Mean Corpuscular Volume as An Early Predictor of Malignant Evolution of Monoclonal Gammopathy of Undetermined Significance

Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant clonal plasma cell proliferative disorder. It occurs in over 3 percent of the general population over the age of 50. MGUS can progress to multiple myeloma (MM) or related cancers at a rate of about 1.0 to 1.5 percent per year. There are no findings at diagnosis of MGUS that reliably distinguish patients who will remain stable from those who will progress to a malignant disease. Size and type of serum monoclonal protein, as well as serum free light chain ratio have been suggested in some studies as independent risk factors for disease progression. In this study, we tried to analyze the relationship between Mean Corpuscular Volume (MCV) and the risk of progression of MGUS into a malignant lymphoproliferative condition.

A total of 1744 patients, from a single institution, with a first diagnosis of MGUS from April 18^th, 1995 till June 24^th, 2010 were included in this study. Patients analyzed were divided into two groups. Group 1 consisted of 345 patients with an elevated MCV (>100fL/red cell) and group 2 consisted of 1399 patients with a normal MCV (between 80fL/red cell and 100fL/red cell). Patients with short follow up (<3 months), low B12/folate levels, hypothyroidism, liver disease or a serum monoclonal protein >1.5g/dL were excluded. The Chi-square test was used to compare the proportion of patients who progressed in group 1 relative to group 2.

After a median follow up of 51 and 58 months for the high MCV and normal MCV respectively, there were 78 progressions (22.6%) versus 267 non-progressions (77.4%) among the high MCV patients (Group1) and 110 progressions (7.9%) versus 1289 non-progressions (92.1%) among the normal MCV patients (Group 2). The difference in progression between the two groups was statistically significant (Chi-square test p-value < 0.001). The odds ratio for the progression comparison of the high versus normal MCV groups was 3.4 with a 95% confidence interval of 2.5 to 4.7.

In our single institution, retrospective study, there seems to be a higher incidence of malignant transformation in the subset of patients with MGUS having an elevated MCV. MCV is a cost effective method that might help identify, at presentation, patients with benign monoclonal gammopathies requiring stricter monitoring.

No relevant conflicts of interest to declare.