Clinical Applications of Bone Marrow CD34 Immunohistochemistry (BM CD34 IHC) Assay: International Council for Standardization in Hematology (ICSH) Guidelines

Introduction: Investigation of bone marrow (BM) trephine biopsies and/or clot sections by CD34 immunohistochemistry (IHC) testing has been used by pathologists for several decades, and its clinical value has been well established with QBEND10 being the most frequently used primary antibody (Ab) clone. However, most other parameters related to the IHC protocol as well as the readout vary widely between clinical laboratories and in the published literature. The ICSH Working Group having reviewed the published evidence has established guidelines that will help to harmonize performance and reporting of CD34 IHC on BM biopsies.

Methods: The methodology is based on the published "guidelines for guidelines" (GRADE, AGREE) with modifications to the specific laboratory medicine environment and to specific key questions. Review of the published literature resulted in 49 articles relevant to clinical applications of the BM CD34 IHC. Five key questions were addressed including testing indications, technical performance, readout methodology, terminology, and reporting.

Results: A total of 23 guidelines were grouped according to the key questions.

Conclusion: BM CD34 IHC testing is complex with both the protocol and the pathologist's readout requiring validation to ensure reported results are reproducible and accurate. The readout/interpretation must be adapted to a specific purpose of the assay (clinicopathological question) and the type and overall sample quality. Standardized terminology and reporting are essential if CD34 IHC assay is being used for clinical diagnostics.