Etiology and pathogenesis of paraproteinemia
The exact cause of the disease remains unknown to this day, although it has been proven that ionizing radiation can slightly increase the risk of its development. The pathological process is based on the malignant transformation of plasma cells. Under a microscope, such mutated plasmacytes appear larger than normal ones, have a pale coloration, and often contain nucleoli.
The main mechanism of the disease is uncontrolled monoclonal secretion of immunoglobulins. Tumor cells produce a paraprotein, whose structure typically includes one heavy chain (classes IgG, IgM, IgA, IgD, or IgE) and one type of light chain. Of particular note is the Bence Jones phenomenon: in this case, plasmacytes synthesize exclusively light chains, which, due to their small size, are easily filtered by the kidneys and enter the urine.
The tumor can grow as a diffuse infiltration of the bone marrow or form local proliferations—solitary plasmacytomas in bones and soft tissues. As the process progresses, the pathological clone displaces normal hematopoiesis lineages, which naturally leads to the development of pancytopenia.
Clinical phases and diversity of syndromes
The course of the disease is divided into two main phases. The preclinical phase can last up to 20 years and be completely asymptomatic. The only marker during this period is often an accidentally discovered, unexplained, and persistent increase in ESR. In the manifest stage, general symptoms appear (malaise, weakness, weight loss) and specific clinical syndromes develop:
- Bone syndrome: Tumor cells release factors that stimulate osteoclast activity. This leads to diffuse osteoporosis and osteolysis. Patients are troubled by spontaneous bone pain that worsens with movement or palpation. The disease frequently manifests as a pathological vertebral fracture with the development of radicular syndrome.
- Renal syndrome (myeloma kidney): Excess Bence Jones protein blocks the lumen of renal tubules, provoking renal failure. Protein and casts appear in the urine, while hematuria is absent or mild. The situation is aggravated by nephrocalcinosis against the background of hypercalcemia.
- Immune deficiency syndrome: Due to a decrease in the level of normal immunoglobulins, humoral immunity suffers, making patients extremely susceptible to infections, especially of the respiratory tract.
- Hyperviscosity syndrome: Hyperproteinemia disrupts blood microcirculation, which clinically manifests as neurological symptoms, such as persistent headaches.
- Amyloidosis and infiltration: The formation of amyloid leads to its deposition in muscles (macroglossia develops, the heart is affected), dermis, and joints (arthralgia). In addition, plasma cell infiltrates can be found in almost all internal organs.
Laboratory and instrumental diagnostics and treatment
The diagnostic workup for suspected multiple myeloma relies on a set of studies:
- Blood test and biochemistry: Anemia, leukopenia, and a significant acceleration of ESR are characteristic (although not found in 100% of patients). Biochemical analysis reveals hyperproteinemia and hypercalcemia (a consequence of calcium mobilization from destroying bone tissue).
- Protein electrophoresis: A key method that allows the detection of the M-spike—a narrow paraprotein band most commonly localized in the blood γ-globulin zone or in the urine.
- Bone marrow examination: The diagnosis is confirmed upon detecting an increase in the proportion of plasma cells by more than 15%.
- Radiological imaging (X-ray, CT): Allows visualization of typical "punched-out" foci of osteodestruction in flat bones (skull, pelvis), including small-sized defects.
It is important to remember that detecting a monoclonal gammopathy requires a differential diagnosis, as such a condition occurs in liver cirrhosis, systemic connective tissue diseases, and other tumors.
The basis of therapy is radiation exposure and the use of cytostatics. Alkylating agents (melphalan, cyclophosphamide) and nitrosourea derivatives are actively used in clinical practice.
Briefly: answers to topical questions
Which specific groups of cytostatics are used to treat multiple myeloma?
Alkylating agents and nitrosourea derivatives are used to treat multiple myeloma.
- Alkylating agents — melphalan, cyclophosphamide.
- Nitrosourea derivatives.
In which flat bones are foci of osteodestruction most frequently visualized in multiple myeloma?
Foci of osteodestruction ("punched-out" defects) are visualized in flat bones: the skull and pelvis.
In which internal organs can amyloid be deposited in multiple myeloma?
In multiple myeloma, the typical localization of amyloid deposits includes muscles (including macroglossia and cardiac involvement), dermis, and joints.
To memorize the key triad of multiple myeloma, use the "PIC" rule: Protein/Kidneys (development of specific nephropathy), Immunoglobulins (secretion of monoclonal pathological protein), Coated bones/Bones (involvement and destruction of bone tissue).
Class and exam questions
What is the Bence Jones phenomenon?
This is a condition where tumor cells produce exclusively immunoglobulin light chains. They are filtered by the kidneys, excreted in the urine, and damage the renal tubules.
Why does immunodeficiency occur in myeloma if the blood protein level is elevated?
The tumor secretes a pathological paraprotein that does not perform protective functions. Meanwhile, the level of normal immunoglobulins decreases, leading to impaired humoral immunity and frequent infections.
Does the detection of an M-spike always mean multiple myeloma?
No, monoclonal gammopathies are nonspecific. They can occur in liver cirrhosis, systemic connective tissue diseases, and other tumors.
How does multiple myeloma affect calcium levels?
Plasmacytes stimulate osteoclasts, leading to the destruction of bone tissue and the mobilization of calcium into the blood. Hypercalcemia develops, which can be complicated by nephrocalcinosis.
What else to study on this topic
- Mechanisms of development of myeloma nephropathy and the role of Bence Jones protein.
- Radiological signs of osteodestruction and differential diagnosis of bone syndrome.
- Pathogenesis of secondary amyloidosis and its systemic manifestations.
- Differential diagnosis of monoclonal gammopathies in cirrhosis and systemic diseases.
- Pharmacology of cytostatics: mechanism of action of alkylating agents and nitrosourea derivatives.
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