difficult to make the difference between a benign and a malignant form, just based on the presentation. However, some of these plasma cell dyscrasias are more easily recognized, such as myeloma and plasma cell leukemia. The moment these conditions are identified, that moment the chemotherapy will be instituted (better prognosis for the patient). Some scientists have also tried to classify these medical conditions according to how urgent the chemotherapy actually is (two main types have been identified, based on this classification).

In patients who have been diagnosed with benign conditions, the follow-up is required – the clinical examination, as well as the laboratory testing can be used to estimate the risk of transformation into a malign condition. In some patients, imaging investigations, such as the MRI, may be useful in identifying early lesions of the bones (these being impossible to detect through other imaging investigations, such as the X-rays).