IgG4-Positive Plasma Cells in Ascending Aortitis: Are They Diagnostic for IgG4-Related Aortitis/Periaortitis?
Kenji Notohara, Dylan V Miller. Kurashiki Central Hospital, Kurashiki, Japan; Intermountain Medical Center & University of Utah, Murray, UT
Background: Aortitis/periaortitis is a manifestation of IgG4-related disease (IgG4-RD), but, so far, reported cases are mostly of the abdominal aorta and aortic arch. Noninfectious ascending aortitis, especially of an isolated variant, may belong to IgG4-RD, but compared to abdominal aorta, the data are limited.
Design: Resected specimens from 98 patients were reviewed, and cases with dense plasmacytic infiltration and fibrosis but without granulomatous reaction were selected for immunostaining for IgG4 and IgG1. Cases with abundant giant cells or granulomatous reaction were presumed unlikely to be IgG4-related due to the rarity of this finding in IgG4-RD, but some cases (particularly those with concomitant dense plasmacytic infiltration) were also included for comparison. The number of IgG4+ plasma cells (PCs) in a high power field were graded as: 1 (10 or fewer), 2 (11-20), 3 (21-30), 4 (31-50), and 5 (51 or more). The ratio of IgG4+:IgG1+ staining PCs was also determined for each case.
Results: Among 14 cases that met the criteria, 11 cases had available paraffin blocks and were selected. 8 cases with plasmacytic plus granulomatous/giant cell reaction were also selected for comparison. Among 11 cases, only one was consistent with IgG4-RD. This case had a marked number (grade 5) of IgG4+ PCs, high IgG4+/IgG1+ PC ratio (80%) and a histological finding of storiform fibrosis mainly in the adventitia. Increased (grade 2-5) IgG4+ PCs were present in 8 other cases, however, all of these cases had lower IgG4+/IgG1+ PC ratios; not consistent with IgG4-RD. 3 cases with a mild (grade 2) increase of IgG4+ PCs and lower ratio of IgG4+/IgG1+ PC showed the typical storiform fibrosis, but the lesion was admixed with mild infiltration of neutrophils, which is unusual for IgG4-RD. IgG4+ PCs were also increased (grade 2-4) in the 8 cases with granulomatous reaction, but all of these cases showed a low IgG4+/IgG1+ PC ratio.
Conclusions: Although IgG4+ PCs were commonly identified in ascending aortitis with or without granulomatous reaction, only one patient (out of 19) was considered to have true IgG4-RD after taking the IgG4+:IgG1+ PC ratio into account. The diagnosis of IgG4-related aortitis/periaortitis should be evaluated with IgG4+/IgG1+ PC ratio. Storiform fibrosis, which is believed to be specific to IgG4-RD, may not be entirely specific to IgG4-related lesion in the aorta when neutrophils are present. The incidence of IgG4-RD affecting the ascending aorta appears to be significantly less than in the abdominal aorta.
Tuesday, March 20, 2012 2:30 PM
Platform Session: Section H2, Tuesday Afternoon