Immunological characteristics of IgG4-related Kuttner tumors

Abstract

Immunoglobulin G4-related disease (IgG4-RD) has recently been well recognized and Kuttner tumor is known to be a chronic sclerosing sialadenitis, representing the focal manifestation of IgG4-RD, in the submandibular gland (SMG). This study is to evaluate the immunologic features of IgG4-related Kuttner tumor in the SMG. We retrospectively chose 13 patients who were confirmed as having Kuttner tumor by surgical biopsy between May 2012 and January 2019. The fine-needle aspiration cytology, serum antibody levels (anti-Ro antibodies, anti-La antibodies), IgG serum levels (total IgG and IgG4), and immunohistochemical findings for IgG and IgG4-positive plasma cells were reviewed. The cytologic results found that 7 of the 9 cases were reported as chronic sialoadenitis, and the other 3 as benign lymphoproliferative lesion. The serum levels of autoantibodies, Sjögren-syndrome-related antigen A/Ro-Ab and Sjögren-syndrome-related antigen A/Ro-La, showed all normal values of serum level. The serum level of IgG was increased in only 4 among the cases. However, the IgG4 levels were significantly increased in 11 among the cases. In all the patients who received resection of SMG, immunohistochemical findings showed all positive for IgG4-RD, with elevated numbers of IgG and IgG4-positive plasma cells. The evaluation of IgG4 serum level should be very informative for the diagnosis of this tumor before surgery. Fine-needle aspiration cytology with ultrasound guidance are not conclusive in this study. The immunological study including IgG4 serum level should be required for proper diagnosis and treatment, with clinical features of the Kuttner tumor. The level of evidence was IV.

Viral DNA in submandibular gland tissue with an inflammatory disorder

“…EBV initially infects the oropharyngeal epithelium and then persists in memory B cells [ 44 , 45 ]. Even though lymphocyte infiltration is a common feature for non-specific types of sialadenitis [ 46 ], Lin et al [ 47 ] found an increased number of memory B cells in the inflammatory infiltrates of submandibular gland samples from patients with IgG4-RD compared to patients with primary Sjögren’s syndrome and healthy controls. Due to its persistence in memory B cells, the presence of EBV DNA in the IgG4-positive samples could hence be in part explained by the dense lymphocyte infiltration and the possible overrepresentation of B lymphocytes in the tissue samples from patients with IgG4-positive sialadenitis, as presented by Lin et al [ 47 ].…”

“…Second, the presence of viral DNA is not a sign of activity and would require more in-depth investigations, such as mRNA studies, to assess the virus activity. Third, since the DNA in the FFPE samples is more fragmented than in fresh tissue samples and salivary gland tissues with CS might comprise relatively low cellularity due to extensive fibrosis in the tissue [ 46 ], the DNA copies might have been undetectable even with the highly sensitive PCR. Furthermore, some regional variation in the virus distribution within the tissue might occur and the punch biopsies represent only a small portion of the salivary gland.…”