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Sporadic occurrence of non-diagnosed IgG4-related disease in lymphoma patients with a previous Sjögren's syndrome diagnosis.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.ORCID iD: 0000-0001-6715-3704
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
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2016 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 9-10, 1139-1144 p.Article in journal (Refereed) Published
Abstract [en]

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.

CONCLUSION: 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.

Place, publisher, year, edition, pages
2016. Vol. 55, no 9-10, 1139-1144 p.
National Category
Rheumatology and Autoimmunity
Research subject
Medical Science
Identifiers
URN: urn:nbn:se:uu:diva-300373DOI: 10.1080/0284186X.2016.1182644ISI: 000385554200012PubMedID: 27196149OAI: oai:DiVA.org:uu-300373DiVA: diva2:951349
Funder
Swedish Rheumatism AssociationSwedish Society of Medicine
Available from: 2016-08-08 Created: 2016-08-08 Last updated: 2017-04-20Bibliographically approved
In thesis
1. Lymphoma studies in patients with Sjögren's syndrome
Open this publication in new window or tab >>Lymphoma studies in patients with Sjögren's syndrome
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Patients with primary Sjögren’s syndrome (pSS) are at increased risk of developing malignant lymphoma. The studies in this thesis aim at broadening our understanding of the association between these two conditions.

Germinal centre (GC)-like structures were found in minor salivary gland biopsies taken at the time of pSS diagnosis in 25% of 175 studied patients. Lymphoma development was observed in 86% of the GC-positive pSS patients and 14% of the GC-negative patients. GC-like structures in salivary gland biopsies at pSS diagnosis might identify pSS patients at high risk for later lymphoma development.

We used the National Patient Register and the Cancer Register to identify pSS patients with lymphoid malignancy for the following studies. The lymphoma tissues were reviewed and classified according to the WHO classification.

In a study of 79 patients with available lymphoma tissues, we identified histopathological and clinical features compatible with IgG4-related disease (IgG4-RD) in one patient (1.3%). Histological features of IgG4-RD in lymphoma tissue in patients with an initial pSS diagnosis seem to be rare but, if present, may indicate underlying IgG4-RD.

We identified and compared pSS patients with (n=18/17%) and without (n=87) pre-existing lymphoma at pSS diagnosis and found similar pSS characteristics in both groups. Mucosa-associated lymphoid tissue (MALT) lymphoma in salivary glands was more common in patients with pre-existing lymphoma. The findings support the removal of pre-existing lymphoma as a general exclusion criterion for a pSS diagnosis in classification criteria. Further, the findings suggest an investigation for pSS in patients presenting with MALT lymphoma in salivary glands.

We compared the distribution of lymphoma subtypes with a general population reference. Both diffuse large B-cell lymphoma (DLBCL) (32%) and marginal zone lymphoma (MZL) (31%) were common, but only MZL (MALT lymphomas) occurred at an increased relative frequency compared to the general population.

Men constituted 15% of 105 pSS patients with lymphoma. Men had a shorter time between the pSS and lymphoma diagnoses and more often had lymphoma in the salivary glands compared with women. Increased awareness of signs of lymphoma in salivary glands already during the first years after pSS diagnosis is justified in men with pSS.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. 94 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1331
Keyword
Sjögren's syndrome, primary Sjögren's syndrome, lymphoma, IgG4-related disease
National Category
Rheumatology and Autoimmunity
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-320220 (URN)978-91-554-9912-9 (ISBN)
Public defence
2017-06-07, Enghoffsalen, Ingång 50 bv, Akademiska sjukhuset, Uppsala, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2017-05-17 Created: 2017-04-18 Last updated: 2017-06-07

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