Symptoms of the following disorders can be similar to those of multiple myeloma. Comparisons may be useful for a differential diagnosis:

Waldenstrom macroglobulinemia is a lymph and blood cell disorder. Abnormally large quantities of homogeneous protein molecules are present in the blood. The disorder may run in families and occurs after the sixth decade. An enlarged spleen and liver with abnormalities of the lymph glands are the most frequent symptoms. Weakness, anemia, fatigue and excessive bleeding, especially from the nose and mouth, also occur. (For more information on this disorder, choose “Waldenstrom” as your search term in the Rare Disease Database.)

Heavy chain diseases are characterized by the presence of too many plasma cells or certain white blood cells (lymphocytes) that resemble plasma cells in the bone marrow and lymph nodes. This condition includes gamma, alpha and Mu heavy chain disease, which are all disorders of the proliferative type. Gamma heavy chain disease is characterized by anemia. The liver, spleen and lymph nodes are enlarged. Alpha heavy chain disease occurs most often in men of Mediterranean ancestry. It involves the digestive tract with severe malabsorption of nutrients, loss of weight, diarrhea, and loss of fat (steatorrhea). Symptoms are most often progressive. Mu heavy chain disease is characterized by a form of chronic lymphocytic leukemia or tumors of the lymph gland. Analysis of the blood serum usually reveals excessively low levels of antibodies in the blood (hypogammaglobulinemia).

Monoclonal gammopathy of undetermined significance (MGUS) is a condition characterized by the presence of M-proteins in the blood. There may be low levels of M-proteins in the urine. Individuals with MGUS do not have the physical symptoms associated with multiple myeloma (e.g., anemia, bony lesions, kidney abnormalities). In some cases, individuals with MGUS eventually develop a malignant disorder such as multiple myeloma, Waldenstrom’s macroglobulinemia, or amyloidosis.

The term amyloidosis includes a group of disorders caused by abnormal folding, clumping, (aggregation) and/or accumulation of particular proteins (amyloids, fibrous proteins and their precursors) outside of the cell (extracellular), but within the tissues of various organs of the body. The accumulated amyloid causes the progressive malfunction of the affected organ. Normally, proteins are broken down at about the same rate as they are produced, however, these unusually stable proteins are deposited more rapidly than they can be broken down. The accumulation may be localized, or systemic. The most widely used classification of the amyloidoses is based on the biochemical nature of the fiber-like protein structures (fibrils) and on the nature of the precursor proteins that give rise to the amyloids. (See Disorder subdivisions above.) The different amyloidoses are named by combining the upper case A (for amyloid) with an abbreviation of the name of the protein that makes up the fibril. There are at least twenty (20) different types of fibrils that make up the human amyloidoses, and each is responsible for a unique clinical presentation. Older discussions of amyloidosis refer often to “primary amyloidosis” or to “myeloma-associated amyloidosis” the fibril protein of each of which is an immunoglobulin light chain peptide or fragment. The newer classification labels both of these as “light chain amyloidosis” or AL. The Light chain amyloidosis (AL) form of the disorder occurs most often, but not always, in association with an increased number of plasma cells in the bone marrow. AL affects the kidney, heart, intestinal tract, liver and/or spleen. Kidney or cardiac involvement may result in renal or congestive heart failure, respectively.

The following disorders may be considered variants of multiple myeloma:

Smoldering multiple myeloma (SMM) is characterized by abnormally high levels of atypical plasma cells in the bone marrow without evidence of symptomatic disease. Many affected individuals exhibit M-proteins in the urine and blood but have no other evidence of the symptoms of multiple myeloma such as anemia, bone lesions or kidney failure. Individuals with smoldering multiple myeloma may eventually develop multiple myeloma.

Plasma cell leukemia is characterized by the presence of excessive amounts of plasma cells in the blood.

Non-secretory myeloma exists when an individual with multiple myeloma does not produce M-protein in either the urine or blood serum. Individuals with non-secretory myeloma make up only one percent of individuals with myeloma.

Osteosclerotic myeloma is a variant of multiple myeloma. Major symptoms may include weakness; numbness in the legs, skin changes, hormonal abnormalities, and lung problems. In osteosclerotic myeloma, there is an association with osteosclerosis, a condition marked by hardening and abnormal density of bone. A common symptom of osteosclerotic myeloma is peripheral neuropathy. The exact cause of osteosclerotic myeloma is not known.

Solitary plasmacytoma of bone is characterized by only one plasma cell tumor (plasmacytoma) of the bone. Diagnosis relies on cell examination, and no evidence of multiple myeloma in the bone marrow.

Extramedullary plasmacytoma occurs when plasma cell tumors arise outside the bone marrow. The upper respiratory tract, which includes the nasal cavity and sinuses, nasopharynx, and larynx, is the most frequent site of involvement. However, extramedullary plasmacytomas have been found in virtually every organ of the body.