IgG4 related disease of the head and neck

Abstract

IgG4 related disease of the head and neck region represents one of the more common manifestations of IgG4 related disease. Involvement of the submandibular and parotid glands, the orbit and thyroid represent some of the more common sites involved by IgG4 related disease. Eosinophilic angiocentric fibrosis, Mikulicz disease and Riedel thyroiditis are also members of the family of IgG4 related disease. Clinically, the disease is characterized by tumefactive lesions, often multicentric, that show a swift response to immunosuppressive therapy. An elevated serum IgG4 represents the only validated blood based biomarker. However, elevated serum IgG4 is detected in only half the patients with this disease. Histology continues to represent the gold standard for the diagnosis of IgG4 related disease: storiform-type fibrosis and obliterative phlebitis constitute characteristic features of this disease. A definitive diagnosis of IgG4 related disease also requires the presence of elevated numbers of IgG4 positive plasma cells as well as an IgG4 to IgG ratio of greater than 40 %. In isolation, elevated numbers of IgG4 positive plasma cells represents a non-specific feature, detected in a variety of other inflammatory as well as neoplastic diseases. Attention to the clinical context, histological features, as well as an elevated IgG4 to IgG ratio is critical to avoiding overdiagnosis of IgG4 related disease.

Fig. 1

IgG4 related sialadenitis. This low power view illustrates the classic features of this disease—jigsaw puzzle-like appearance. Note the reactive germinal centers

Fig. 2

IgG4 related sialadenitis. Partially obliterated vein, (a) and totally obliterated vein (b). Arrow marks the totally obliterated vein

Fig. 3

Comparison of an in situ hybridization assay for IgG4/IgG with the immunohistochemistry platform. In situ hybridization for IgG4, (a) and IgG, (b) (ViewRNA, Affymetrix, CA). Immunohistochemistry for IgG4, (c) and IgG, (d). The IgG immunohistochemistry is generally associated with strong background signal, precluding the quantification of the IgG4 to IgG ratio, a critical element of the diagnostic algorithm

Fig. 4

IgG4 related sialadenitis (a). Note the dense lymphoplasmacytic infiltrate and storiform type fibrosis in the interlobular septum. Chronic sialadenitis—not otherwise specified (b). Note the relatively acellular interlobular stroma. However, increased numbers of IgG4 positive plasma cells are noted, in isolation, a relatively non-specific feature (inset)

Fig. 5

IgG4 related disease involving the nasal cavity paranasal sinuses. Note the storiform pattern. Virtually all the plasma cells were positive for IgG4 (image not shown)