Prospective Evaluation of Virtual MR Elastography With Diffusion-Weighted Imaging in Subjects With Nonalcoholic Fatty Liver Disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is increasingly common worldwide and can lead to the development of cirrhosis, liver failure and cancer. Virtual magnetic resonance elastography (VMRE), which is based on a shifted apparent diffusion coefficient (sADC), is a potential noninvasive method to assess liver fibrosis without the specialized hardware and expertise required to implement traditional MR elastography (MRE). Although hepatic steatosis is known to confound ADC measurements, previous studies using VMRE have not corrected for hepatic fat fraction. PURPOSE: To compare VMRE, corrected for the confounding effects of unsuppressed fat signal, to MRE and biopsy in subjects with suspected NAFLD. STUDY TYPE: Prospective, cross-sectional. POPULATION: A total of 49 adult subjects with suspected NAFLD (18 male; median age 55 years, range 33-74 years) who underwent liver biopsy. FIELD STRENGTH/SEQUENCE: 3T, diffusion-weighted spin echo planar, chemical-shift encoded (IDEAL IQ) and MRE sequences. ASSESSMENT: Two observers drew regions of interest on sADC, proton density fat fraction and MRE-derived stiffness maps. Fat-corrected sADC values were used to calculate the diffusion-based shear modulus according to the VMRE method. Predicted fibrosis stage for MRE and VMRE was determined using previously published cut-off values. STATISTICAL TESTS: The relationship between VMRE and MRE was assessed with least-squares linear regression (coefficient of determination, R2 ). Agreement between MRE and VMRE-predicted fibrosis stage was evaluated with a kappa coefficient and accuracy compared using McNemar's test. A one-way ANOVA determined if the fat-corrected sADC (VMRE) and MRE differed by fibrosis stage. A P value < 0.05 was considered statistically significant. RESULTS: Least squares regression of VMRE vs. MRE revealed R2  = 0.046 and a slope that was not significantly different from zero (P = 0.14). There was no agreement between MRE and VMRE-predicted fibrosis stage (kappa = -0.01). The proportion of correctly predicted fibrosis stage was significantly higher for MRE compared to VMRE. MRE was significantly associated with fibrosis stage, but fat-corrected sADC was not (P = 0.24). DATA CONCLUSION: Fat-corrected VMRE was not associated with fibrosis stage in NAFLD. Further investigation is required if VMRE is to be considered in subjects with NAFLD. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Benign Neoplasms, Mass-Like Infections, and Pseudotumors That Mimic Hepatic Malignancy at MRI.

A variety of conditions may mimic hepatic malignancy at MRI. These include benign hepatic tumors and tumor-like entities such as focal nodular hyperplasia-like lesions, hepatocellular adenoma, hepatic infections, inflammatory pseudotumor, vascular entities, and in the cirrhotic liver, confluent fibrosis, and hypertrophic pseudomass. These conditions demonstrate MRI features that overlap with hepatic malignancy, and can be challenging for radiologists to diagnose accurately. In this review we discuss the MRI manifestations of various conditions that mimic hepatic malignancy, and highlight features that may allow distinction from malignancy. Level of Evidence 5 Technical Efficacy Stage 3.

Rat Hepatitis E Virus Linked to Severe Acute Hepatitis in an Immunocompetent Patient.

Hepatitis E virus (HEV) is a major public health concern in developing countries where the primary transmission is via contaminated water. Zoonotic HEV cases have been increasingly described in Europe, Japan, and the United States, with pigs representing the main animal reservoir of infection. We report an unusual acute hepatitis infection in a previously healthy man caused by a rat HEV with a considerably divergent genomic sequence compared with other rat HEV strains. It is possible that rat HEV is an underrecognized cause of hepatitis infection, and further studies are necessary to elucidate its potential risk and mode of transmission.

cHCC-CCA: Consensus terminology for primary liver carcinomas with both hepatocytic and cholangiocytic differentation.

Primary liver carcinomas with both hepatocytic and cholangiocytic differentiation have been referred to as "combined (or mixed) hepatocellular-cholangiocarcinoma." These tumors, although described over 100 years ago, have attracted greater attention recently because of interest in possible stem cell origin and perhaps because of greater frequency and clinical recognition. Currently, because of a lack of common terminology in the literature, effective treatment and predictable outcome data have been challenging to accrue. This article represents a consensus document from an international community of pathologists, radiologists, and clinicians who have studied and reported on these tumors and recommends a working terminology for diagnostic and research approaches for further study and evaluation. CONCLUSION: It is recommended that diagnosis is based on routine histopathology with hematoxylin and eosin (H&E); immunostains are supportive, but not essential for diagnosis. (Hepatology 2018;68:113-126).

Development of a novel histologic diagnostic algorithm for hepatic graft-versus-host disease.

The histopathologic diagnosis of hepatic graft-versus-host disease post bone marrow and stem cell transplantation can be challenging, but timely and unambiguous diagnosis is essential for appropriate patient management. To address this diagnostic dilemma, we identified histologic features specific for hepatic graft-versus-host disease and developed a diagnostic algorithm. Two hepatopathologists blindly evaluated 40 liver biopsies from patients with clinically and biologically confirmed graft-versus-host disease, as well as 44 controls, for percent bile duct loss, bile duct damage, intraepithelial lymphocytes, ductular reaction, acidophilic bodies/10 high power fields (HPF), cholestasis, portal and lobular inflammation, and endotheliitis. Compared with controls, graft-versus-host disease cases had significantly more bile duct loss (P<0.0001), bile duct damage (P=0.0002), cholestasis (P<0.0001), and acidophilic bodies/10 HPF (P=0.0006), as well as significantly less ductular reaction (P<0.0001). Significance was maintained with a drug-induced liver injury-only control group. No histologic differences were noted in acute versus chronic graft-versus-host disease, nor cholestatic versus hepatitic types. An algorithm to predict likelihood of graft-versus-host disease was developed, with a three-tiered scoring system: 1-2 not, 3-4 probable, and 5-8 unequivocal graft-versus-host disease. This algorithm had a sensitivity of 93%, specificity of 93%, and accuracy of 92%. We identified histologic features with specificity for hepatic graft-versus-host disease and developed a simple algorithm for pathologists to predict its likelihood, distinguishing this critical diagnosis promptly from mimickers having vastly different treatments and prognoses.

Lymphoepithelioma-Like Carcinoma in Liver.

Liver cancer, primarily encompassing hepatocellular carcinoma and intrahepatic cholangiocarcinoma, has become the second leading cause of worldwide cancer-related death during the past two decades. Lymphoepithelioma-like carcinomas (LELCs) are defined as tumors composed of undifferentiated epithelial cells with a prominent lymphoid infiltrate, and can arise in the liver as hepatocellular or cholangiocarcinoma forms. Patients with liver LELC display distinctive demographics and tumor characteristics. LELCs also appear to be associated with strikingly better outcomes compared to typical liver cancers, with 5-year survival rates of 57% to 100% versus 12% to 68%, respectively. Liver LELCs represent a unique model of immune response in liver cancer. Data on LELCs of the liver remain limited, and future comprehensive studies are needed to further elucidate this disease, which could ultimately offer precious insights for immunotherapeutic strategies in liver cancer.

Detection of liver fibrosis using qualitative and quantitative MR elastography compared to liver surface nodularity measurement, gadoxetic acid uptake, and serum markers.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) combining different techniques such as MR elastography (MRE) has emerged as a noninvasive approach to diagnose and stage liver fibrosis with high accuracy allowing for anatomical and functional information. PURPOSE: To assess the diagnostic performance of mpMRI including qualitative and quantitative assessment of MRE, liver surface nodularity (LSN) measurement, hepatic enhancement ratios postgadoxetic acid, and serum markers (APRI, FIB-4) for the detection of liver fibrosis. STUDY TYPE: IRB-approved retrospective. SUBJECTS: Eighty-three adult patients. FIELD STRENGTH/SEQUENCE: 1.5T and 3.0T MR systems. MRE and T1 -weighted postgadoxetic acid sequences. ASSESSMENT: Two independent observers analyzed qualitative color-coded MRE maps on a scale of 0-3. Regions of interest were drawn to measure liver stiffness on MRE stiffness maps and on pre- and postcontrast T1 -weighted images to measure hepatic enhancement ratios. Software was used to generate LSN measurements. Histopathology was used as the reference standard for diagnosis of liver fibrosis in all patients. STATISTICAL TESTS: A multivariable logistic analysis was performed to identify independent predictors of liver fibrosis. Receiver operating characteristic (ROC) analysis evaluated the performance of each imaging technique for detection of fibrosis, in comparison with serum markers. RESULTS: Liver stiffness measured with MRE provided the strongest correlation with histopathologic fibrosis stage (r = 0.74, P < 0.001), and the highest diagnostic performance for detection of stages F2-F4, F3-F4, and F4 (areas under the curve [AUCs] of 0.87, 0.91, and 0.89, respectively, P < 0.001) compared to other methods. Qualitative assessment of MRE maps showed fair to good accuracy for detection of fibrosis (AUC range 0.76-0.84). Multivariable logistic analysis identified liver stiffness and FIB-4 as independent predictors of fibrosis with AUCs of 0.90 (F2-F4), 0.93 (F3-F4) and 0.92 (F4) when combined. DATA CONCLUSION: Liver stiffness measured with MRE showed the best performance for detection of liver fibrosis compared to LSN and gadoxetic acid uptake, with slight improvement when combined with FIB-4. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1552-1561.

The impact of donor liver allograft fibrosis on patients undergoing liver transplantation.

BACKGROUND: The utilization of extended criteria liver allografts (ECD) shortens time to transplantation. OBJECTIVE: To characterize the effect of liver allograft fibrosis on graft and patient survival after liver transplantation (LT), with particular attention to fibrosis progression. METHODS: Retrospective database search of donor and recipient liver allograft histology of liver transplants performed between 2007 and 2011. Donor and patient characteristics were analyzed. RESULTS: One hundred and one patients underwent LT with donor liver allografts with early-stage fibrosis (stage 1 fibrosis and stage 2 fibrosis). The level of liver fibrosis did not progress in 40% of the patients tested, and there was a regression of fibrosis in 30%. At a median follow-up of 71 months, of 101 patients transplanted with fibrotic livers, 63 patients (63%) were alive with functioning initial grafts, six patients (6%) were retransplanted, and 35 patients expired. The graft survival rates were 82% and 69% at 1 and 5 years, respectively. Graft survival differences were not found to be statistically significant between the degrees of liver allograft fibrosis: 5-year graft survival (73% for stage 1 fibrosis and 62% for stage 2 fibrosis, P = .24). The entire fibrosis group was further compared with a control group of 208 consecutive primary liver transplant patients with allografts having no fibrosis. The 5-year graft survival was not significantly different between the groups (69% for the fibrosis group vs 75% for the nonfibrosis group, P = .19). Survival was also not statistically different between the groups (5-year survival of 73% for the fibrosis group vs 79% for the nonfibrosis group, P = .2). In patients with HCV, graft survival differences were not found to be statistically significant with the use of early-stage fibrotic livers: 5-year graft survival of 60% for fibrosis group vs 70% for the nonfibrosis group, P = .22). CONCLUSION: This study demonstrates that allografts with early-stage fibrosis achieve acceptable long-term survival after liver transplantation. Given these preliminary results, the use of organs with early-stage fibrosis warrants further studies at a larger scale to validate these results.

Evaluation of HCC response to locoregional therapy: Validation of MRI-based response criteria versus explant pathology.

BACKGROUND AND AIMS: This study evaluates the performance of various magnetic resonance imaging (MRI) response criteria for the prediction of complete pathologic necrosis (CPN) of hepatocellular carcinoma (HCC) post locoregional therapy (LRT) using explant pathology as a reference. METHODS: We included 61 patients (male/female 46/15; mean age 60years) who underwent liver transplantation after LRT with transarterial chemoembolization plus radiofrequency or microwave ablation (n=56), or 90Yttrium radioembolization (n=5). MRI was performed <90days before liver transplantation. Three independent readers assessed the following criteria: RECIST, EASL, modified RECIST (mRECIST), percentage of necrosis on subtraction images, and diffusion-weighted imaging (DWI), both qualitative (signal intensity) and quantitative (apparent diffusion coefficient [ADC]). The degree of necrosis was retrospectively assessed at histopathology. Intraclass correlation coefficient (ICC) and Cohen's kappa were used to assess inter-reader agreement. Logistic regression and receiver operating characteristic analyses were used to determine imaging predictors of CPN. Pearson correlation was performed between imaging criteria and pathologic degree of tumor necrosis. RESULTS: A total of 97HCCs (mean size 2.3±1.3cm) including 28 with CPN were evaluated. There was excellent inter-reader agreement (ICC 0.77-0.86, all methods). EASL, mRECIST, percentage of necrosis and qualitative DWI were all significant (p<0.001) predictors of CPN, while RECIST and ADC were not. EASL, mRECIST and percentage of necrosis performed similarly (area under the curves [AUCs] 0.810-0.815) while the performance of qualitative DWI was lower (AUC 0.622). Image subtraction demonstrated the strongest correlation (r=0.71-0.72, p<0.0001) with pathologic degree of tumor necrosis. CONCLUSIONS: EASL/mRECIST criteria and image subtraction have excellent diagnostic performance for predicting CPN in HCC treated with LRT, with image subtraction correlating best with pathologic degree of tumor necrosis. Thus, MR image subtraction is recommended for assessing HCC response to LRT. LAY SUMMARY: The assessment of hepatocellular carcinoma (HCC) tumor necrosis after locoregional therapy is essential for additional treatment planning and estimation of outcome. In this study, we assessed the performance of various magnetic resonance imaging (MRI) response criteria (RECIST, mRECIST, EASL, percentage of necrosis on subtraction images, and diffusion-weighted imaging) for the prediction of complete pathologic necrosis of HCC post locoregional therapy on liver explant. Patients who underwent liver transplantation after locoregional therapy were included in this retrospective study. All patients underwent routine liver MRI within 90days of liver transplantation. EASL/mRECIST criteria and image subtraction had excellent diagnostic performance for predicting complete pathologic necrosis in treated HCC, with image subtraction correlating best with pathologic degree of tumor necrosis.

Mixed hepatocellular cholangiocarcinoma tumors: Cholangiolocellular carcinoma is a distinct molecular entity.

BACKGROUND & AIMS: Mixed hepatocellular cholangiocarcinoma (HCC-CCA) is a rare and poorly understood type of primary liver cancer. We aimed to perform a comprehensive molecular characterization of this malignancy. METHODS: Gene expression profiling, DNA copy number detection, and exome sequencing using formalin-fixed samples from 18 patients with mixed HCC-CCA were performed, encompassing the whole histological spectrum of the disease. Comparative genomic analysis was carried out, using independent datasets of HCC (n=164) and intrahepatic cholangiocarcinoma (iCCA) (n=149). RESULTS: Integrative genomic analysis of HCC-CCAs revealed that cholangiolocellular carcinoma (CLC) represents a distinct biliary-derived entity compared with the stem-cell and classical types. CLC tumors were neural cell adhesion molecule (NCAM) positive (6/6 vs. 1/12, p<0.001), chromosomally stable (mean chromosomal aberrations 5.7 vs. 14.1, p=0.008), showed significant upregulation of transforming growth factor (TGF)-ß signaling and enrichment of inflammation-related and immune response signatures (p<0.001). Stem-cell tumors were characterized by spalt-like transcription factor 4 (SALL4) positivity (6/8 vs. 0/10, p<0.001), enrichment of progenitor-like signatures, activation of specific oncogenic pathways (i.e., MYC and insulin-like growth factor [IGF]), and signatures related to poor clinical outcome. In the classical type, there was a significant correlation in the copy number variation of the iCCA and HCC components, suggesting a clonal origin. Exome sequencing revealed an average of 63 non-synonymous mutations per tumor (2 mean driver mutations per tumor). Among those, TP53 was the most frequently mutated gene (6/21, 29%) in HCC-CCAs. CONCLUSIONS: Mixed HCC-CCA represents a heterogeneous group of tumors, with the stem-cell type characterized by features of poor prognosis, and the classical type with common lineage for HCC and iCCA components. CLC stands alone as a distinct biliary-derived entity associated with chromosomal stability and active TGF-ß signaling. LAY SUMMARY: Molecular analysis of mixed hepatocellular cholangiocarcinoma (HCC-CCA) showed that cholangiolocellular carcinoma (CLC) is distinct and biliary in origin. It has none of the traits of hepatocellular carcinoma (HCC). However, within mixed HCC-CCA, stem-cell type tumors shared an aggressive nature and poor outcome, whereas the classic type showed a common cell lineage for both the HCC and the intrahepatic CCA component. The pathological classification of mixed HCC-CCA should be redefined because of the new molecular data provided.

An Unusual Cause of Acute Liver Failure: Three Cases of Hemophagocytic Lymphohistiocytosis Presenting at a Transplant Center.

Acquired hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disorder of the immune system. Hemophagocytic lymphohistiocytosis has been associated with infections, autoimmune disorders, and malignancy. This case series describes three patients admitted to an academic liver transplant center from February 2014 to February 2015 with acute liver failure (ALF) who were ultimately diagnosed with HLH. All cases were female patients (44 to 53 years of age) transferred for workup of ALF. All developed fevers and cytopenias and underwent rapid evaluation for liver transplant by a multidisciplinary team. A complete workup for ALF was negative for intrinsic liver disease and none had significant alcohol or toxin exposure. The patients had liver biopsies showing diffuse lobular necroinflammation, of which two had evidence of hemophagocytosis on histopathology. The diagnosis of HLH was made by bone marrow biopsy featuring histiocytes with hemophagocytosis. All cases were treated with chemotherapy, but died during their hospitalization. Hemophagocytic lymphohistiocytosis can present as ALF in adult patients. Given the low success rate of treatment, early diagnosis is critical. Therefore, a high degree of suspicion should be exercised in patients with unexplained ALF.

Hepatocyte buds derived from progenitor cells repopulate regions of parenchymal extinction in human cirrhosis.

UNLABELLED: Repair of cirrhotic livers occurs, in part, by repopulation with hepatocytes through the stem/progenitor pathway. There remain many uncertainties regarding this pathway. Hepatocyte "buds" occurring in broad septa are hypothesized to be the anatomic manifestation of this pathway. Our purpose was to define a morphologic sequence of bud maturation to allow a quantitative measure of the importance of the stem/progenitor pathway in humans. Histologic sections from 37 liver resection specimens were stained with trichrome, epithelial cell adhesion molecule (EpCAM), K19, CD34, glutamine synthetase (GS), and Ki-67. Specimens were stratified by etiology (10 biliary, 22 nonbiliary, five controls) and stage. Buds were defined as clusters of hepatocytes within septa. Five levels of bud maturation (0-4) were defined by the progressive increase in hepatocyte progeny relative to cholangiocytes. Level 0 single-cell buds are K19(+) /GS(+) /EpCAM(+) /Heppar1(-) . In level 1, the progeny are morphologically hepatocytes (K19(-) /GS(+) /EpCAM(+) /Heppar1(+) ). In level 2-4 buds, hepatocytes increase and become progressively GS(-) and EpCAM(-) . Associated endothelium is CD34(+) in level 1-2 buds and becomes CD34(-) near hepatic veins in level 3-4 buds. Progeny of the bud sequence may represent up to 70% of hepatocytes (immaturity index of 70%). In biliary disease, bud number is reduced in association with duct loss and cholestatic destruction of nascent buds. CONCLUSIONS: The stem/progenitor pathway, manifested anatomically by the bud sequence, is a major mechanism for repopulation of cirrhotic livers. The bud sequence reveals some critical features of hepatic morphogenesis, including that 1) the majority of distal cholangiocytes have stem-like properties, and 2) availability of bile ducts and/or venous drainage are limiting factors for regeneration.

Hepatocellular Carcinoma Arising in an HNF-1α-Mutated Adenoma in a 23-Year-Old Woman with Maturity-Onset Diabetes of the Young: A Case Report.

Hepatocyte nuclear factor-1α mutated hepatocellular adenomas (H-HCA) are thought to have no to minimal malignant potential. This report describes a 23-year-old woman with maturity-onset diabetes of the young who developed a 12.5-cm hepatic mass with a radiographically and pathologically distinct 3.0-cm region. Histologically and immunohistochemically, the bulk of the mass was an H-HCA with extensive pseudoglandular formation and only focal steatosis. The 3.0-cm nodule showed small cell change, thickened hepatocyte plates, pleomorphic and hyperchromatic nuclei, reticulin loss, and stromal and vascular invasion, diagnostic of hepatocellular carcinoma (HCC). Immunohistochemically, increased expression of glutamine synthetase in tumor cells and CD34 expression in sinusoidal endothelial cells were seen in the HCC component. Nuclear expression of ß-catenin, and exon 3 of CTNNB1 and TERT promoter mutations were absent in this case. Thus, we report a HCC arising in an H-HCA; although cases appear exceedingly rare, they reinforce the potential of H-HCA for malignant transformation.

Isolated hepatic sarcoidosis: A case series.

Sarcoidosis is a multi-organ inflammatory disease that can have hepatic involvement in up to 80% of cases. Rarely, sarcoidosis can manifest with only confined disease to the liver. While most patients with hepatic sarcoidosis are clinically silent, certain cases can have insidious onset leading to cirrhosis and secondary complications. Here, we describe three cases of isolated hepatic sarcoidosis to illustrate the range of presentations that may be associated with this condition. Clinicians should be vigilant in consideration of hepatic sarcoidosis as a culprit when investigating patients with undifferentiated liver disease.

The Hydroxypyridinone Iron Chelator DIBI Reduces Bacterial Load and Inflammation in Experimental Lung Infection.

Iron plays a critical role in lung infections due to its function in the inflammatory immune response but also as an important factor for bacterial growth. Iron chelation represents a potential therapeutic approach to inhibit bacterial growth and pathologically increased pro-inflammatory mediator production. The present study was designed to investigate the impact of the iron chelator DIBI in murine lung infection induced by intratracheal Pseudomonas aeruginosa (strain PA14) administration. DIBI is a polymer with a polyvinylpyrrolidone backbone containing nine 3-hydroxy-1-(methacrylamidoethyl)-2-methyl-4(1H) pyridinone (MAHMP) residues per molecule and was given by intraperitoneal injection either as a single dose (80 mg/kg) immediately after PA14 administration or a double dose (second dose 4 h after PA14 administration). The results showed that lung NF-κBp65 levels, as well as levels of various inflammatory cytokines (TNFα, IL-1ß, IL-6) both in lung tissue and bronchoalveolar lavage fluid (BALF), were significantly increased 24 h after PA14 administration. Single-dose DIBI did not affect the bacterial load or inflammatory response in the lungs or BALF. However, two doses of DIBI significantly decreased bacterial load, attenuated NF-κBp65 upregulation, reduced inflammatory cytokines production, and relieved lung tissue damage. Our findings support the conclusion that the iron chelator, DIBI, can reduce lung injury induced by P. aeruginosa, via its anti-bacterial and anti-inflammatory effects.

Evaluation of Minimum-to-Severe Global and Macrovesicular Steatosis in Human Liver Specimens: A Portable Ambient Light-Compatible Spectroscopic Probe.

BACKGROUND AND AIMS: Hepatic steatosis (HS), particularly macrovesicular steatosis (MaS), influences transplant outcomes. Accurate assessment of MaS is crucial for graft selection. While traditional assessment methods have limitations, non-invasive spectroscopic techniques like Raman and reflectance spectroscopy offer promise. This study aimed to evaluate the efficacy of a portable ambient light-compatible spectroscopic system in assessing global HS and MaS in human liver specimens. METHODS: A two-stage approach was employed on thawed snap-frozen human liver specimens under ambient room light: biochemical validation involving a comparison of fat content from Raman and reflectance intensities with triglyceride (TG) quantifications and histopathological validation, contrasting Raman-derived fat content with evaluations by an expert pathologist and a "Positive Pixel Count" algorithm. Raman and reflectance intensities were combined to discern significant (≥ 10%) discrepancies in global HS and MaS. RESULTS: The initial set of 16 specimens showed a positive correlation between Raman and reflectance-derived fat content and TG quantifications. The Raman system effectively differentiated minimum-to-severe global and macrovesicular steatosis in the subsequent 66 specimens. A dual-variable prediction algorithm was developed, effectively classifying significant discrepancies (> 10%) between algorithm-estimated global HS and pathologist-estimated MaS. CONCLUSION: Our study established the viability and reliability of a portable spectroscopic system for non-invasive HS and MaS assessment in human liver specimens. The compatibility with ambient light conditions and the ability to address limitations of previous methods marks a significant advancement in this field. By offering promising differentiation between global HS and MaS, our system introduces an innovative approach to real-time and quantitative donor HS assessments. The proposed method holds the promise of refining donor liver assessment during liver recovery and ultimately enhancing transplantation outcomes.

The 1000 Mitoses Project: A Consensus-Based International Collaborative Study on Mitotic Figures Classification.

Introduction. The identification of mitotic figures is essential for the diagnosis, grading, and classification of various different tumors. Despite its importance, there is a paucity of literature reporting the consistency in interpreting mitotic figures among pathologists. This study leverages publicly accessible datasets and social media to recruit an international group of pathologists to score an image database of more than 1000 mitotic figures collectively. Materials and Methods. Pathologists were instructed to randomly select a digital slide from The Cancer Genome Atlas (TCGA) datasets and annotate 10-20 mitotic figures within a 2 mm2 area. The first 1010 submitted mitotic figures were used to create an image dataset, with each figure transformed into an individual tile at 40x magnification. The dataset was redistributed to all pathologists to review and determine whether each tile constituted a mitotic figure. Results. Overall pathologists had a median agreement rate of 80.2% (range 42.0%-95.7%). Individual mitotic figure tiles had a median agreement rate of 87.1% and a fair inter-rater agreement across all tiles (kappa = 0.284). Mitotic figures in prometaphase had lower percentage agreement rates compared to other phases of mitosis. Conclusion. This dataset stands as the largest international consensus study for mitotic figures to date and can be utilized as a training set for future studies. The agreement range reflects a spectrum of criteria that pathologists use to decide what constitutes a mitotic figure, which may have potential implications in tumor diagnostics and clinical management.

Hepatic graft-versus-host disease: what we know, when to biopsy, and how to diagnose.

Graft-versus-host disease (GVHD) is one of the serious complications that may develop after hematopoietic cell transplantation (HCT), for hematologic malignancies, solid organ transplantation, and other hematologic disorders. GVHD develops due to T lymphocytes present in the graft attacking the host antigens, which results in tissue damage. A significant number of HCT patients develop acute or chronic GVHD, which may affect multiple organs including the liver. The diagnosis of hepatic GVHD (hGVHD) is challenging as many other conditions in HCT patients may lead to liver dysfunction. Particularly challenging among the various conditions that give rise to liver dysfunction is differentiating sinusoidal obstruction syndrome and drug-induced liver injury (DILI) from hGVHD on clinical grounds and laboratory tests. Despite the minimal risks involved in performing a liver biopsy, the information gleaned from the histopathologic changes may help in the management of these very complex patients. There is a spectrum of histologic features found in hGVHD, and most involve histopathologic changes affecting the interlobular bile ducts. These include nuclear and cytoplasmic abnormalities including dysmorphic bile ducts, apoptosis, and cholangiocyte necrosis, among others. The hepatitic form of hGVHD typically shows severe acute hepatitis. With chronic hGVHD, there is progressive bile duct loss and eventually fibrosis. Accurate diagnosis of hGVHD is paramount so that timely treatment and management can be initiated. Techniques to prevent and lower the risk of GVHD from developing have recently evolved. If a diagnosis of acute GVHD is made, the first-line of treatment is steroids. Recurrence is common and steroid resistance or dependency is not unusual in this setting. Second-line therapies differ among institutions and have not been uniformly established. The development of GVHD, particularly hGVHD, is associated with increased morbidity and mortality.

Non-Mass-Forming Myeloid Sarcoma of the Colon Presenting With Diarrhea.

A female patient in her mid-70s, with a history of diverticulosis, presented with a 2-month history of severe diarrhea, left lower quadrant abdominal pain, decreased appetite, and fever. She was treated for diverticulitis, but did not improve. Subsequent workup revealed leukocytosis and circulating myeloblasts on a peripheral blood smear. Bone marrow evaluation and flow cytometry confirmed the diagnosis of acute myeloid leukemia. Abdominal computed tomography and sigmoidoscopy were performed for her persistent diarrhea. While both failed to show an obvious mass or anatomical abnormality, pathology from the colorectum showed infiltration by leukemic cells consistent with myeloid sarcoma. The diarrhea improved with acute myeloid leukemia chemotherapy.