Banff 2022 Liver Group Meeting report: Monitoring long-term allograft health.

The Banff Working Group on Liver Allograft Pathology met in September 2022. Participants included hepatologists, surgeons, pathologists, immunologists, and histocompatibility specialists. Presentations and discussions focused on the evaluation of long-term allograft health, including noninvasive and tissue monitoring, immunosuppression optimization, and long-term structural changes. Potential revision of the rejection classification scheme to better accommodate and communicate late T cell-mediated rejection patterns and related structural changes, such as nodular regenerative hyperplasia, were discussed. Improved stratification of long-term maintenance immunosuppression to match the heterogeneity of patient settings will be central to improving long-term patient survival. Such personalized therapeutics are in turn contingent on a better understanding and monitoring of allograft status within a rational decision-making approach, likely to be facilitated in implementation with emerging decision-support tools. Proposed revisions to rejection classification emerging from the meeting include the incorporation of interface hepatitis and fibrosis staging. These will be opened to online testing, modified accordingly, and subject to consensus discussion leading up to the next Banff conference.

Donor plasmacytoid dendritic cells modulate effector and regulatory T cell responses in mouse spontaneous liver transplant tolerance.

We assessed the role of donor liver non-conventional plasmacytoid dendritic cells (pDCs) in spontaneous liver transplant tolerance in a fully MHC-mismatched (C57BL/6 (H2b ) to C3H (H2k )) mouse model. Compared with spleen pDCs, liver pDCs expressed higher levels of DNAX-activating protein of 12 kDa and its co-receptor, triggering receptor expressed by myeloid cells 2, and higher ratios of programed death ligand-1 (PD-L1):costimulatory CD80/CD86 in the steady state and after Toll-like receptor 9 ligation. Moreover, liver pDCs potently suppressed allogeneic CD4+ and CD8+ T cell proliferative responses. Survival of pDC-depleted livers was much poorer (median survival time: 25 days) than that of either untreated donor livers or pDC-depleted syngeneic donor livers that survived indefinitely. Numbers of forkhead box p3 (FoxP3)+ regulatory T cells in grafts and mesenteric lymph nodes of mice given pDC-depleted allogeneic livers were reduced significantly compared with those in recipients of untreated livers. Graft-infiltrating CD8+ T cells with an exhausted phenotype (programed cell death protein 1+ , T cell immunoglobulin and mucin domain-containing protein 3+ ) were also reduced in recipients of pDC-depleted livers. PD1-PD-L1 pathway blockade reversed the reduction in exhausted T cells. These novel observations link immunoregulatory functions of liver interstitial pDCs, alloreactive T cell exhaustion, and spontaneous liver transplant tolerance.

Heterotopic Transplantation of Allogeneic Vertical Rectus Abdominis Myocutaneous Flaps in Miniature Swine.

BACKGROUND: Vascularized composite tissue allotransplantation (VCA) opens new possibilities for reconstruction of complex tissue defects, including upper extremity and facial transplantation. The main challenges in VCA transplantation are the side effects of long-term immunosuppression and chronic graft rejection. Translational preclinical animal models are crucial for VCA research to improve clinical outcomes and to study underlying immunologic mechanisms. Herein, we describe a novel, large animal, non-bone-bearing VCA model in inbred, swine leukocyte antigen-typed miniature swine. METHODS: Transplantation of vertical rectus abdominis myocutaneous (VRAM) flaps was performed between fully swine leukocyte antigen-mismatched miniature swine. The flaps were transferred to the posterolateral aspect of the neck of recipients and anastomosed to the common carotid artery and internal jugular vein. Different immunosuppressive drug regimens were used. Clinical graft evaluation was performed daily, and punch biopsies were taken for histology. RESULTS: Ten VRAM transplants were performed. The mean ischemia time was 89.4 min (SD ± 47), mean pedicle length 7.5 cm (SD ± 2), mean venous diameter 2.5 mm (SD ± 0.4), and mean arterial diameter 2.2 mm (SD ± 0.3). Follow-up demonstrated good correlation between clinical appearance and progression of graft rejection confirmed by histologic assessment. Complications were intraoperative cardiac arrest in one recipient and one flap loss due to venous compromise. CONCLUSIONS: VRAM transplantation in miniature swine is an appropriate preclinical VCA model, with the advantage of good clinical and histologic correlation during the course of rejection, as well as easy access to the graft. The availability of inbred, haplotyped animals allows studies across different major histocompatibility complex barriers in a non-bone-bearing VCA.

Neutrophil extracellular traps promote inflammation and development of hepatocellular carcinoma in nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is a progressive, inflammatory form of fatty liver disease. It is the most rapidly rising risk factor for the development of hepatocellular carcinoma (HCC), which can arise in NASH with or without cirrhosis. The inflammatory signals promoting the progression of NASH to HCC remain largely unknown. The propensity of neutrophils to expel decondensed chromatin embedded with inflammatory proteins, known as neutrophil extracellular traps (NETs), has been shown to be important in chronic inflammatory conditions and in cancer progression. In this study, we asked whether NET formation occurs in NASH and contributes to the progression of HCC. We found elevated levels of a NET marker in serum of patients with NASH. In livers from STAM mice (NASH induced by neonatal streptozotocin and high-fat diet), early neutrophil infiltration and NET formation were seen, followed by an influx of monocyte-derived macrophages, production of inflammatory cytokines, and progression of HCC. Inhibiting NET formation, through treatment with deoxyribonuclease (DNase) or using mice knocked out for peptidyl arginine deaminase type IV (PAD4-/- ), did not affect the development of a fatty liver but altered the consequent pattern of liver inflammation, which ultimately resulted in decreased tumor growth. Mechanistically, we found that commonly elevated free fatty acids stimulate NET formation in vitro. CONCLUSION: Our findings implicate NETs in the protumorigenic inflammatory environment in NASH, suggesting that their elimination may reduce the progression of liver cancer in NASH. (Hepatology 2018).

Value of Texture Analysis on Gadoxetic Acid-Enhanced MRI for Differentiating Hepatocellular Adenoma From Focal Nodular Hyperplasia.

OBJECTIVE: The objective of our study was to assess the diagnostic performance of texture analysis (TA) on gadoxetic acid-enhanced MR images for differentiation of hepatocellular adenoma (HCA) from focal nodular hyperplasia (FNH). MATERIALS AND METHODS: This study included 40 patients (39 women and one man) with 51 HCAs and 28 patients (27 women and one man) with 32 FNH lesions. All lesions were histologically proven with preoperative MRI performed with gadoxetic acid. Two readers reviewed all the imaging sequences to assess the qualitative MRI characteristics. The T2-weighted fast spin-echo, hepatic arterial phase (HAP), and hepatobiliary phase (HBP) sequences were used for TA. Textural features were extracted using commercially available software (TexRAD). The differences in distributions of TA parameters of FNHs and HCAs were assessed using the Mann-Whitney U test. Area under the ROC curve (AUROC) values were calculated for statistically significant features. A logistic regression analysis was conducted to explore the added value of TA. A p value < 0.002 was considered statistically significant after Bonferroni correction for multiple comparisons. RESULTS: Multiple TA parameters showed a statistically different distribution in HCA and FNH including skewness on T2-weighted imaging, skewness on HAP imaging, skewness on HBP imaging, and entropy on HBP imaging (p < 0.001). Skewness on HBP imaging showed the largest AUROC (0.869; 95% CI, 0.777-0.933). A skewness value on HBP imaging of greater than -0.06 had a sensitivity of 72.5% and a specificity of 90.6% for the diagnosis of HCA. Six of 51 (11.8%) HCAs lacked hypointensity on HBP imaging. A binary logistic regression analysis including hypointensity on HBP imaging and the statistically significant TA parameters yielded an AUROC of 0.979 for the diagnosis of HCA and correctly predicted 96.4% of the lesions. CONCLUSION: TA may be of added value for the diagnosis of atypical HCA presenting without hypointensity on HBP imaging.

Use of percutaneous imaging-guided biopsy for Liver Imaging and Reporting Data System (LI-RADS) observations: A retrospective study from two liver transplant centers.

Since the adoption of guidelines for the non-invasive imaging diagnosis of hepatocellular carcinoma (HCC), the need for sampling of a lesion in cirrhosis has decreased. We aimed to retrospectively investigate the use of percutaneous imaging-guided biopsy for LI-RADS observations in cirrhosis in two large liver transplant centers. A review of the pathology database in the two Institutions (Institution A, Institution B) was conducted to identify patients that underwent percutaneous imaging-guided biopsy for a liver lesion in the interval time 01/01/2015-12/312020. Liver observations on pre-procedure contrast-enhanced CT or MRI were classified according to LI-RADS v2018. Among the 728 patients who underwent imaging guided biopsy of a liver lesion in Institution A, and among the 749 patients who underwent imaging guided biopsy of a liver lesion in Institution B, respectively 50 (6.8 %) and 16 (2.1 %) were cirrhotic with available pre-procedural contrast-enhanced CT or MRI. A total of 67 lesions were biopsied. 30/67 (45 %) biopsied observations were classified as LR-M. 55/67 (82 %) biopsies were positive for malignancy at histopathology and among them 33 (60 %) were HCC. In conclusion, a small percentage of percutaneous, imaging-guided biopsies for liver lesions are performed in cirrhosis, and more frequently for LR-M observations.

Banff scoring of kidney allograft biopsies: "Manual" application vs software-assisted sign-out.

OBJECTIVES: Pathologists interpreting kidney allograft biopsies using the Banff system usually start by recording component scores (eg, i, t, cg) using histopathologic criteria committed to memory. Component scores are then melded into diagnoses using the same manual/mental processes. This approach to complex Banff rules during routine sign-out produces a lack of fidelity and needs improvement. METHODS: We constructed a web-based "smart template" (software-assisted sign-out) system that uniquely starts with upstream Banff-defined additional diagnostic parameters (eg, infection) and histopathologic criteria (eg, percent interstitial inflammation) collectively referred to as feeder data that is then translated into component scores and integrated into final diagnoses using software-encoded decision trees. RESULTS: Software-assisted sign-out enables pathologists to (1) accurately and uniformly apply Banff rules, thereby eliminating human inconsistencies (present in 25% of the cohort); (2) document areas of improvement; (3) show improved correlation with function; (4) examine t-Distributed Stochastic Neighbor Embedding clustering for diagnosis stratification; and (5) ready upstream incorporation of artificial intelligence-assisted scoring of biopsies. CONCLUSIONS: Compared with the legacy approach, software-assisted sign-out improves Banff accuracy and fidelity, more closely correlates with kidney function, is practical for routine clinical work and translational research studies, facilitates downstream integration with nonpathology data, and readies biopsy scoring for artificial intelligence algorithms.

Tacrolimus before CTLA4Ig and rapamycin promotes vascularized composite allograft survival in MGH miniature swine.

BACKGROUND: We evaluated the outcome of vertical rectus abdominus myocutaneous flap (VRAM) allotransplantation in a mini-pig model, using a combined co-stimulation blockade (Co-SB) and mechanistic target of rapamycin inhibition (mTORi)-based regimen, with or without preceding calcineurin inhibition (CNI). MATERIALS AND METHODS: VRAM allotransplants were performed between SLA-mismatched MGH miniature swine. Group A (n = 2) was treated continuously with the mTOR inhibitor rapamycin from day -1 in combination with the Co-SB agent cytotoxic T lymphocyte antigen 4-Ig (CTLA4-Ig) from post-operative day (POD) 0. In group B (n = 3), animals received tacrolimus daily from POD 0 to POD 13, followed by rapamycin daily from POD 7 and CTLA4-Ig weekly from POD 7-28. Graft rejection was determined by Banff criteria and host cellular and humoral immunity monitored. RESULTS: In group A, allografts developed grade-I acute rejection by POD 2 and POD 7, and reached grade-IV by POD 17 and POD 20, respectively. By contrast, in group B, two allografts demonstrated grade-I rejection on POD 30 and grade-IV on POD 74, while the third exhibited grade-I rejection starting on POD 50, though this animal had to be euthanized on POD 58 due to Pneumocystis jirovecii infection. Time-to-event incidence of grade-I rejection was significantly lower in group A compared to group B. During the first 3 weeks post-transplant, no significant differences in anti-donor immunity were observed between the groups. CONCLUSION: A short course of CNI, followed by combined Co-SB and mTORi significantly delays acute rejection of VRAM allografts in SLA-mismatched miniature swine.

Moderately Macrosteatotic Livers Have Acceptable Long-Term Outcomes but Higher Risk of Immediate Mortality.

BACKGROUND AND AIMS: Liver transplantation is the most effective treatment for end-stage liver disease (ESLD). Whether moderately macrosteatotic livers (30%-60%) represent a risk for worsened graft function is controversial. The uncertainty, in large part, is owing to the heterogeneous steatosis grading. Our aim was to determine the short- and long-term outcomes of moderately macrosteatotic allografts that were graded according to a standardized institutional protocol. METHODS: We performed a retrospective analysis of transplants performed between 1994 and 2014. All patients with allografts biopsied pretransplantation were included. Relevant donor and recipient variable were recorded. Moderately macrosteatotic livers were compared with mildly macrosteatotic and nonsteatotic livers. Primary outcomes of interest were patient survival at 90 days, 1 year, and 5 years. Cox regression analyses were carried out to compare survival between the 2 groups. RESULTS: We compared 65 allografts with moderate macrosteatosis and 810 with no or mild macrosteatosis. Patients with moderately macrosteatotic allografts were 2.69 times as likely to die within the first 90 days after transplant (75.1% vs 91.6% survival) after adjusting for donor age, donor race, recipient age, recipient race, recipient body mass index, recipient diabetes, presence of hepatocellular carcinoma, days on waitlist, Model for End-Stage Liver Disease (MELD) score at transplantation, cold ischemia time. However, for recipients who survive 90 days, moderately macrosteatotic allografts had comparable long-term survival. CONCLUSION: Our study shows that moderate macrosteatosis is a strong predictor of early but not late mortality. Further studies are needed to distinguish the specific cohort of patients for whom moderately macrosteatotic allografts will lead to acceptable outcomes.

Focal liver diseases in neonatal and pediatric liver transplant candidates: a pictorial essay.

The aim of this review is to present the wide spectrum of common and uncommon focal liver diseases affecting neonatal and pediatric liver transplant candidates, analyzed using ultrasonography (US), 16- or 64-multidetector row helical CT (MDCT) and 1.5-T magnetic resonance (MR) fast imaging. Correlation of imaging findings and explanted liver or histology is illustrated in representative cases. Associated uncommon congenital anomalies are shown.

Liver stiffness measurement in patients with nodular regenerative hyperplasia undergoing magnetic resonance elastography.

PURPOSE: Nodular regenerative hyperplasia (NRH) may mimic cirrhosis at imaging. We aim to investigate the effect of NRH on liver stiffness measurement (LSM) obtained with magnetic resonance elastography (MRE). METHODS: This retrospective, Institutional Review Board-approved study included 37 subjects with NRH (Group 1) and no or minimal fibrosis (F0-F1), a control group (Group 2) made of 30 subjects with non-advanced fibrosis (F0-F2), and a control group (Group 3) made of 30 subjects with advanced fibrosis (F3-F4), all with available MRE. LSM was measured in each subject along with assessment of hepatic morphological features of cirrhosis and signs of portal hypertension. The significance of the difference in mean LSM between Group 1 and 2 and between Group 1 and 3 was evaluated using the Mann-Whitney U test. The difference in distribution of imaging features among groups was assessed using the Pearson χ2 or Fisher exact test. RESULTS: The mean ± SD LSM in Group 1 (3.56 ± 1.10 kPa) was significantly higher compared to Group 2 (2.91 ± 0.52 kPa, P = 0.019) and significantly lower compared to Group 3 (7.18 ± 2.08 kPa, P < 0.001). Twelve (32%) patients with NRH had LSM ≥ 4.11 kPa, and 6 (16%) patients had LSM ≥ 4.71 kPa. Surface nodularity (P = 0.032) and caudate lobe hypertrophy (P = 0.004) were more commonly visualized in Group 1 than in Group 2. At least one feature of portal hypertension was observed in 16 (43%) NRH subjects. CONCLUSION: NRH may increase the LSM obtained with MRE and may represent a confounding factor when using liver stiffness for the non-invasive diagnosis of fibrosis.

Liver biopsy findings from healthy potential living liver donors: reasons for disqualification, silent diseases and correlation with liver injury tests.

BACKGROUND/AIMS: Liver biopsies detect silent donor disease in potential living liver donors and provide material for studies of subclinical non-alcoholic fatty liver disease (NAFLD). Our primary goal was to determine the contribution of biopsy findings to potential donor evaluation. Factors contributing to pre-clinical NAFLD and correlations between liver injury tests and histopathology have been also determined. METHODS: Patient records, laboratory tests and results of the histopathologic examination and diagnoses of 284 patients from 2001 to 2005 were retrospectively extracted from the EDIT database. Hepatic histology was correlated with liver injury tests and with general demographic characteristics in an otherwise normal healthy population. RESULTS: A minority (n=119; 42%) of biopsies from this population of 143 males/141 females (average age=36.8years; mean BMI=26.6) were completely normal. The remainder showed steatosis (n=107; 37%), steatohepatitis (n=44; 15%), or unexplained low-grade/early stage chronic hepatitis, primary biliary cirrhosis, or nodular regenerative hyperplasia (n=16; 6%). Biopsy findings disqualified 29/56 donors. Independent risk factors for NAFLD by multivariate modeling, which differed by sex, included: BMI (p=0.0001), age (p=0.003), iron (p=0.01), and ALT (p=0.004). CONCLUSIONS: Liver biopsies provide valuable information about otherwise undetectable liver disease in potential liver donors. Obesity, age and iron, which are influenced by sex, contribute to NAFLD pathogenesis. Blood tests other than standard liver profiles are needed to detect early NAFLD.

Enhancement pattern of hepatocellular adenoma (HCA) on MR imaging performed with Gd-EOB-DTPA versus other Gd-based contrast agents (GBCAs): An intraindividual comparison.

PURPOSE: To conduct an intraindividual comparison of the enhancement pattern of hepatocellular adenoma (HCA) on dynamic MRI study obtained following the injection of Gadoxetic acid (Gd-EOB-DTPA) and other gadolinium-based contrast agents (GBCAs). METHOD: This is a retrospective, Institutional Review Board-approved study conducted in a single institution. A search of medical records between 2008 and 2017 revealed 17 patients (all females) with at least one pathologically-proven HCA who underwent liver MRI with Gd-EOB-DTPA and another GBCA within 1 year. Enhancement of each lesion on hepatic arterial (HAP), portal venous (PVP), 2 min and 4-5 minutes phases was subjectively evaluated by two abdominal radiologists. Lesions were categorized as hyper-, iso- or hypointense compared to the surrounding liver parenchyma. The presence of a peripheral pseudocapsule was also recorded. The differences in lesion enhancement were assessed using the McNemar Test. A p-value <0.05 was considered statistically significant. RESULTS: The final population included 35 HCAs (83% inflammatory subtype). There was no significant difference in lesion size (P = 0.708) and enhancement on HAP (P = 0.625) or PVP (P = 0.125). HCAs showed more frequently hypointensity on 2 min (13/35 vs. 1/35, P < 0.001) and 4-5 minutes (P < 0.001) images obtained after injection of Gd-EOB-DTPA compared to those obtained after other GBCAs. A pseudocapsule was more frequently noted after administration of Gd-EOB-DTPA (13/35 vs 1/35, P = 0.002). CONCLUSIONS: Enhancement pattern of HCA differs significantly after the injection of Gd-EOB-DTPA compared to other GBCAs. Lesion hypointensity on 2 min and 4-5 minutes images is more frequent when using Gd-EOB-DTPA.

Evaluation of texture analysis for the differential diagnosis of focal nodular hyperplasia from hepatocellular adenoma on contrast-enhanced CT images.

PURPOSE: To explore the value of CT texture analysis (CTTA) for differentiation of focal nodular hyperplasia (FNH) from hepatocellular adenoma (HCA) on contrast-enhanced CT (CECT). METHODS: This is a retrospective, IRB-approved study conducted in a single institution. A search of the medical records between 2008 and 2017 revealed 48 patients with 70 HCA and 50 patients with 62 FNH. All lesions were histologically proven and with available pre-operative CECT imaging. Hepatic arterial phase (HAP) and portal venous phase (PVP) were used for CTTA. Textural features were extracted using a commercially available research software (TexRAD). The differences between textural parameters of FNH and HCA were assessed using the Mann-Whitney U test and the AUROC were calculated. CTTA parameters showing significant difference in rank sum test were used for binary logistic regression analysis. A p value < 0.05 was considered statistically significant. RESULTS: On HAP images, mean, mpp, and skewness were significantly higher in FNH than in HCA on unfiltered images (p ≤ 0.007); SD, entropy, and mpp on filtered analysis (p ≤ 0.006). On PVP, mean, mpp, and skewness in FNH were significantly different from HCA (p ≤ 0.001) on unfiltered images, while entropy and kurtosis were significantly higher in FNH on filtered images (p ≤ 0.018). The multivariate logistic regression analysis indicated that the mean, mpp, and entropy of medium-level and coarse-level filtered images on HAP were independent predictors for the diagnosis of HCA and a model based on all these parameters showed the largest AUROC (0.824). CONCLUSIONS: Multiple explored CTTA parameters are significantly different between FNH and HCA on CECT.

Common pitfalls when using the Liver Imaging Reporting and Data System (LI-RADS): lessons learned from a multi-year experience.

The goal of the Liver Imaging Reporting and Data System (LI-RADS) is to standardize the interpretation and reporting of liver observations on contrast-enhanced CT and MR imaging of patients at risk for hepatocellular carcinoma. Although LI-RADS represents a significant achievement in standardization of the diagnosis and management of cirrhotic patients, complexity and caveats to the algorithm may challenge correct application in clinical practice. The purpose of this paper is to discuss common pitfalls and potential solutions when applying LI-RADS in practice. Knowledge of the most common pitfalls may improve the diagnostic confidence and performance when using the LI-RADS system for the interpretation of CT and MR imaging of the liver.

Metastatic extrapleural malignant solitary fibrous tumor presenting with hypoglycemia (Doege-Potter syndrome).

We report a rare case of metastatic malignant solitary fibrous tumor (SFT) that presented with hypoglycemia because of insulin growth factor-2 production. Initial workup included computed tomography imaging that revealed a large, partially necrotic liver mass, a hypervascular pancreatic head lesion, and 2 renal lesions. Following hepatic resection, pancreatic head resection and nephrectomy, all these lesions demonstrated pathological findings that were consistent with SFT. The patient also had a history of an intracranial mass that had been previously resected and treated with gamma knife therapy at an outside institution, which was found to also be SFT. Six months after initial pancreatic head resection, the patient developed a new lesion involving the pancreatic tail that was found to represent recurrent metastatic SFT. This case emphasizes the highly aggressive nature of extrapleural SFT, while rare, and the role of imaging in follow-up for disease recurrence.

A massive hepatic tumor demonstrating hepatocellular, cholangiocarcinoma and neuroendocrine lineages: A case report and review of the literature.

INTRODUCTION: Mixed hepatocellular and cholangiocarcinoma tumors (MHCC) are described in the literature, as are the more rare mixed adenoneuroendocrine carcinomas (MANC) of hepatobiliary origin. Only two cases of tumors with characteristics of all three histologies/phenotypes have been previously described in one Chinese study. PRESENTATION OF CASE: Herein we report clinical, microscopic and molecular features of a 25cm mixed hepatic tumor with hepatocellular, cholangiocarcinoma and neuroendocrine differentiation arising in an otherwise healthy 19-year-old North American Caucasian male without any identifiable risk factors. DISCUSSION: The patient underwent multimodality imaging and the tumor was biopsied preoperatively, and it was initially interpreted to be hepatocellular carcinoma fibrolamellar type. A left trisegmentectomy with lymphadenectomy was performed and the tumor was definitively diagnosed based on the surgically resected specimen. Integrated microscopic and molecular features defined the differing biological aggressiveness of growth pattern components. Cases in the literature of MHCC and rare cases of MANC have largely undergone aggressive surgical resection as well, however the majority of studies on mixed hepatic tumors to date reflect Eastern patient cohorts and populations with underlying liver disease, thereby limiting extrapolation on management or outcomes in this case. CONCLUSION: This is one of the only reports of a hepatic tumor arising from hepatocellular carcinoma, cholangiocarcinoma and neuroendocrine lineages. Increased awareness of this tumor type may optimize improve future management.

Hepatic Sinusoidal Dilatation: A Review of Causes With Imaging-Pathologic Correlation.

Hepatic sinusoids are vascular conduits connecting the portal triad with the central vein. Multiple conditions can lead to sinusoidal dilatation and congestion with resultant stasis of blood within the lumen. The altered hemodynamics associated with hepatic sinusoidal dilatation generally result in heterogeneous enhancement of the hepatic parenchyma on contrast-enhanced computed tomography and magnetic resonance imaging, a pattern often described as "mosaic" enhancement. In this article, we review the causes of hepatic sinusoidal dilatation and the imaging manifestations on contrast-enhanced computed tomography and magnetic resonance.

Posttransplant lymphoproliferative disorders presenting at sites of previous surgical intervention.

Early diagnosis of posttransplant lymphoproliferative disorder (PTLD) requires a high level of clinical suspicion. PTLD occurs mainly in the lymphoid tissue, allograft organ, bowel, and central nervous system. The diagnosis may not be considered initially when disease is localized to other sites. Retrospective review of the PTLD series at the University of Pittsburgh Medical Center showed that 4 of 418 patients (1%) presented with signs and symptoms localized to sites of previous surgical intervention (choledochojejunostomy site, ileosigmoid anastomotic site, site of saphenous vein stripping, and intrabiliary site of percutaneous transhepatic catheter). All patients showed symptomatic, Epstein-Barr virus-positive B-cell PTLD of varying histology. Three of four patients ultimately died with tumor, and the fourth died of unrelated causes. PTLD should be included in the differential diagnosis when clinical signs and symptoms localize to anastomotic sites, surgical incision sites, or sites of longstanding catheter placement in immunosuppressed organ transplant recipients.