With the introduction of cyclosporine during the 1980s, transplantation has emerged as an effec-tive therapy for a large number of patients with severe kidney, heart, lung, liver, and hematopoi-etic diseases. As the transplant population grows, surgical pathologists will encounter an increasing number of specimens from transplant recipients. These surgical pathologists play a pivotal role in the multidisciplinary management of transplant recipients.
Handling a specimen from a transplant recipi-ent is in many ways guided by an understanding of the complications associated with transplanta-tion. It is therefore useful to keep in mind the pathology unique to transplantation when han-dling a biopsy or resection specimen from a trans-plant recipient. These unique situations include
Complications related to the primary dis-ease for which the transplant was performed. Specifically, samples must be handled in a way that allows one to diagnose recurrence of the patient’s underlying pathology. For example, although electron microscopy and immuno-fluorescence are generally not helpful for es-tablishing a diagnosis of acute renal allograft rejection, they can be essential for establishing the diagnosis of a recurrent glomerular disease.
Complications of the surgical procedure itself. For example, arterial stenosis in the donor seg-ment of an artery is often due to accelerated graft arteriosclerosis (chronic rejection), whereas stric-ture at the anastomotic site may be related to the surgery. (3) Complications of acute rejection.
Acute rejection can develop rapidly and have a devastating impact on the graft and patient sur-vival. Biopsies from transplant recipients are therefore often rushed. Failure to recognize the urgent nature of most transplant biopsies can result in delayed therapy, which can have a dev-astating impact on patient management. (4) In-fectious complications. Infections in transplant recipients are remarkable for the diversity and multiplicity of the organisms involved. Multiple cultures and the up-front ordering of special stains to detect a variety of infectious agents (fungi, bacteria, viruses) are often indicated.
Complications related to the patient’s clini-cal treatment. In addition to a host of immuno-suppressive agents, transplant recipients are often treated with a variable pharmacopoeia of drugs. They can cause a host of pathologies that may mimic or be superimposed on rejection. The appropriate management of a specimen from a transplant recipient therefore includes a thor-ough understanding of the patient’s clinical history, including a detailed record of the medica-tions the patient is receiving.
In addition to these five general considera-tions, there are a number of organ-specific guide-lines for handling surgical pathology specimens from transplant recipients. These guidelines are frequently updated; as of January 2003, they in-cluded the following.
Heart.The International Society for Heart andLung Transplantation (ISHLT) established a “work-ing formulation” for grading heart allograft rejection in 1990.4This working formulation includes a number of technical considerations. Because acute allograft rejection can be focal, the ISHLT standard grading system requires four to six undivided pieces of myocardium. The indi-vidual handling these biopsy specimens should document the number of pieces received. The tissue should be fixed in 10% buffered formalin and paraffin-embedded. Once processed, a mini-mum of three step levels should be prepared through the block with at least three sections per level. The slides should be stained routinely with hematoxylin and eosin and one slide stained with a connective tissue stain such as a Masson’s trichrome. In addition, during the first 6 weeks after transplantation at least one piece should be placed in OCT and fresh-frozen for possible immunofluorescence examination to rule out antibody-mediated rejection.
Kidney.The “Banff” criteria for grading renalallograft rejection were established in 1991.6 These criteria have been periodically modified, and the current Banff ’97 guidelines provide spe-cific recommendations for the handling of biopsy specimens from renal transplant recipients.7 The recommendation is that seven slides be prepared containing multiple sequential sections. Three of the seven should be stained with hematoxylin and eosin, three with periodic acid–Schiff or silver stains, and one with a trichrome stain. It is also recommended that these sections be pre-pared at 3 to 4 mm.
Lung.In 1996 the ISHLT presented a revisionof the 1990 working formulation for the grading of lung allograft rejection.8This revision included the following recommendations for handling transplant lung biopsies from lung transplant re-cipients. At a minimum, sections of three levels should be stained with hematoxylin and eosin. In addition, one level should be stained with a connective tissue stain to evaluate the biopsy for the presence of submucosal fibrosis associated with the development of bronchiolitis obliterans, and one level should be silver stained for fungi/Pneumocystis. In addition, the ISHLT group em-phasized that all biopsy specimens should be studied by pathologists with full knowledge of the native recipient disease and the results of the last biopsy and current bronchioloalveolar lavage.
Liver.The Banff system for grading liver allo-graft rejection was presented in 1997.Their recommendations included that at least two hematoxylin and eosin-stained sections from at least two levels should be prepared from each needle core biopsy.
The criteria for evaluating transplant biopsy specimens for rejection are beyond the scope of this book, but there are some centralized resources. For example, the University of Pitts-burgh’s website contains both the current diag-nostic criteria and standardized templates for evaluating biopsies from transplant recipients (http://tpis.upmc.edu/).
· Evidence of recurrence of a patient’s primary or underlying disease
· Any complications related to the transplant procedure itself
· Degree of rejection (both acute and chronic)
· Presence of any infections
· Presence of any neoplasms, particularly post-transplant lymphoproliferative disease
· Presence of any complications related to ther-apy (drug toxicity)
· When appropriate sampling has not occurred, it is essential to note in the pathology report that the biopsy findings may not be fully repre-sentative of the changes in the graft.