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Defining the Disease

Module 1: Screening, Diagnosis, and Staging of Multiple Myeloma

Section 1: Defining the Disease

View Topic Summary by Brian G.M. Durie, MD

What is multiple myeloma?

(Multiple Myeloma Epidemiology)

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Dr. Robert Kyle: Multiple myeloma is a neoplastic proliferation of the clones of a single plasma cell, producing a monoclonal immunoglobulin.

This clone proliferates in the bone marrow and destroys the bone itself, which is manifested by osteopenia, osteolytic lesions, and pathologic fractures. Anemia, renal insufficiency, and hypercalcemia may also occur. (Active Multiple Myeloma)

View Topic Summary by Robert A. Kyle, MD

What is MGUS? What is the difference between MGUS and multiple myeloma?

Monoclonal gammopathy of undetermined significance (MGUS) is characterized by the proliferation of a small clone of plasma cells. These patients are generally defined as having an M-protein of less than 3 g/dL, and if a bone marrow evaluation is performed, fewer than 10% plasma cells will be found in the sample. These patients have no anemia, hypercalcemia, or renal insufficiency related to the M-protein production. There are no bone lesions.

Mayo Clinic Study Defines Patients at Greater Risk for Developing Multiple Myeloma and Related Bone Marrow Cancers

What is Waldenström's macroglobulinemia?

Waldenström's macroglobulinemia is a malignant disease manifested by the proliferation of a clone of lymphocytes that produces a monoclonal IgM protein. The World Health Organization classifies it as a lymphoplasmacytic lymphoma. The bone marrow has an increased number of lymphocytes and hepatosplenomegaly; lymphadenopathy may also occur. Anemia and constitutional symptoms are indications for treating Waldenström's macroglobulinemia.

What is solitary plasmacytoma?

Solitary plasmacytoma of bone is manifested by a tumor of plasma cells in the bone marrow. These patients have no evidence of multiple myeloma. The bone marrow contains no increase in monoclonal plasma cells, and there are no other lytic bone lesions. The patients do not have anemia, hypercalcemia, or renal insufficiency.

If M-protein is present in the serum or urine of a patient with solitary plasmacytoma, it is usually small and should disappear following radiation of the plasmacytoma.

What are extramedullary plasmacytomas? Do they inevitably lead to multiple myeloma?

Extramedullary plasmacytomas are plasma cell tumors that occur outside the bone marrow. Approximately 80% are in the upper respiratory tract. The remainder may be found in virtually any organs of the body. In contrast to solitary plasmacytoma of bone, only 15% of patients with extramedullary plasmacytoma will develop overt generalized multiple myeloma.

What is POEMS syndrome (osteosclerotic myeloma)?

POEMS syndrome or osteosclerotic myeloma is characterized by Polyneuropathy, Organomegaly, Endocrine disturbances, Monoclonal protein in the serum, and Skin changes (which are manifested by hyperpigmentation or hypertrichosis). These patients have sclerotic lesions that are usually localized but sometimes may be generalized. If the osteosclerotic plasmacytoma is localized, radiation to that lesion is usually quite helpful.

What is amyloidosis, and in what ways can symptoms overlap with multiple myeloma?

Amyloidosis is closely related to multiple myeloma. The amyloid fibrils consist of light chains of amino acids (AL amyloidosis). In this disease, monoclonal light chains deposit as fibrils in tissues of the body. These fibrils damage the normal cells, and patients present with involvement of the heart, producing congestive heart failure or conduction disturbances, or involvement of the kidney, manifested by renal insufficiency or proteinuria. This is often nephrotic. Approximately one sixth of patients will exhibit peripheral neuropathy, and about 10% of patients with AL amyloidosis will have orthostatic hypotension.

There is some overlap with multiple myeloma. About 10% of patients with typical multiple myeloma will eventually develop systemic amyloidosis during the course of their disease. The reverse also occurs. There are patients who appear to have primary amyloidosis but, when evaluated, are found to have large numbers of plasma cells in their bone marrow. These patients may actually have lytic lesions as well, thus fulfilling the criteria for a diagnosis of multiple myeloma.

You have discussed light-chain diseases. Are there heavy-chain diseases?

The heavy-chain diseases are very rare. In this country, we see occasional cases of gamma heavy-chain disease. Patients with this disease have a variable clinical picture most often associated with a lymphoid or plasmacytoid proliferative process. Patients with alpha heavy-chain disease are found in Mediterranean countries, and some cases now are being reported from Iran and Iraq. These patients do not have a monoclonal light chain in the urine. The third type of heavy-chain disease is mu heavy-chain disease. About 50% of these patients will have a monoclonal spike in the serum, and about 40% will have a monoclonal light chain (Bence-Jones protein) in the urine. Most of the patients who have been treated thus far or have been diagnosed with this condition have had either chronic lymphocytic leukemia or a lymphoproliferative disorder.

Defining the Disease | Initial Detection and Diagnosis | Prognosis and Staging | Planning Treatment | Monitoring Patients | Complications Associated With This Disease

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