Pathology
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Haematology
A 75 year old female presents to ED with right arm pain. X-ray shows lytic bone lesions and you suspect multiple myeloma. Overproduction of which type of immunoglobulin is most commonly associated with this condition:
Answer:
The paraprotein is IgG in 60% of cases, IgA in 20% and light chain only in almost all the rest.Multiple Myeloma
Pathology / Haematology / Malignancy
Last Updated: 25th April 2019
Multiple myeloma is a neoplastic disease characterised by plasma cell accumulation in bone marrow, the presence of monoclonal protein in the serum and/or urine and, in symptomatic patients, related tissue damage.
Incidence
98% of cases of myeloma occur over the age of 40 years with a peak incidence between 65 and 70 years. The disease is twice as common in black individuals compared to those of white or Asian origin.
Clinical Features
A useful acronym for tissue damage in myeloma is CRAB:
- Hypercalcaemia
- Renal impairment (proteinaceous deposits from light chain proteinuria, hypercalcaemia, uric acid, amyloid and pyelonephritis may all contribute to renal failure)
- Anaemia
- Bone pain (especially backache, resulting from vertebral collapse and pathological fractures)
Other features include:
- Amyloidosis (features include macroglossia, carpal tunnel syndrome, diarrhoea)
- Hyperviscosity syndrome (features include purpura, haemorrhages, visual disturbance, CNS symptoms, neuropathies and heart failure)
- Recurrent infections (related to deficient antibody production, abnormal cell-mediated immunity and neutropaenia)
- Abnormal bleeding tendency (resulting from paraprotein interfering with platelet function and coagulation factors and from thrombocytopaenia in advanced disease)
- Peripheral neuropathy
- Deep vein thrombosis
Laboratory Findings
- Presence of a paraprotein in serum/urine (the paraprotein is IgG in 60% of cases, IgA in 20% and light chain only in almost all the rest)
- Elevated serum immunoglobulin-free light chains (κ or λ light chain proteins, synthesised by plasma cells, that have not been paired with heavy chains; they are normally made in small quantities and filtered from the serum into the kidney but they are produced by almost all malignant plasma cells and so the serum free light chain assay is useful in diagnosis and monitoring of myeloma
- Bence-Jones protein (free light chains) in urine
- Reduced serum IgG, IgA and IgM levels (immunoparesis)
- Normochromic normocytic or macrocytic anaemia
- Marked Rouleaux formation on blood film
- Neutropaenia and thrombocytopaenia in advanced disease
- High ESR
- Increased plasma cells in the bone marrow (usually more than 20%), often with abnormal forms
- Hypercalcaemia (45% of patients)
- Elevated creatinine (20% of cases)
- Low serum albumin in advanced disease
- Osteolytic lesions (60% of patients), osteoporosis (20% of patients) or pathological fractures/vertebral collapse on radiological investigation
- Raised serum β2-microglobulin (useful indicator of prognosis)
Management
The life expectancy of patients with myeloma has improved markedly in recent years with the introduction of new drugs such as proteasome inhibitors and immunomodulatory agents. The major initial treatment decision is between the use of intensive combination chemotherapy (mostly for patients aged less than 70 years old) or non-intensive therapy for older patients.
Prognosis
The outlook for patients with myeloma is improving markedly. The overall median survival is now 7-10 years and in younger (less than 50 years) patients it can be over 10 years.
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
