L. Kater

Morphometric study of histological changes in sublabial salivary glands due to aging process.

The sublabial salivary glands were studied by morphometric methods in 68 healthy volunteers to establish possible changes related to age in those tissue components that are affected in Sjögrens syndrome and connective tissue diseases (and which might stimulate Sjögrens syndrome). There was an increase in the amount of connective tissue and intralobular ducts with age and a corresponding decrease in acinar tissue. During the aging process changes in the intralobular ducts occurred: the outer and inner diameters of these ducts and the thickness of the epithelium decreased, but the ratio of the outer and inner diameters of the ducts remained constant. The amount of diffuse lymphoplasmacytic infiltrate and the vascularity of the tissue remains constant with age. In 15 of the subjects, however, discrete lymphocytic foci were seen and in six of these more than one focus/4 mm2 of salivary tissue was found, which has been described as suggestive of Sjögrens syndrome. The volume percentage of lymphocytic foci is constant during the aging process. The histological features commonly used to diagnose Sjögrens syndrome may occur in normal people, and false positive diagnoses will occur if these criteria are rigidly adhered to. Morphometry may provide more reliable criteria for distinguishing changes induced by inflammation and related to age which occur in salivary tissue.

Monotypic plasma cells in labial salivary glands of patients with Sjögren's syndrome: prognosticator for systemic lymphoproliferative disease.

AIMS: To determine the prevalence of plasma cell monotypia in labial salivary gland tissue of patients with and without Sjögrens syndrome, and to evaluate its relation to the development of systemic monoclonal lymphoproliferative disorders. METHODS: A quantitative immunohistological study was performed on labial salivary gland tissue of 45 patients with Sjögrens syndrome, 18 with rheumatoid arthritis without Sjögrens syndrome, and 80 healthy controls. In none of the patients with Sjögrens syndrome was there evidence of systemic monoclonal lymphoproliferative disease at the time of biopsy. RESULTS: Monotypic plasma cell populations, defined by a kappa:lambda ratio of > or = 3, were only observed in older patients (above 43 years) with Sjögrens syndrome. In almost all these patients monotypic plasma cell populations were present in multiple labial salivary gland tissues and the IgM/kappa monotypia was observed most frequently. The prevalence of monotypic plasma cell populations in the group with Sjögrens syndrome was 22% (10/45) and there was no significant predilection for primary Sjögrens syndrome. Of special clinical interest was the observation that progression to systemic monoclonal lymphoproliferative disease had occurred exclusively in this subgroup of patients with Sjögrens syndrome, with a prevalence of 30% (3/10). CONCLUSION: Quantitative immunohistological examination of labial salivary gland tissues provides pathologists with a simple method to select those patients with Sjögrens syndrome who have an increased relative risk at the time of biopsy to develop benign or malignant lymphoproliferative disorders.

Long-term course of tear gland function in patients with keratoconjunctivitis sicca and Sjogren's syndrome

AIMS To assess the course of tear gland function of patients with keratoconjunctivitis sicca (KCS) associated with primary (KCS-PSS) or secondary Sjögren’s syndrome (KCS-SSS), and of patients with KCS not related to Sjögren’s syndrome (KCS-NS). METHODS In 106 patients with dry eye an ophthalmic diagnosis of KCS was made. Subsequent evaluations revealed a diagnosis of KCS-PSS in 31, KCS-SSS in 19, and KCS-NS in 56 patients. Follow up assessments have been performed 10–12 years after initial diagnosis. RESULTS At baseline and at follow up tear gland function tests were worse in patients with KCS-PSS compared with the other forms of KCS. At follow up in the KCS-SSS patient group the tear gland function variables returned to marginal normal limits. In contrast with expectation, a marked improvement of the tear gland function variables in the KCS-NS patient group was noted. CONCLUSIONS In KCS-PSS patients tear gland function is characterised by a steady state situation. In KCS-SSS patients the normalisation of tear gland function variables most probably reflects a remission of the underlying disease. In view of the overall improvement in KCS-NS patients the term age related KCS should be avoided.

Quantitative immunohistologic study of lip biopsies evaluation of diagnostic and prognostic value in Sjögren's syndrome

In a group of 45 patients with Sjögrens syndrome (SS) and 80 controls the high specificity (95%) and sensitivity (100%) of a recently proposed bivariate quantitative immunohistologic (QIH) criterion for SS, based on percentages of IgA and IgG-containing plasma cells in labial salivary gland (LSG) tissue, was confirmed. The best univariate QIH criterion for discrimination between LSG biopsies of SS patients and controls appeared to be based on the percentage of IgA containing plasma cells, and had a specificity of 99% and a sensitivity of 96%. A criterion based only on the percentages of IgM-containing plasma cells, proposed in another recent study, resulted in a high number (31%) of false negatives. Interobserver reproducibility of QIH diagnoses was excellent. Moreover it was demonstrated that accuracy, precision and the interobserver reproducibility of plasma cell counting depends on the choice of tissue fixation and immunohistologic staining procedure. The combination of formol sublimate fixation and peroxidase anti-peroxidase procedure appeared to be the best combination for QIH examination. Furthermore, in 2 SS patients systemic monoclonal IgM/kappa gammopathy was preceded by high predominance of IgM and kappa containing plasma cells in the plasma cellular infiltrate of the LSG tissue.

Multinucleate giant cells in sublabial salivary gland

The presence of multinucleate giant cells in the sublabial salivary gland tissue in Sjögrens syndrome is an unusual phenomenon which can give rise to differential diagnostic problems. We found in 4 cases of 55 patients with Sjögrens syndrome multinucleate giant cells. In 2 of these 4 patients epimyoepithelial islands were also present. The combination of both multinucleate giant cells as epimyoepithelial islands can mimic the histological picture of a non-caseating granulomatous disease. To discriminate between an epimyoepithelial island and an epithelioid granuloma the immunoperoxidase technique with antibodies directed against muramidase appeared an useful tool. The epithelioid cells contain muramidase whereas the cells in the epimyoepithelial island do not contain this enzyme. Thus, multinucleate giant cells are a rare phenomenon in Sjögrens syndrome, therefore restricting its diagnostic significance. When they occur in Sjögrens syndrome staining for muramidase can be of help to avoid a false positive diagnosis of diseases in which non-caseating granulomatous inflammation occur, such as in sarcoidosis.

Quantiative Immunohistologic and Histomorphometric Diagnostic Criteria for Sjögren's Syndrome

Summary Sjogrens syndrome (SS) is a chronic auto-immune exocrinopathy, especially affecting the lacrimal and salivary glands. The aim ofthis study is to improve the diagnotic possibilities of the sublablial salivary gland (SSG) biopsy. The SSG biopsies of 1 9 patients with SS and 65 healthy control subjects were used in a quantitative immunohistologic and histomorphometric study. Statistical analysis of the immunohistochemical data resulted in a diagnostic criterion, which is based on the percentages of IgA-and IgG-containing plasma cells. Statistical analysis of 3 immunohistologic and 6 histomorphometric features resulted in a combined immunohistologic and histomorphometric criterion, which is based on 2 immunohistologic parameters (the percentages IgA- and IgG-containing plasma cells) and 3 histomorphometric parameters (the volume percentages of acini, intralobular ducts and diffuse lymphoplasmacytic infiltrate). The immunohistologic diagnostic criterion has a specificity of 95.4%, a sensitivity of 100% and an overall percentage of misclassification of 3.6%. The combined diagnostic criterion has a specificity of 98.5%, a sensitivity of 100% and an overall percentages of misclassification of 1.2%. Furthermore it reduces the number of false positive diagnoses with a factor 6 from 9% to 1.5%.