MKSAP Quiz: Evaluation for an elevated globulin fraction
A 67-year-old woman undergoes follow-up evaluation for an elevated globulin fraction of total serum protein level. She has no symptoms. Following a physical exam and lab studies, what is the most appropriate management?
A 67-year-old woman undergoes follow-up evaluation for an elevated globulin fraction of total serum protein level. She has no symptoms. Medical history is notable for hypertension treated with hydrochlorothiazide and atorvastatin.
On physical examination, vital signs are normal. No lymphadenopathy or hepatosplenomegaly is noted.
Laboratory studies:
| Hemoglobin | 14.5 g/dL (145 g/L) |
| Leukocyte count | 7000/µL (7 × 109/L) |
| Platelet count | 300,000/µL (300 × 109/L) |
| Calcium | 9.1 mg/dL (2.3 mmol/L) |
| Creatinine | 0.8 mg/dL (70.7 µmol/L) |
Serum protein electrophoresis and immunofixation show an IgG monoclonal spike of 0.7 g/dL. Serum free light chain assay and 24-hour urine protein electrophoresis are normal.
Skeletal survey shows no lytic lesions.
Which of the following is the most appropriate management?
A. Kidney biopsy
B. MRI of the cervical, thoracic, and lumbar spine
C. Repeat laboratory studies in 6 months
D. Serum β2-microglobulin I measurement
MKSAP Answer and Critique
The correct answer is C. Repeat laboratory studies in 6 months. This content is available to MKSAP 18 subscribers as Question 14 in the Hematology and Oncology section. More information about MKSAP is available online.
This patient should have laboratory studies repeated in 6 months. She has incidentally found low-risk monoclonal gammopathy of undetermined significance (MGUS); follow-up in 6 months to 1 year with repeat serum protein electrophoresis, hemoglobin and calcium levels, and kidney function is appropriate. At that time, if the MGUS is stable, the interval for follow-up could be extended further. The risk of progression of MGUS to multiple myeloma or other lymphoproliferative disorders is determined by various risk factors. In this patient with IgG MGUS, an M spike of less than 1.5 g/dL, and normal serum free light chain assay findings, the risk of progression is low at 5% over 20 years. Patients with low-risk MGUS with no other concerning clinical features do not require bone marrow biopsy to evaluate the plasma cell burden. MGUS is seen in 3% of the population older than 50 years, and most of them do not progress, so extensive evaluation is not recommended unless other concerning features are present.
Although kidney injury attributed to multiple myeloma has long been recognized, recent evidence suggests that a portion of patients with MGUS who do not meet criteria for myeloma will, nonetheless, have kidney disease without any other contributing cause beyond the monoclonal protein. These patients have monoclonal gammopathy of renal significance and have characteristic findings on a kidney biopsy specimen. But in this patient with normal kidney function and no proteinuria, kidney biopsy is not indicated.
In this patient with low-risk MGUS and no symptoms, MRI of the spine is not appropriate. An MRI or CT is more sensitive at detecting bone lesions than plain radiography and should be considered when used to risk stratify patients with smoldering multiple myeloma. MRI or CT may be important to assess spinal cord compression in patients with multiple myeloma and back pain. A skeletal survey is adequate in this low-risk patient.
Measurement of the β2-microglobulin I level is a part of the risk stratification strategy for patients with multiple myeloma but not for those with MGUS.
Key Point
- In patients with IgG monoclonal gammopathy of undetermined significance, an M spike of less than 1.5 g/dL, and normal findings on serum free light chain assay and urine protein electrophoresis, the risk of progression is low, so extensive evaluation is not recommended.