Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue of the Salivary Glands: A Multicenter, International Experience of 248 Patients (IELSG 41)

Abstract

Background. The salivary gland is one of the most common sites involved by nongastric, extranodal marginal zone lymphomas of mucosa‐associated lymphoid tissue (MALT). A large series of patients with long‐term follow‐up has not been documented. This multicenter, international study sought to characterize the clinical characteristics, treatment, and natural history of salivary gland MALT lymphoma. Methods. Patients with biopsy‐confirmed salivary gland MALT lymphoma were identified from multiple international sites. Risk factors, treatment, and long‐term outcomes were evaluated. Results. A total of 247 patients were evaluated; 76% presented with limited‐stage disease. There was a history of autoimmune disorder in 41%, with Sjögren disease being the most common (83%). Fifty‐seven percent of patients were initially treated with local therapy with surgery, radiation, or both; 37 of patients were treated with systemic therapy initially, with 47% of those receiving rituximab; and 6% of patients were observed. The median overall survival (OS) was 18.3 years. The median progression‐free survival (PFS) following primary therapy was 9.3 years. There was no difference in the outcomes between patients receiving local or systemic therapy in first‐line management. On multivariate analysis, age <60 years and low to intermediate international prognostic index were associated with improved OS and PFS; Sjögren disease was associated with improved OS. Conclusion. Salivary gland MALT lymphoma has an excellent prognosis regardless of initial treatment, and patients with Sjögren disease have improved survival. Risks for long‐term complications must be weighed when determining initial therapy. Implications for Practice: Patients with salivary gland extranodal marginal zone lymphoma of mucosa‐associated lymphoid tissue (MALT) have an excellent prognosis, particularly those with associated Sjögren's disease. A wide range of available therapies may provide similar durable rates of disease control and survival. Therefore, an important goal in selection of therapy should be to minimize morbidity from treatment. When determining initial therapy for these patients, practitioners should consider the potential side effects and long‐term toxicities of treatment.

Primary hepatic extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type

“…MALT lymphoma usually arises in background of chronic inflammation associated with infective agents, such as H pylori -associated chronic gastritis, [47] or autoimmune diseases, such Sjogren syndrome [48] and Hashimoto thyroiditis. [49] However, the etiology of hepatic malignant lymphomas, especially MALT lymphomas, remains unknown.…”

Short survival and frequent transformation in extranodal marginal zone lymphoma with multiple mucosal sites presentation

“…Based on the Ann Arbor staging classification, bilateral lungs and multiple distant skin involvement were classified as stage IV, while bilateral organ involvement in other anatomical sites was defined as stage I disease . Involvement of multiple mucosal sites (MMS) was defined as EMZL in two or more different anatomical organs independent of spleen and BM involvement.…”

“…However, these studies lacked statistical power to demonstrate such an association due to a small number of MMS patients at presentation (eg, n = 17 and 24) . Moreover, some studies defined MMS to include bilateral involvement of the same organ, which is usually considered a stage I presentation . Similarly, the incidence and prognostic significance of monoclonal gammopathy (MG) in EMZLs at presentation are unclear.…”

Radiation for MALT of the Submandibular Gland

“…The International External Lymphoma Study Group (IELSG) reported on 247 patients with MALT lymphoma of the salivary glands [12]. In this study, only 5% had primary submandibular gland involvement; in the majority (78%), the parotid gland was involved.…”

“…Risk factors associated with salivary gland MALT lymphoma include chronic immune system dysregulation such as Sjögren's syndrome [5–8] and chronic inflammatory conditions such as sialadenitis [9–11]. In a large multicenter international study on MALT lymphoma of the salivary gland, 40% of patients had history of autoimmune disease [12]. In the Rare Cancer Network multicenter study [13], 28% of patients had documented history of sialadenitis.…”