To transplantation pathologists, there are still many difficulties and controversies in diagnosing and grading lung transplant rejection . The transbronchial lung puncture biopsy is one of the accepted standards. Histological results are widely used in diagnosing and monitoring pulmonary graft rejection. In clinic, it is reasonable to modify the therapeutic strategy according to histological report. Generally, patients with positive histological results demonstrate good response to immunotherapy. Interestingly, patients with symptoms but negative biopsy results also benefit from immunotherapy such as intensive corticosteroid therapy. The reasons for this phenomenon are yet to be known. However, this phenomenon indicates that, to a certain extent, there may be potential ongoing rejection that is not discovered . Therefore, a more reliable method to diagnose the rejection in transplanted lung is warranted.
Although the International Society for Heart and Lung Transplantation has published detailed classification of lung graft rejection, there are still many difficulties in clinical practice. This guideline emphasizes that at least five gassy lung tissue samples are needed for diagnosis. The diagnostic accuracy can be improved with increasing biopsy frequency which, however, may cause more complications associated with needle biopsy. Furthermore, perivascular mononuclear cell infiltration is not specific for acute rejection. The same changes also happen in other diseases, such as cytomegalovirus infection and post-transplantation lymphopoiesis, and thus lead to difficult rejection diagnosis. It is of great importance that pathologic diagnosis for the same lesion varies among different centers and even among pathologists in the same center [3–5]. Given all that, there are inaccuracy and uncertainty during the diagnostic process for lung transplant rejection.
A number of factors contribute to this situation. Insufficient graft tissue collection by needle biopsy, limited diagnostic information from routine H&E staining, pathologists’ different perceptions about the standard of rejection status and selective bias with diagnosis all affect diagnostic accuracy. Recently, Fabio Tavora and colleagues studied lung tissue sections by immunohistochemistry (IHC). They found that T lymphocyte infiltration was helpful to diagnosing and grading rejection . Additionally, further information from other methods can also help improve diagnostic accuracy.
In this study, histological changes in the whole transplanted lungs, instead of graft tissues harvested by needle biopsy, were examined, which enabled us to understand the full extent of rejection. We also performed CD3, CD4 and CD8 IHC to detect the variation of T cells in lung grafts, and evaluated the value of quantitating interstitial T lymphocytes by IHC in rejection diagnosis and grading. We found that T cell IHC may provide additional information to avoid interobserver variability.