Evaluating the association between histological manifestations of cord colitis syndrome with GVHD

Abstract

Cord colitis syndrome (CCS) is a recently proposed clinical entity characterized by a persistent diarrheal illness after cord blood transplantation (CBT), which is not caused by GVHD or CMV colitis. CCS is histologically characterized by chronic active colitis with granulomatous inflammation and Paneth cell metaplasia suggesting chronicity. However, the specificity of these pathological features to CCS remains to be validated. We conducted a retrospective study of 49 patients who had diarrhea and underwent diagnostic colonoscopy with biopsy following allogeneic hematopoietic SCT. None of the patients met the clinical criteria for CCS. Chronic active colitis with granulomatous inflammation and Paneth cell metaplasia was present in 12/33 (36%) patients with biopsy-proven GVHD, 4/6 (67%) patients with CMV colitis and 2/15 (13%) patients with nonspecific colitis. In patients with GVHD and/or CMV colitis, these pathological features were present in 4/8 (50%) patients after CBT and in 11/26 (42%) patients undergoing BMT or PBSCT. These results demonstrate that chronic active colitis with granuloma and Paneth cell metaplasia is not only a specific feature of CCS but also is present in GVHD and CMV colitis, irrespective of stem cell source.

Reciprocal Expression of Enteric Antimicrobial Proteins in Intestinal Graft-Versus-Host Disease

“…Thus, it is tempting to assume that enhanced production of RegIIIg is a natural adaptation mechanism for the dysbiosis in GVHD. Paneth cell metaplasia is also observed in the colon of GVHD patients, probably as an adaptation mechanism for Paneth cell loss and the dysbiosis [30]. We have shown that Paneth cellederived a-defensin production is markedly inhibited in GVHD that have selective bactericidal activity mostly against Gram-negative bacteria [7,31,32].…”

NIH Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: II. The 2014 Pathology Working Group Report

“…The DFCI investigators used a unique non-standard definition of GVHD that excluded GVHD in colonic biopsies showing low or rare apoptosis or any features of chronicity as described above. Subsequently, two much larger studies including controls who received cord blood and non-cord blood hematopoietic stem cell transplants showed that neither the histological features of chronicity (crypt distortion, Paneth cell metaplasia, chronic active colitis) nor granulomas were confined to cord blood recipients [73, 74]. In the study by Milano et al, all of the non-cord blood allogeneic recipients with late onset secretory diarrhea and symptoms ascribed to CCS responded to anti-GVHD treatment [73].…”

“…In the study by Milano et al, all of the non-cord blood allogeneic recipients with late onset secretory diarrhea and symptoms ascribed to CCS responded to anti-GVHD treatment [73]. The presence of granulomas with neutrophilia was more common in a Japanese study that included many cases with both GVHD and CMV [74]. These studies serve as a reminder that GVHD and infection are not mutually exclusive diagnoses and reinforce the need to use standardized histological definitions for GVHD.…”

Acute graft-versus-host disease of the gut: considerations for the gastroenterologist

“…Colonoscopy reveals erythematous mucosa with or without ulceration, and biopsy demonstrates chronic active colitis, frequently with associated granulomas 136 . This clinical entity remains controversial, as studies have suggested that CCS is not a histopathologically distinct disease from acute GVHD 137,138 .…”