Abstract:

Objective: To analyze the clinicopathological characteristics of mucosa associated lymphoid tissue (MALT) lymphoma secondary to Sj?gren’s syndrome (SS) (SS-MALT lymphoma) in salivary gland and to explore the value of the combined application of histopathological morphology, protein expression and molecular phenotype in pathological diagnosis and prognostic evaluation of SS-MALT lymphoma.Methods: Sixteen patients with SS-MALT lymphoma were collected from 260 patients who were diagnosed with SS in Peking University School and Hospital of Stomatology from January 1997 to December 2016. Twelve patients with non-MALT lymphoma secondary to SS (non-SS-MALT lymphoma) in salivary gland were selected as controls. The clinical data of the patients were retrospectively reviewed and analyzed. All the patients were followed up until December 20, 2019. Hematoxylin-eosin staining, immunohistochemistry, polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) techniques were used to observe the histologic characteristics and to detect the manifestations of light chain restrictive expression, immunoglobulin (Ig) gene clonal rearrangement, chromosome translocation and gene abnormality, so as to evaluate their values in pathological diagnosis and prognostic evaluation.Results: The malignant transformation rate of SS to MALT lymphoma was about 6.15%, ranged from 3 to 240 months, during which 2 patients died due to high-level deterioration. Microscopically, the acini of the glandular tissue were atrophied and destroyed. The tumor cells dominated by central cell-like lymphocytes grew diffusely, destroying the epithelial islands. All SS-MALT lymphoma cases were positive in CD20 and Pax5. Half of them had the Ki-67 proliferation index of 10% or less, and half greater than 10%. 93.75% cases expressed AE1/AE3 protein, which showed the residual glandular epithelium. All the tumor cells were negative in CD3ε, and the plasma cells were detected by CD138 antigen. The light chain restrictive expression of κ and λ was 37.5% in SS-MALT lymphoma group. The positive detection rates of immunoglobulin heavy chain (IgH)-FR1, IgH-FR2, IgH-FR3, immunoglobulin kappa chain (IgK)-A, and IgK-B in SS-MALT lymphoma group were 33.3%, 53.3%, 33.3%, 20.0%, and 26.7%, respectively, and 93.3% when together used with IgH and IgK. The positive rates of the MALT1, IGH and BCL6 genes with dual color break-apart probes were 36.4%, 27.3% and 27.3%, and the detection rate of chromosome translocation and gene abnormality by applying the three probes was 72.7%.Conclusion: There are no specific histological characteristics and protein phenotypes in the histologic diagnosis of SS-MALT lymphoma in salivary gland. The combined application of histopathological manifestations, immunohistochemistry, PCR and FISH techniques helps the accurate pathologic diagnosis of the disease. Although SS-MALT lymphoma is considered as an indolent lymphoma with a relatively favorable prognosis, the regular return visit and long-term follow-up should be conducted to detect the clues of recurrence and advanced deterioration.

Key words: Sj?gren’s syndrome, Mucosa associated lymphoid tissue lymphoma, Immunohistochemistry, Polymerase chain reaction, In situ hybridization, fluorescence