Immunohistochemistry for IgG4 on Paraffin Sections for the Diagnosis of Pemphigus.
Xuefeng Zhang, Elizabeth Hyjek, Keyoumars Soltani, Vesna Petronic-Rosic, Christopher R Shea. University of Chicago Medical Center, IL
Background: Pemphigus is a group of autoimmune vesiculobullous diseases characterized by the presence of tissue-bound and circulating IgG antibodies directed against desmosomal adhesion proteins (desmoglein 1 and desmoglein 3) on the surface of keratinocytes. Both the IgG1 and IgG4 subclasses are produced, with IgG4 being predominant. Direct immunofluorescence (DIF) for IgG performed on fresh-frozen tissue plays a crucial role in diagnosing pemphigus. However, when paraffin sections of a biopsy specimen are histologically suspicious for pemphigus, frozen tissue may not be available to confirm the diagnosis. Immunohistochemical detection of total IgG performed on paraffin sections is of no diagnostic value because of the high background. In this study, we used immunohistochemistry for IgG4 performed on paraffin sections as a diagnostic test for pemphigus.
Design: Nineteen IF-proven pemphigus cases (12 pemphigus vulgaris, 6 pemphigus foliaceus, and 1 paraneoplastic pemphigus) were studied. Four normal skin specimens and 10 non-pemphigus vesiculobullous disease specimens served as controls. Paraffin sections of all cases were examined immunohistochemically for IgG4 expression. Positivity was defined as distinct, condensed, continuous immunoreactivity localized to the intercellular junctions of keratinocytes.
Results: The results were independently evaluated by three pathologists, with a 100% inter-observer agreement. Nine of 12 pemphigus vulgaris cases (sensitivity 75.0%), 4 of 6 pemphigus foliaceus cases (sensitivity 66.7%), and the paraneoplastic pemphigus case were positive for IgG4 immunohistochemical stain. The overall sensitivity was 73.7%. None of the control specimens showed IgG4 positivity (specificity of 100%), although non-specific staining was present in some cases. In the specimens demonstrating acantholysis, 8 of 10 pemphigus vulgaris cases (sensitivity 80.0%) and 4 of 4 pemphigus foliaceus cases (sensitivity 100.0%) were positive for IgG4. The overall sensitivity for specimens with acantholytic lesions was 86.7%.
Conclusions: Immunohistochemical labeling for IgG4 provides a sensitive and specific diagnostic tool for diagnosing pemphigus; it is likely to be particularly valuable in cases where frozen tissue is not available for DIF, and especially when active acantholytic lesions are examined.
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 73, Monday Morning