Establishment of solid organ transplantation as a routine procedure has required parallel progress in multiple medical and basic science disciplines. In the last 3 decades, the discovery of better immunosuppressive drugs and treatment of infectious complications had led to progressive improvement in clinical outcomes with remarkable prolongation of graft survival. Since the 1950s, systematic evaluation of transplanted tissue has provided essential information that has helped shape the treatment protocols in use today.
In the early period, when graft rejection was the rule rather than the exception, pathological studies could only document the histological features of catastrophic graft loss. Subsequently, accumulation of morphological knowledge has led to a much better understanding of rejection reactions and to the development of sophisticated morphological classifications, such as the Banff schema.
Although acknowledging the complexity of the immune system, allograft rejection is schematically divided into antibody-mediated (AMR) and cell-mediated (CMR) rejections.
Antibody-mediated rejection results from circulating antidonor antibodies which—in conjunction with complement—target vascular structures with a predilection for the microvasculature leading to capillary inflammation (capillaritis) and injury. Staining for the C4d complement fragment helps identify cases of AMR in kidney, heart, and pancreas transplants by demonstrating this component in the microvasculature.
Cell-mediated rejection, on the other hand, is characterized by interstitial accumulation of inflammatory cells including abundant T-cell infiltrates that preferentially target the epithelium (renal tubules, bronchial epithelium, bile ducts, and intestinal crypts) but can also involve vascular structures. Based on their radically different pathogenesis, AMR and CMR in their pure forms can be distinguished on morphological grounds alone; however, it is not uncommon for these processes to occur simultaneously, greatly complicating the morphological diagnosis. Great advances have been made in recent years for the recognition of the clinicopathological features of AMR, and for that reason, AMR in the kidney (L. Cornell), heart (P. Revelo), and pancreas (R. Munivenkatappa) are specifically featured in this issue.
Tubulointerstitial infiltrates that do not fulfill the Banff criteria for acute CMR are classified as “borderline.” This morphological entity, which has engendered controversy since the termed was first coined in the early 1990s, is discussed in detail with emphasis on practical diagnostic aspects (L. Lin and P. Randhawa).
Owing to its evolving complexity and increasing demands in expertise and experience, transplantation pathology is often considered as a subspecialty of anatomic pathology in its own right. On the other hand, pathologists dealing with any type of allograft biopsies can attest to the very significant overlap of pathological processes that involve both transplanted and native organs. In the current issue three articles exemplify this situation: focal segmental glomerulosclerosis (M. Troxell), autoimmune hepatitis (W. Twaddell), and atypical mesothelial proliferations in lung biopsies (T. Huebner).
Finally, polyomavirus allograft nephropathy, which continues to be an important cause of premature renal allograft failure, is discussed in detail in one article with emphasis on the differential diagnosis from other viral infections (E. Bracamonte).
Although only a limited number of topics can be discussed in one issue, this group of articles was selected with the purpose of highlighting some of the currently important areas in the field. I hope these study cases can be seen as a springboard for further learning, particularly for pathologists less familiar with transplantation pathology.