Person:

Ferry, Judith

BACKGROUND: Chronic sclerosing sialadenitis is a fibroinflammatory disease of the salivary glands, characteristically of the submandibular gland. One prior Asian study proposed that chronic sclerosing sialadenitis is a part of the spectrum of IgG4-associated disease. This association has not been confirmed in Western populations. We therefore, investigated the relationship between IgG4 and chronic sclerosing sialadenitis, and compared the histomorphologic features of this condition with those of chronic sialadenitis-not otherwise specified, Sjögren syndrome, and lymphoepithelial sialadenitis. MATERIALS AND METHODS: We evaluated 13 cases of chronic sclerosing sialadenitis and compared them with 15 cases of chronic sialadenitis-not otherwise specified, 8 lip biopsies from individuals with Sjögren syndrome, and 4 cases of lymphoepithelial sialadenitis. Immunohistochemistry for IgG, and IgG4 was carried out. IgG4-positive plasma cells were quantified and the IgG4/IgG ratio was calculated. RESULTS: Seven patients with chronic sclerosing sialadenitis were female and 6 were male. Their mean age was 61 years (range: 27 to 80). Twelve chronic sclerosing sialadenitis cases involved the submandibular gland (bilaterally in 3) and in 1 there was a parotid lesion. Three of these 12 cases had manifestations of IgG4-associated systemic disease. Morphologically these specimens had preservation of lobular architecture, hypercellular interlobular fibrosis, florid lymphoid hyperplasia, and numerous plasma cells. Obliterative phlebitis was observed in 6 cases. The histologic features of chronic sclerosing sialadenitis were reminiscent of autoimmune pancreatitis, and were either not observed or were present only focally in cases of chronic sialadenitis, Sjögren syndrome, and lymphoepithelial sialadenitis.Eleven of 12 evaluable cases showed an increased number of IgG4 plasma cells with a mean of 229/high-power field (HPF) (range 75 to 608) and an overall IgG4/IgG ratio of 0.86 (range 0.5 to 1). The only patient whose biopsy lacked IgG4-positive plasma cells had pathologic evidence of cytomegalovirus infection. Chronic sclerosing sialadenitis cases, in comparison with the other 3 groups studied, showed a significantly higher number of IgG4 positive plasma cells (P<0.05). Patients with chronic sialadenitis-not otherwise specified had a median number of only 16 IgG4-positive plasma cells/HPF (range 2 to 44), with an IgG4/IgG ratio of 0.14 (range 0.02 to 0.28). The Sjögren syndrome patients had a median of 1 IgG4-positive plasma cell/HPF (range 0 to 3), with an IgG4/IgG ratio of 0.02 (range 0 to 0.07). Patients with lymphoepithelial sialadenitis had a median of 0 IgG4-positive plasma cells per HPF. CONCLUSION: Chronic sclerosing sialadenitis has a characteristic morphologic appearance. This morphologic appearance, in conjunction with the elevated IgG4 expression, distinguishes chronic sclerosing sialadenitis from other inflammatory diseases of the salivary glands. Chronic sclerosing sialadenitis belongs to the spectrum of IgG4-related diseases.

IgG4-related disease is a newly recognized fibro-inflammatory condition characterized by several features: a tendency to form tumefactive lesions in multiple sites; a characteristic histopathological appearance; and—often but not always—elevated serum IgG4 concentrations. An international symposium on IgG4-related disease was held in Boston, MA, on 4–7 October 2011. The organizing committee comprising 35 IgG4-related disease experts from Japan, Korea, Hong Kong, the United Kingdom, Germany, Italy, Holland, Canada, and the United States, including the clinicians, pathologists, radiologists, and basic scientists. This group represents broad subspecialty expertise in pathology, rheumatology, gastroenterology, allergy, immunology, nephrology, pulmonary medicine, oncology, ophthalmology, and surgery. The histopathology of IgG4-related disease was a specific focus of the international symposium. The primary purpose of this statement is to provide practicing pathologists with a set of guidelines for the diagnosis of IgG4-related disease. The diagnosis of IgG4-related disease rests on the combined presence of the characteristic histopathological appearance and increased numbers of IgG4+ plasma cells. The critical histopathological features are a dense lymphoplasmacytic infiltrate, a storiform pattern of fibrosis, and obliterative phlebitis. We propose a terminology scheme for the diagnosis of IgG4-related disease that is based primarily on the morphological appearance on biopsy. Tissue IgG4 counts and IgG4:IgG ratios are secondary in importance. The guidelines proposed in this statement do not supplant careful clinicopathological correlation and sound clinical judgment. As the spectrum of this disease continues to expand, we advocate the use of strict criteria for accepting newly proposed entities or sites as components of the IgG4-related disease spectrum.