title: Lymphocytic infiltration and enlargement of the lacrimal glands: a new subtype of primary Sjögren's syndrome?
abstract: OBJECTIVE
  To review the clinical, radiologic, serologic, histopathologic, immunohistochemical, and molecular genetic features of patients having Sjögren's syndrome (SS) with lacrimal gland enlargement.
  
  
  METHODS
  Retrospective case series review.
  
  
  METHODS
  Fourteen patients histopathologically diagnosed with SS with lacrimal enlargement. Twenty-three age- and gender-matched controls were used for comparison on radiologic analysis.
  
  
  METHODS
  Clinical and serologic data were determined directly or by chart review. Computed tomography images from patients were compared with those from the control group. Histopathologic sections were reviewed and graded using the Chisholm-Mason scale, and quantitative immunohistochemical analysis was applied.
  
  
  METHODS
  Clinically, patients were assessed for age, gender, onset, symptoms and signs, systemic features, treatment, and outcome. Existing histologic specimens were reviewed according to the Chisholm-Mason scale, and then the percentages of plasma cells containing immunoglobulin (Ig) A, IgG, and IgM were determined. Imaging was assessed for lacrimal gland thickness, prolapse, density, and margin contour; extraocular muscle size; orbital tissue displacement; and proptosis.
  
  
  RESULTS
  Clinical and histopathological data fulfilled the revised American-European criteria for primary SS in 79% of patients. Compared with other large series of primary SS patients, similarities were found with age, xerophthalmia, parotidomegaly, and articular involvement. Differences included a lower incidence of autoantibodies, xerostomia, and extraglandular features and a higher male-to-female ratio. In almost all patients (93%), the percentage of plasma cells positive for IgA was less than 70%, consistent with SS. Compared with controls, the lacrimal glands were enlarged significantly (P<0.0001) and prolapsed (P<0.001). Involved glands had blurred margins (P<0.007), caused displacement of adjacent tissues (P = 0.03), and were associated with hyperdense fat (P = 0.007). Lymphocytic infiltration of orbital fat was present in all patients for whom fat biopsy results were available. Three patients had monoclonal infiltrates, and 1 patient experienced subsequent extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type, 4 years after presentation.
  
  
  CONCLUSIONS
  The criteria used to diagnose primary SS are controversial, but both diagnostic and quantitative immunohistochemical criteria suggest that these patients, with lacrimal gland enlargement resulting from lymphocytic infiltration, represent a new subtype of primary SS. This is clinically important in view of the increased risk of lymphoma associated with SS, compared with idiopathic nonspecific lacrimal inflammation.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of British Columbia and the Vancouver General Hospital, Vancouver, Canada.
authors.forename: Ben
authors.initials: B
authors.lastname: Parkin
authors.forename: Jason B
authors.initials: JB
authors.lastname: Chew
authors.forename: Valerie A
authors.initials: VA
authors.lastname: White
authors.forename: Graciela
authors.initials: G
authors.lastname: Garcia-Briones
authors.forename: Mukesh
authors.initials: M
authors.lastname: Chhanabhai
authors.forename: Jack
authors.initials: J
authors.lastname: Rootman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000974:Antibodies, Antinuclear / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D006801:Humans; D006984:Hypertrophy; D007124:Immunoenzyme Techniques; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007136:Immunoglobulins / Q000097:blood; D007765:Lacrimal Apparatus / Q000276:immunology / Q000473:pathology*; D008218:Lymphocytosis / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D018442:Lymphoma, B-Cell, Marginal Zone / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000276:immunology; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D012859:Sjogren's Syndrome / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014057:Tomography, X-Ray Computed
chemical_list: D000974:Antibodies, Antinuclear; D007143:Immunoglobulin Heavy Chains; D007136:Immunoglobulins; C035356:SS-A antibodies; C035357:SS-B antibodies