Histopathological and immunophenotypic features of ipilimumab-associated colitis compared to ulcerative colitis.
BACKGROUND
Use of the immune checkpoint inhibitor ipilimumab is sometimes complicated by ipilimumab-associated colitis (Ipi-AC), an immune-mediated colitis that mimics inflammatory bowel disease.


OBJECTIVE
We sought to characterize the histopathologic and immunophenotypic features of Ipi-AC and to directly compare these features to ulcerative colitis (UC).


METHODS
This is a retrospective cohort study of 22 patients with Ipi-AC, 12 patients with treatment-naïve UC and five controls with diarrhoea but normal endoscopic findings. Immunohistopathologic features were described, and quantitative immunohistochemistry (IHC) was performed for CD4, CD8, CD20, CD138 and FOXP3.


RESULTS
Endoscopic findings in both the Ipi-AC and UC groups included ulcerated, oedematous and erythematous mucosa. Involvement of the GI tract was more diffuse in Ipi-AC. As compared to UC, a smaller proportion of Ipi-AC biopsies had basal plasmacytosis (14% for Ipi-AC vs. 92% for UC, P < 0.0001) and crypt distortion (23% for Ipi-AC vs. 75% for UC, P = 0.003), whereas Ipi-AC biopsies had more apoptotic bodies in the left colon (17.6 ± 15.3 for Ipi-AC vs. 8.2 ± 4.2 for UC, P = 0.011). Cryptitis, ulcerations and crypt abscesses were common in both groups. Biopsy specimens from Ipi-AC had a lower density of CD20-positive lymphocytes than UC (275.8 ± 253.3 cells mm-2 for Ipi-AC vs. 1173.3 ± 1158.2 cells mm-2 for UC, P = 0.022) but had a similar density of CD4, CD8, CD138 and FOXP3-positive cells.


CONCLUSIONS
Ipi-AC is a distinct pathologic entity with notable clinical and histopathological differences compared to UC. These findings provide insights into the pathophysiology of immune-related adverse events (iAEs) from ipilimumab therapy.
['Adler|B L|BL|', 'Pezhouh|M K|MK|', 'Kim|A|A|', 'Luan|L|L|', 'Zhu|Q|Q|', 'Gani|F|F|', 'Yarchoan|M|M|', 'Chen|J|J|', 'Voltaggio|L|L|', 'Parian|A|A|', 'Lazarev|M|M|', 'Lauwers|G Y|GY|', 'Pawlik|T M|TM|', 'Montgomery|E A|EA|', 'Jaffee|E|E|', 'Le|D T|DT|', 'Taube|J M|JM|', 'Anders|R A|RA|']
D000328:Adult D000074322:Antineoplastic Agents, Immunological D003092:Colitis D003093:Colitis, Ulcerative D003967:Diarrhea D005260:Female D006801:Humans D007150:Immunohistochemistry D007413:Intestinal Mucosa D000074324:Ipilimumab D008297:Male D008875:Middle Aged D009369:Neoplasms D012189:Retrospective Studies
colitis ipilimumab inflammatory bowel disease immunotherapy