Gastric Graft-Versus-Host Disease: A Blinded Histologic Study

Abstract

Acute graft-versus-host disease (GvHD) of the upper gastrointestinal (GI) tract is common after allogeneic bone marrow transplantation (BMT). However, diagnosis cannot be made on clinical presentation and endoscopic findings alone, because these are nonspecific, and histologic confirmation is often desirable. The diagnosis of gastric GvHD is often based on subtle findings with considerable potential for variability in interpretation. Evaluation of the reproducibility of diagnosis and recognition of histologic features of gastric GvHD was based on blinded review of 56 gastric biopsies (24 from patients with allogeneic BMT or unrelated umbilical cord blood transplantation and 32 control biopsies from patients who did not undergo BMT, of whom eight had active GI cytomegalovirus [CMV] infection). Histologic criteria for GvHD were apoptosis and gland destruction, sparse inflammatory infiltrate, and granular eosinophilic debris in dilated glands. Seventeen patients (22 biopsies) were judged to have clinical GvHD on the basis of skin or liver involvement and GI symptoms without other known cause. Eighteen of these 22 gastric biopsies were classified as GvHD by at least two of the three pathologists on initial review. Blinded histologic diagnosis of GvHD had a positive predictive value of 69%, a sensitivity of 82%, and specificity of 76%. False-positive results occurred in CMV gastritis, human immunodeficiency virus (HIV) infection, primary immunodeficiency, and after renal transplantation. Of individual features, granular debris in glands was a specific (94% specificity), but insensitive (41% sensitivity) marker for GvHD. Distinction between GvHD and CMV infection can be difficult, and GvHD can be confused with changes seen in HIV infection and other immunodeficiency states.

18F-FDG PET/CT for the assessment of gastrointestinal GVHD: results of a pilot study

“…The latter may reflect the absence of consensus for the definition of histological signs of acute GI-GVHD, with the minimum criterion being the presence of apoptotic lesions, although not specific of GI-GVHD. 16,22 Also, several studies have reported discrepancies between the clinical and histological localizations of acute GI-GVHD, 23,24 which is represented in our study by the case of one patient who had clinical symptoms of grade 2 acute GI-GVHD, but had a morphologically normal sigmoidoscopy and only grade 1 histological acute GI-GVHD. Therefore, the segment of the gastrointestinal tract that should be biopsied for diagnosis of acute GI-GVHD remains subject to controversy.…”

“…New PET tracers targeting specific targets are under clinical investigation in other settings and might be used more specifically than 18 F-FDG in GI-GVHD. Washington et al 16 demonstrated that the crypt cell apoptosis was one of the histological hallmark of GI-GVHD. Thus, apoptotic cells might be considered as a good target to improve Sp of PET imaging in GI-GVHD.…”

Prospective evaluation for upper gastrointestinal tract acute graft-versus-host disease after hematopoietic stem cell transplantation

“…Several investigators have reported GVHD-like histopathologic findings in immunodeficiency states including HIV infection, common variable immunodeficiency, and severe T cell deficiency, and also following renal transplantation. 7,[21][22][23] Hematopoietic stem cell transplantation can lead to immunodeficiency states due to myeloablative conditioning regimens or use of immunosuppressants. It is possible that GVHD-like histologic changes are related to immunodeficiency in some of our asymptomatic patients.…”

“…[1][2][3][4][5][6][7][8] It has been suggested that clinical features of GVHD differ by geographic area or among races because of different immunogenetic backgrounds. [11][12][13][14] Therefore, the clinical significance of upper GI GVHD in previous reports may not necessarily apply to patients outside the United States.…”

Peptic ulcer disease in children

“…More recently, the stomach has been shown to be an important area for the histological diagnosis of gastrointestinal GVHD even when diarrhoea is the main symptom and the small bowel is more damaged. 91,92 Chronic GVHD rarely involves the stomach.…”