Transplantation and Hepatic Pathology University of Pittsburgh Medical Center November, 2007

Transplantation and Hepatic Pathology University of Pittsburgh Medical Center November, 2007

Resident Handbook Division of Transplantation and Hepatic Pathology University of Pittsburgh Medical Center November, 2007 For private use of residents only- not for public distribution Table of Contents Anatomic Transplantation Pathology Rotation Clinical Responsibilities of the Division ........................................................3 Categorizations of Specimens and Structure of Signout.................................3 Resident Responsibilities................................................................................4 Learning Resources.........................................................................................4 Transplantation Pathology on the World-Wide Web......................................4 Weekly Schedule ............................................................................................6 Staff Locations and Telephone Numbers........................................................7 Background Articles Landmarks in Transplantation ........................................................................8 Trends in Organ Donation and Transplantation US 1996-2005.....................18 Perspectives in Organ Preservation………....................................................26 Transplant Tolerance- Editorial……………………………………….…….36 Kidney Grading Systems Banff 2005 Update……………………….....................................................42 Banff 97 Components (I t v g etc.) ................................................................44 Readings Banff 05 Meeting Report………………………………………...................47 Role of Donor Kidney Biopsies in Renal Transplantation ...........................56 BK Virus Infection Overview and Update……………………. ..................61 Recurrent Glomerulonephritis…………………………………………...…67 Liver Grading Systems Banff Schema for Acute Liver Allograft Rejection......................................75 Banff Rejection Activity Index.....................................................................76 Banff Schema for Chronic Liver Rejection .................................................78 Modified Hepatitis Activity Index ...............................................................80 Autoimmune Hepatitis Scoring System 1999...............................................82 Staging and Grading Disease Activity in Fatty Liver Disease......................85 Readings Banff Schema for Grading Liver Allograft Rejection .................................87 Liver Biopsy in Late Allograft Dysfunction.................................................93 Heart Grading System Standardized Cardiac Biopsy Grading.......................................................106 Readings Working Formulation for Grading Cardiac Allograft Rejection ...............108 Update on Cardiac Transplant Pathology……...........................................115 Page 1 Lung Grading System Revised Working Formulation for Lung Transplant Rejection .................138 Readings Working Formulation for Grading Lung Transplant Rejection..................140 Bronchiolitis obliterans update ..................................................................156 Lung Transplant Curent Status and Challenges………………….……….170 Pancreas Grading System Grading of Acute Pancreas Allograft Rejection ........................................177 Readings Evaluation of Pancreas Transplant Needle Biopsy.....................................178 Histology of Pancreas Allograft Loss ........................................................195 Long-term Management of Pancreas Transplantation……………………203 Intestine Readings Pathology of Human Intestinal Transplants...............................................216 Current Status of Small Bowel Transplantation ........................................224 Posttransplant Lymphoproliferative Disorders and Neoplasia Grading Systems WHO Classification....................................................................................230 Readings Clinicopathologic Spectrum of PTLD……………………........................232 Tumors and Solid Organ Transplantation……………………….………..242 Page 2 Anatomic Transplantation Pathology Rotation Clinical Responsibilities of the Division The Division of Transplantation Pathology is responsible for pathology support for the Thomas E. Starzl Transplantation Institute. This includes evaluation of primary recipient disease, resected donor organs, and resected allografts. Evaluation of post-transplant biopsies for rejection and other causes of graft dysfunction comprise the main daily workload. This Division also evaluates biopsies of native organs from transplant patients and handles all native liver biopsy specimens. Some native kidney biopsies are also performed in this Division; these are not incorporated into resident rotations. The Division conducts six separate weekly clinicopathologic conferences to ensure quality control of biopsy results and to keep an open channel of communication between the clinical physicians and transplantation pathologists. In addition, there are two intradivisional quality assurance slide review conferences per week, to ensure agreement among the pathologists in grading rejection and to discuss interesting and/or difficult cases. Categorization of Specimens and Structure of “Signout” Specimens that come to the Division for review fall into five categories. They include “Bigs,” of which the majority are diseased native organs removed at the time of transplantation; “Quicks,” mainly biopsies such as surveillance gastrointestinal biopsies; native liver biopsies; skin biopsies for GVHD; lymph node biopsies to evaluate for PTLD, etc; “Stats,” mainly organ allografts biopsies used to monitor rejection; and “Consults” which consist of outside slides submitted for review. The Division also handles a portion of medical kidney biopsies. The priority ranking the specimens receive, the structure of signout and reporting of the results are designed to best serve the transplant patients and clinical physicians involved in their care. “Stat” specimens receive the highest priority. These biopsies are submitted to Pathology before 11 AM and permanent H&E slides are ready for review by 2:30-3:30 PM the same day. “Quicks” and “Consults” are next in priority, and have a one day or less turnaround whenever possible. “Bigs” receive the next highest priority, and are signed out as expeditiously as possible. Native kidney biopsy results are transmitted to physicians in a provisional manner and signed out as special studies become available. The staff service responsibilities are divided as follows: One staff pathologist takes weekly responsibility for the Quicks and Stats, and also handles any frozens that occur during the workday. This rotation runs from 7:30 AM until 5 PM, Monday through Friday. A second pathologist takes responsibility for all Bigs and Consults for this time period. This second pathologist covers nightly call during the week, and additionally covers the entire service for the weekend. The services are staggered in the following way: Saturday and Sunday, pathologist A covers everything. Monday through Friday, Pathologist A covers Bigs/Consults/Night call and Pathologist B covers Quicks and Stats. Saturday and Sunday, Pathologist C covers everything. Monday through Friday Pathologist C covers Bigs/Consults/Night call and Pathologist D covers Page 3 Quicks and Stats…and so forth. Holidays are treated like any other day of the week or weekend. The turnover times between shifts are 7:30 AM and 5:00 PM. Resident Responsibilities The level of resident responsibility depends upon three factors: the level of training, competence, and the desire to assume responsibility. PGY-1 level residents are generally responsible for all “big” cases, including gross evaluation, organization, and review of the slides and finally, signout with the pathologists. The gross processing of cases can usually be accomplished by mid-morning or early afternoon. The resident is expected to sit in on signouts and to participate according to the level of his/her experience. When more than one resident is on rotation, it is the residents’ responsibility to divide the workload between them. Residents >PGY-1 may want to assume more responsibility by reviewing “quicks” and “consults” to enhance learning opportunities. A satisfactory division of labor in the past has been for the PGY-1 to assume responsibilities for “bigs”and >PGY-1 to take “quicks” and “consults.” The cases are then shared at signout time. Unfortunately, because of the urgency of Stat specimens, it is often not possible for the residents to review the cases before the official signout. The pathologist and resident review the cases together on a daily basis, and the preliminary results are recorded daily in the “Stat Book,” immediately outside the signout room. A recent change has been to deliver the “quicks” at 10:30 AM. Depending upon the signout time, this may give the resident an opportunity to review these cases upon delivery. The “big” specimens offer excellent learning opportunities in inflammatory and neoplastic liver disease and cardiovascular pathology. Most renal disease tends to be endstage and native kidneys are often not resected at the time of transplant, in contrast to other organs. “Consult” cases offer excellent review of late posttransplant liver, kidney, and heart pathology, and review of native liver disease. The resident will be provided with desk space in Transplantation Pathology, and should remain “on-site” during the rotation. If the resident will be away from the Division, it is his/her

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