J. clin. Path., 1970, 23, 690-694 J Clin Pathol: first published as 10.1136/jcp.23.8.690 on 1 November 1970. Downloaded from Lymphocytic sialadenitis in the major and minor glands: a correlation in postmortem subjects D. M. CHISHOLM, J. P. WATERHOUSE, AND D. K. MASON From the Department of Oral Medicine and Pathology, University of Glasgow Dental Hospital and School, Glasgow, Scotland, and the Department of Oral Pathology, University ofIllinois, Chicago, USA SYNOPSIS In the present investigation, the prevalence offocal lymphocytic adenitis in the submandibular salivary gland was observed in a series of 116 postmortem subjects after suitable exclusions had been made. Focal lymphocytic adenitis could not be demonstrated in the labial salivary glands. The degree of lymphocytic infiltration in the labial salivary glands is positively correlated with the level of focal lymphocytic adenitis in the submandibular glands in the same subject. Lymphocytic foci and lymphocytic infiltrations found under thesecopyright. circumstances are probably related. This finding provides conceptual support for the examina- tion, by biopsy, of the labial glands in patients suspected of Sjogren's syndrome. The aim of the present study was to investigate muscle layer of the lower lip were excised at the prevalence and degree of lymphocytic sial- necropsy. Tissue was obtained from necropsies adenitis in the submandibular and minor labial at the Bernhard Baron Institute of Pathology, glands in a series of postmortem subjects. London Hospital, and the University Depart- Waterhouse (1963) has shown that the changes ment of Pathology, Royal Infirmary, Glasgow,http://jcp.bmj.com/ observed in the submandibular gland in the between March and June 1967. They were taken postmortem subject reflect the degree of focal from all necropsies on fixed days of the week adenitis present in the parotid and lacrimal excepting a few not obtainable for administrative glands. Furthermore, Waterhouse and Doniach reasons. (1966) have provided strong evidence for the The necropsy material was fixed in 10% association of focal lymphocytic sialadenitis and formalin, and routine paraffin sections, stained rheumatoid arthritis and have suggested that this with haematoxylin and eosin, were prepared. on October 2, 2021 by guest. Protected lesion may represent a focal manifestation of the Each submandibular gland and each ellipse of lesion in Sjogren's syndrome. Recently, Chisholm oral mucosa was bisected so that a large represen- and Mason (1968) have shown focal lymphocytic tative histological section would be obtained. adenitis of the labial salivary glands to be a The total number of cases examined was 129 consistent finding in patients with Sjogren's and, of these, 13 were excluded for the reasons syndrome. In view of these findings, therefore, given below, leaving 116 cases admitted to the we felt that it would be of value to observe and present series. The histological assessment was correlate the changes noted in the submandibular done independently by three observers. and labial salivary glands for each subject in a postmortem series of over 100 subjects. Criteria of Exclusion Materials and Methods Before a gland was included in the series, the following criteria, designed to exclude infection A submandibular salivary gland and an ellipse and neoplasm as effective causes of pathological of oral mucosa and subjacent tissue down to the change, were applied. Gland lobules were accep- Received for publication 26 March 1970. table if they were free from duct dilatation 691 Lymphocytic sialadenitis in the major and minor glands: a correlation in postmortem subjects indicating obstruction to flow of secretion, and gland acini (Fig. 1). Such foci are commonly J Clin Pathol: first published as 10.1136/jcp.23.8.690 on 1 November 1970. Downloaded from were free from extravascular polymorphonuclear found in relation to small veins and at the edge leucocytes. These pathological changes, when of intralobular ducts (Waterhouse and Doniach, present, were not infrequently limited to isolated 1966). lobules. Glands were acceptable if a representa- The grading standard used for the submandi- tive section of the gland (approximately 4 sq cm bular gland is shown in Table I. for the submandibular and 4 sq mm for the labial) In order to standardize the area examined and remained after exclusion of abnormal lobules. record the degree of histopathological change, Cases were admitted to the series if they were the grading standard shown in Table II was free from neoplasm of lymphocyte-like clls, and employed for the labial salivary glands. All had not received cytotoxic drugs within the last minor salivary gland tissue in the sections was three months before death. Leukaemia patients were excluded altogether. The 13 exclusions comprised seven with auto- Grade Lymphocytic Foci /4 sq cm ofSalivary Tissue lysis of gland parenchyma, and therefore not 0 None 0-I 1 'Slight' 2-8 suitable, one with neoplastic material present in 2 'Moderate' 9-40 the ducts, and five with extravascular polymor- 3 'Severe' 40 + phonuclear leucocytes, together with duct dilata- 4 'Very Severe' >half gland parenchyma replaced tion. Table I Grading standardfor submandibular gland Grade Lymphocytic Infiltration or Foci/sq mm of Salivary Tissue Criteria of Focal Lymphocytic Adenitis 0 Absent 1 Slight infiltrate A 'focus' was defined as one consisting of an 2 Moderate infiltrate 3 One focus aggregate of 50 or more lymphocytes and histio- 4 More than one focus cytes, usually with a few plasma cells placed peripherally, adjacent to and apparently replacing Table II Grading standardfor labial glands copyright. http://jcp.bmj.com/ on October 2, 2021 by guest. Protected Fig. 1 A focus oflymphocytes around a small Fig. 2 Moderate lymphocytic infiltration oflabial duct ofa submandibular salivary gland. H & E x 282 salivary gland tissue. H & E x 450 692 D. M. Chisholm, J. P. Waterhouse, and D. K. Mason J Clin Pathol: first published as 10.1136/jcp.23.8.690 on 1 November 1970. Downloaded from examined and scanned for the presence oflympho- cytic foci and/or diffuse lymphocytic infiltration. Females (All positives) 23 (41 %) The degree of lymphocytic infiltration and/or AllAll56 (Grades 2, 3, & 4 only) 17 (30%) cases number of foci were expressed as a value per (116) 4 sq mm of minor salivary tissue. Males (All positives 26 (43°/) An example of moderate lymphocytic infiltra- L 60 (Grades 2, 3, & 4 only) 16 (27%) tion (grade 2) in the minor glands is illustrated Table III Prevalence offocal lymphoc.ytic in Figure 2. adenitis (submandibular gland) The level of correlation between the grade of focal lymphocytic adenitis in the submandibular gland and the degree of lymphocytic infiltration ( Females (All positives) 31 (55%) in the labial glands of each subject was computed 56 (Grade 2) 14 as the non-parametric Spearman rank correla- All (25,%) cases tion coefficient applying the correction for tied (116) ranks, and a significance test was carried out Males (All positives) 39 (65 %) (Siegel, 1956). The non-parametric correlation L 60 (Grade 2) 12 (20%) coefficient was used in order to avoid the assump- Table IV Prevalence ofslight or n7vderate tion that the data were normally distributed. lymphocytic infiltration oflabial gland Age in No. with Grade of Severity, Total Percentage Results Years Positive 0 1 2 3 0-44 7 2 1 0 10 30 SUBMANDIBULAR GLANDS 45-64 12 1 5 3 2 1 43 The figures for the prevalence offocal lymphocytic 65+ 14 3 6 2 25 44 submandibular sialadenitis found in 56 female Total 33 6 12 5 56 41 and 60 male subjects are given in Tables III, V, Table V Numbers offemales with submandibular VI, and IX and Figure 3. In this series of 116 lymphocytic sialadenitis copyright. 70 r Grade 1 or worse GradeG 2 or worse 60 F Grade 3 or worse http://jcp.bmj.com/ 50 I 40 [ 7 on October 2, 2021 by guest. Protected 30 F 20 Z 10 _ : LL1 IL d.A Age group (yrs) < 45 45-64 > 65 < 45 45-64 > 65 No. of subjects 10 21 25 11 31 18 Sex distribution females males Fig. 3 The prevalence oflymphocytic submandibular sialadenitis in males andfemales. 693 Lymphocytic sialadenitis in the major and minor glands: a correlation in postmortem subjects subjects the frequency of involvement by sial- Age in No. with Grade of Severity Total Percentage J Clin Pathol: first published as 10.1136/jcp.23.8.690 on 1 November 1970. Downloaded from adenitis is not significantly different in males or Years Positive females. This is so, either when all degrees of 0 1 2 3 sialadenitis (X2 = 0003, p = greater than 0-5), 0-44 6 3 2 0 11 45 or when moderate and severe degrees of sial- 45-64 18 4 6 3 31 42 65+ 9 4 5 0 18 50 adenitis (X2 = 005, p = greater than 05) are considered. Affected glands occur in the three age Total 33 11 13 3 60 43 groups listed (Tables V and VI and Figure 3). Table VI Numbers ofmales with submandibular A tendency for more severe degrees to occur in lymphocytic sialadenitis females aged 45-64 appears in Table V and Fig. 3, but numbers in the groups are too small for a Age in No. with Grades of Severity Total Percentage formal test of significance to be carried out. Years Positive 0 1 2 0-44 8 1 1 10 20 LABIAL GLANDS 45-64 6 9 6 21 71 The figures for the prevalence of lymphocytic 65+ 1 1 7 7 25 56 infiltration of the labial salivary glands (the Total 25 17 14 56 55 exclusions quoted above having been made) are Table VII Numbers offemales with lymphocytic given in Tables IV and IX and Figure 4. infiltration of the labial glands The frequency of involvement of the glands in males or females is not significantly different, Age in No.