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Histopathological and immunophenotypic features of ipilimumab‐associated colitis compared to ulcerative colitis
Author(s) -
Adler B. L.,
Pezhouh M. K.,
Kim A.,
Luan L.,
Zhu Q.,
Gani F.,
Yarchoan M.,
Chen J.,
Voltaggio L.,
Parian A.,
Lazarev M.,
Lauwers G. Y.,
Pawlik T. M.,
Montgomery E. A.,
Jaffee E.,
Le D. T.,
Taube J. M.,
Anders R. A.
Publication year - 2018
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/joim.12744
Subject(s) - medicine , ulcerative colitis , gastroenterology , colitis , ipilimumab , cd20 , biopsy , inflammatory bowel disease , pathology , plasmacytosis , immunohistochemistry , cancer , immunotherapy , multiple myeloma , disease
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.