Can Immunohistochemistry On Routine Formalin-Fixed, Paraffin-Embedded Skin Tissue Be Helpful In The Diagnosis Of Bullous Pemphigoid?

초록

Background: The gold standard for the diagnosis of bullous pemphigoid (BP) is the detection of linear deposition of IgG and/or C3 on the dermoepidermal junction by direct immunofluorescence (DIF). As DIF has several disadvantages because of use of frozen specimens, we hypothesized that immunohistochemical (IHC) staining of complements and IgG using FFPE tissue could help diagnose BP, thereby making immunopathologic confirmation of the bullous process possible without disadvantages of DIF. Design: Eighty-eight cases of bullous lesions were included. IHC studies for C3d, C4d, and IgG were performed in 88 cases (DIF-confirmed BP [n=43], clinicopathologically suspicious BP with negative DIF results [n=9], and other bullous disease [n=36]). Considering the existence of false-negative DIF results, we compared DIF and IHC staining findings, including those of clinicopathologically suspected BP cases with negative results on DIF. Results: When the diagnosis was based on C3d, C4d, or IgG positivity on IHC staining, 86% of BP cases diagnosed via DIF could be diagnosed using IHC staining with deposition of C3d, C4d, or IgG as the diagnostic criterium. The sensitivity of IHC staining in detecting BP and suspicious BP cases was similar to that of DIF (80.8% vs. 84.3%), and the specificity was higher (83.3% vs. 75.0%). Furthermore, five of nine (55.6%) cases with negative DIF results could be diagnosed as BP using IHC staining. Considering that DIF is more sensitive than IHC staining, we reviewed IHC-positive and DIF-negative cases and found that 66.7% of discordant cases based on IgG, 100% of discordant cases based on C3d, and 100% of discordant cases based on C4 were treated as BP cases. Conclusions: To the best of our knowledge, our study, which evaluated the diagnostic value of IHC staining as an alternative to DIF, has the second largest number of BP cases yet reported. Although DIF remains the gold standard, IHC staining could be another useful strategy for BP diagnosis, especially when DIF cannot be performed. In addition, we suggest that additional IHC staining of FFPE tissue may be helpful in cases of clinicopathologically suspicious BP with negative or suboptimal DIF results, instead of conducting a second biopsy.