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Diagnostic algorithm when suspecting Multiple myeloma
5MM Diagnostic criteria
M. Gorky Donetsk National Medical University
Methodic guidelines for the 6th year students
Self-training on the practical study
at the Internal medicine # 1 department
Donetsk – 2010
N. V. Kalinkina, PhD
T.A. Parkhomenko, MD, PhD, Internal medicine #2 department
R.V. Basiy, MD, PhD, Anatomy department.
Multiple myeloma (MM) is a bone marrow cancer. Despite periodic media attention, eneral public awareness about myeloma is low. Although several things appear capable of causing or triggering myeloma, all of the details are not known. Things associated with an increased risk of myeloma and related diseases are toxic chemicals (for example, agricultural chemicals and Agent Orange used in Vietnam), radiation (including atomic radiation), and several viruses including human immunodeficiency virus (HIV), hepatitis viruses, human herpes virus 8 (HHV-8), and others. There is not a strong family tendency for myeloma; a few families do, however, have an increased predisposition to the disease. Myeloma occurs in adults. The average age of onset of myeloma is in one’s early 60s. Only 5–10% of patients are under the age of 40 years. It occurs more commonly in men and in some racial groups, such as African-Americans. There are approximately 20,000 new cases of myeloma in the U.S. each year. The incidence ranges from ~0.5–1 /100,000 among Asians to as high as ~10–12 /100,000
among African-American men. At any one time there are over 100,000 myeloma patients undergoing treatment for their disease in the U.S.
II. Aims of studying the topic
^ you need to know how to diagnose MM, define main strategies of treatment and approach to the patient, know possible complications and common outcomes of the disease..
Literature for material revise:
1. Harrison's Principles of Internal Medicine, 16th ed., Ch. 98, Plasma Cell Disorders, Dan L. Longo, Kenneth C. Anderson.
2. Harousseau JL, Moreau P (June 2009). "Autologous hematopoietic stem-cell transplantation for multiple myeloma". N. Engl. J. Med. 360 (25): 2645–54. doi:10.1056/NEJMct0805626. PMID 19535803.
3. International Myeloma Working Group (2003). "Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group". Br. J. Haematol. 121 (5): 749–57. doi:10.1046/j.1365-2141.2003.04355.x. PMID 12780789
Tests of initial level
1. Patient A., suffering from MM, complains of the loss of appetite, nausea, vomiting, constipation, polyuria and general muscle weakness, drowsiness. Blood pressure is 80/50 mm Hg. On the ECG - shortening of the QT interval.
Which metabolic abnormality could result in the mentioned clinical features?
2. On the skull X-ray of the patient B. who suffers from MM, several bone lesions were found. What is type of the lesions caused by MM?
A. diffuse osteoporosis without osteodestruction foci.
B. Osteoporosis with isolated foci of osteolysis.
C. Osteoporosis with multiple foci of destruction.
D. metastatic tumors.
E. pathological fractures.
3. In the chemistry blood analysis of the patient B., who suffers from MM with a massive osteolysis, increased serum calcium index was observed.
What was level of this microelement in this patient?
A. 0.9 mmol / l.
B. 1.5 mmol / l.
C. 1.9 mmol / l.
D. 2.6 mmol / l.
E. 4.5 mmol / l.
4. In the patients D with the diagnosis of MM complaining of general weakness progression, bleeding (hemorrhagic rash, nasal bleeding), pain in the thoracic region of the spine. CBC: Hb 50 g/l, RBC 1,5x1012 /l, CI 1.0, L 5,8x109/l, pt 63x109 /l, ESR 60 mm/h. Urinalysis: Bence Jones protein - 30g/day.
What is the cause of anemia in this patient?
A. plasmocyte infiltration of bone marrow.
C. hemodilution because of the high paraprotein level.
D. Erythropoietin production defect.
E. alimentary factor
5. Patient Z., 68 years old, was admitted to the clinic with complaints of weakness, fatigue progression, pain in the lumbar-sacral area. He considers himself ill during about 9 months and underwent long-term treatment with neurologist with the diagnosis of radiculitis. The general condition of the patient is moderate. Skin and visible mucous are pale. Feels pain on palpation of ribs, lumbar spine area. CBC: RBC 2.4 x1012 /l. Hb-60 g/l, L 4.2x109 /l: bands-2%, eosinophils 2%, segments 70%, lymphocytes 21%, monocytes 5%. ESR 84 mm/h, CI. 1.0, platelets 140x109 /l. Urinalisys: Bence-Jones protein 30 grams per day. X-ray: Osteoporosis of lumbar vertebrae, isolated foci of osteolysis.
Which disease can you suspect?
A. metastasis of malignant tumors in bones.
B. hemolytic anemia.
C. multiple myeloma.
D. lumbo-sacral radiculitis.
E. bone sarcoma.
Test answer samples.
1–А. Described symptoms can be seen in the patients who have hypocalcaemia – increased calcium level, also found in MM patients.
4–С. Kidneys are affected in MM patients quite frequently. The described syndrome in the test is nephrotic – proteinuria, hypoalbuminemia, dysproteinemia, hyperlipidemia and swelling of varying severity.
IV. Study plan
The following topic parts should be studied to archive aims listed above:
1. MM etiology and pathogenesis.
2. Classification of MM.
3. Methods for clinical and instrumental MM diagnosing.
4. MM differential diagnostics.
5. Complications of MM.
6. Treatment of MM and its complications.
Literature for studying theoretical aspects of the topic:
Short methodic guidelines for the classes on the topic “Multiple Myeloma”
First the teacher checks students’ initial knowledge level using initial level tests and corrects it if necessary. Then students examine patients on the topic of the lesson and start detailed discussion of the patients with the teacher. The discussion is followed by the end-level tests. In the end of the lesson the teacher summarizes students’ work on the topic.
Structural logic scheme of the topic “Multiple Myeloma”
Tactics of treatment
1. Polichemotherapy. 2.Radiological therapy. 3.Симптоматическая терапия
M protein level of less than 3 g per dL (30 g per L) Less than 10 percent plasma cells in bone marrow. Absence of myeloma-related organ and tissue impairment
M protein level of 3 g per dL or greater. 10 percent or more plasma cells in bone marrow. Absence of myeloma-related organ and tissue impairment
Biopsy findings are hypercellular with lymphocytes, plasma cells, and lymphoplasmacytoid cells. Epistaxis; vision, retinal, or neurologic problems
Incomplete heavy chains without light chains. Variable lymphocytes, plasma cells, lymphoplasmacytoid in bone marrow
Solitary bone or soft tissue plasmacytoma shows plasma cells in the tumor; otherwise, there is no evidence of multiple myeloma in the bone marrow
MM Diagnostic criteria
In 2003, the International Myeloma Working Group agreed on diagnostic criteria for symptomatic myeloma, asymptomatic myeloma and MGUS (monoclonal gammopathy of undetermined significance):
1. Clonal plasma cells >10% on bone marrow biopsy or (in any quantity) in a biopsy from other tissues (plasmacytoma)
2. A monoclonal protein (paraprotein) in either serum or urine
3. Evidence of end-organ damage (related organ or tissue impairment, ROTI):
- Hypercalcemia (corrected calcium >2.75 mmol/L)
- Renal insufficiency attributable to myeloma
- Anemia (hemoglobin <10 g/dL)
- Bone lesions (lytic lesions or osteoporosis with compression fractures)
- Frequent severe infections (>2 a year)
- Amyloidosis of other organs
- Hyperviscosity syndrome
1. Serum paraprotein >30 g/L AND/OR
2. Clonal plasma cells >10% on bone marrow biopsy AND
3. NO myeloma-related organ or tissue impairment
Monoclonal gammopathy of undetermined significance (MGUS):
1. Serum paraprotein <30 g/L AND
2. Clonal plasma cells <10% on bone marrow biopsy AND
3. NO myeloma-related organ or tissue impairment
The following stages are used for multiple myeloma:
Stage I: Relatively few cancer cells have spread throughout the body. The number of red blood cells and the amount of calcium in the blood are normal. No tumors (plasmacytomas) are found in the bone. The amount of M-protein in the blood or urine is very low. There may be no symptoms of disease.
All of the following features must be present:
Stage II: A moderate number of cancer cells have spread throughout the body. Features are between stage I and stage III.
Stage III: A relatively large number of cancer cells have spread throughout the body. There may be one or more of the following:
A decrease in the number of red blood cells, causing anemia
High levels of M-protein in the blood or urine
A large number of myeloma cells are found. One or more of the following features must be present:
Summary Test Control
1. In the CBC of the patient suffering from MM: RBC 2.5 x1012 /l. Hb-105 g/l, L 3.61x109 /l, platelets 247x109 /l, ESR 53 mm p h. Clinical chemistry: total protein 87.8 g/l, albumin 35.7 g / l, calcium 2.27 mmol / l.
What study should be performed to determine the stage of MM?
A. quantification of immunoglobulins.
B. immunoelectrophoresis of blood plasma.
S. X-Ray-study flat bones.
D. immunoelectrophoresis of urine.
E. all from the above.
2.Osteoporosis with multiple osteolysis foci, of different diameters (from a few millimeters to 3 cm), were found in the patient's R. X-ray .
What’s your preliminary diagnosis?
A. metastatic cancer in bone.
B. skull bone fracture.
S. subdural hematoma. '
D. bone sarcoma.
E. multiple myeloma.
3. Patient C., was admitted to the hospital in serious condition. He can’t move because of pain in the thoracic spine and hip joints. Petechial rash is present on most of the skin. CBC: Hb-66 g/l, L 5.9x109 /l, ESR 70 mm/h, platelets 63x109 /l. Total serum protein 108g / l, paraprotein 53.3 g / l. On the X-ray: destruction of thoracic vertebrae, ribs, large foci of destruction in the sciatic and iliac bones and in the cervix and upper third of the femur.
What is the disease to be suspected?
B. metastases in bone.
S. rheumatoid arthritis.
D. Bekhterev disease.
E. multiple myeloma.
4. Patient A. who suffers from MM underwent X-ray. What were the typical radiographic changes detected in this patient?
A. Periarthric diffuse osteoporosis.
B. blurring of bone edges, destructive changes of upper and lower parts of the vertebrae, "square vertebrae.
C. Edge condyli osteophytes, intracondylar elevation, dense symmetric thickening (Hyberden’s nodules).
D. Generalized osteoporosis, single or multiple osteolysis foci, pathological fractures.
E. rounded epiphysis defects with the formation of bone tophi, osteoarthrosis.
5. In the CBC of the patient M., who suffers from MM, were found the following changes: RBC 2,6x1012 / l, Hb 77g/l, Ca 3.0 mmol/l, IgG 90 g/l, IgA 70 g/l, creatinine 40mcmol/l: X-ray: generalized osteoporosis.
What stage of MM does the patient have?
A. Stage 1.
B. Stage 2.
C. Stage 3
D. Stage 4.
E Stage 5.
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