Mucosa-Associated Lymphoid Tissue Lymphoma in Sjögren's Syndrome: Risks, Management, and Prognosis

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Sjögren's syndrome is a chronic inflammatory disease primarily affecting the exocrine glands. Its association with lymphoma is well documented, with salivary extranodal marginal zone lymphomas of the mucosa-associated lymphoid tissue type being the most common and constituting a major disease complication. These neoplasms are antigen-stimulated B-cell lymphomas characterized by localized stage, indolent clinical course, and recurrence in other extranodal sites. This article presents a review of the literature and discusses the clinical, histopathologic, therapeutic, and prognostic aspects of these tumors in Sjögren's syndrome. In addition, it highlights the predictor markers of lymphoma development.

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Mucosa-associated lymphoid tissue lymphoma in Sjögren's syndrome: clinical aspects and histopathology

NHL has a 4.3% prevalence in patients who have SS. In these patients the median age at lymphoma diagnosis is 58 years, and the median time from SS diagnosis to lymphoma diagnosis is 7.5 years.3, 12 Various histologic subtypes of NHL occurring in patients who have SS have been described in the literature, including follicle center lymphoma, lymphoplasmacytoid lymphoma, and diffuse large B-cell lymphoma (DLBCL), but mucosa-associated lymphoid tissue (MALT) lymphomas are by far the most common.3, 4

Clinical and serologic risk factors of lymphoma development in Sjögren's syndrome

Despite its unequivocal association with SS, the development of lymphoma constitutes a complication rather than the rule. Only 5% of patients who have SS ultimately manifest lymphoma. Several investigations have attempted to establish predictive markers for this progression. In 1971 Anderson and Talal29 showed that a decrease in the level of serum immunoglobulins and disappearance of rheumatoid factor coincided with the time of progression to lymphoma. Kassan and colleagues3 showed that

Management of mucosa-associated lymphoid tissue lymphomas associated with Sjögren's syndrome

Large series have demonstrated that nongastric MALT lymphomas in patients who do not have SS seem to have a good outcome, with a 5-year overall survival rate from diagnosis ranging from 86% to 100%.37, 38 Although 30% of these patients presented with disseminated disease, their outcome remained unaffected by the multifocal nature of the lymphoma.28 The finding that patients presenting with extranodal MALT lymphoma affecting multiple mucosal sites have a favorable outcome with survival curves

Prognostic factors

The overall survival of patients who have MALT lymphoma is 85% to 95% at 5 years, with little difference between sites.28, 38, 51 Regardless of site, approximately 25% to 35% of patients relapse after a CR, often late and to further extranodal or nodal sites, although significantly more relapses occur in nongastric cases than in gastric cases.37, 52 In MALT lymphomas in general, however, the 10-year expected survival rate is greater than 75%.28 Several investigations have attempted to establish

Summary

Patients who have SS and who have high risk factors such as palpable purpura, low C4 levels, and MMC constitute a separate subgroup that should be monitored more closely than other patients who have SS. These patients seem to have a strong predisposition for the development of lymphoproliferation, especially low-grade extranodal MALT lymphomas. Therefore, the clinical follow-up of patients who have SS should include routine complement determination and serum immunoelectrophoresis to detect the

References (59)

  • E. Zucca et al.

    The gastric marginal zone B-cell lymphoma of MALT type

    Blood

    (2000)
  • T. Radaszkiewicz et al.

    Gastrointestinal malignant lymphomas of the mucosa-associated lymphoid tissue: factors relevant to prognosis

    Gastroenterology

    (1992)
  • C. Montalbán et al.

    Gastric B-cell mucosa-associated lymphoid tissue (MALT) lymphoma. Clinicopathological study and evaluation of the prognostic factors in 143 patients

    Ann Oncol

    (1995)
  • H. Liu et al.

    Resistance of t(11;18) positive gastric mucosa-associated lymphoid tissue lymphoma to Helicobacter pylori eradication therapy

    Lancet

    (2001)
  • M.J. Leandro et al.

    Rheumatic diseases and malignancy—is there an association?

    Scand J Rheumatol

    (2001)
  • J.J. Bunim et al.

    Development of malignant lymphoma in the course of Sjogren's syndrome

    Trans Assoc Am Physicians

    (1963)
  • S.S. Kassan et al.

    Increased risk of lymphoma in sicca syndrome

    Ann Intern Med

    (1978)
  • H.M. Moutsopoulos et al.

    High incidence of free monoclonal lambda light chains in the sera of patients with Sjogren's syndrome

    J Immunol

    (1983)
  • A.G. Tzioufas et al.

    Cryoglobulinemia in autoimmune rheumatic diseases. Evidence of circulating monoclonal cryoglobulins in patients with primary Sjogren's syndrome

    Arthritis Rheum

    (1986)
  • G. Valesini et al.

    Differential risk of non-Hodgkin's lymphoma in Italian patients with primary Sjogren's syndrome

    J Rheumatol

    (1997)
  • J. Zulman et al.

    Evidence that the malignant lymphoma of Sjogren's syndrome is a monoclonal B-cell neoplasm

    N Engl J Med

    (1978)
  • U. Schmid et al.

    Development of malignant lymphoma in myoepithelial sialadenitis (Sjogren's syndrome)

    Virchows Arch A Pathol Anat Histol

    (1982)
  • E.K. Pisa et al.

    High frequency of t(14;18) translocation in salivary gland lymphomas from Sjogren's syndrome patients

    J Exp Med

    (1991)
  • E. Zintzaras et al.

    The risk of lymphoma development in autoimmune diseases: a meta-analysis

    Arch Intern Med

    (2005)
  • M. Voulgarelis et al.

    Malignant lymphoma in primary Sjogren's syndrome: a multicenter, retrospective, clinical study by the European concerted action on Sjogren's syndrome

    Arthritis Rheum

    (1999)
  • X. Mariette

    Lymphomas in patients with Sjogren's syndrome: review of the literature and physiopathologic hypothesis

    Leuk Lymphoma

    (1999)
  • A. Ambrosetti et al.

    Most cases of primary salivary mucosa-associated lymphoid tissue lymphoma are associated either with Sjoegren syndrome or hepatitis C virus infection

    Br J Haematol

    (2004)
  • K.E. Smedby et al.

    Autoimmune and chronic inflammatory disorders and risk of non-Hodgkin lymphoma by subtype

    J Natl Cancer Inst

    (2006)
  • The Non-Hodgkin's Lymphoma Classification Project. A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma

    Blood

    (1997)
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