Liver allograft pathology: approach to interpretation of needle biopsies with clinicopathological correlation

Abstract

The spectrum of diseases encountered in post-transplant liver pathology biopsies is broad. In this review, these have been divided as belonging to one of three categories: (1) new-onset/de novo post-transplant abnormalities (early and late), (2) rejection, and (3) recurrence of original disease. The clinical and pathological features of the entities making up each category, with the relevant differential diagnosis and overlaps between and within these groups, are discussed and illustrated. Recurrent or de novo neoplasms make up a fourth category not included in this review. Early new-onset conditions are mostly related to surgical complications, donor factors and ischaemia to the graft. These include reperfusion/preservation injury, lipopeliosis, small-for-size-syndrome, biliary sludge syndrome and hepatic artery thrombosis. The various forms of rejection (cellular, chronic, antibody-mediated, and late atypical rejection) are detailed. Most chronic liver diseases can and do recur in the graft. They may display features that overlap with de novo conditions (eg, primary sclerosing cholangitis versus chronic rejection). As with most cases of allograft biopsy interpretation, accurate diagnosis rests with careful correlation of histological features with clinical, imaging and laboratory findings, and often comparison with previous sequential and follow-up biopsies. Late-onset new diseases include biliary strictures, idiopathic chronic hepatitis and de novo autoimmune hepatitis, among others. This review provides a practical approach to the interpretation of these challenging biopsies. Selected difficult scenarios or conundrums are identified and discussed in the relevant sections.

Infiltrative (sinusoidal) and hepatitic patterns of injury in acute cellular rejection in liver allograft with clinical implications

“…The typical histopathological features contributing to final acute cellular rejection severity grade have been well described, 3,5 which dictate appropriate therapeutic interventions. 1 In summary, these features include portal-based mixed inflammation consisting of activated lymphocytes, eosinophils, and a few plasma cells.…”

“…6,8,9 This variant in our and others' experience typically occurs www.modernpathology.org beyond the first year of transplant, and is characterized by a hepatitic, plasma cell-rich, perivenularaccentuated histologic picture and relative steroid resistance, when seen in adult population. 5,8,9 Two other features of acute cellular rejection have been recognized but are rarely reported or studied to determine their clinical relevance. These patterns either demonstrate active sinusoidal infiltration or hepatitic component, different from plasma cell hepatitis both in histopathological and clinical features.…”

“…Pathologists have recognized additional patterns of injury in acute cellular rejection after liver transplantation, not incorporated in the Banff criteria. 1,[5][6][7] One such pattern is plasma cell hepatitis variant, variably referred to as de novo autoimmune hepatitis, hepatitic/atypical late-onset acute cellular rejection, or isolated central perivenulitis. 6,8,9 This variant in our and others' experience typically occurs www.modernpathology.org beyond the first year of transplant, and is characterized by a hepatitic, plasma cell-rich, perivenularaccentuated histologic picture and relative steroid resistance, when seen in adult population.…”

Individual Stability of Stereotypes of Immune Reacting and Modern Possibilities of Their Diagnostic in Organ Transplantation (Immune-Physiological Analysis of a Problem)

“…Понятие функционального модуля было введено [56], когда стало очевидно, что прежняя теория ре-гуляции иммунного ответа, определяющую роль в которой играло отношение Th1/Th2-хелперов, рух-нула под напором новых фактов, полученных сов-ременными методами исследования. Субпопуляци-онный состав Т-хелперных клеток оказался намного больше, и возможно, что они еще не все охарактери-зованы к настоящему времени.…”

“…Кроме того, среди лимфоцитов с маркером CD4 находят субпопуляции, имеющие в цитозоле гранзимы и перфорин [59], т. е. фактически CD4-киллеры. Все эти находки органично привели разработчиков функционального диагностического модуля [56] к возникновению потребности совмес-тить каждый фенотип Т-клеток или каждый Т-лим-фоцитарный модуль с выполняемой ими специфи-ческой функцией (реакцией) в иммунном ответе, обеспечивающей или регуляторную функцию (на-пример, Т или В-лимфоцитарную помощь или суп-рессию), или эффекторную функцию против различ-ных типов патогенов (инфекционных агентов) [56]. Описание функции каждого модуля потребовало включения молекулярных и клеточных характерис-тик его, в терминах поляризованных маркеров, та-ких как индуцирующие дифференцировку и созре-вание цитокины, факторы транскрипции, рецепторы хоуминга, клетки мишени, а также перекрестная связь с другими иммунными или тканевыми клетка-ми.…”