C4d immunohistochemical stain of formalin-fixed paraffin-embedded tissue as a sensitive method in the diagnosis of bullous pemphigoid.

Background: Bullous pemphigoid (BP) is the most common type of subepidermal bullous disease. Direct immunofluorescence (DIF) is the gold standard for diagnosis, but it requires a fresh tissue specimen. This study was conducted to evaluate the accuracy of using immunohistochemical (IHC) analysis for the detection of C4d in paraffin-embedded tissue of BP cases.

Methods: A retrospective study was performed on 30 BP cases (confirmed by Hematoxylin and eosin [H&E] and DIF) and 30 controls. IHC studies were performed on formalin-fixed paraffin-embedded (FFPE) tissues.

Results: Of 30 BP patients (11 male and 19 female), 27 (90%) were C4d positive and three patients (10%) were C4d negative. The C4d deposits were seen as linear brown stain along the dermoepidermal junction (18 cases), around basal keratinocytes (eight cases), or Civatte-like (three cases). Two cases revealed more than one pattern in IHC staining. Of 30 control specimens, 26 (86%) cases were C4d negative and four (13.4%) were positive for granular deposits of C4d which were diagnosed as dermatitis herpetiformis.

Conclusions: C4d IHC study is a valuable diagnostic tool with sensitivity of 90% and specificity of 86.7%, and is especially useful in cases in which frozen specimens are not available or FFPE specimens are the only available material for analysis.