Correct answer: A, B, C

Rationale

The patient has a monoclonal gammopathy given the presence of M protein or a paraprotein on testing. Monoclonal gammopathies are a group of clonal plasma cell disorders that can be premalignant (monoclonal gammopathies of undetermined significance [MGUS]) or malignant (smoldering multiple myeloma and active or symptomatic multiple myeloma). To determine the type of monoclonal gammopathy that a patient has, a bone marrow biopsy is needed as the marrow clonal plasma cell percentage defines the monoclonal gammopathy in question. A 24-hour urine collection is needed to detect and quantify the protein in the urine, which can help confirm the diagnosis. A bone survey (x-ray) can detect any lytic bone lesions that may arise from multiple myeloma. By definition, MGUS requires bone marrow clonal plasma cells of less than 10% and no evidence of lytic lesions on skeletal imaging; however, these tests can be omitted in some patients with low-risk MGUS (see question 3).

Case continued

Question 2 of 10

Correct answer: Monoclonal gammopathy of undetermined significance (MGUS)

Rationale

Table 1¹ shows the diagnostic criteria for MGUS based on the percentage of clonal bone marrow plasma cells (< 10%), the size of the M protein (< 3 g/dL), and the absence of any myeloma-defining events. Given the patient’s test results, it would be correct to suspect MGUS.

Question 3 of 10

Correct answer: Low intermediate risk

Rationale

Table 2 shows the current risk stratification model used for patients with MGUS.^1,2 Given this patient’s abnormal serum free light chain ratio, he falls into the low intermediate risk category. As noted earlier, in patients with low risk MGUS without bone pain or clinical concern for myeloma, both the bone marrow biopsy and bone survey can be omitted as < 2% of low-risk patients have bone lesions on bone survey and 7% have a bone marrow plasma cell percentage above 10%.³

Table 2.*

Question 4 of 10

Correct answer: 10%

Rationale

According to a cohort study from Mayo Clinic in which 1,384 patients with MGUS were followed for a median of 15 years, the 20-year risk of progression for low intermediate risk MGUS is 10%, 2% for low risk, 18% for high intermediate risk, and 27% for high risk.⁴ This compares with a 1% per year risk of progression collectively for all forms of MGUS.⁵

Case continued

Results from anemia workup revealed normal levels of vitamin B12, folate, iron, and ferritin. His total iron-binding capacity was low.

Question 5 of 10

Correct answer: Anemia of chronic inflammation

Rationale

The patient likely has anemia of chronic inflammation associated with his polymyalgia rheumatica, especially with his low total iron-binding capacity. MGUS, by definition, should not cause anemia. Given his normal ferritin level and low total iron-binding capacity level, iron deficiency is unlikely. His marrow biopsy did not show a primary disorder.

Question 6 of 10

Correct answer: 6 months

Discussion

Patients with MGUS should be re-evaluated in 6 months as the risk of progression is highest in the first year.^2,3,6 At follow-up, practitioners should test for M protein along with a complete blood count and creatinine and calcium levels.³ Bone imaging could be obtained if the patient reports new pain.

Question 7 of 10

Correct answer: Every year

Rationale

Based on the International Myeloma Working Group (IMWG),³ all patients with intermediate and high risk MGUS should have paraprotein monitoring on a yearly basis along with the labs noted in the question 6 rationale. Patients with low-risk MGUS could be seen every 2 or 3 years.

Case continued

The patient develops new onset shortness of breath 2 years after his diagnosis of MGUS. An echocardiogram shows diastolic dysfunction and a thickened myocardium. His electrocardiogram shows low QRS voltage.

Question 8 of 10

Correct answer: Infiltrative cardiomyopathy

Rationale

Patients with MGUS are at risk for immunoglobulin light chain (AL) amyloidosis. The presence of left ventricular hypertrophy, diastolic dysfunction, and low voltage on electrocardiogram are highly suggestive of infiltrative cardiomyopathy, namely AL amyloidosis, in a patient with a history of MGUS.

Question 9 of 10

Correct answer: Chronic kidney disease

Rationale

Chronic kidney disease can cause decreased excretion of free light chains that results in an abnormal kappa-lambda ratio in the 2 to 3 range.

Question 10 of 10

Correct answer: C and D

Rationale

Proximal tubulopathy and proliferative glomerulonephritis are considered monoclonal gammopathies of renal significance (MGRS) and are associated with kidney dysfunction caused by monoclonal immunoglobulin deposits in the kidney. MGRS is a relatively new disease in which the kidneys are affected by the monoclonal protein without a diagnosis of myeloma.^7,8 Treatment of MGRS involves that of the plasma cell clone and is usually considered after a discussion with a hematologist and nephrologist.

KEY POINTS

• MGUS is a premalignant plasma cell disorder that can progress to a lymphoplasmacytic disorder.
• MGUS is typically found incidentally and requires long-term follow-up given the risk of malignant progression.
• Patients need to be risk stratified based on the type and size of the M protein as well as the serum free light chain ratio.
• A bone marrow biopsy and a skeletal survey may be foregone in patients with low risk MGUS.
• Most patients are followed on a yearly basis with repeat paraprotein testing along with complete blood count, calcium, and creatinine checks.
• Clinicians should be vigilant about conducting appropriate testing if progression is suspected.
• AL amyloidosis should be considered in patients with MGUS and infiltrative cardiomyopathy.