Consensus on the histopathological evaluation of liver biopsies from patients following allogeneic hematopoietic cell transplantation

Abstract

After allogeneic hematopoietic cell transplantation (alloHCT) liver biopsy is performed for enigmatic liver disorders when noninvasive diagnostic steps have failed in establishing a definitive diagnosis. This document provides an updated consensus on the prerequisites for proper evaluation of liver biopsies in alloHCT patients and the histological diagnostic criteria for liver graft-versus-host disease (GvHD). The Working Group's recommendations for the histological diagnosis of liver GvHD were derived from the peer-reviewed literature and from the consensus diagnosis of a total of 30 coded liver biopsies. Acceptance of the recommendations was tested by a survey distributed to all HCT centers in Austria, Germany and Switzerland. Consensus was achieved for biopsy indications, methods of sample acquisition and processing, reporting and interpretation of biopsy findings. As GvHD is variably treated and the treatment modalities have changed over time, the panel endorses the use of more frequent biopsies in clinical studies in order to improve the present challenging clinical and diagnostic situation.

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

“…This schema separates the objective histological findings in the microscopic description from the subjective global interpretation and allows the diagnosis to be expressed as a continuum rather than “yes” or “no.” This approach has been subjected to study for reproducibility by a European consortium [148]. Based on this study, we recommend reducing the categories for the diagnosis of GVHD from four to three: Not GVHD, Possible GVHD and Likely GVHD (Table 2).…”

Consensus diagnostic histopathological criteria for acute gastrointestinal graft versus host disease improve interobserver reproducibility

“…However, in early cases with subtle features as well as in cases with heterogeneous features, subjective interpretation by individual pathologists may result in interindividual differences in both diagnosis and grading. Discrepancies may be marginal when pathologists from single or cooperating institutions have an opportunity to adjust each other's diagnostic criteria [5,20], but when there is no such exchange of experience, they could more profoundly affect inter-institutional reproducibility [19,24]. Additionally, other diagnostic considerations include infection [2,3] and toxic side effects of applied therapies [11,18], which are both frequent in patients after HCT and could mimic GvHD histologically as well as clinically.…”

Pathology of Gastrointestinal and Liver Complications of Hematopoietic Stem Cell Transplantation

“…16,84 Apoptotic biliary epithelial cells, however, are infrequent. 11, 85 Lymphocytic infiltration into the biliary epithelium is commonly seen, but is generally mild ( Figure 6, A). 84,86 The minimal bile duct alterations required for the diagnosis of hepatic GVHD remain to be determined.…”

“…Grading/scoring of GVHD on a liver biopsy is not recommended, but bile duct loss should be mentioned in the pathology report. 11, 85 The reader is referred to the Table for the standardized reporting of liver GVHD.…”