FRONTIERS IN BIOSCIENCE;
PLASMACYTOMA



DISTINCTIVE FEATURES

The term "plasma cell dyscrasia" is applied to disorders which are associated with growth of single clone of immunoglobulin producing cells. The immunoglobulin or its components are monoclonal and are released into the serum, hence the term "monoclonal gammopathies". The serum electrophoresis revelas presence of a spike which is called "M component". This component may be due to the presence of complete immunoglobulin or light chain or heavy chain. The light chain may be "kappa" or "lambda" light chain. These chains may appear in the urine (Bence Jones proteinuria). These dyscrasias include:

Soliatary plasmacytoma
Multiple myeloma
Waldenstrom's macroglobulinemia
Heavy chain disease
Primary or immunocyte-associated amyloidosis
Monoclonal gammopathy of undetermined significance (MGUS)
3-5% of gammopathies are solitary plasmacytomas which occur either in soft tissues or bone. On the other hand, multiple myeloma is the most common form of the malignant gammopathy.
Clinically, The M protein is found in the serum and/or urine in 99% of patients with multiple myeloma.
The constituents of the M protein in patients with multiple myeloma is shown in the table below.
The peak incidence of multiple myeloma is in the 5th and 6th decades of life. Occurs in equal frequency in both males and females.
Clinically, the tumor presents with:
Bone pain
Pathologic bone fracture
Hypercalcemia due to bone resorption. The destruction of bone has been attributed to the production of osteoclast activating cytokines such as IL-1, IL-6, M-CSF and TNF-beta. Hypercalcemia leads to weakness, polyuria, constipation, confusion and lethargy.
Suppression of normal immunoglobulins leads to recurrent infections with encapsulated bacteria such as penumococci.
Excess immunoglobulins in the blood leads to the hyperviscosity syndrome.
Toxic damage to the renal epithelium and excretion of the light chains of immunoglobulin may lead to renal insufficiency. The renal involvement which is called myeolma nephrosis occurs in 60-80% of patients.
Patients (10%) may develop amyloidosis of the AL type.
Multiple myeloma may start as a solitary plasmacytoma.
For both solitary and multiple myeloma, the most common bones that are involved include the vertebral column, ribs and skull. However, any bone may be involved. In solitrary plasmacytoma, extraosseous lesions may be found in the lungs, oropharynx, and nasal sinuses. The soft tissue involvement in multiple myeloma may occur in the lungs, lymph nodes, spleen, liver, and nerve root trunks.
Grossly, the tumor appears as multiple destructive soft, red-tan lesions.
Microscopically, the tumor consists of the plasma cell infiltrates that appear as aggregates. The neoplastic cells range from immature to mature plasma cells. The tumor cells may exhibit plasma cell associated proteins such as PCA-1. However, presence of other markers such as B cell antigen (CD10), myelomonocytic antigens (CD33), megakaryocytic antigen (GpIIa/IIIa) and erythroid cell antigens indicates that multiple myeloma is a disease of the stem cells of the hematopoeitic system.
The renal involvement consists of infiltration of the kidneys by plasma cells and other mononuclear inflammatory cells. Protein casts are present within tubules. These casts contain albumin, immunoglobulin and Tamm-Horsfall protein. Metastatic calcifications due to hypercalcemia may be present. Pyelonephritis due to infections may also be seen.