Revisiting the Pathology of Bullous Pemphigoid: Basal Cell Necrosis as a Diagnostic Clue and Its Pathogenic Role

Bullous pemphigoid (BP) is an autoimmune blistering disease caused by autoantibodies against the hemidesmosomal proteins BP180 and BP230. Although the histopathological features of BP are well documented, basal cell necrosis (BCN) in the blister roof has not been systematically studied. We retrospectively reviewed the clinicopathological findings of BP cases to assess the prevalence and extent of BCN and to explore its underlying mechanisms. Forty-one BP cases diagnosed between 2011 and 2017 were analyzed, with 35 cases of other subepidermal blistering disorders serving as controls. BCN was identified along the base of the blister roof in 92.7% (38/41) of BP cases, typically in a confluent linear array, whereas only 8.6% (3/35) of control cases showed BCN. The extent of BCN correlated strongly with eosinophil density in the blister cavity but not with the serum levels of anti-BP180 or anti-BP230 antibodies. Immunohistochemical study showed that BCN in BP was mediated by caspase-3 (CASP3)-dependent apoptosis and/or receptor-interacting protein kinase-3 (RIP3)-dependent necroptosis pathways. Our study indicated that BCN, mediated via CASP3-dependent apoptosis and/or RIP3-dependent necroptosis pathways, is a very common histological feature of BP and may serve as a useful diagnostic clue.