Ipilimumab-induced perforating colitis

Abstract

Recently, a monoclonal antibody to cytotoxic T-lymphocyte-associated antigen 4, ipilimumab, was approved for the treatment of metastatic melanoma. One of the most common side effects associated with this therapy is diarrhea and colitis. We report 3 cases of perforating colitis induced by ipilimumab requiring colectomy. The histologic findings of mucosal biopsies have been previously described. Herein, we describe novel associated histologic findings (pseudopolyp formation, fissuring ulcers, dilated crypts, and lack of intraepithelial lymphocytosis and epithelial apoptosis) of segmental resections in patients who required subtotal colectomy after perforation due to the severity of their ipilimumab-induced colitis. Although steroid therapy is the standard treatment for ipilimumab-induced colitis, surgery may be necessary. In the setting of progressive or worsening diarrhea after steroid therapy in patients with colitis, bowel perforation should be considered.

FIGURE 1.

A, Colon biopsy with reactive epithelium with dilated crypts, surface epithelial damage, and increased lamina propria inflammation (× 100, hematoxylin and eosin). B, Grossly ulcerated colon with multiple pseudopolyps (formalin-fixed resection). C, Colon resection with multifocal deep ulcers and residual polypoid (pseudopolyp) mucosa (× 20, hematoxylin and eosin). D, Dilated crypts within nonulcerated mucosa of resection (× 100, hematoxylin and eosin).

FIGURE 2.

A, Grossly perforated colon with residual boggy, polypoid mucosa (formalin-fixed resection). B, Multifocal deep ulcers with pseudopolyps (× 20, hematoxylin and eosin). C, Mucosa of resection with dilated crypts with crypt abscesses, reactive epithelium, and increased lamina propria lymphoplasmacytic inflammation without chronic colitis (resection—× 100, hematoxylin and eosin). D, Fissuring-type inflammation in area of perforation (resection—× 20, hematoxylin and eosin).

FIGURE 3.

A, Gross perforation of colon oozing fecal material (unfixed resection). B, Ulcerated colon with erythematous residual mucosa lacking plaque-like exudate (unfixed resection specimen). C, Multifocal deep ulcers with pseudopolyps (× 20, hematoxylin and eosin). D, Reactive epithelium, crypt abscesses, and increased lamina propria inflammation (× 100, hematoxylin and eosin).