Rashmi Samdani

Endoscopic and Histologic Features of Immune Checkpoint Inhibitor-Related Colitis

BackgroundnDiarrhea and colitis are the second most common immune checkpoint inhibitor (ICPI)-induced adverse events. However, a comprehensive characterization of the endoscopic and histologic features of ICPI-induced diarrhea and colitis is lacking. Therefore, we aimed to describe endoscopic and histologic features of ICPI-induced gastrointestinal toxicities and to assess their association with patients clinical characteristics and outcomes.nnnMethodsnWe retrospectively reviewed records of 53 patients with ICPI-related diarrhea/colitis between 2011 and 2017. We collected data on demographics, diarrhea/colitis grade, treatment, and endoscopic and histologic findings. Long-term follow-up included repeat endoscopy findings, diarrhea recurrence, and overall survival. We compared groups by treatment, endoscopic and histologic findings, and constructed Kaplan-Meier survival curves.nnnResultsnMost patients had grade 2 or higher diarrhea (87%) and colitis (60%). Thirty-one patients were successfully treated with corticosteroids, and 22 additionally required infliximab. On endoscopy, 21 (40%) patients had ulcerations and 22 (42%) had nonulcerative inflammation. Patients with ulcerations had more steroid-refractory disease (P = 0.044) and high-grade diarrhea (P = 0.033). Histology showed mostly acute (23%) or chronic (60%) inflammation. During mean follow-up duration of 18.9 months, 19 (36%) developed recurrent diarrhea. Most patients had persistent endoscopic (8/13, 62%) and histologic (9/11, 82%) inflammation. Patients with higher-grade adverse events had improved survival. Higher-grade colitis was associated with endoscopic inflammation (P = 0.039), but grade of diarrhea was not associated with endoscopic inflammation or grade of colitis.nnnConclusionn10.1093/ibd/izy104_video1izy104.video15808053084001.

Index report of cutaneous angiosarcomas with strong positivity for tyrosinase mimicking melanoma with further evaluation of melanocytic markers in a large angiosarcoma series

Cutaneous angiosarcoma can be challenging to diagnose particularly when poorly vasoformative and studied on biopsies. We report a case of a cutaneous angiosarcoma with strong positivity for tyrosinase, the first to our knowledge, initially misdiagnosed as melanoma. We subsequently evaluated the reactivity of panmelanocytic cocktail (tyrosinase, HMB‐45 and Melan‐A), SOX10, tyrosinase and MITF in a large tissue microarray (TMA) of angiosarcoma. The TMA included 142 cases of angiosarcomas (29 cutaneous, 22 primary breast, 41 post‐radiation breast, 15 visceral, 26 deep soft tissue and bone, 5 chronic lymphedema‐associated and 4 angiosarcomas arising in other sarcomas). Immunohistochemical studies were performed with anti‐panmelanocytic cocktail, anti‐SOX10, anti‐MITF and anti‐tyrosinase antibodies. TMA staining results were scored on intensity and percentage of tumoral labeling. Aside from the index case, no cases (0 of 133) showed positivity for tyrosinase including 28 cutaneous angiosarcomas. One breast angiosarcoma (1 of 131) was positive for MITF. All cases were negative for SOX10 and panmelanocytic cocktail (0 of 132). Angiosarcomas can rarely be positive for tyrosinase and MITF. Pathologists should be cognizant of these rare exceptions to prevent confusion with melanoma. Additional immunohistochemical markers for vascular and melanocytic differentiation, thorough histological examination for vasoformative and in situ areas as well as clinical impression are helpful in these exceptionally problematic cases.

Can Immune Checkpoint Inhibitors Induce Microscopic Colitis or a Brand New Entity

BackgroundnMicroscopic colitis (MC) has been described as 1 pattern of injury in immune checkpoint inhibitor (ICPI)-induced colitis. The main objective of this study was to characterize ICPI-induced MC by exploring the differences in risk factors, colitis treatments, endoscopic features, and clinical outcomes between cancer and noncancer patients with MC with and without exposure to ICPIs.nnnMethodsnA retrospective chart review was conducted among patients diagnosed with MC from our institutional pathology database from January 2012 to January 2018. Patients were categorized into MC in cancer patients with or without ICPI exposure and in noncancer patients. Risk factors (use of tobacco and certain medications), colitis treatments (antidiarrheals and immunosuppressants), endoscopic features (with or without mucosal abnormality), and clinical outcomes (diarrhea recurrence, hospitalization, mortality) were collected and compared among the 3 groups.nnnResultsnOf the 65 eligible patients with MC, 15 cancer patients had exposure to ICPI, 39 cancer patients had no exposure to ICPI, and 11 had no cancer diagnosis. Among the risk factors, proton pump inhibitor was more frequently used in the ICPI-induced MC cohort (P = 0.040). Furthermore, in this population, mucosal abnormality was the most common endoscopic feature compared with normal findings in the non-ICPI-induced MC groups (P = 0.106). Patients with ICPI-induced MC required more treatments with oral and intravenous steroids and nonsteroidal immunosuppressive agents (all P < 0.001) and had a higher rate of hospitalization (P < 0.001).nnnConclusionnThis study suggests that despite some similarities between MC with and without exposure to ICPIs, ICPI-induced MC has a more aggressive disease course that requires more potent immunosuppressive treatment regimens and greater need for hospitalization. 10.1093/ibd/izy240_video1izy240.video15828223597001.