title: Sporadic occurrence of non-diagnosed IgG4-related disease in lymphoma patients with a previous Sjögren's syndrome diagnosis.
abstract: BACKGROUND
  IgG4-related disease (IgG4-RD) is a recently recognized fibro-inflammatory disorder, which may affect many organs, and often comes to clinical attention due to tumor-like organ swelling or is identified incidentally by specific biopsy findings. Typical histopathology of IgG4-RD is lymphoplasmacytic infiltration rich in IgG4 + plasma cells (PCs), storiform fibrosis, and obliterative phlebitis. Patients with sicca symptoms can be misdiagnosed as primary Sjögren's syndrome (pSS) instead of IgG4-RD because of clinical and histopathological similarities. Moreover, an association with lymphoma development is described in both diseases. This study investigated signs of IgG4-RD in a population-based cohort of patients diagnosed with pSS complicated by lymphoma.
  
  
  METHODS
  Patients with pSS and lymphoma diagnoses and available lymphoma specimens were identified by linkage with the Swedish Patient Register 1964-2007 and the Cancer Register 1990-2007 (n = 79). Clinical data and lymphomas were reviewed and the diagnoses evaluated. All lymphoma tissues and available minor salivary gland biopsies (n = 11) were immunostained for IgG4 + PCs and evaluated for other histopathological signs of IgG4-RD. In a case with specific findings of IgG4-RD, other available tissue specimens of the same patient were investigated for IgG4-RD.
  
  
  RESULTS
  Only one patient of 79 (1.3%) had >10 IgG4 + PCs/high power field (HPF) in the lymphoma tissue, an unspecified low-grade B-cell lymphoma localized in the submandibular gland. This patient also had other histopathological features of IgG4-RD in the lymphoma and a surgical lung biopsy taken five years before lymphoma diagnosis and, therefore, fulfilled the criteria for IgG4-RD. Occasional IgG4 + PCs (<10/HPF) without signs of IgG4-RD were observed in another six lymphomas. No IgG4 + PCs were identified in the minor salivary gland biopsies.
  
  
  CONCLUSIONS
  Histopathological findings of IgG4-RD may co-exist with low malignant B-cell lymphoma in patients with initially suspected pSS and may be associated with an underlying IgG4-RD.
authors.affiliation: a Section of Rheumatology, Department of Medical Sciences , Uppsala University , Uppsala , Sweden.
authors.forename: Lilian
authors.initials: L
authors.lastname: Vasaitis
authors.affiliation: b Department of Immunology, Genetics and Pathology, Rudbeck Laboratory , Uppsala University , Uppsala , Sweden.
authors.forename: Christer
authors.initials: C
authors.lastname: Sundström
authors.affiliation: a Section of Rheumatology, Department of Medical Sciences , Uppsala University , Uppsala , Sweden.
authors.forename: Carin
authors.initials: C
authors.lastname: Backlin
authors.affiliation: a Section of Rheumatology, Department of Medical Sciences , Uppsala University , Uppsala , Sweden.
authors.forename: Gunnel
authors.initials: G
authors.lastname: Nordmark
authors.affiliation: a Section of Rheumatology, Department of Medical Sciences , Uppsala University , Uppsala , Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Baecklund
mesh_terms: D000328:Adult; D001706:Biopsy; D003951:Diagnostic Errors; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D007150:Immunohistochemistry; D008168:Lung / Q000473:pathology; D008223:Lymphoma / Q000175:diagnosis / Q000453:epidemiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000473:pathology*; D012042:Registries / Q000706:statistics & numerical data*; D012189:Retrospective Studies; D012469:Salivary Glands / Q000473:pathology; D012859:Sjogren's Syndrome / Q000175:diagnosis / Q000453:epidemiology* / Q000473:pathology; D055815:Young Adult
chemical_list: D007074:Immunoglobulin G