Hans-Udo Kasper

Hepatic granulomas: histological and molecular pathological approach to differential diagnosis–a study of 442 cases

Background/Aims: The incidence of hepatic granulomas is reported in 2–15% of liver biopsies. This study was carried out to evaluate the incidence and aetiology of hepatic granulomas in a German Institute of Pathology with specialization in liver diseases.

Experimental bile duct protection by intraductal cooling during radiofrequency ablation.

The use of radiofrequency ablation (RFA) for liver tumours is limited by the proximity of large bile ducts to the targeted lesion. The aim of this randomized study was to evaluate intraductal cooling as a mean of protecting the bile ducts during RFA.

Mixed hepatoblastoma in an adult

We report a case in an elderly adult of a highly malignant liver tumor with blastoid features that resembled hepatoblastoma. A liver tumor with a diameter of 23 cm was removed in a 78-year-old woman. The tumor showed highly differentiated epithelial hepatocellular and poorly differentiated epithelial and mesenchymal components. The blastoid nature and pluripotent differentiation potential were supported by immunohistologic analysis and suggest an origin of a poorly differentiated pluripotent hepatic cell with the potential to mature. We believe that this case of a mixed hepatoblastoma in an adult should be added to the growing number of presumed hepatic precursor cell neoplasms in adults.

Rhinoscleroma associated with Rosai–Dorfman reaction of regional lymph nodes

Rhinoscleroma is an uncommon chronic, destructive infection of the respiratory mucosa caused by Klebsiella rhinoscleromatis. This coccobacillus can be found in the typical histiocytes, the Mikulicz cells. Extranasal and nodal involvement in this disease is rare, but documented. Rosai–Dorfman disease or sinus histiocytosis with massive lymphadenopathy is also a rare, non‐hereditary disorder. Bilateral cervical lymphadenopathy with emperipolesis, as the main histological characteristic, is the most common presentation. It can also occur extranodally. We report a case of rhinoscleroma occurring in a 62‐year‐old woman since 1984, who developed parotid gland and lymph node involvement. The changes in the nasal mucosa and the parotid gland showed chronic inflammation with Mikulicz cells. In the lymph nodes, features characteristic of Rosai–Dorfman disease were seen. Taking into consideration the literature dealing with both of these diseases, we discuss that Rosai–Dorfman disease could be a special type of lymph node reaction and is not necessarily an entity of its own. Therefore, it should be known as Rosai–Dorfman lymph node reaction. Furthermore, there seems to be an interconnection between Rosai–Dorfman disease and rhinoscleroma.

Pathomorphological changes after radiofrequency ablation in the liver.

Radiofrequency ablation (RFA) has become a widespread treatment option for liver carcinoma. There is limited knowledge regarding the macroscopic and histomorphological changes of induced lesions. Twelve domestic pigs underwent RFA using a Starburst XL device with ablation diameter of 3 cm. One animal died within 24 h, two animals were killed after 2 weeks, and nine after 4 weeks. Their livers were used for macroscopic and histological investigation. Six human liver resection specimens after previous treatment with RFA were also investigated. In pig samples, acute RFA change showed a necrosis zone demarcated by resorption zone with granulocytes and hyperemia. In subchronic and chronic RFA change, the zone of thermofixation was followed by a fibrous capsule and a liver reaction zone. Small blood vessels in the lesions showed damage involving endothelial destruction and thrombosis. Larger vessels within the lesions were observed with intact vessel walls, surrounded by a rim of vital hepatocytes. In the human samples, tumor‐infiltrating lymphocytes were reduced (CD3+ cells: 8.4 ± 3.7/10 high‐power fields (HPF); CD4+ cells: 4.2 ± 1.9/10 HPF), whereas the number of histiocytes was found to be increased (CD68+ cells: 15.5 ± 9.02/10 HPF). The recognition of thermofixation and the process of resorption of the RFA lesion is important for the interpretation of biopsies and surgical resection specimens.

Competition Between Native Liver and Graft in Auxiliary Liver Transplantation in a Rat Model

The competition between the native and the grafted liver in heterotopic auxiliary liver transplantation (HALT) with portal vein arterialization (PVA) was investigated in a rat model. The experimental groups were: HALT with flow-regulated PVA and 70% resection of a native liver and graft (n = 32; group I) versus 70% liver resection (n = 32; group II). After HALT, the weight of the native liver increased until the sixth postoperative week (431% +/- 55% of the intraoperative weight), whereas, the graft weight was only 76% +/- 31% of the intraoperative weight at this time. In group II, liver weight increased continuously to 529% +/- 30% of the intraoperative weight after 6 weeks. On postoperative day 2, there was significantly increased proliferative hepatocellular activity in all groups. This was highest in the resected livers of group II, followed by the native livers of group I, and the grafts of group I (301 +/- 126 vs 262 +/- 97 vs 216 +/- 31 Ki-67-positive hepatocytes/10 visual fields). However, the differences between the groups were not significant. With regard to hepatocellular apoptosis, the livers were similar among all groups and at all time points, M30-positive hepatocyte counts were <or=1/10 visual fields, which was equivalent to normal values. After HALT with flow-regulated PVA, the native liver regenerated and the graft showed atrophy, most likely caused by the lack of hepatotrophic factors in the arterialized graft portal vein blood. Regeneration of the 70% resected native liver in the presence of an arterialized heterotopic auxiliary liver graft was less pronounced than the regeneration of a 70% resected liver without HALT. Native liver regeneration seemed negatively influenced by a graft, suggesting a competition between the 2 livers.

Liver distribution of γδ-T-cells in patients with chronic hepatitis of different etiology

The γδ T cells represent a minor unique T‐cell subpopulation long been considered as innate‐like immune cells. They are found in increased numbers in tissues from various inflammatory conditions. Their role in chronic hepatitis, however, is still discussed controversially. Fresh frozen tissues from 50 patients (18 cases hepatitis B infection, 25 hepatitis C, three cases with co‐infection of hepatitis B and C and four patients with autoimmune hepatitis) were investigated. Immunohistochemistry with primary antibodies detecting αβ and γδ TCR was used to evaluate their incidence and distribution in the different histological structures of the liver. The inflammatory infiltrate in all cases of chronic hepatitis was dominated by αβ T cells and was mainly localized in the portal tracts with formation of an interface hepatitis (95.3%αβ T cells; 4.7%γδ T cells). There were neither significant differences between inflammatory infiltrate nor the amount or percentage of γδ T cells between hepatitis B, C or autoimmune hepatitis. No accumulation of γδ T cells could be observed in cases of chronic hepatitis of different etiologies. The immune‐mediated phenomena in chronic hepatitis are dominated by αβ T cells. Thus, the adapted immune system is responsible for the inflammatory processes in chronic hepatitis.

Morphology of drug induced liver damage

ZusammenfassungLeberschäden sind eine häufige Komplikation einer medikamentösen Therapie. Ihre Diagnose ist schwierig und meist nur als Ausschlussdiagnose zu stellen, da medikamentös-toxische Leberschäden fast alle Formen einer Hepatopathie imitieren können. Morphologisch werden je nach der betroffenen Zielzelle akute und chronische Leberschäden vom hepatitischen Typ, eine Granulombildung und Verfettung, eine akute oder chronische cholestatische Schädigung in Form einer reinen Cholestase, einer Cholestase mit Entzündung oder gemischte Schäden unterschieden. Eine Fibrose kann bei jeder Schädigung als portale Fibrose oder als perisinusoidale Fibrose auftreten. Vaskuläre Schäden oder Neubildungen sind selten. Den Veränderungen liegt häufiger ein nichtvorhersehbarer und im Tierexperiment nicht nachzuvollziehender Typ-B-Schaden als ein aus Toxizitätsstudien bekannter Typ-A-Schaden vor. Da es keine spezifische Therapie gibt, sind eine frühzeitige Erkennung und das Absetzen des Medikaments notwendig.AbstractHepatotoxicity is a significant complication of therapeutic drug use. As ist can imitate nearly all hepatopathies, the diagnosis of drug-induced liver disease is difficult. Most often, it is a diagnosis of exclusion. The following morphological changes are known, dependent on the target cell type: acute and chronic hepatitis, granuloma formation, and fatty liver disease, cholestatic type acute and chronic liver damage with or without inflammation,or mixed forms of liver injury. Portal or perisinusoidal fibrosis can occur following each type of liver damage. Vascular changes or neoplasms are rare. Drug induced liver injuries are more likely induced by type B damage, which is not expectable and cannot be reproduced in animal testing. Type A damage, which is known from toxicity assays, is less likely. A specific therapeutic regime is not available. Therefore, early recognition and cessation of the use of the drug is necessary.

Florid ischemic cholangitis due to leucocytoclastic vasculitis

Ischemia-induced biliary tract lesions, called ischemic cholangitis, often lead to strictures of biliary ducts and cholestasis. Causes of ischemic changes of the biliary tract can be found in the arterial blood supply or in the peribiliary capillary plexus. Known examples are thrombosis after transplantation, intraoperative ligation, or the application of chemotherapeutic drugs. Rarely, such changes are due to inflammation of the blood vessels, such as occurs in polyarteritis nodosa or giant cell arteritis. We present a report of a 49-year old man with leucocytoclastic vasculitis after viral infection, influenza vaccination, and antibiotic treatment, leading to florid ischemic cholangitis. We conclude that hypersensitivity vasculitis must be included in the differential diagnosis of cholestasis and cholangitis.

Cryopreservation of precision cut tissue slices (PCTS): Investigation of morphology and reactivity

Precision cut tissue slices (PCTS) represent a suitable and convenient tool for pharmacological, toxicological and morphological studies. Cryopreservation would enable to overcome the shortage of liver tissue, in particular in settings using human liver tissue. We investigated the potential of cryopreservation of porcine PCTS as a morphological tool by rapid freezing with 10% and 30% dimethyl sulfoxide as cryopreservation agents and with or without medium using a Brendel/Vitron tissue slicer. Incubation after thawing was done in a static incubation system. Slices were cultured for 3 h, 6 h, 24 h and 48 h and assessed histologically and immunohistologically for proliferation (Ki67) and spontaneous as well as induced apoptotic activity (M30Cytodeath). Vitality was tested using the Tox-8 test. After cryopreservation, morphology of PCTS was well preserved up to 24 h. A reduction of vitality rate took place. Compared to non-frozen PCTS, the rate of spontaneous proliferation of Kupffer cells and apoptosis of hepatocytes were significantly reduced independent of the freezing conditions. The reactivity of PCTS to apoptotic stimuli was significantly reduced in tissue slices after cryopreservation. Apoptotic stimuli could not induce the same amount of cell deaths compared to non-frozen sections. Thus, cryopreservation of PCTS does interfere with pathomechanisms of apoptosis in PCTS.