Pathologie der hepato-pankreato-biliären Tumoren

Zusammenfassung. Die malignen Tumoren der hepato-pankreato-biliären Organe sind mehrheitlich typische Adenokarzinome mit Ausnahme der Leber, wo sie wegen ihrer charakteristischen Morphologie als hepatozelluläre Neoplasien bezeichnet werden. Neben diesen klassischen morphologischen Ansätzen haben in den letzten Jahren molekulare und vor allem morphomolekulare Untersuchungen viele neue Erkenntnisse ergeben, immer mit dem Ziel, den Patienten eine bestmögliche Therapie zukommen zu lassen. So wird heute zum Beispiel die fokale noduläre Hyperplasie (FNH) der Leber als reaktive Veränderung angesehen, welche keine weiteren Therapien braucht. Auf der einen Seite erlaubt die molekulare Stratifizierung der Leberzelladenome, Risikotumoren zu erkennen und entsprechend operativ zu behandeln. Als weiteres Beispiel seien Tumoren der extra- und intrahepatischen Gallengänge aufgeführt, welche heute in «Small-Duct-Type» und «Large-Duct-Type» unterschieden werden, welche unterschiedliche, therapeutisch relevante molekulare Profile aufweisen. Die vorliegende Arbeit gibt eine Übersicht über die wichtigsten und häufigsten Tumoren der hepato-pankreato-biliären Organe.

Cytokeratin 7 and Copper Stains Facilitate Diagnosis of Small Duct Primary Sclerosing Cholangitis

Introduction/Objective Classic primary sclerosing cholangitis (PSC) involves extrahepatic and/or intrahepatic biliary ducts with segmental biliary strictures and dilatations that often allow the diagnosis to be made via cholangiogram. Small duct PSC (sdPSC) is a rare subtype that presents similarly with a cholestatic pattern of injury, yet due to the small size of involved ducts, a cholangiogram is non-diagnostic and diagnosis is dependent on clinical suspicion and liver biopsy. The histopathological features of sdPSC are often subtle and may easily be overlooked. Diagnosis of this entity- though difficult- is important, as early recognition can facilitate the identification of associated disease processes and life-threatening complications. Methods/Case Report We encountered a 33-year-old female presenting with intermittent pruritis, episodes of jaundice, and persistently elevated alkaline phosphatase who was misdiagnosed with only fatty liver at an outside institution. Evaluation with MRCP showed no abnormalities within the biliary tract and a liver biopsy was performed to aid in the diagnosis. The H&E and trichrome findings of atrophic bile ducts and some peribiliary sclerosis were extremely subtle and may have been overlooked without clinical suspicion. Cytokeratin 7 (CK7) highlighted cholangiolar metaplasia in hepatocytes and the bile ductular reaction that occurs in cholestatic disease states. A Rhodamine copper stain showed periportal deposition suggestive of chronic biliary obstruction. Use of CK7 and copper stains supported the presence of chronic biliary injury and suboptimal bile flow, confirming the diagnosis of sdPSC. Results (if a Case Study enter NA) NA Conclusion Diagnosis of sdPSC has historically relied on H&E and trichrome stains. In this case, the findings on H&E and trichrome stains were non-diagnostic, while the use of CK7 and copper stains confirmed the diagnosis of sdPSC. We recommend using CK7 and copper stains to evaluate for sdPSC.

Histological Heterogeneity of Primary Liver Cancers: Clinical Relevance, Diagnostic Pitfalls and the Pathologist’s Role

Primary liver cancers (PLCs) mainly comprise hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and cHCC-CCA. Combined HCC-CCA and small duct type iCCA show similar clinical presentations, and their histological features are more complex than seen in HCC. Therefore, while their treatment strategy differs, it is difficult to properly diagnose these tumors. Currently, HCC is the only tumor that can be treated by liver transplantation. In addition, small duct type iCCA harbors IDH1/2 mutations and FGFR2 fusions, which can be used for targeted therapy. Thus, improving diagnostic accuracy is crucial. A further point to note is that PLCs often present as multiple liver tumors, and they can be a combination of different types of PLCs or HCCs. In the case of HCCs, two different scenarios are possible, namely intrahepatic metastasis, or multicentric occurrence. Therefore, it is essential to characterize the type of multiple liver tumors. This review aims to clarify the pathological features of HCC, iCCA and cHCC-CCA, including their diagnostic pitfalls and clinical relevance. It is designed to be of use to clinicians who are dealing with PLCs, to provide a better understanding of the pathology of these tumors, and to enable a more accurate diagnosis and optimal treatment choice.

Prognostic Value of Inflammatory and Tumour Markers in Small-Duct Subtype Intrahepatic Cholangiocarcinoma after Curative-Intent Resection

Intrahepatic cholangiocarcinoma (ICC) is characterised by heterogeneity, and it can be subdivided into small-duct and large-duct types. Inflammatory and tumour markers could effectively predict prognosis in many cancers, but no similar studies have been conducted in the histological subtypes of ICC. A total of 102 and 72 patients with ICC undergoing curative-intent resection were retrospectively subclassified into large-duct and small-duct types by chemical staining, respectively. The prognostic value of inflammatory and tumour markers was studied for the first time in histological subtypes of ICC by using a Cox regression model. A novel predictor named prognostic inflammatory index (PII) was proposed and defined as neutrophil × monocyte / lymphocyte count (109/L). Survival analysis showed that PII, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), CA242, and ferritin were all predictors of DFS and OS in patients with ICC ( P < 0.040 ). Subgroup analysis showed that PII, CA19-9, and ferritin were risk predictors of disease-free survival (DFS) and overall survival (OS) in small-duct type ICC ( P < 0.015 ). In addition, in small-duct type ICC, NLR and LMR were correlated with OS ( P < 0.025 ), whilst CEA and CA242 were correlated with DFS ( P ≤ 0.010 ). In conclusion, PII is a convenient and efficient inflammatory predictor of DFS and OS in ICCs and their small-duct type. NLR and LMR, rather than platelet-to-lymphocyte ratio, were correlated with OS in small-duct type ICC. In addition, ferritin may be a supplement to CA19-9 in stratifying the survival outcome of patients with small-duct type ICC.

Different iron-handling in inflamed small and large cholangiocytes and in small and large-duct type intrahepatic cholangiocarcinoma

Cholangiocarcinoma (CCA) represents the second most common primary hepatic malignancy and originates from the neoplastic transformation of the biliary cells. The intrahepatic subtype includes two morpho-molecular forms: large-duct type intrahepatic CCA (iCCA) and small-duct type iCCA. Iron is fundamental for the cellular processes, contributing in tumor development and progression. The aim of this study was to evaluate iron uptake, storage, and efflux proteins in both lipopolysaccharide-inflamed small and large cholangiocytes as well as in different iCCA subtypes. Our results show that, despite an increase in interleukin-6 production by both small and large cholangiocytes, ferroportin (Fpn) was decreased only in small cholangiocytes, whereas transferrin receptor-1 (TfR1) and ferritin (Ftn) did not show any change. Differently from in vitro models, Fpn expression was increased in malignant cholangiocytes of small-duct type iCCA in comparison to large-duct type iCCA and peritumoral tissues. TfR1, Ftn and hepcidin were enhanced, even if at different extent, in both malignant cholangiocytes in comparison to the surrounding samples. Lactoferrin was higher in large-duct type iCCA in respect to small-duct type iCCA and peritumoral tissues. These findings show a different iron handling by inflamed small and large cholangiocytes, and small and large-duct type iCCA. The difference in iron homeostasis by the iCCA subtypes may have implications for the tumor management.