S2257 Immune Checkpoint Inhibitor-Induced Colitis or Ulcerative Colitis: A Histopathological Dilemma

Abstract

INTRODUCTION: Immune checkpoint inhibitor (ICI) induced colitis occurs in 1-2% of treated patients. The onset of symptoms is usually between 6-18 weeks after therapy initiation. It can often appear endoscopically and histologically similar to ulcerative colitis (UC). It may also share similar pathological mechanisms of injury. We present a case of colitis that appears to have worsened with ICI therapy. CASE DESCRIPTION/METHODS: An 81 year old male with a history of stage 4 poorly differentiated non-small cell carcinoma (favoring adenocarcinoma) of the lung presented to our clinic for 7 months of diarrhea. Patient had a prior colonoscopy 6 months earlier for the same complaint with noted left sided diverticulitis and colitis. Pathology revealed erythematous tissue with shallow ulceration and friability without crypt abscesses, architectural distortion, granulomas, dysplasia, or malignancy. Mesalamine was started with mild improvement. After starting pembrolizumab he noted worsening diarrhea, at which time prednisone was prescribed, with partial improvement. However, even with loperamide use, he had numerous non-bloody diarrheal bowel movements daily. Sigmoidoscopy was performed, with colitis noted. Pathology of the sigmoid and rectum revealed cryptitis, focal crypt abscesses, and mild architectural distortion with focal paneth cell metaplasia and an increase in chronic inflammatory cells including lymphocytes, plasma cells and eosinophils within the lamina propria without dysplasia or malignancy. Budensonide was started with plans for potential institution of vedolizumab. DISCUSSION: After ruling out infection, the next step in diagnosing ICI mediated colitis is a colonoscopy. Endoscopy may reveal ulcers, erythema, and erosions. Microscopy may reveal crypt abscesses, neutrophilic infiltrate, or an increase in the number of cells within the lamina propria. Occasionally, chronic inflammatory findings such as crypt architecture alterations and lymphocyte predominant infiltrate may be seen. Differentiation with ulcerative colitis is done via clinical history. Treatment for ICI induced colitis is dependent on symptoms. For those with < 4 bowel movements daily (grade 1), symptomatic treatment only is reasonable. For those with 4-6 per day (grade 2), ICI therapy is withheld, and steroids utilized if diarrhea is not self-resolving after 1 week. For >7 stools daily (grade 3 or 4) therapy is discontinued permanently. In some cases, when patients are steroid refractory, infliximab and vedolizumab have been utilized.Image 1.: Colitis on endoscopy.Image 2.: Cryptitis with crypt abscesses along with lymphocytes, plasma cells, and eosinophils.Image 3.: Paneth cells.