IgG4-related hypophysitis is highly prevalent among cases of histologically confirmed hypophysitis

Abstract

IgG4-related disease is an immune-mediated disease with manifestations in most organ systems among them the pituitary gland. To date, few cases of histologically confirmed cases of IgG-related hypophysitis have been reported. The aim of this study was to retrospectively determine the prevalence of IgG4-related hypophysitis among cases previously diagnosed as primary hypophysitis (lymphocytic hypophysitis, granulomatous hypophysitis and hypophysitis not otherwise specified). Histological and immunohistochemical analysis revealed that 12 of 29 cases (41.4%) previously diagnosed as primary hypophysitis fulfilled the criteria for IgG4-related disease and, thus, IgG4-related hypophysitis should always be considered in the differential diagnosis of primary hypophysitis. All cases of IgG4-related hypophysitis showed a dense lymphoplasmacytic infiltrate with more than 10 IgG4-positive cells per high power field and a ratio of IgG4/IgG-positive cells of more than 40%, whereas storiform fibrosis was an inconsistent histological feature and was also seen in few cases of non-IgG-related hypophysitis, thus lacking sensitivity and specificity. Obliterative phlebitis was not seen in any case. Thus, histological criteria defined for IgG4-related disease in other organs should be modified for IgG4-related hypophysitis, accordingly.

Keywords: IgG4; histological criteria; hypophysitis; prevalence.

Figure 1

Histologic features of IgG4‐related hypophysitis. In the left panel, representative histological (H&E) and immunohistochemical pictures of a case of IgG4‐related hypophysitis that had previously been diagnosed as lymphocytic hypophysitis showing a dense lymphoplasmacytic infiltrate (a) with abundant IgG‐positive cells (b) and IgG4‐positive cells (c) and storiform fibrosis (d). In the right panel, a case of granulomatous hypophysitis showing a dense lymphoplasmacytic infiltrate (e) with abundant IgG‐positive cells (f) but only disseminated IgG4‐positive cells (g) and nonstoriform fibrosis (h). Scale bar = 100 µm.

Figure 2

Statistical analysis of hypophysitis cases. (a) Absolute numbers of cases previously diagnosed as hypophysitis fulfilling the criteria for IgG4‐related hypophysitis (IgG4+) or failing to fulfill these criteria (IgG4−). (b) Percentages of IgG4+ and IgG4− hypophysitis among cases previously diagnosed as lymphocytic hypophysitis, granulomatous hypophysitis, or hypophysitis, not otherwise specified (NOS). (c) Mean ages ± standard deviation of all 29 cases analyzed and of IgG4+ and IgG4− hypophysitis. (d) Percentages of male and female patients among all cases and IgG4+ and IgG4− hypophysitis. (e) Sensitivity of different thresholds for the number of IgG4‐positive cells per high power field in the diagnosis of IgG4‐related hypophysitis. (f) Percentages of storiform fibrosis among all cases and IgG4+ and IgG4− hypophysitis.