Graft-versus-host disease (GVHD) is a significant complication of allogeneic hematopoietic stem cell transplantation, arising when donor-derived immune cells recognize recipient tissues as foreign and initiate an immune-mediated attack. The primary target organs affected by GVHD are the skin, liver, and gastrointestinal (GI) tract [1]. The incidence of GVHD varies widely depending on donor compatibility. Up to 50 % of transplants involving human leukocyte antigen (HLA)- matched donors have acute GVHD, and the rate is even higher in cases with mismatched donors [[2], [3], [4]]. Chronic GVHD affects approximately 30 % to 70 % of recipients [5,6]. Given the prevalence of GVHD, biopsies to assess for GI GVHD are commonly encountered by pathologists.

Diagnosing GI GVHD is particularly challenging due to its variable clinical presentations, non-specific and overlapping histologic features, and broad differential diagnosis. Diagnosis typically requires clinical, histological, and endoscopic correlation. Histologically, GI GVHD is characterized by epithelial cell apoptosis within the crypts, crypt loss, and variable inflammatory infiltrates. However, these findings are not specific as similar changes can be observed in other conditions, including infections, e.g., cytomegalovirus (CMV), and drug-induced injury, complicating histologic diagnosis [5].

Some guidelines for histologic diagnosis of GI GVHD have been developed, but the adoption of these guidelines is inconsistent [5,7]. Various diagnostic thresholds, such as the number of apoptotic bodies per crypt, have been proposed to help distinguish GI GVHD from other mimicking conditions. Unfortunately, there is no universal consensus on these thresholds, leading to variability in diagnostic criteria [5,7]. Over the years, multiple histologic grading systems for GVHD have been developed, with the Lerner system being the most commonly utilized. Despite these efforts, substantial inter-observer variability remains, particularly in lower-grade GVHD, where subtle findings contribute to inconsistent interpretations, and most grading systems fail to provide clinical prognostication [8,9].

Our study aimed to conduct a survey to gain insights into current practices for diagnosing histologic gastrointestinal (GI) graft-versus-host disease (GVHD) and to explore the diagnostic challenges pathologists encounter in routine clinical practice.