Question: Dr. Chiragbhai, thank you for explaining last time about simple rule to follow, so as not to miss a serious diagnosis and at the same time not to over investigate? Can you tell us more about how to confirm diagnosis in a suspected case of myeloma?
Answer: Myeloma diagnosis is based on a number of criteria, not just one test. This is very important to understand, since many people make a diagnosis of myeloma on basis of just M-band (abnormal protein seen on protein electrophoresis). M-band can be seen in many conditions, including many acute infections, chronic infections like tuberculosis, collagen vascular diseases, many cancers and other disorders. However, these patients do not meet other criteria for diagnosis of myeloma.
For example, we had a doctor from Mumbai who came to us with a diagnosis of myeloma, for transplant. While looking at his tests, all things did not seem to match. He had already received one cycle of chemotherapy. We reviewed tests done at diagnosis, and ordered few more tests. He turned out to be a patient of disseminated tuberculosis, with M-band and mild increase in reactive plasma cells in bone marrow. We treated him only with medicines for tuberculosis, and his M-band gradually reduced, without any treatment for myeloma.
Remember, all M-band is not Myeloma.
Also, a number of patients have only M-band and no other active underlying disease. Such patients are diagnosed as MGUS – monoclonal gammopathy of uncertain significance. As the name suggests, etiology of this M-band is not known. Few patients develop myeloma over many years, majority remain stable or resolve. Such patients are not to be treated with any medicine, unless they develop an obvious disease.
Que: So, then what are the criteria for myeloma diagnosis?
Ans: This has evolved over last several years to make it more practical. At present, active myeloma can be diagnosed if there is M-band beyond a certain value, clonal plasma cells in bone marrow more than 10%, and presence of at least one of the CRAB (calcium increased, renal insufficiency, anemia, bone lesions).
Work up requires blood tests, bone marrow biopsy, and skeletal survey (several x rays looking at majority of large bones especially skull x ray-showing lytic lesions or osteopenia).
Many patients present with renal dysfunction – raised creatinine or proteinuria, and renal biopsy shows cast nephropathy, which leads to diagnosis of myeloma.
Beta 2 microglobulin, albumin, and bone marrow cytogenetics help in defining prognosis.
A small number of myeloma patients present with features of CRAB, increased number of plasma cells in bone marrow, but there is no M-band. These patients were earlier classified as non secretory myeloma. Many of these patients were missed, as negative M-band made clinicians think of other diagnoses, and bone marrow biopsy was not done.
However, now most such patients are diagnosed as myeloma (light chain type) based on increased levels of light chains, using FLC (free light chain) assay. This test is highly sensitive and detects very small amount of increased light chains, and hence makes myeloma diagnosis very accurate and early. FLC assay is one of the most important advances in myeloma diagnosis and monitoring in last few years.
One other test sometimes useful in myeloma diagnosis and monitoring is PET–CT scan.
Dr. Chirag A. Shah; M.D. Oncology/Hematology (USA), 079 26754001. Diplomate American Board of Oncology and Hematology. Ahmedabad. firstname.lastname@example.org
Shyam Hem-Onc Clinic. 402 Galaxy, Near Shivranjani, Opp Jhansi ki Rani BRTS, Ahmedabad. www.shyamhemoncclinic.com