Mycophenolic Acid (Cellcept and Myofortic) Induced Injury of the Upper GI Tract

Abstract

As noted by others (Parfitt JR, Jayakumar S, Driman DK. Am J Surg Pathol. 2008; 32:1367-1372), mycophenolate mofetil-associated injury of the upper GI tract, like that in the colon, is characterized by prominent apoptosis similar to that of mild or grade I graft-versus-host-disease injury. We offer apoptotic count guidelines, which we hope will facilitate recognition of mycophenolate mofetil-associated injury in the upper GI tract.

Apoptotic Colonopathy under Immunosuppression: Mycophenolate-Related Effects and Beyond

“…This observation in our practice was paralleled by a growing body of literature on MPA-related histopathological findings [3,4,5,6]. MPA is an inhibitor of inosine-5′-monophosphate dehydrogenase and blocks the de novo purine synthesis required for DNA synthesis and cell division.…”

“…These include points to be addressed from a basic research as well as a clinicopathological perspective. (1) Do the histopathological findings found in association with MPA treatment [3,4,6,10] correlate with the clinical symptoms, in particular diarrhea? The current concept is based on this assumption, but there are no data on the frequency of MPA-typical histopathological changes in patients not suffering from diarrhea.…”

“…Typical clinical presentations of MPA-related gastrointestinal toxicity include afebrile, watery diarrhea with mostly unremarkable or mild endoscopy findings. The entire gastrointestinal tract including the upper part can be affected by MPA toxicity [3], and macroscopic features may include ulcers and erosions throughout the entire gut. The epithelial or glandular compartment is the main target of MPA-related toxicity.…”

Characterization of Epithelial Apoptosis in Biopsies of Small-Bowel Allografts Using Cleaved Caspase 3 Immunostaining

“…1 Others have been more liberal in their assessment of ABs of the upper-gastrointestinal tract, including fragments of pyknotic basophilic material resembling a fried-egg in their AB counts. 3 In our experience, we have observed that individual pathologists define ABs differently, ranging from well-developed vacuolated cells to the presence of isolated basophilic granules. We typically consider both in our AB counts when evaluating small-bowel biopsies, and patients diagnosed with mild ACR using these features typically respond clinically and histologically to immunosuppression in an expected fashion.…”

The impact of histopathologic examination of graft-versus-host disease in the era of reduced-intensity conditioning regimen: a study from the Gruppo Italiano Trapianto di Midollo Osseo

“…Thus, the diagnosis of GvHD in the GI tract should not be based on histology alone but on a combination of clinical signs and symptoms, endoscopic findings, histopathology, and absence of infection by culture and histology [17]. Furthermore, apoptosis in any part of the GI tract can occur following various medications, including the immunosuppressive MMF, which can produce GVHD-like features, like dilated damaged crypts, edema in the lamina propria, increased crypt epithelial apoptosis, and patchy neutrophilic inflammation [26,27]. In our series, 46% of patients received CSA + MMF, and this treatment may have been a potential cause of misinterpretation of subtle histopathologic findings.…”