In order to arrive at the diagnosis of WM, your physician will perform a number of tests. Many of these same tests are also used for monitoring your disease status in order to determine if you need treatment of if you can postpone it.
The most common blood tests used in the diagnosis and monitoring of WM include the Complete Blood Count (CBC), Metabolic or Chemistry Panel, Quantitative Immunoglobulins, Serum Protein Electrophoresis (SPEP) and Immunofixation, Serum Viscosity (SV), and Free Light Chain Assay.
The Complete Blood Count measures the numbers of red blood cells, white blood cells, and platelets circulating in your bloodstream and compares your numbers to so-called reference ranges, as determined by your laboratory. Red blood cells (RBCs or erythrocytes) contain hemoglobin and carry oxygen to your tissues; the number of RBCs you have, your hemoglobin and hematocrit levels, and other red blood cell indicators can point to the presence of anemia. White blood cells (WBCs or leukocytes) are the main cells that fight infection, and they are differentiated into various types – neutrophils, monocytes, lymphocytes, basophils, and eosinophils. A high WBC count may indicate the presence of infection; conversely, a low count may indicate a problem with WBC production (for example, because of bone marrow depression from chemotherapy). Platelets are important in blood clotting, and a very low platelet count is a risk factor for uncontrolled bleeding.
The Metabolic or Chemistry Panel includes substances such as: total protein (albumin, globulins); electrolytes such as sodium, chloride, calcium, magnesium, potassium, carbon dioxide; blood urea nitrogen (BUN) and creatinine that monitor kidney function; AST, ALT, and bilirubin that monitor liver function; alkaline phosphatase; and blood sugar (glucose). Again, your values are compared to reference ranges determined by your laboratory. Total protein in a WM patient is elevated if he has a significant amount of monoclonal IgM, and other values may also be affected.
Quantitative Immunoglobulin testing determines the total IgG, IgA, and IgM immunoglobulins present. In the case of WM, the IgM result includes both normal and abnormal IgM and is elevated if the patient has a significant amount of monoclonal IgM.
Serum Protein Electrophoresis followed by Immunofixation is frequently one of the first diagnostic tests performed when a physician suspects WM or similar disorders. SPEP will determine the presence of and quantify a monoclonal immunoglobulin protein, sometimes referred to as an M-spike. Immunofixation identifies the particular type of protein (such as IgM in the case of WM). Immunofixation will also identify whether the light chains on the monoclonal protein are kappa-type or lambda-type. It is important to know that when monitoring your disease you need to compare SPEP results to each other and not to quantitative IgM immunoglobulin results. The two test methods are different and yield somewhat different values.
Serum Viscosity measures the thickness of your blood. The IgM monoclonal protein produced in WM has a tendency to thicken the blood, and this thickening can cause problems as it increases.
The Free Light Chain Assay is another method of measuring the amount of kappa and lambda light chains produced by immunoglobulins, including monoclonal IgM.
Bone Marrow Biopsy
The bone marrow biopsy (BMB) is the definitive test for confirming the diagnosis of WM. This procedure can be performed in a physician’s office or in a monitored setting (such as a hospital) under local anesthetic or light sedation. The specimen is usually obtained from the posterior iliac crest (back of the hip bone) by using a large-bore needle. Both a liquid bone marrow sample and a solid bone sample may be taken. A pathologist examines the bone marrow cells under a microscope and may also perform additional testing with special stains, flow cytometry, or FISH analysis to further identify the type of cancer cells present. In WM, the pathologist will note an increased amount of lymphoplasmacytic cells (which have features of both lymphocytes and plasma cells) and estimate the amount of infiltration of these cells into the bone marrow. He will also examine the marrow to determine how healthy it is and whether it appears capable of generating adequate amounts of normal blood cells. Because a bone marrow biopsy is a costly and invasive technique, frequent biopsies are not usually recommended for disease monitoring.
Imaging and Scans
In a small number of patients, masses or tumors of the malignant cells may be found outside the bone marrow and lymph nodes (extramedullary masses). These tumors may appear without significant elevation of IgM or other typical signs and symptoms of WM. CT (computed tomography) scans or MRI (magnetic resonance imaging) may offer an opportunity to assess this possibility and can be obtained as warranted by unusual signs or symptoms.
The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for WM include the use of CT scans of the chest, abdomen, and pelvis as part of the essential workup following a WM diagnosis to determine the presence and degree of lymphadenopathy (enlarged lymph nodes), splenomegaly (enlarged spleen), and masses or tumors of malignant cells in extramedullary sites. The NCCN is a non-profit alliance of 21 cancer centers in the U.S. whose goal is to improve the quality and effectiveness of care provided to cancer patients.
The physical exam is the process by which a health care professional investigates the body of a patient for signs of disease. It generally follows the taking of a medical history – an account of the symptoms experienced by the patient as well as questions regarding the patient’s current and past health history. The physical exam aids in determining the correct diagnosis and devising the treatment plan.
A complete physical examination includes evaluation of general patient appearance and specific organ systems. A systematic examination generally starts at the head and finishes at the extremities. After the main organ systems have been investigated by inspection, palpation (feeling with the hands), percussion (tapping of the thorax and abdomen), and auscultation (listening to internal sounds with a stethoscope), specific tests may follow if a particular disease is suspected.
For instance, a physician who is examining a WM patient may look for and palpate an enlarged liver or spleen and enlarged lymph nodes in the neck, armpit, or groin. He may note pallor if the patient is anemic. He will listen to the heart and lungs with a stethoscope to ascertain if they sound normal. He may assess the response of fingers and toes to stimulation to see if peripheral neuropathy is present.
Ophthalmology exams are recommended for WM patients at least once a year. They should be done more frequently if the patient has any blurring or loss of vision or if hyperviscosity (excessive thickening of the blood) is suspected. The back of the eye (fundus) is examined with an ophthalmoscope, which magnifies the blood vessels, nerves, and retina. Retinal hemorrhages, retinal detachments, and swollen blood vessels can be easily viewed using this technique.