High frequency of light chain restriction in labial gland biopsies of Sjögren's syndrome detected by in situ hybridization.

A well-recognized complication of Sjögren's syndrome (SS) is the development of malignant lymphoma, with a risk 44 times that of the general population. Although a few clinical signs may indicate the onset of lymphoma, there are few reliable laboratory markers which predict the development of neoplasia. A non-isotopic in situ hybridization technique has been applied to routinely processed labial salivary gland (LSG) biopsies of patients under investigation for SS. Serial section of 70 LSGs were examined for a kappa and gamma immunoglobulin light chain mRNA using digoxigenin-labelled oligonucleotide probes. As controls, 39 biopsies from non-SS-associated sialadenitis were also examined. Sections were analysed using computer-assisted quantification to determine the percentage of kappa-expressing cells in each case. The range of kappa expression in the SS group was 24.1-93.4 percent and in the non-SS group 48.3-75.4 per cent. Light chain restriction was found in 13/70 (18.6 percent) cases from the SS group but in no cases of the control group. Of the SS cases showing restriction, 4/13 (30.7 percent) have subsequently developed extrasalivary gland lymphoma. Two patients not showing light chain restriction in LSG have subsequently developed lymphoma. The positive predictive value of this test to identify patients at risk of lymphoma was 30.7 percent with a detection rate (sensitivity) of 66.7 percent and a false-positive rate of 14.1 per cent(specificity 85.9 percent). This study has identified a high prevalence of light chain restriction in labial gland biopsies of patients with SS and provides objective quantitative criteria to identify those patients at greater risk of lymphoma development.