Objective: Mucosa-associated lymphoid tissue (MALT) lymphoma of the salivary glands occurring in 6 patients affected by primary Sjögren’s syndrome is reported. Methods: Clinical findings, histologic type, stage, treatment and outcome of the 6 patients have been revised. Results: In all 6 cases the lymphoma was of the MALT type. Four patients had stage IE disease, 1 patient had stage IIE disease and 1 patient had stage IV disease. The patients received different treatments resulting in all cases in prolonged remission. After 7 years of complete remission 1 patient developed a diffuse large B-cell lymphoma. Conclusion: MALT lymphoma of the salivary glands is an indolent disease. Though the best therapy of this lymphoproliferative disorder remains to be established, prolonged remission has been obtained in our cases with different therapeutic approaches. We review the literature regarding the relationship between Sjögren’s syndrome and MALT lymphomas and study the mechanisms which may be involved in the transformation from a lymphoepithelial lesion into a neoplastic disorder.

Keywords:
Lymphoma, Mucosa-associated lymphoid tissue, Salivary glands, Sjögren’s syndrome, primary
1.
Sharkey FE: Systemic evaluation of the World Health Organization classification of salivary gland tumors: A clinicophatologic study of 366 cases. Am J Clin Pathol 1977;67:272–278.
2.
Gleeson MJ, Bennett MH, Cawson RA: Lymphomas of salivary glands. Cancer 1986;58:699–704.
3.
Schustermann MA, Granick MS, Erickson ER, Newton D, Hanna DC, Brighten R: Lymphomas presenting as a salivary gland mass. Head Neck Surg 1988;10:411–415.
4.
Batsakis JG: Primary lymphomas of the salivary glands. Ann Otol Rhinol Laryngol 1986;95:107–108.
5.
Sarris AH, Papadimitrakopoulou V, Dimopoulos MA, Smith T, Pugh W, Ha CS, McLaughlin P, Callender D, Cox J, Cabanillas F: Primary parotid lymphoma: The effect of International Prognostic Index on outcome. Leuk Lymphoma 1997;26:49–56.
6.
Barnes L, Myers EN, Prokopakis EP: Primary malignant lymphoma of the parotid gland. Arch Otolaryngol Head Neck Surg 1998;124:573–577.
7.
Chan JKC, Tsang WYW, Hui PK, Sin VC, Siu LPP: T- and T/natural killer-cell lymphomas of the salivary gland: A clinicopathologic, immunohistochemical and molecular study of six cases. Hum Pathol 1997;28:238–245.
8.
Harris NL: Lymphoid proliferation of the salivary glands. Am J Clin Pathol 1999;111(suppl 1):S94–S103.
9.
Mehle MF, Kraus DH, Wood BG, Tubbs R, Tucker HM, Lavertu P: Lymphoma of the parotid gland. Laryngoscope 1993;103:17–21.
10.
Kassan SS, Thomas TL, Moutsopoulos HM, Hoover R, Kimberly RP, Budman DR, Costa J, Decker JL, Chused TM: Increased risk of lymphoma in sicca syndrome. Ann Intern Med 1978;89:888–892.
11.
Shin SS, Sheibani K, Fishleder A, Ben-Ezra J, Bailey A, Koo CH, Burke JS, Tubbs R, Rappaport H: Monocytoid B-cell lymphoma in patients with Sjögren’s syndrome: A clinicopathologic study of 13 patients. Hum Pathol 1991;22:422–430.
12.
Royer B, Cazals-Hatem D, Sibilia J, Agbalika F, Cayuela JM, Soussi T, Maloisel F, Clauvel JP, Brouet JC, Mariette X: Lymphomas in patients with Sjögren’s syndrome are marginal zone B-cell neoplasms, arise in diverse extranodal and nodal sites, and are not associated with viruses. Blood 1997;90:766–775.
13.
Anaya JM, McGuff HS, Banks PM, Talal N: Clinicopathological factors relating malignant lymphoma with Sjögren’s syndrome. Semin Arthritis Rheum 1996;25:337–346.
14.
Zufferey P, Meyer OC, Grossin M, Kahn MF: Primary Sjögren’s syndrome (SS) and malignant lymphoma. A retrospective cohort study of 55 patients with SS. Scand J Rheumatol 1995;24:342–345.
15.
Sutcliffe N, Inanc M, Speight P, Isenberg D: Predictors of lymphoma development in primary Sjögren’s syndrome. Semin Arthritis Rheum 1998;28:80–87.
16.
Biasi D, Mocella S, Caramaschi P, Carletto A, Baracchino F, Colletti V, Bambara LM: Utility and safety of parotid gland biopsy in Sjögren’s syndrome. Acta Otolaryngol (Stockh) 1996;116:896–899.
17.
Alexander EL, Arnett FC, Provost TT, Stevens MB: Sjögren’s syndrome: Associated of anti-Ro(SS-A) antibodies with vasculitis, hematologic abnormalities, and serologic hyperreactivity. Ann Intern Med 1983;98:155–159.
18.
Voulgarelis M, Dafni UG, Isenberg DA, Moutsoupoulos HM: Malignant lymphoma in primary Sjögren’s syndrome: A multicenter, retrospective clinical study by the European Concerted Action of Sjögren’s Syndrome: Arthritis Rheum 1999;42:1765–1772.
19.
Isaacson PG: Mucosa-associated lymphoid tissue lymphoma. Semin Hematol 1999;36:139–147.
20.
Wotherspoon AC, Ortiz-Hidalgo C, Falzon MR, Isaacson PG: Helicobacter pylori-associated gastritis and primary B-cell gastric lymphoma. Lancet 1991;338:1175–1176.
21.
De Vita S, Boiocchi M, Sorrentino D, Carbone A, Avellini C, Dolcetti R, Marzotto A, Gloghini A, Bartoli E, Beltrami CA, Ferraccioli GF: Characterization of prelymphomatous stages of B cell lymphoproliferation in Sjögren’s syndrome. Arthritis Rheum 1997;40:318–331.
22.
Burke JS: Are there site-specific differences among the MALT lymphomas – Morphologic, clinical? (review). Am J Clin Pathol 1999;111 (suppl 1):S133–S143.
23.
Fishleder A, Tubbs R, Hesse B, Levine H: Uniform detection of immunoglobulin-gene rearrangement in benign lymphoepithelial lesions. N Engl J Med 1987;316:1118–1121.
24.
Burke JS: Extranodal hematopoietic/lymphoid disorders. Am J Clin Pathol 1999;111 (suppl 1):S40–S45.
25.
Diss TC, Wotherspoon AC, Speight P, Pan L, Isaacson PG: B-cell monoclonality, Epstein-Barr virus, and t(14;18) in myoepithelial sialadenitis and low-grade B-cell MALT lymphoma of the parotid gland. Am J Surg Pathol 1995;19:531–536.
26.
Jordan RCK, Odell EW, Speight PM: B-cell monoclonality in salivary lymphoepithelial lesions. Eur J Cancer Oral Oncol 1996;32B:38–44.
27.
Falzon M, Isaacson PG: The natural history of benign lymphoepithelial lesion of the salivary gland in which there is a monoclonal population of B-cells. A report of two cases. Am J Surg Pathol 1991;15:59–65.
28.
Speight PM, Jordan RCK: The molecular pathology of Sjögren’s syndrome; in Isemberg DA, Horsfall AC (eds): Autoimmune Diseases. Oxford, Bios Scientific Publishers 1994, pp 25–42.
29.
Hyjek E, Smith WJ, Isaacson PG: Primary B cell lymphoma of the salivary gland and its relationship to myoepithelial sialadenitis. Hum Pathol 1988;19:766–776.
30.
Terada K, Katamine S, Eguchi K, Moriuchi R, Kita M, Shimada H, Yamashita I, Iwata K, Tsuji Y, Nagataki S, Miyamoto T: Prevalence of serum and salivary antibodies to HTLV-I in Sjögren’s syndrome. Lancet 1994;344:1116–1119.
31.
Mariette X, Gozlan J, Clerc D, Bisson M, Morinet F: Detection of Epstein-Barr virus DNA by in situ hybridization and polymerase chain reaction in salivary gland biopsy specimens from patients with Sjögren’s syndrome. Am J Med 1991;90:286–294.
32.
Mariette X, Cherot P, Cazals D, Brocheriou C, Brouet JC, Agbalika F: Antibodies to HTLV-1 in Sjögren’s syndrome. Lancet 1995;345:71.
33.
Matthews JB, Deacon EM, Kitas GD, Salmon M, Potts AJC, Hamburger J, Bacon PA: Primed and naive helper T cells in labial glands from patients with Sjögren’s syndrome. Virchows Arch A Pathol Anat Histopathol 1991;419:191–197.
34.
Fox RI, Kang HI, Ando D, Abrams J, Pisa E: Cytokine mRNA expression in salivary gland biopsies of Sjögren’s syndrome. J Immunol 1994;152:5532–5539.
35.
Boumba D, Skopouli FN, Moutsopoulos HM: Cytokine mRNA expression in the labial salivary gland tissue from patients with primary Sjögren’s syndrome. Br J Rheumatol 1995;34:326–333.
36.
Guo K, Major G, Foster H, Bassendine M, Collier J, Ross D, Griffiths I: Defective repair of O6-methylguanine-DNA in primary Sjögren’s syndrome patients predisposed to lymphoma. Ann Rheum Dis 1995;54:229–234.
37.
Pisa EK, Pisa P, Kang HI, Fox RI: High frequency of t(14;18) translocation in salivary gland lymphomas from Sjögren’s syndrome patients. J Exp Med 1991;174:1245–1250.
38.
Tapinos NI, Polihronis M, Moutsopoulos HM: Lymphoma development in Sjögren’s syndrome: Novel p53 mutations. Arthritis Rheum 1999;42:1466–1472.
39.
Martin T, Weber JC, Levallois H, Labouret N, Soley A, Koenig S, Korganow AS, Pasquali JL: Salivary gland lymphomas in patients with Sjögren’s syndrome may frequently develop from rheumatoid factor B cells. Arthritis Rheum 2000;43:908–916.
40.
Mariette X: Lymphomas in patients with Sjögren’s syndrome: Review of the literature and physiopathologic hypothesis. Leuk Lymphoma 1999;33:93–99.
41.
Vitali C, Bombardieri S, Moutsopoulos HM, Balestrieri G, Bencivelli W, Bernstein RM, Bjerrum K, Braga S, Coll J, De Vita S, Drosos AA, Ehrenfeld M, Hatron PY, Hay EM, Isenberg DA, Janin A, Kalden JR, Kater L, Konttinen YT, Maddison PJ, Maini RN, Manthorpe R, Meyer O, Ostuni P, Pennec Y, Prause JU, Richards A, Sauvezie B, Schiodt M, Sciuto M, Scully C, Shoenfeld Y, Skopuli FN, Smolen JS, Snaith ML, Tishler M, Todesco S, Valesini G, Venables PJW, Wattiaux MJ, Youinou P: Preliminary criteria for the classification of Sjögren’s syndrome. Results of a prospective concerted action supported by the European Community. Arthritis Rheum 1993;36:340–347.
42.
Kraaijenhagen HA: Technique for parotid biopsy. J Oral Surg 1975;33:328.
43.
Harris NL, Jaffe ES, Stein H, Banks PM, Chan JKC, Cleary ML, Delson G, De Wolf-Peeters C, Falini B, Gatter KC, Grogan TM, Isaacson PG, Knowles DM, Mason DY, Muller-Hermelink HK, Pileri SA, Piris MA, Ralfkiaer E, Warnke RA: A Revised European-American classification of lymphoid neoplasms: A proposal from the International Lymphoma Study Group. Blood 1994;84:1361–1392.
44.
Isaacson PG, Wright DH: Malignant lymphoma of mucosa associated lymphoid tissue. A distinctive type of B-cell lymphoma. Cancer 1983;52:1410–1416.
45.
Isaacson PG: Lymphomas of mucosa associated lymphoid tissue (MALT-type lymphomas). Forum 1993;3.3:234–245.
46.
Harris NL, Isaacson PG: What are the criteria for distinguishing MALT from non-MALT lymphoma at extranodal sites? Am J Clin Pathol 1999;111(suppl 1):S126–S132.
47.
Coiffier B, Thieblemont C, Felman P, Salles G, Berger F: Indolent nonfollicular lymphomas: Characteristics, treatment, and outcome. Semin Hematol 1999;36:198–208.
48.
Rohatiner A, Isaacson PG, Gospodarowicz M: Report on a workshop convened to discuss the pathological and staging classification of gastrointestinal tract lymphoma. Ann Oncol 1994;5:397–400.
49.
Thieblemont C, Bastion Y, Berger F, Rieux C, Salles G, Dumontet C, Felman P, Coiffier B: Mucosa-associated lymphoid tissue gastrointestinal and nongastrointestinal lymphoma behaviour: Analysis of 108 patients. J Clin Oncol 1997;15:1624–1630.
50.
Balm AJ, Delaere P, Hilgers FJ, Somers R, Van-Heerde P: Primary lymphoma of mucosa associated lymphoid tissue (MALT) in the parotid gland. Clin Otolaryngol 1993;18:528–532.
51.
Wolvius EB, van der Walk P, van der Wal JE, van Djest PJ, Huijgens PC, van der Waal I, Snow GB: Primary non-Hodgkin’s lymphoma of the salivary glands. An analysis of 22 cases. J Oral Pathol Med 1996;25:177–181.
52.
Luppi M, Longo G, Ferrari MG, Ferrara L, Marasca R, Barozzi P, Morselli M, Emilia G, Torelli G: Additional neoplasms and HCV infection in low-grade lymphoma of MALT type. Br J Haematol 1996;94:373–375.
53.
De Vita S, Sansonno D, Dolcetti R, Ferraccioli GF, Carbone A, Cornacchiulo V, Santini G, Crovatto M, Gloghini A, Dammacco F, Boiocchi M: Hepatitis C virus within a malignant lymphoma lesion in the course of type II mixed cryoglobulinemia. Blood 1995;86:1887–1892.
54.
Cerroni L, Zochling N, Putz B, Kerl H: Infection by Borrelia burgdorferi and cutaneous B-cell lymphoma. J Cutan Pathol 1997;24:457–461.
55.
Zinzani PL, Magagnoli M, Galieni P, Martelli M, Poletti V, Zaja F, Molica S, Zaccaria A, Cantonetti AM, Gentilini P, Guardigni L, Gherlinzoni F, Ribersani M, Bendandi M, Albertini P, Tura S: Nongastrointestinal low-grade mucosa-associated lymphoid tissue lymphoma: Analysis of 75 patients. J Clin Oncol 1999;17:1254–1258.
56.
Cha I, Long SR, Ljung BM, Miller TR: Low-grade lymphoma of mucosa-associated tissue in the parotid gland: A case report of fine-needle aspiration cytology diagnosis using flow cytometric immunophenotyping. Diagn Cytophatol 1997;16:345–349.
57.
Wotherspoon AC, Doglioni DC, Diss TC, Pan L, Moschini A, de Boni M, Isaacson PG: Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori. Lancet 1993;342:575–577.
© 2001 S. Karger AG, Basel
2001
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