Conditions Related to Multiple Myeloma
Plasma Cell Dyscrasias
Multiple myeloma, MGUS, and smoldering myeloma are plasma cell dyscrasias. A dyscrasia is an abnormality of the body, typically of the blood. A plasma cell dyscrasia is a disease in which the body makes too many plasma cells. MGUS and smoldering myeloma are plasma cell dyscrasias that are considered precursors to myeloma. Other plasma cell dyscrasias include plasmacytoma and amyloidosis. At Mount Sinai, we treat all of these conditions, as well as related diseases such as Castleman Disease, POEMS Syndrome, and Waldenstrom Macroglobulinemia.
Monoclonal Gammopathy of Undetermined Significance (MGUS)
In MGUS, less than 10 percent of the bone marrow is made up of abnormal plasma cells. As in myeloma, the abnormal plasma cells make M protein, which is sometimes detected during a routine blood or urine test. In most patients, the amount of M protein stays the same, there are no symptoms or health problems, and treatment is not required. The risk of MGUS increases with age. Approximately 3 percent of adults 50 and older and 5 percent of adults 70 and older have M-protein in their blood. While MGUS is considered a benign condition, myeloma typically develops in 1 to 2 percent of MGUS patients each year. It is important to monitor MGUS on a regular basis and to be on the alert for symptoms such as bone pain and fatigue that may develop.
Smoldering Multiple Myeloma (SMM)
SMM, an asymptomatic precursor to multiple myeloma, is characterized by increased levels of plasma cells in the bone marrow—10 percent or more— and higher than normal levels in the blood of M protein, the abnormal protein produced by plasma cells. Patients do not typically have symptoms. SMM is usually detected through routine blood work. Like myeloma and MGUS, SMM is more common in men than women and is more common in African Americans. It accounts for about 15 percent of all cases of newly diagnosed myeloma.
As is the case with MGUS, it is important to monitor SMM on a regular basis and to be on the alert for symptoms such as bone pain and fatigue. SMM is categorized as low-, intermediate-, or high-risk for progression to myeloma based on the amount of myeloma cells in the bone marrow, the amount of M protein in the blood, the amount of excess free light chains in the blood, and the genetics of the tumor cells.
High-risk SMM tends to progress to myeloma more quickly than low-risk SMM, and therefore needs to be closely monitored. We are investigating whether this subset of patients may benefit from early treatment before symptoms occur.
A plasmacytoma forms when the abnormal plasma cells are in one place and form one tumor. There are two types of plasmacytoma. In a solitary plasmacytoma of bone, one plasma cell tumor is found in the bone. There are no other signs of cancer elsewhere. Over time, plasmacytoma of the bone can progress to multiple myeloma. Plasmacytomas of bone can cause pain or broken bones. In extramedullary plasmacytomas, one plasma cell tumor is found in soft tissue but not in the bone or the bone marrow. Extramedullary plasmacytomas commonly form in tissues of the throat, tonsil and paranasal sinuses. They can cause pain or other problems, such as difficulty swallowing.
Amyloidosis occurs when antibody proteins stick together in sheets and coat the organs, resulting in enlarged organs (organomegaly), such as enlarged tongue, liver, and spleen; thickened heart causing heart failure; damage to the filtration unit of the kidneys, causing kidney failure; easy bruising; or injury to peripheral nerves, causing tingling, numbness, and nerve damage.
Castleman Disease is a rare disease of lymph nodes and related tissues that results from the overgrowth of benign cells in the body’s lymphatic system—the tissues and organs that produce, store and carry white blood cells that fight infections and other diseases. In Unicentric Castleman Disease, only one group of lymph nodes in one part of the body—usually the chest or abdomen—is affected. In Multicentric Castleman Disease many groups of lymph nodes and lymphoid tissue throughout the body are affected and the immune system is weakened. Castleman Disease involving plasma cells tends to be multicentric. Patients with Multicentric Castleman Disease are at increased risk of developing lymphoma.
POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, Skin changes) is a rare, multi-system condition associated with plasma cell neoplasms. This rare form of plasma cell tumor is associated with areas of hardening of the bone close to the tumor rather than the common bone destruction—lytic lesions—common in myeloma. Moreover, the substance produced by the tumor, known as VEGF, causes increased fluid retention; swelling of the nerve disc in the retina, which can cause loss of vision; and other hormonal disorders such as diabetes or thyroid disease. Nerve damage can be debilitating, and if diagnosis is delayed, the ability to walk may be affected. Skin pigmentary changes or rashes can also occur.
Waldenstrom Macroglobulinemia (also called lymphoplasmacytic lymphoma) is an indolent (slow-growing) type of non-Hodgkin lymphoma characterized by abnormal levels of monoclonal immunoglobulin (IgM) proteins in the blood and an enlarged liver, spleen, or lymph nodes. It is a cancer of B lymphocytes (B cells)—a type of white blood cell that is part of the immune system. In Waldenstrom’s, the malignant B cells build up in the liver, spleen and lymph nodes, causing them to swell. They also grow in the bone marrow, crowding out normal red cells, white cells, and platelets. The abnormal amount of IgM protein in the blood can cause it to become thick which can cause problems with blood flow in small blood vessels. Waldenstrom macroglobulinemia is rare, with an incidence rate of about 3 cases per million people per year in the United States. About 1,000 to 1,500 people are diagnosed with Waldenstrom’s each year in the United States. Since Waldenstrom’s grows slowly it can often times be well-controlled when diagnosed early.