Anatomical, histomorphological, and molecular classification of cholangiocarcinoma

Cholangiocarcinoma constitutes a heterogeneous group of malignancies that can emerge at any point of the biliary tree. Cholangiocarcinoma is classified into intrahepatic, perihilar and distal based on its anatomical location. Histologically, conventional perihilar/distal cholangiocarcinomas are mucin-producing adenocarcinomas or papillary tumours; intrahepatic cholangiocarcinomas are more heterogeneous and can be sub-classified according to the level or size of the displayed bile duct. Cholangiocarcinoma develops through multistep carcinogenesis and is preceded by dysplastic and in situ lesions. Definition and clinical significance of precursor lesions, including biliary intraepithelial neoplasia, intraductal papillary neoplasms of the bile duct, intraductal tubulopapillary neoplasms and mucinous cystic neoplasm, are discussed in this review. A main challenge in diagnosing cholangiocarcinoma is the fact that tumour tissue for histological examination is difficult to obtain. Thus, a major clinical obstacle is the establishment of the correct diagnosis at a tumour stage that is amenable to surgery which still represents the only curable therapeutic option. Current standards, methodology and criteria for diagnosis are discussed. Cholangiocarcinoma represents a heterogeneous tumour with regard to molecular alterations. In intrahepatic subtype, mainly two distinctive morpho-molecular groups can currently be discriminated. Large-duct type intrahepatic cholangiocarcinoma shows a high mutation frequency of oncogenes and tumour suppressor genes, such as KRAS and TP53 while Isocitrate Dehydrogenase 1/2 mutations and Fibroblast Growth Factor Receptor 2-fusions are typically seen in small-duct type tumours. It is most important to ensure the separation of the given anatomical subtypes and to search for distinct subgroups within the subtypes on a molecular and morphological basis

Analytical histopathological diagnosis of small hepatocellular nodules in chronic liver diseases

Due to the recent progress in radiology and increased clinical and pathological interest, small hepatocellular nodules about 1 cm in size are frequently being detected in patients with chronic liver disease, particularly liver cirrhosis. Two new types of small hepatocellular nodules are now known: low-grade hepatocellular carcinomas (HCC) and dysplastic nodules, in addition to the previously known HCC (classical) and regenerative nodules. Ultrasound-guided needle biopsies from these nodules are routinely used for the differential diagnosis. For comparison, a simultaneous needle biopsy from the liver remote from the nodule is strongly recommended. Low- grade HCC, which are different from classical HCC in their morphological atypia and also biological behaviors, show local invasion into the portal tracts and surrounding hepatic parenchyma, but not intrahepatic or extrahepatic metastasis. Dysplastic nodules show mild cellular and structural atypia, a finding which is not sufficient for making a diagnosis of malignancy. An increased nuclear/cytoplasmic (N/C) ratio and nuclear crowding, small cell-dysplasia, increased cytoplasmic staining, clear cell change, pseudogland formation, and fatty change of hepatocytes are variably seen in these nodules. Nuclear changes, local invasion to the portal tract and surrounding liver, and loss of the reticulum fibers along the hepatocytes are useful markers favoring low-grade HCC rather than dysplastic nodules. These low-grade HCC and dysplastic nodules should also be distinguished from classical HCC as well as large-sized regenerative nodules. A comparative analysis of the histological findings observed in individual nodules is a reasonable approach to differential diagnosis at present. The recognition and analysis of these two new hepatocellular nodules may augur a new horizon in the study of hepatocellular neoplasm

Histological Course of Nonalcoholic Fatty Liver Disease in Japanese Patients: Tight glycemic control, rather than weight reduction, ameliorates liver fibrosis

金沢大学医薬保健研究域医学系OBJECTIVE - The goal of this study was to examine whether metabolic abnormalities are responsible for the histological changes observed in Japanese patients with nonalcoholic fatty liver disease (NAFLD) who have undergone serial liver biopsies. RESEARCH DESIGN AND METHODS - In total, 39 patients had undergone consecutive liver biopsies. Changes in their clinical data were analyzed, and biopsy specimens were scored histologically for stage. RESULTS - The median follow-up time was 2.4 years (range 1.0-8.5). Liver fibrosis had improved in 12 patients (30.7%), progressed in 11 patients (28.2%), and remained unchanged in 16 patients (41%). In a Cox proportional hazard model, decrease in A1C and use of insulin were associated with improvement of liver fibrosis independent of age, sex, and BMI. However, ΔA1C was more strongly associated with the improvement of liver fibrosis than use of insulin after adjustment for each other (χ2; 7.97 vs. 4.58, respectively). CONCLUSIONS - Tight glycemic control may prevent histological progression in Japanese patients with NAFLD. © 2010 by the American Diabetes Association

A huge intraductal papillary mucinous carcinoma of the bile duct treated by right trisectionectomy with caudate lobectomy

<p>Abstract</p> <p>Background</p> <p>Because intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) is believed to show a better clinical course than non-papillary biliary neoplasms, it is important to make a precise diagnosis and to perform complete surgical resection.</p> <p>Case presentation</p> <p>We herein report a case of malignant IPMN-B treated by right trisectionectomy with caudate lobectomy and extrahepatic bile duct resection. Radiologic images showed marked dilatation of the left medial sectional bile duct (B4) resulting in a bulky cystic mass with multiple internal papillary projections. Duodenal endoscopic examination demonstrated very patulous ampullary orifice with mucin expulsion and endoscopic retrograde cholangiogram confirmed marked cystic dilatation of B4 with luminal filling defects. These findings suggested IPMN-B with malignancy potential. The functional volume of the left lateral section was estimated to be 45%. A planned extensive surgery was successfully performed. The remnant bile ducts were also dilated but had no macroscopic intraluminal tumorous lesion. The histopathological examination yielded the diagnosis of mucin-producing oncocytic intraductal papillary carcinoma of the bile duct with poorly differentiated carcinomas showing neuroendocrine differentiation. The tumor was 14.0 × 13.0 cm-sized and revealed no stromal invasiveness. Resection margins of the proximal bile duct and hepatic parenchyma were free of tumor cell. The patient showed no postoperative complication and was discharged on 10^thpostoperative date. He has been regularly followed at outpatient department with no evidence of recurrence.</p> <p>Conclusion</p> <p>Considering a favorable prognosis of IPMN-B compared to non-papillary biliary neoplasms, this tumor can be a good indication for aggressive surgical resection regardless of its tumor size.</p

Role of aetiology in the progression, regression, and parenchymal remodelling of liver disease: implications for liver biopsy interpretation

Clinicopathological concepts on acute and chronic liver disease have evolved rapidly during the last few years, with advances in general and specific treatment options and improved patient outcomes. The old paradigm of ‘irreversibility’ of cirrhosis had been challenged in major ways, and the validity of the usage of the term ‘cirrhosis’ has come into question. This paper addresses aetiology-based clinicopathological concepts and features that may deserve attention because they may determine disease outcome and, specifically, patterns of regression and remodelling. A variety of therapeutic interventions may influence remaining disease features after elimination of damaging agents (virus, alcohol, etc.), and determine the final clinical outcome including the risk of hepatocellular carcinoma (HCC). New concepts create new responsibilities and opportunities for the pathologist to contribute to the understanding of liver pathology and communicate this with clinical colleagues and researchers

Histology of portal vascular changes associated with idiopathic non-cirrhotic portal hypertension: nomenclature and definition.

Idiopathic non-cirrhotic portal hypertension (INCPH) is a rare vascular liver disease that has attracted new interest in recent years. It is characterised by clinical signs of portal hypertension in the absence of cirrhosis or severe fibrosis and any known cause of portal hypertension. As much uncertainty exists about INCPH pathophysiology, and no definite diagnostic tests are available, liver biopsy is an essential tool for achieving a definite diagnosis. Unfortunately, the histological diagnosis of INCPH is not always straightforward, as the characteristic lesions are unevenly distributed, vary greatly in their severity, are often very subtle, and are not all necessarily present in a single case. Furthermore, specifically for the characteristic portal vessel changes observed in INCPH, the terminology and definition are ambiguous, which adds complexity to the already complex clinicopathological scenario. An international study group of liver pathologists and hepatologists pursued a consensus on nomenclature for the portal vascular lesions of INCPH. Such standardisation may assist pathologists in the recognition of such lesions, and will possibly facilitate further advancement in this field

Acute deterioration of idiopathic portal hypertension requiring living donor liver transplantation: a case report.

Case reports of severe idiopathic portal hypertension (IPH) requiring liver transplantation are very rare. We report the case of a 65-year-old woman who was diagnosed as having IPH. At the age of 60 years, her initial symptom was hematemesis, due to ruptured esophageal varices. Computed tomography of the abdomen showed splenomegaly and a small amount of ascites, without liver cirrhosis. She was diagnosed as having IPH and followed-up as an outpatient. Five years later, she developed symptoms of a common cold and rapidly progressive abdominal distension. She was found to have severe liver atrophy, liver dysfunction, and massive ascites. Living donor liver transplantation was then performed, and her postoperative course was uneventful. Histopathological findings of the explanted liver showed collapse and stenosis of the peripheral portal vein. The areas of liver parenchyma were narrow, while the portal tracts and central veins were approximate one another, leading to a diagnosis of IPH. There was no liver cirrhosis. The natural history of refractory IPH could be observed in this case. Patients with end-stage liver failure due to severe IPH can be treated by liver transplantation

Diagnostic Dilemma in a Patient with Jaundice: How to Differentiate between Autoimmune Pancreatitis, Primary Sclerosing Cholangitis and Pancreas Carcinoma

A 68-year-old male patient was referred to our institution in May 2011 for a suspected tumor in the pancreatic head with consecutive jaundice. Using magnetic resonance imaging, further differentiation between chronic inflammation and a malignant process was not possible with certainty. Apart from cholestasis, laboratory studies showed increased values for CA 19-9 to 532 U/ml (normal <37 U/ml) and hypergammaglobulinemia (immunoglobulin G, IgG) of 19.3% (normal 8.0–15.8%) with an elevation of the IgG4 subtype to 2,350 mg/l (normal 52–1,250 mg/l). Endoscopic retrograde cholangiopancreatography revealed a prominent stenosis of the distal ductus hepaticus communis caused by pancreatic head swelling and also a bihilar stenosis of the main hepatic bile ducts. Cytology demonstrated inflammatory cells without evidence of malignancy. Under suspicion of autoimmune pancreatitis with IgG4-associated cholangitis, immunosuppressive therapy with steroids and azathioprine was started. Follow-up endoscopic retrograde cholangiopancreatography after 3 months displayed regressive development of the diverse stenoses. Jaundice had disappeared and blood values had returned to normal ranges. Moreover, no tumor of the pancreatic head was present in the magnetic resonance control images. Due to clinical and radiological similarities but a consecutive completely different prognosis and therapy, it is of fundamental importance to differentiate between pancreatic cancer and autoimmune pancreatitis. Especially, determination of serum IgG4 levels and associated bile duct lesions induced by inflammation should clarify the diagnosis of autoimmune pancreatitis and legitimate immunosuppressive therapy