A 74-year-old woman presents to her family doctor with an aching upper back pain which has been progressively worsening for the past 2 weeks. She describes the pain as worse on movement and sometimes feels it in her ribs and chest. The patient has been urinating more but defecating less frequently and has noticed her belt is buckled one notch tighter than it used to be. Over the past few weeks, she admits to feeling tired and weaker, with less appetite than usual. She thinks that this is due to her husband being hospitalized with a heart condition. She has a history of hypertension for which she takes lisinopril 10mg once daily. She has a 20-pack-year smoking history. Vital signs reveal a slight tachycardia at 105 beats/minute but otherwise are within normal limits.
Laboratory results show the following:
- Urinalysis is positive for Bence-Jones proteins
- Hemoglobin: 9.9 g/dL
- Erythrocyte count: 2.9x1012/L
- Serum calcium: 11.5 mg/dL
- Serum creatinine 1.4 mg/dL
- Glomerular filtration rate: 49 mL/min
Considering the most likely diagnosis, which of the following complications would is unlikely to occur from the underlying disease processes?
- A) AL amyloidosis
- B) Cast nephropathy
- C) Polycythemia
- D) Radiculopathy
- E) Recurrent infection
Based on a typical presentation of hypercalcemia, renal dysfunction, anemia and bone pain, the most likely diagnosis is multiple myeloma (MM). MM is a malignant proliferation of plasma cells in the bone marrow. Plasma cell proliferation in bone marrow leads to outcompeting for space of all other hematopoietic stem cells in the parenchyma. This results in reduced erythropoiesis and platelet production. Therefore, you would expect anemia and thrombocytopenia in MM, rather than an overproduction, despite some other cancers being associated with polycythemia.
In 15-20% of cases, malignant plasma cells do not produce a complete immunoglobulin resulting in an overproduction of light chains, or Bence-Jones proteins, small enough to pass through the kidneys and be detected in urine. Light chains also accumulate in complexes with Tamm-Horsfall proteins called casts, leading to a cast nephropathy, the commonest cause of renal disease in MM. Light chains can also directly be nephrotoxic.
Type AL amyloidosis results in misfolded light-chains being deposited in nerves, tissues, and organs throughout the body, eventually affecting organ function and resulting in symptoms.
Osteolytic tumor lesions cause thinning and weakening of the bone leading to pathological fractures, most commonly in the vertebrae. This can lead to radiculopathy if a nerve root is pinched. Note that serum alkaline phosphatase (ALP) is not typically increased in MM. ALP is released by osteoblasts, and in MM there is osteolysis through an isolated increase in osteoclastic activity.
MM causes immunosuppression through overproduction of faulty immunoglobulins and suppression of normal immunoglobulin production. MM also suppresses other cells, such as natural killer (NK) cells and macrophages. Additionally, treatment regimens can also increase immunosuppression. Both can lead to recurrent infections.
Key Learning Point
Overproduction of immunoglobulins and light chains in multiple myeloma has systemic effects correlated to the physical impact of protein overproduction or the physiological consequences of plasma cell proliferation and resulting deficiencies.