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| Year : 2018 | Volume
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| Issue : 3 | Page : 319-322 |
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| Histopathological differences between primary Sjögren's syndrome and Sjögren's syndrome accompanied by scleroderma |
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Ulku Kucuk1, Sulen Sarioglu2, Pinar Cetin3, Ismail Sari3, Merih Birlik3
1 Department of Pathology, Tepecik Research and Training Hospital, Izmir, Turkey
2 Department of Pathology, Dokuz Eylul University Faculty of Medicine, Izmir, Turkey
3 Department of Rheumatology, Dokuz Eylul University Faculty of Medicine, Izmir, Turkey
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| Date of Web Publication | 13-Jul-2018 |
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 Abstract | | |
Background: Investigation of morphological differences in relation with serological variables between primary versus secondary Sjögren's syndrome associated with systemic scleroderma (Scl-SS). Materials and Methods: A total of 69 primary Sjögren's syndrome (pSS) and Scl-SS patients were grouped according to the American–European Consensus Group criteria. Serum autoantibody information was obtained from the patient records. Hematoxylin and eosin sections of the minor salivary gland biopsy were reevaluated, and the lymphocyte focus score (FS), plasma cell focus, and fibrosis rates were all evaluated. Results: There were 43 pSS and 26 Scl-SS cases. Both biopsy and autoantibody were positive in 16 pSS cases while only biopsy was positive in 25 cases and only antibody in 1 case. Both biopsy and antibody were positive in 5 Scl-SS cases while only biopsy was positive in 18 and only antibody in 3 cases. The plasma cell focus was statistically significantly higher in pSS cases (P = 0.003). No difference was seen between Sjögren' syndrome (SS) subtypes in terms of lymphocyte FS, fibrosis, and autoantibody positivity. Conclusion: We found that plasma cell focuses could be found more frequently in pSS than Scl-SS. In addition, our study reveals that the coexistence of SS and systemic scleroderma decreases the incidence of FS value ≥1 compared to pSS.
Keywords: Differences, histopathological, scleroderma, Sjögren's syndrome
How to cite this article:
Kucuk U, Sarioglu S, Cetin P, Sari I, Birlik M. Histopathological differences between primary Sjögren's syndrome and Sjögren's syndrome accompanied by scleroderma. Indian J Pathol Microbiol 2018;61:319-22 |
How to cite this URL:
Kucuk U, Sarioglu S, Cetin P, Sari I, Birlik M. Histopathological differences between primary Sjögren's syndrome and Sjögren's syndrome accompanied by scleroderma. Indian J Pathol Microbiol [serial online] 2018 [cited 2023 Dec 1];61:319-22. Available from: https://www.ijpmonline.org/text.asp?2018/61/3/319/236610 |
| Introduction | |  |
Sjögren's syndrome (SS) is a chronic, systemic, inflammatory disease primarily affecting the exocrine glands. This syndrome is clinically characterized with dry eye and dry mouth due to CD4-positive T-lymphocyte infiltration and destruction in the salivary and lacrimal glands.[1] SS is not diagnosed with a single clinical or laboratory test but by using clinical, serological, functional, and morphological parameters together.[2] The American–European Consensus Group (AECG) has revised the SS diagnosis and classification criteria in 2002.[3]
Primary SS (pSS) is seen in 0.1%–3% of the population. It is 9 times more common in females than males.[4] Secondary SS is the concurrence of a well-defined autoimmune connective tissue disease and SS.[5],[6] Rheumatoid arthritis can accompany SS at a rate of 9%–15%, systemic lupus erythematosus 12%, and systemic scleroderma (Scl) 17%–29%.[7],[8]
Scl is an autoimmune disease characterized with increased extracellular matrix accumulation as a result of small-vessel vasculopathy, autoantibody production, and fibroblast dysfunction, leading to fibrosis of the skin and internal organs.[7]
Minor salivary gland biopsy (MSGB) is accepted as the golden standard for SS diagnosis.[9] The presence of >50 lymphocytes/4 mm 2 on the MSGB is diagnostic for SS (FS ≥1).[3] However, some studies report that immunoglobulin (Ig) G- and IgA-containing plasma cells in the MSGB may be an alternative to focus score (FS) for SS diagnosis.[10],[11] We investigated the significance of the numerical evaluation of the plasma cells, resembling the lymphocyte focus in MSGB profiles of pSS and Scl-SS cases, and whether there was a difference between SS subtypes regarding the histopathological data in sections of FS, plasma cell focus, and fibrosis.
| Material and Methods | | |
A total of 69 pSS and Scl-SS patients who were diagnosed with the help of MSGB between 2007 and 2014 were included in our retrospective study.
The dry mouth and dry eye symptoms and the results of the objective eye and salivary gland tests had been recorded in the rheumatology records in detail. We obtained all necessary clinical data including diagnoses and also demographic data such as age and gender from the medical records at the same clinic. SS-associated specific autoantibody results (both anti-Ro and anti-La) were documented from the patient records. The patients were grouped using the available data obtained into the pSS and secondary SS (Scl-SS) groups according to the AECG criteria. All Scl cases classified according to the 1980 American College of Rheumatology criteria.[12]
Hematoxylin and eosin sections of the MSGB were reevaluated, and the lymphocyte cell focus, plasma cell focus, and fibrosis rates were determined. A group of >50 lymphocytes was accepted as a lymphocytic focus on the biopsy, and Chisholm scoring was performed.[13] Cases with FS >1 were considered to be consistent with SS.
A group of >20 plasma cells was accepted as a plasma cell focus on the biopsy.[14] Fibrosis was evaluated using a semiquantitative method and grouped as none, mild, and moderate/severe.
Statistically, the Chi-square test and Fisher's exact test were used to determine correlations between the variables. Statistical significance was set at P < 0.05. Statistical analyses were performed with SPSS for Windows, Version 15.0. Chicago, SPSS Inc.
| Results | | |
There were 43 (62%) pSS and 26 (37.7%) Scl-SS cases. The pSS cases consisted of 41 (95.3%) females and 2 (4.7%) males with a mean age of 50.9 ± 13.2 (range: 22–79) years. The Scl-SS cases consisted of 25 (96.2%) females and 1 (3.8%) male, and the mean age was 55.4 ± 10.9 (range: 33–73) years. In the pSS group, the mean duration of the symptoms was 4.71 ± 3.81 (range: 1–16) months. In the Scl-SS group, the Raynaud's symptom duration was 12.5 ± 12.9 (range: 1–49) years and the non-Raynaud symptom duration was 8.8 ± 9.8 (range: 1–33) years. The total 26 Scl-SS patients consisted of 19 (73.1%) limited cutaneous scleroderma (Ic-Scl) and 7 (26.9%) generalized cutaneous scleroderma (gen-Scl) patients.
Both biopsy and autoantibody (anti-Ro and/or anti-La) were positive in 16 (38.1%) pSS cases while only biopsy was positive in 25 cases (59.5%) and only autoantibody in 1 case (2%). Autoantibody results of one patient could not be reached.
Both biopsy and antibody were positive in 5 (19.2%) Scl-SS cases while only biopsy was positive in 18 (69.2%) and only antibody in 3 cases (11.5%).
We compared the FS value, plasma cell focus, fibrosis degree, and serum autoantibody positivity rate in the pSS and Scl-SS groups [Table 1]. The plasma cell focus in salivary gland biopsy was higher in pSS cases than in Scl-SS cases. The plasma cell focus was statistically significantly higher in pSS cases (P = 0.003). No difference was seen between SS subtypes in terms of lymphocyte FS, fibrosis, and autoantibody positivity. | Table 1: Lymphocyte focus score, plasma cell focus, fibrosis degree, and autoantibody positivity rates in Sjögren's syndrome subtypes
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The relationship between lymphocyte FS and plasma cell focus and fibrosis presence was reevaluated case by case in all pSS and Scl-SS cases. No statistically significant relationship was found between FS and plasma cell focus and fibrosis values in SS subtypes [Table 2]. The relationship between serum autoantibody positivity and plasma cell focus and fibrosis values in pSS and Scl-SS cases was reevaluated [Table 3]. No statistically significant relationship was found between serum autoantibody positivity and plasma cell focus and fibrosis values in SS subtypes. | Table 2: The relationship between lymphocyte focus score and fibrosis and plasma cell focus in Sjögren's syndrome and Scl-SS cases
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 | Table 3: The relationship between serum autoantibody positivity and plasma cell focus and fibrosis in primary Sjögren's syndrome and Scl-SS cases
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| Discussion | | |
SS is defined as autoimmune epithelitis characterized by lymphocytic infiltration of exocrine glands. The prevalence rates of pSS have been reported wide range in the general population (from 0.026% in females to 4.8% in a geriatric population).[15] Secondary SS is the concurrence of a well-defined autoimmune connective tissue disease and SS.[5],[6] Scleroderma can accompany SS at a rate of 17%–29%.[7],[8]
Lc-Scl is a Scl subtype that clinically involves the parts distal to the knee and elbows and is known to frequently accompany Scl-SS cases.[1],[7],[16] Many clinical studies showed that there are no major differences between lc-Scl and gen-Scl in relation to visceral organ involvement, immunological features, and average survival rates. However, a higher prevalence of sicca syndrome was identified in lc-Scl subtype. The Ic-Scl subtype has been detected in 22 of 27 Scl-SS cases by Salliot et al. and 18 of 19 Scl-SS cases by Avouac et al.[16],[7] In this sense, our study also showed that most of our Scl-SS cases were of the lc-Scl subtype (19/26 cases) as reported in the literature.
Labial MSGB is reported as the gold standard for SS diagnosis.[9] Groups that consist of ≥50 lymphocytes/4 mm 2 at biopsy are accepted as lymphocytic foci, and scoring (Chisholm scoring) is performed. Accordingly, FS ≥1 is diagnostic for SS.[13]
Earlier studies by Salliot et al. reported an FS value ≥1 in 90.9% of 202 pSS cases and 84.2% of 27 Scl-SS cases.[16] Avouac et al. reported a lymphocyte FS value ≥1 in 18 of 19 Scl-SS cases as well.[7] In the present study, we found an FS value ≥1 in 97.7% of pSS cases and 88.5% of Scl-SS cases in our case series. Although statistically insignificant, the trend of fewer cases with FS value ≥1 is also seen in our cases in Scl-SS group.
Some studies report that IgG and IgA-producing plasma cells in MSGB may be an alternative to FS for SS diagnosis.[10],[11] Salomonsson et al. have reported that the ratio of IgG-producing plasma cells show a significant increase in pSS and secondary SS cases compared to non-SS cases.[17] IgA-producing plasma cells were also found to decrease significantly in pSS cases compared to non-SS and secondary SS cases, indicating the possibility of using this decrease in the differentiation of pSS and secondary SS, in the same study.
Plasma cells are known to be present in the normal minor salivary glands. Yarom et al. suggested that the plasma cell population is abundant in SS in comparison with other types of sialadenitis.[18] Stewart et al. evaluated the presence of plasma cells and plasma cell aggregates in series including SS and chronic sialadenitis cases.[14] They described the plasmacytic focus as plasma cell aggregates of 10–30 cells, and they identified plasma cell foci in 43.8% of SS cases and 21.4% of chronic sialoadenitis cases without the information about the number of foci in a certain tissue area.[14] There is no strict criterion for the number of plasma cells in the literature other than this one particular article. In our study, we preferred 20 cells as a cut point to call a group of plasma cells a “focus.” We did not have any case with a focus more than 50 plasma cells. Higher plasma cell focus values were observed in pSS cases compared to Scl-SS cases, and this difference was found to be statistically significant (56.8%–19.2%). Our study reveals that plasma cell focuses could be found more dominant in pSS than Scl-SS.
Lymphocytic FS was <1, while plasma cell focus was >1 in one case in our series. Plasma cell focus may have diagnostic value in this patient, but studies of the diagnostic significance of plasma cell focus in larger series are required to determine such significance. The lymphocytic FS already had diagnostic value in the other cases with a plasma cell focus of ≤1 in our series.
Fibrosis was another criterion we assessed with histopathological evaluation, and it was found at similar rates in the two groups in our series (P = 0.503). Avouac et al. reported fibrosis in only two (1 mild and 1 moderate) of 19 Scl-SS cases.[7] There is a general opinion that fibrosis should be interpreted as a positive finding for sialadenitis. Beside this fibrosis can also be seen at rates that are not negligible in these patients None of our relevant cases had significant findings of chronic sialadenitis (diffuse chronic inflammation, ductal dilatation, and acinar atrophy), and the clinical diagnosis was consistent with SS.
Serum anti-Ro and/or anti-La autoantibody positivity is highly diagnostic in SS. Salliot et al. reported that only anti-Ro autoantibodies were positive in 28.2% of pSS cases and 29.6% of Scl-SS cases with no significant difference between pSS and Scl-SS in terms of autoantibody positivity.[16] Avouac et al. reported finding autoantibody positivity in only 4 of 19 Scl-SS cases.[7] Autoantibody positivity was reported in 26.1% of SS + CREST syndrome cases by Akiyama et al. and 21% of Scl-SS cases by Avouac et al.[19],[7] We found the positivity rate for anti-Ro and/or anti-La antibodies to be 40.8% in pSS cases and 30.8% in Scl-SS cases with no significant difference between SS subtypes in terms of antibody positivity, as reported in the literature.
Salliot et al. reported that anti-Ro autoantibody positivity was observed at similar rates in pSS and Scl-SS cases and that the anti-La antibody positivity rate was higher in pSS than in Scl-SS cases.[16] However, this difference was not statistically significant. In contrast, our anti-Ro autoantibody positivity rate was higher in pSS (40.5%) cases than in Scl-SS (23.1%) cases, but this difference was not statistically significant. The rates of anti-La autoantibody positivity were similar between pSS and Scl-SS (7.1%–7.7%). This indicates that evaluation of autoantibodies in SS subtypes separately may not be quite useful.
Fibrosis was not seen in the biopsies of these cases. We similarly found no relationship between autoantibody positivity and fibrosis in our series. There was also no relationship between autoantibody positivity and the plasma cell focus value.
| Conclusion | | |
We found that the coexistence of scleroderma and SS decreases the incidence of FS value ≥1 compared to pSS. In addition, our study reveals that plasma cell focuses could be found more often in pSS than Scl-SS.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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Correspondence Address:
Ulku Kucuk
Department of Pathology, Tepecik Research and Training Hospital, Izmir
Turkey
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/IJPM.IJPM_416_17
[Table 1], [Table 2], [Table 3] |
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