Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH -Mutant Molecular Profiles

Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance

Hepatic perihilar amphicrine cholangiocarcinoma: A case report

Mixed neuroendocrine nonneuroendocrine neoplasms (MiNEN) are tumors composed of adenocarcinoma and neuroendocrine neoplasm and include collision, combined, and amphicrine. Within the hepatobiliary tree, tumors of this histologic type are extremely rare, particularly the amphicrine type. In this case study, we describe a 63-year-old man with a hepatic hilar amphicrine tumor. An initial diagnosis of neuroendocrine tumor was made based on biopsy (chromogranin and synaptophysin positivity). On resection, the tumor contained histologic features of both adenocarcinoma and neuroendocrine carcinoma. Immunohistochemically, all tumor cells expressed both chromogranin and synaptophysin, keratin 7, and Cam5.2. Mucin production was evident in both components demonstrated by mucicarmine stain. Albumin RNA in situ hybridization (ISH) was positive, supporting hepatic source. The tumor is classified as an amphicrine carcinoma given the dual expression of both adenocarcinoma and neuroendocrine markers in both components. This is the first amphicrine carcinoma of the hepatic hilum reported in the literature. Keywords: Cholangiocarcinoma, Mixed neuroendocrine-nonneuroendocrine carcinoma, Neuroendocrine tumor, Liver, Immunohistochemistry, Hepatobiliar

CT of hepatocellular carcinoma in non-alcoholic fatty liver disease: imaging characteristics and inter-rater agreement

Aim: To determine the computed tomography (CT) features of non-alcoholic fatty liver disease (NAFLD) associated hepatocellular carcinoma (HCC).Methods: In this institutional review board approved study, we reviewed 38 patients with NAFLD (68.4% male; mean age 63 years) with histology confirmed HCC and triphasic liver CT. CT images were independently reviewed by four readers blinded to clinical and pathology data. The reviewers assessed HCC for arterial phase hyper enhancement (APHE), portal venous phase washout (PVWO), delayed phase washout (DPWO), and enhancing capsule. Features of cirrhotic morphology and portal hypertension (PH) were also evaluated. The final CT features were determined by majority and a fifth reader reviewed cases lacking majority. Inter-rater agreement was determined by prevalence-adjusted kappa.Results: Mean HCC size was 3.6 ± 2.8 cm (range, 1.1-16.0 cm). The HCCs showed APHE in 92.1%, PVWO in 55.3%, DPWO in 81.6%, and enhancing capsule in 44.7%. Cirrhotic morphology was present in 65.8% and PH in 63.2%. Inter-rater agreement was moderate to almost perfect for APHE (0.74-1.0), cirrhosis (0.79-0.89), and PH (0.79-0.95), weak to perfect for DPWO (0.47-0.95) and poor for PVWO (0-0.42).Conclusion: NAFLD associated HCC demonstrate less frequent portal venous washout on CT which may affect their imaging diagnosis

Association between Visceral Adipose Tissue and Non-Alcoholic Steatohepatitis Histology in Patients with Known or Suspected Non-Alcoholic Fatty Liver Disease

(1) Purpose: To determine the association between visceral adipose tissue (VAT) and proton density fat fraction (PDFF) with magnetic resonance imaging (MRI), and hepatic steatosis (HS), non-alcoholic steatohepatitis (NASH) and hepatic fibrosis (HF) in patients with known or suspected non-alcoholic fatty liver disease (NAFLD). (2) Methods: 135 subjects that had a liver biopsy performed within 3 months (bariatric cohort) or 1 month (NAFLD cohort) of an MRI exam formed the study group. VAT volume was quantified at L2-L3 level on opposed-phase images with signal intensity-based painting using a semi-quantitative software. Liver PDFF and pancreas PDFF were calculated on fat fraction maps. Liver volume (Lvol) and spleen volume (Svol) were also calculated using a semi-automated 3D volume tool available on PACS. A histological analysis was performed by an expert hepatopathologist blinded to imaging findings. (3) Results: The mean Lvol, Svol, liver PDFF, pancreas PDFF and VAT of the study population were 2492.2 mL, 381.6 mL, 13.2%, 12.7% and 120.6 mL, respectively. VAT showed moderate correlation with liver PDFF (r = 0.41, p < 0.001) and weak correlation with Lvol (r = 0.38, p < 0.001), Svol (r = 0.20, p = 0.025) and pancreas PDFF (rs = 0.29, p = 0.001). VAT, Lvol and liver PDFF were significantly higher in patients with HS (p < 0.001), NASH (p < 0.05) and HF (p < 0.05). VAT was also significantly higher in the presence of lobular inflammation (p = 0.019) and hepatocyte ballooning (p = 0.001). The cut-off VAT volumes for predicting HS, NASH and HF were 101.8 mL (AUC, 0.7), 111.8 mL (AUC, 0.64) and 111.6 mL (AUC, 0.66), respectively. (4) Conclusion: The MRI determined VAT can be used for predicting the presence of HS, NASH and HF in patients with known or suspected NAFLD

Leiomyoma with KAT6B-KANSL1 fusion: case report of a rapidly enlarging uterine mass in a postmenopausal woman

Abstract Background Uterine leiomyomas, in contrast to sarcomas, tend to cease growth following menopause. In the setting of a rapidly enlarging uterine mass in a postmenopausal patient, clinical distinction of uterine leiomyoma from sarcoma is difficult and requires pathologic examination. Case presentation A 74-year-old woman presented with postmenopausal bleeding and acute blood loss requiring transfusion. She was found to have a rapidly enlarging uterine mass clinically suspicious for sarcoma. An abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. A 15.5 cm partially necrotic intramural mass was identified in the uterine corpus. The tumor was classified as a cellular leiomyoma. RNA sequencing identified a KAT6B-KANSL1 fusion that was confirmed by RT-PCR and Sanger sequencing. After 6 months of follow-up, the patient remains asymptomatic without evidence of disease. Conclusion Prior studies of uterine leiomyomas have identified KAT6B (previously MORF) rearrangements in uterine leiomyomas, but this case is the first to identify a KAT6B-KANSL1 gene fusion in a uterine leiomyoma. While alterations of MED12 and HMGA2 are most common in uterine leiomyomas, a range of other genetic pathways have been described. Our case contributes to the evolving molecular landscape of uterine leiomyomas