Programmed cell death protein 1 (PD-1) blocking agents are novel immunotherapeutics used for treatment of advanced-stage
malignancies. They have shown promise in the treatment of several
malignancies, with greater efficacy and better tolerability than
cytotoxic T-lymphocyte antigen 4 (CTLA-4) blocking agents. However, as with anti-CTLA-4 agents, clinically significant
colitis remains an important complication. Although there is growing awareness of the histopathologic features of anti-CTLA-4
therapy, there is little information on the pathologic features of anti-PD-1
colitis. We describe here the histopathologic findings in 8 patients who developed
colitis while on anti-PD-1 monotherapy. The most common pattern of injury observed (5/8 cases) was an active
colitis with neutrophilic crypt microabscesses and with prominent crypt epithelial cell apoptosis and crypt
atrophy/dropout. These latter features are reminiscent of other
colitides with prominent apoptosis such as acute
graft-versus-host disease or certain
drug-induced
colitides. The remainder of cases (3/8) showed a
lymphocytic colitis-like pattern, characterized by increased intraepithelial lymphocytes and surface epithelial injury. Apoptosis was also often increased in these cases but crypt
atrophy/dropout was not present. In patients who experienced recurrence of anti-PD-1
colitis, histologic features were similar to the initial insult but, in addition, features of chronicity developed that mimicked
inflammatory bowel disease (basal lymphoplasmacytosis and crypt architectural irregularity, and Paneth cell
metaplasia in 1 case). Awareness of the clinical scenario, however, should allow pathologists to suggest anti-PD-1
colitis. Interestingly, recurrent
colitis was observed in patients who had been off anti-PD-1
therapy for many months. As anti-PD-1 agents are increasingly used in oncology, we present this series to increase awareness of anti-PD-1
colitis among pathologists, to facilitate its timely diagnosis and treatment.