Dr. Talaat Mirza
Plasma Cell Dyscrasis
5 pages
PLASMA CELL DYSCRASIS
This is the term given for a group of diseases where the malignant cell is the fully
mature and differentiated B lymphocyte, the plasma cell, or plasmocytoid
lymphocytes.
These diseases are also known as Monoclonal Gammopathies.
Monoclonal refers to the clonal origin of the malignancy i.e., from one cell type
(polyclonal describes an abnormality caused by more than one cell type). The term
gammopathies refers to the gamma region of the serum electrophoresis in which, the
neoplasm occurs. Electrophoresed serum is separated to albumin, alpha 1, alpha 2,
beta, and gamma regions.
The gamma region contains the 5 types of
Immunogolbulins (Ig’s): G, A, M, E, and D. Any increase in this region is considered
as an increase in 2 or more of the immunoglobulins (polyclonal) which shows as an
expansion of the whole gamma region (in the electrophoresis gram). On the other
hand, if the increase shows as a sharp peak in the gamma region, this is conclusive of
an increase in one of the Ig's only, i.e., “monoclonal”.
Monoclonal disorders are characterized by the presence of a special protein in serum
known as the “M” protein or paraprotein, the protein of the malignant plasma cell
and/or some fragments of the Ig itself.
There are many types of monoclonal gammopathies, the most important of which is
Multiple Myeloma (MM).
Others include Waldenstrom’s macroglobulinemia,
Plasma Cell Leukemia (PCL), Amyloidosis, and Heavy Chain Disease (HCD).
Dr. Talaat Mirza
Plasma Cell Dyscrasis
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Dr. Talaat Mirza
Plasma Cell Dyscrasis
5 pages
MULTIPLE MYELOMA (MM)
Also known as Plasma Cell Myeloma, it is the most common malignancy of plasma
cell affecting males more than females especially between the ages of 50-75. The
etiological factor is unknown but predisposing factors include: exposure to radiation,
hereditary, chronic antigenic stimulations, etc. The neoplasm is thought to have risen
at the level of the pluri-potential stem cell due to the presence of the pre-B antigen
known as CALLA (CD10), as well as some myelomonocytic, megakaryocytic, and
erythroid markers, on the malignant cells. Ig G proteins are increased in 50% of the
cases, Ig A about 20%, Ig D, and E are rare, while Ig M is very prevalent in
macroglobulinemia. Up to 15% of the cases belong to another clone, where only the
light chain is produced known as the Light Chain Disease or Bence Jones Myeloma.
Furthermore, free light chains (usually Kappa) are seen in up to 80% of all myeloma
patients.
Pathology
Malignant cells start proliferation in the BM taking over the normal tissue space, and
may invade other organs. Plasma cells activate osteoclasts, which in turn accelerate
bone resorption (bone loss).
Therefore, patients usually complain from bone
problems ranging from bone pain and tenderness to back pain, repeated fractures, lytic
bone diseases, and vertebral collapse.
Clinical presentation
Additional to bone problems, patients suffer from the typical symptoms associated
with the “replacement of normal marrow tissue” such as fatigue, weakness, anemia,
Dr. Talaat Mirza
Plasma Cell Dyscrasis
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Dr. Talaat Mirza
Plasma Cell Dyscrasis
5 pages
bleeding, and re-current infections. The increased susceptibility to infections can be
attributed to the lack of normal Ig’s synthesis. There might be enlargement of the
lymph nodes, liver, and spleen. Patients could also complain from kidney problem
due to the presence of M proteins (some of which are low molecular weight light
chain). These light chains put extra demand on the kidney for their re-absorption
leading renal failure. Up to 15% of cases might show a form of Amyloidosis, a
disease caused by the deposition of amyloid substance in the skin, and other organs.
Lab findings
Hematological routine work ups usually reveal a mild normocytic normochromic
anemia with hemoglobin (Hgb) ranging between 7 and 12 g/dL. Plasma cells might
not be seen until late stages of the disease. However, a few or many rouleaux
formations might be seen due to the extra-viscosity of the serum caused by the Ig’s
molecules. Meanwhile, the macroglobulinemia present lead to an elevated ESR.
BM shows up to 15% plasma cells of uniformed shape within the same patient.
However, the shape might vary dramatically from one case to another. The cells
could be very large with smooth chromatin or small with condensed chromatin.
Prominent nucleoli are always seen (1-3). Cytoplasm could be dark or pale possibly
with inclusions such as crystallized abnormal Ig’s, circular aggregation of Ig’s called
Russell bodies, vacuoles, etc.
Urinalysis might show some hyaline casts and epithelial cells.
Chemistry results show a monoclonal peak in the gamma region of serum and
concentrated urine electrophoresis.
ImmunoElectroPhoresis (IEP) or Immuno
Fixation Electrophoresis (IFE) has to be done to find out the specific Ig responsible
for the increase.
Radiological investigations could show osteoporosis ands lytic bone disease.
Dr. Talaat Mirza
Plasma Cell Dyscrasis
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Dr. Talaat Mirza
Plasma Cell Dyscrasis
5 pages
Treatment
Chemotherapy prolongs survival up to 4 years in 40% of the cases.
With no
treatment, patients might die within a year of diagnosis. The presence of Bence Jones
protein in urine is correlated with accelerated fatality.
Dr. Talaat Mirza
Plasma Cell Dyscrasis
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Dr. Talaat Mirza
Plasma Cell Dyscrasis
5 pages
PLASMA CELL LEUKEMIA (PCL)
Patients with PCL are usually younger than that of MM with less bone trouble but
other organ involvements such as enlarged lymph nodes and liver. PCL could be seen
in late stages of MM. It is recognized by the heavy infiltration of the malignant cell
of the BM (up to 45%) and pb accompanied with general pancytopenia (plasma cells
absolute count of more than 2 × 109/L). The plasma cells are usually small with an
exaggerated unsynchronized nucleus (found in the extreme edge of the cytoplasm).
WALDENSTROM’S MACROGLOBULINEMIA
This disease usually affects old patients (over 50), where the malignant plasmocytoid
cells secrete excessive abnormal Ig M. Normally Ig M is up 10% of all Ig’s but in
this disease it reaches more than 15%. Ig M interferes with coagulation factors
leading to bleeding and other hemorrhagic problems (in the ear, nose, and eyes).
Hyper-viscosity is another complication of the disease. Upon serum electrophoresis,
increased Ig M is noticed between the beta and gamma regions.
Treatment
No treatment is necessary for early stages while chemotherapy could be somewhat
useful in the late stages. Additionally, and as a supportive therapy, plasmapheresis is
used to lower the amount of Ig M and to lower the burden inflicted by hyper-viscosity
of blood.
HEAVY CHAIN DISEASE (HCD)
HCD is a very rare form of plasma cell dyscrasis where there is an abnormal synthesis
of the heavy chain (alpha, beta, or mu) in the Fc portion.
The neoplastic cell
resembles plasma cell with clinical presentation similar to lymphomas.
Dr. Talaat Mirza
Plasma Cell Dyscrasis
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