Rectal Endometriosis: A Case Report of with a Clinical Analysis of Other Cases Reported in Related Korean Literature

Hemobilia is defined as a hemorrhage in the biliary tract and is most commonly associated with accidental or iatrogenic trauma. A case is herein reported of hemobilia developed in a hepatic artery aneurysm after biliary stenting was performed in patient with cholangiocarcinoma. A 63-year-old man was admitted with melena and had history of cholangiocarcinoma with an intraductal biliary stent. A hepatic artery angiography revealed two pseudoaneurysms at the common hepatic artery and right hepatic artery. Transarterial embolization with gelfoam was successfully received and hemobilia was not developed later.ope

Large Cell Calcifying Sertoli Cell Tumor of the Testis : Case Report with Ultrastructural Study

Large cell calcifying Sertoli cell tumor (LCCST) is a rare testicular tumor, usually occurring in young men before the age of 20. Ultrastructural study has been performed rarely demonstrating Sertoli cell features. We report a case of LCCST in a 7-year-old boy. A well-circumscribed yellowish-tan, 1.5-cm-sized mass was located within the left testicular parenchyma. The cut surface was somewhat resilient with multiple calcifications. On microscopic examination, the tumor was composed of large eosinophilic polygonal cells with abundant eosinophilic cytoplasm arranging in solid tubular and trabecular patterns, superficially mimicking Leydig cell tumor. However, there were multiple calcifications and the tumor cell nests were surrounded by PASpositive basement membrane. Ultrastructural examination revealed the features of the Sertoli cell with Spangaro's crystals. The right testis showed a normal appearance by ultrasonogram and there were no other clinical features associated with Carney syndrome.ope

A case of tubulovillous adenoma of the common bile duct

Adenomas of the bile ducts are rare and unusual causes of bile duct obstruction. In Korea, 1 case of papillary adenoma, 5 cases of villous adenoma, 10 cases of biliary papillomatosis, and 1 case of tubulovillous adenoma have been reported. Preoperative diagnosis for these lesions is difficult to render as they can often mimic biliary stones. A case of bile duct tubulovillous adenoma with high grade epithelial dysplasia in a 65-year-old man, is herein reported. It was difficult to diagnose because of coexisting biliary stones. In addition, confusing classification and terminology of bile duct adenomas were reviewed.ope

Ductular reaction is helpful in defining early stromal invasion, small hepatocellular carcinomas, and dysplastic nodules

BACKGROUND: Stromal invasion is 1 of the main features used to distinguish high-grade dysplastic nodules (DNs) from well-differentiated hepatocellular carcinomas (HCCs). The authors hypothesized that ductular reaction (DR) takes place around noninvasive hepatocellular nodules but not within the stroma contiguous to invasive HCC. METHODS: DR/cytokeratin 7 (CK7)-positive patterns were evaluated in 105 resected small hepatic nodules according to the level of invasion. The nodules were classified histologically prior to immunostaining as noninvasive (large regenerative nodules, low-grade DNs, and high-grade DNs), minimally invasive (early HCCs with a vaguely nodular type), and overtly invasive (typical HCCs with a distinctly nodular type) in a review by expert pathologists, the current gold standard. Intranodular DR (inner DR) and DR around the nodule periphery (outer DR) were assessed separately on a semiquantitative scale from 0 to 4+. RESULTS: DR was 3 or 4+ in the majority of noninvasive nodules (inner DR, 81%; outer DR, 91%), whereas DR was 0 or 1+ in overtly invasive HCCs (inner DR, 96%; outer DR, 81%). Minimally invasive HCCs showed an intermediate DR pattern (2 or 3+ inner DR, 75%; 2+ outer DR, 67%). DR characteristically was absent at the stromal-invasive, leading edge of tumor cells in both minimally invasive HCCs (focal loss of DR/CK7) and overtly invasive HCCs (diffuse loss of DR/CK7). The DR patterns in 41 needle-biopsy samples were similar to the patterns observed in resected nodules. CONCLUSIONS: DR/CK7 immunostaining may help to identify small foci of invasion and to distinguish noninvasive, high-grade DNs from both minimally invasive and overtly invasive HCCs.ope

Recurrence-associated pathways in hepatitis B virus-positive hepatocellular carcinoma

BACKGROUND: Despite the recent identification of several prognostic gene signatures, the lack of common genes among experimental cohorts has posed a considerable challenge in uncovering the molecular basis underlying hepatocellular carcinoma (HCC) recurrence for application in clinical purposes. To overcome the limitations of individual gene-based analysis, we applied a pathway-based approach for analysis of HCC recurrence. RESULTS: By implementing a permutation-based semi-supervised principal component analysis algorithm using the optimal principal component, we selected sixty-four pathways associated with hepatitis B virus (HBV)-positive HCC recurrence (p < 0.01), from our microarray dataset composed of 142 HBV-positive HCCs. In relation to the public HBV- and public hepatitis C virus (HCV)-positive HCC datasets, we detected 46 (71.9%) and 18 (28.1%) common recurrence-associated pathways, respectively. However, overlap of recurrence-associated genes between datasets was rare, further supporting the utility of the pathway-based approach for recurrence analysis between different HCC datasets. Non-supervised clustering of the 64 recurrence-associated pathways facilitated the classification of HCC patients into high- and low-risk subgroups, based on risk of recurrence (p < 0.0001). The pathways identified were additionally successfully applied to discriminate subgroups depending on recurrence risk within the public HCC datasets. Through multivariate analysis, these recurrence-associated pathways were identified as an independent prognostic factor (p < 0.0001) along with tumor number, tumor size and Edmondson's grade. Moreover, the pathway-based approach had a clinical advantage in terms of discriminating the high-risk subgroup (N = 12) among patients (N = 26) with small HCC (<3 cm). CONCLUSIONS: Using pathway-based analysis, we successfully identified the pathways involved in recurrence of HBV-positive HCC that may be effectively used as prognostic markers.ope

Epigenetic modifications precede molecular alterations and drive human hepatocarcinogenesis

Development of primary liver cancer is a multistage process. Detailed understanding of sequential epigenetic alterations is largely missing. Here, we performed Infinium Human Methylation 450k BeadChips and RNA-Seq analyses for genome-wide methylome and transcriptome profiling of cirrhotic liver (n = 7), low- (n = 4) and high-grade (n = 9) dysplastic lesions, and early (n = 5) and progressed (n = 3) hepatocellular carcinomas (HCC) synchronously detected in 8 patients with HCC with chronic hepatitis B infection. Integrative analyses of epigenetically driven molecular changes were identified and validated in 2 independent cohorts comprising 887 HCCs. Mitochondrial DNA sequencing was further employed for clonality analyses, indicating multiclonal origin in the majority of investigated HCCs. Alterations in DNA methylation progressively increased from liver cirrhosis (CL) to dysplastic lesions and reached a maximum in early HCCs. Associated early alterations identified by Ingenuity Pathway Analysis (IPA) involved apoptosis, immune regulation, and stemness pathways, while late changes centered on cell survival, proliferation, and invasion. We further validated 23 putative epidrivers with concomitant expression changes and associated with overall survival. Functionally, Striatin 4 (STRN4) was demonstrated to be epigenetically regulated, and inhibition of STRN4 significantly suppressed tumorigenicity of HCC cell lines. Overall, application of integrative genomic analyses defines epigenetic driver alterations and provides promising targets for potentially novel therapeutic approaches.ope

Hepatocellular adenomas: recent updates

Hepatocellular adenoma (HCA) is a heterogeneous entity, from both the histomorphological and molecular aspects, and the resultant subclassification has brought a strong translational impact for both pathologists and clinicians. In this review, we provide an overview of the recent updates on HCA from the pathologists' perspective and discuss several practical issues and pitfalls that may be useful for diagnostic practice.ope

Prevalence and Clinicopathologic Features of Mucinous Cystic Tumor and Intraductal Papillary Mucinous Tumor of Pancreas in Korea

Background : Mucin producing cystic neoplasms, such as mucinous cystic tumor (MCT) and intraductal papillary mucinous tumor (IPMT) of the pancreas, are uncommon but become increasing in their incidences. The pathologic classification and biologic potential of these neoplasms remain the subject of controversy. Methods : The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists analyzed the clinicopathologic characteristics of 85 cases of MCT and 72 cases of IPMT and examined the expression patterns of p53, CEA and MUC1. Results : IPMT was located largely in the head, and showed connection with the main pancreatic duct (MPD, 68.1%), no ovarian-like stroma (0/72), and presence of intervening intratumoral normal or atrophic parenchyma. On the other hand, MCT was located largely in the tail (73%), and showed common ovarian-like stroma (66/80), rare connection with the MPD (7/85) and no intervening pancreatic parenchyma. CEA and p53 immunoexpressions were significantly increased from adenoma through borderline to carcinoma, but MUC 1 was expressed only in the invasive carcinoma among cases of MCT and IPMT. Conclusions : The tumor location, ovarian-like stroma, connection with the MPD and intratumoral intervening nonneoplastic tissue were helpful in the differential diagnosis between IPMT and MCT. CEA and p53 expressions can be indicators of malignancy, while MUC 1 expression can indicate invasion.ope

Reappraisal of pathological features of intraductal papillary neoplasm of bile duct with respect to the type 1 and 2 subclassifications

The pathological spectrum of intraductal papillary neoplasm of bile duct (IPNB) remains to be clarified. A total of 186 IPNBs were pathologically examined using the type 1 and 2 subclassifications proposed by Japanese and Korean biliary pathologists incorporating a two-tiered grading system (low-grade and high-grade dysplasia), with reference to four subtypes (intestinal [i], gastric [g], pancreatobiliary [pb], and concocytic [o] subtype). IPNBs were classifiable into type 1 composed of low-grade dysplasia and 'high-grade dysplasia with regular structures' (69 IPNBs), and type 2 of 'high grade dysplasia with irregular structures and complicated lesions' (117 IPNBs). Type 1 was more common in the intrahepatic bile duct (78%), whereas type 2 was frequently located in the extrahepatic bile duct (58%). Mucin hypersecretion was more common in type 1 (61%) than in type 2 (37%). IPNBs were classifiable into the four subtypes: 86 iPNBs, 40 gIPNBs, 31 pbIPNBs, and 29 oIPNBs. The four subtypes were histologically evaluable with reference to the type 1 and 2 subclassifications. iIPNB and pbIPNBs were frequently classified as type 2, whereas types 1 and 2 were observed at similar rates in gIPNB and oIPNB. Stromal invasion was almost absent in type 1, irrespective of subtype, but was found in 66 of 117 type 2 IPNBs (P < .01), and postoperative outcome was favorable in IPNBs without invasion compared with IPNBs with invasion (P < .05). The type 1 and 2 subclassifications with reference to the four subtypes may provide useful information for understanding IPNB.ope

SALL4 Expression in Hepatocellular Carcinomas Is Associated with EpCAM-Positivity and a Poor Prognosis

BACKGROUND: There is increasing interest in hepatocellular carcinomas (HCC) expressing "stemness"-related markers, as they have been associated with aggressive behavior and poor prognosis. In this study, we investigated the usefulness of Sal-like protein 4 (SALL4), a recently proposed candidate marker of "stemness." METHODS: Immunohistochemical stains were performed for SALL4, K19, and epithelial cellular adhesion molecule (EpCAM) on tissue microarrays constructed from 190 surgically resected HCCs, and the results were correlated with the clinicopathological features and patient survival data. RESULTS: Nuclear SALL4 expression was observed in 39/190 HCCs (20.5%), while K19 and EpCAM were expressed in 30 (15.9%) and 92 (48.7%) HCCs, respectively. The nuclear expression was generally weak, punctate or clumped. SALL4 expression was significantly associated with a poor overall survival compared to SALL4-negative HCCs (p = .014) compared to SALL4-negative HCCs. On multivariate analysis adjusted for tumor size, multiplicity, vascular invasion, and pathological tumor stage, SALL4 remained as a significant independent predictor of decreased overall survival (p= .004). SALL4 expression was positively correlated with EpCAM expression (p = .013) but not with K19 expression. HCCs that expressed both SALL4 and EpCAM were associated with significantly decreased overall survival, compared to those cases which were negative for both of these markers (p = .031). CONCLUSIONS: Although SALL4 expression was not significantly correlated with other clinicopathological parameters suggestive of tumor aggressiveness, SALL4 expression was an independent predictor of poor overall survival in human HCCs, and was also positively correlated with EpCAM expression.ope