Salivary Gland Pathology in IgG4-Related Disease: A Comprehensive Review

Abstract

IgG4-related disease (IgG4-RD) is a rare fibroinflammatory condition that can affect almost any organ, characterized by swollen lesions and often by eosinophilia and elevated serum IgG4 concentrations. The diagnosis of IgG4-RD is a challenging task: in fact, single or multiple organs can be affected and clinical, serological, and histological findings can be heterogeneous. In IgG4-RD, the involvement of salivary glands is observed in 27% to 53% of patients. Several organ-specific conditions, now recognized as different manifestations of IgG4-related sialadenitis (IgG4-RS), were viewed in the past as individual disease entities. The study of salivary glands may sometimes be complex, because of the number of pathological conditions that may affect them, often with overlapping clinical pictures. Integration of different imaging techniques is often required in the case of swelling of salivary glands, even though biopsy remains the gold standard for a definite diagnosis of IgG4-RS. Thus, in this review, we discuss new insights in the pathogenesis of IgG4-RD, focusing on its clinical aspects and the tools that are currently available for a correct differential diagnosis when the salivary glands are involved.

An unusual presentation of chronic sclerosing sialadenitis of submandibular gland (Kuttner’s tumour)

“…Kuttner’s tumour is a localised submandibular gland enlargement in IgG4 disease. The pathogenesis of IgG4 disease is secondary to the interactions between the cells of the B cell lineage and a novel CD4 SLAMF7 cytotoxic T cells, which cause tissue inflammation and fibrosis 3…”

Marginal zone B-cell lymphoma: lessons from Western and Eastern diagnostic approaches

“…Plasma-cell differentiation occurs in one-third of cases. Special attention should be paid to IgG4-related sialadenitis, including Mikulicz disease and Küttner tumour (chronic sclerosing sialadenitis), 94,95 which is seen in 27-53% of patients with IgG4-related disease 96 and may develop into MALT lymphoma. 97 In the Waldeyer ring, MALT lymphoma is often difficult to diagnose because the epithelium is normally infiltrated by activated lymphoid cells (including plasma cells) activated with bacterial colonies in the crypts.…”

Ultrasonographic echogenicity of normal salivary glands in adults: comparison of submandibular and parotid glands

“…First, bilateral homogeneous hypoechogenicity of the SMG should not be mistaken for salivary gland disorders such as autoimmune sialadenitis (Sjögren syndrome) or IgG4-related disease if the case involves no clinical suspicion of sialadenitis and no other concurrent US abnormality of the PG and SMG. Although Sjögren syndrome or IgG4-related disease may cause hypoechogenicity of the SMG, in most cases this can be differentiated from physiologic hypoechogenicity of the normal SMG by the presence of a heterogeneous echotexture, nodular hypoechoic lesions, asymmetrical involvement, and glandular enlargement or atrophic change [10][11][12][13]. Second, the echogenicity of the normal SMG seems inappropriate as a reference standard for assessing the echogenicity of thyroid nodules in cases of thyroiditis with decreased parenchymal echogenicity because, based on our study results, the normal SMG may exhibit physiologic hypoechogenicity.…”