Echinococcus multilocularis: Diagnostic problem in a liver core biopsy.

Echinococcus multilocularis causes an aggressive form of hydatidosis whose histomorphological picture is generally not well recognized. We report a case of 39-year-old women presenting with poorly circumscribed nodules in the right hepatic lobe. Owing to the clinical suspicion of focal nodular hyperplasia and hepatocellular adenoma, a core biopsy was performed. The histological findings of necrotic fibrous tissue infiltrated by narrow epithelial cords and small cysts containing cytokeratin positive material were in concordance with the diagnosis of cholangiocarcinoma. Subsequent examination of the surgically resected necrotic nodules with a vital tissue at the periphery corresponded to a reparative fibrosis accompanied by a striking ductular proliferation. Serological and molecular genetic work-up led to the diagnosis of Echinococcus multilocularis. The aim of this report is to point out the unusual histological features of the solid foci of alveolar hydatidosis, which consisted of necrotic fibrous tissue with ductular reaction. Such findings in a core biopsy may simulate regressively altered carcinoma.

Esophageal dysplasia and adenocarcinoma: a study with double immunostaining for intestinal and gastric markers.

Columnar lined esophagus is a complication of long term gastroesophageal reflux disease and the main precursor of esophageal adenocarcinoma. Incomplete intestinal metaplasia in reflux esophagitis represents one of the most important risk factors for neoplastic transformation through the metaplasia-dysplasia-adenocarcinoma sequence. However, recent studies suggest that cardiac type mucosa also shows molecular abnormalities which are similar to those of incomplete intestinal metaplasia. Immunohistochemically, three types of esophageal dysplasia and adenocarcinoma are recognized: adenomatous-intestinal, hybrid/mixed and foveolar gastric types. We are interested in the phenotypes of these dysplasias and adenocarcinomas, especially in the possible relationship between them. For this reason, we evaluated the immunohistochemical expression of intestinal and gastric markers in a series of 30 cases of esophageal high-grade dysplasia (high-grade intraepithelial neoplasia) and of 70 adenocarcinomas. For immunohistochemical classification, we used double immunohistochemical reactions CDX2/MUC5AC and CDX2/MUC6, respectively. In cases of incomplete intestinal metaplasia, hybrid/mixed high-grade dysplasia and hybrid/mixed adenocarcinoma, we found the expression of gastric mucins MUC5AC and MUC6 only in cells with intestinal differentiation (with nuclear positivity for CDX2). The double immunostaining excluded the presence of the cells with "pure" foveolar gastric phenotype in hybrid lesions. Thus, the hybrid category actually represents the intestinal type dysplasia/adenocarcinoma (which is known to have a better prognosis than the foveolar gastric type). Keywords: immunohistochemistry - double immunostaining - reflux esophagitis - Barrett esophagus - esophageal dysplasia - esophageal adenocarcinoma.

[Serrated adenomas and carcinomas of the colon]. / Serrated adenomy a karcinomy tlustého streva.

Approximately 5 - 35 % of colorectal carcinomas arise through serrated carcinogenesis. The precursor of such carcinomas are serrated adenomas, which differ from conventional adenomas morphologically as well as genetically. Herein, we provide a basic overview of serrated lesions of the large intestine with the focus on histological diagnosis and molecular biology.

Pyloric gland adenoma: a histologic, immunohistochemical and molecular genetic study of 23 cases.

Pyloric gland adenoma is a rare neoplasm with a gastric epithelial differentiation. We report 23 cases of pyloric gland adenoma in older persons, with a mean age of 74 years (range 52 - 87 years). They occurred in the esophagus (3 cases), corporal gastric mucosa (7 cases), duodenum (10 cases), gallbladder (2 cases), and choledochus (one case). Histologically, they were characterized by closely packed pyloric gland-type tubules with a monolayer of cuboidal to low columnar epithelial cells containing basally located round nuclei, and a superficial layer of tall, columnar, foveolar-type epithelium. Immunohistochemically, most tumor glands expressed pyloric gland mucin MUC6, whereas MUC5AC was positive in superficial gastric foveolar epithelium, and in a minority of glands. In addition, scattered neuroendocrine cells positive for chromogranin A and/or synaptophysin were seen in all cases. In 3 cases (two cases in the gallbladder and one case in the esophagus), areas of intestinal metaplasia with CK20, CDX2, and MUC2 positivity were found. Focal low-grade dysplasia was found in five cases (21.7%), and diffuse high-grade dysplasia was seen in one adenoma (4.4%), i.e., 6 of 23 PGAs (26.1%) showed dysplastic features. In one esophageal case, an invasive adenocarcinoma was diagnosed. Scattered p53 positive cells were found in all cases. Their number was higher in lesions with low-grade dysplasia and it was substantially increased in adenoma with high-grade dysplasia and in adenocarcinoma. Our molecular genetic results indicate that pyloric gland adenomas neoplastic nature is associated with p53 accumulation, mutations in oncogenes GNAS, KRAS, CTTNB1 and tumor suppressor genes SMAD4, and TP53. Pyloric gland adenoma can evolve into dysplasia and adenocarcinoma.

Intestinal metaplasia of the stomach and esophagus: an immunohistochemical study of 60 cases including comparison with normal and inflamed intestinal mucosa.

Recently, a new classification of intestinal metaplasia (IM) using immunohistochemical mucin markers was proposed. Two following types of IM were defined: (1) a mixed gastric and intestinal type also called incomplete IM; (2) a purely intestinal type, also called complete IM. We present a series of 30 cases of gastric IM and 30 cases of IM of the esophagus, using this new classification. In all gastric cases, IM developed in the mucus-neck region in the form of incomplete IM. Toward the mucosa surface, it matured gradually into complete IM. This maturation showed a gradual reduction of both foveolar mucin MUC5AC and pyloric gland mucin MUC6. In two of 30 cases, IM was of the incomplete hyperproliferative type. In one case, focal high-grade adenomatous dysplasia was found in the incomplete IM. In the esophageal cases, IM was found in inflamed cardiac-type mucosa, and it was usually of the incomplete type, with almost diffuse positivity for MUC5AC and with rare positivity of MUC6. The goblet cells and some cylindrical cells expressed intestinal mucin MUC2. The proliferation was higher than in the complete IM, and in one case, focal low grade adenomatous dysplasia was found. In addition, we examined the expression of mucins in normal and inflamed intestinal mucosa. These cases included 50 duodenal biopsies, 50 biopsies from the ileum, and 50 biopsies from the colon. The inflamed cases included celiac disease, Crohn's disease, and ulcerative colitis. Some goblet cells of the normal intestinal mucosa expressed both MUC2 and MUC5AC. More numerous MUC5AC+ goblet cells were found in the inflamed intestinal mucosa. In the duodenal and small intestinal mucosa, even the MUC6 positivity of a few goblet or cylindrical cells was found. In sum, our results indicate that incomplete IM is an initial step of the metaplastic process. It can mature into complete IM, or alternatively, it can develop dysplasia or adenocarcinoma. In addition, we found that gastric-type mucins are also present in normal or inflamed intestinal mucosa, and that the expression of these mucins is even enhanced in some inflammatory conditions. The expression of MUC5AC in complete IM and in normal or inflamed mucosa suggests that MUC5AC cannot be regarded as a marker of immaturity. In Barrett esophagus, our results were similar to those of previous studies, except for CDX2 of which reactivity was seen also in incomplete type of IM.

Angiofibroma-like perineurioma. Report of a case.

We report an unusual perineurioma with numerous vessels, showing a strong similarity with angiofibroma. A 2,5 x 2 x 2 cm subcutaneous/dermal tumor occurred in 58-ys-old male in the left brachial region. Histologically, it was composed of haphazardly arranged bland spindle cells and it contained prominent vasculature. In rare foci, the tumor cells showed thin bipolar processes and an onion-like perivascular whorling pattern. Immunohistochemically, expression of perineural cell markers EMA, claudin-1 and CD34 was limited to perivascular foci and to rare cells among the vessels. In addition, the tumor expressed CD10 diffusely. Our finding indicates that diagnosis of perineurioma should be considered also by tumors with an "angiofibromatous" morphology. Especially soft tissue angiofibroma, which often express EMA (perineural cell marker), shows a strong resemblance to angiofibroma-like perineurioma.

Gastric dysplasias. A clinicopathological study of 35 cases.

Gastric epithelial dysplasia (GED) represents a recognized precursor lesion of gastric adenocarcinoma. GED types can be classified according to its morphology and patterns of mucin expression into adenomatous (intestinal), foveolar (gastric) and hybrid (mixed) types. We examined gastroscopic specimens with GED in 35 patients (21 men and 14 women, mean age 69.6 years). Adenomatous dysplasia was present in 17 patients (49 %), and was of low grade in 14 cases and high grade in 3 cases. Foveolar type dysplasia was found in 16 patients (46 %), and almost in one half of the cases it was high grade (in 7 cases, i.e. 46 %). In one woman, low grade foveolar dysplasia was found in polypoid mucosal prolapse of the gastric antrum. Hybrid dysplasia was found in only 2 cases (0.6 %), and in both of them this dysplasia was predominantly of foveolar type. One case was of low-grade and the second case was of a high-grade type. In our series GED was found mostly in the antrum. The findings in the adjacent mucosa usually included HP negative inactive chronic gastritis with intestinal metaplasia of both complete and incomplete types. In our series, foveolar type dysplasia was more frequent in comparison with previous studies. Our findings show that high grade dysplasia is more frequent in foveolar GD than in adenomatous GD, and this is in keeping with previous published findings.

Inhibition of transforming growth factor beta-1 augments liver regeneration after partial portal vein ligation in a porcine experimental model.

BACKGROUND/AIMS: TGF-ß1 is a pleiotropic cytokine that is over expressed in terminal phase of liver regeneration. METHODOLOGY: Twenty-four hours after partial portal vein ligation monoclonal antibody against TGF-ß1 (TGF-ß1 group, 7 piglets) or physiological solution (control group, 9 piglets) were applied into the central venous catheter. The biochemical parameters (bilirubin, urea, creatinine, alkaline phosphatase, gamma- glutamyl transferase, cholinesterase, aspartate aminotransferase, alanine aminotransferase and albumin) were assessed. The compensatory hypertrophy of the non-occluded liver lobes was evaluated by periodic ultrasonography during the next fourteen days and by histological examination. RESULTS: The acceleration of growth of the hypertrophic liver lobes was maximal between 3rd and 7th postoperative days in comparison with the control group (p<0.05). No important differences in the biochemical or studied histological parameters were proved. CONCLUSIONS: The present study describes a new usage of monoclonal antibody against TGF-ß1 in large animal experimental model of partial portal vein ligation.

Tumour necrosis factor-alpha stimulates liver regeneration in porcine model of partial portal vein ligation.

BACKGROUND/AIMS: Portal vein ligation (PVL) could multiply the future liver remnant volume (FLRV). Tumor necrosis factor- alpha (TNF-α) is a pleiotropic cytokine that is connected with initial phase of liver regeneration. The aim of this basic pilot study was to accelerate regeneration of liver parenchyma after PVL. The experimental porcine model was developed to be as much compatible as possible with portal vein embolization (PVE) in human medicine. METHODOLOGY: After ligation of portal branches of caudate and right lateral and right medial liver lobes recombinant porcine TNF-α (TNF-α group) or physiological solution (control group) were applied into non-occluded portal vein branches. The biochemical and immunoanalytical parameters were assessed. The compensatory hypertrophy was evaluated by periodic ultrasonography. The histological examination of liver was performed. RESULTS: The acceleration of growth of hypertrophic liver lobes was maximal at the 7th postoperative day in comparison with the control group (p<0.05); nevertheless this stimulating effect was lost at the end of experiment. The important differences in biochemical or histological studied parametres between study groups were not proved. CONCLUSIONS: The achieved acceleration of growth of hypertrophic liver lobes after application of TNF-α confirms the role of studied cytokine in priming of liver regeneration.

Interleukin-6 augments activation of liver regeneration in porcine model of partial portal vein ligation.

BACKGROUND: Portal vein ligation (PVL) could multiply the future liver remnant volume (FLRV). Interuleukin-6 (IL-6) is a pleiotropic cytokine that is associated with an initial phase of liver regeneration. The aim of this study was to accelerate the regeneration of liver parenchyma after PVL by intraportal cytokine application. MATERIALS AND METHODS: After ligation of portal branches of caudate and right lateral and right medial liver lobes, recombinant porcine IL-6 (IL-6 group) or physiological solution (control group) were applied into non-occluded portal vein branches. The biochemical and immunoanalytical parameters were assessed. The compensatory hypertrophy was evaluated by periodic ultrasonography. The histological examination of liver was performed. RESULTS: The acceleration of growth of hypertrophic liver lobes was maximal at the 7th postoperative day in comparison with the control group (p<0.05), nevertheless, this stimulating effect was lost at the end of the experiment. Important differences in biochemical or histological studied parametres were not proved. CONCLUSION: The presented study describes the use of IL-6 for stimulation of the first phase of liver regeneration. The achieved acceleration of growth of hypertrophic liver lobes after application of IL-6 confirmed the key role of the studied cytokine in priming regenerating liver parenchyma after portal vein ligation.

Intraportal injection of porcine multipotent mesenchymal stromal cells augments liver regeneration after portal vein embolization.

UNLABELLED: Portal vein embolization (PVE) can be used prior to liver surgery to increase the volume of the remaining liver tissue after an extensive resection. However, the application of PVE is limited and new strategies to augment liver regeneration by cellular therapy are promising alternatives. MATERIALS AND METHODS: The influence of syngeneic multipotent mesenchymal stromal cells (MSC) on liver regeneration was analysed after the ligation of the right portal vein branches in a porcine model, closely mimicking the situation of human surgery. Liver regeneration was monitored by ultrasonography, immunohistological analysis and serum biochemistry. RESULTS: The volume of the contra-lateral, non-ligated liver lobe increased in all piglets after portal vein ligation. This hyperplasia occurred earlier and was more pronounced in those piglets receiving MSC infusions as compared to non-treated controls. Biochemical liver function was stable in all pigs. Only solitary transplanted MSC were detected in recipient livers two weeks after the infusion. CONCLUSION: The infusion of porcine MSC into the portal vein in a setting of liver regeneration after surgical resection leads to accelerated and augmented hyperplasia. This effect is most likely due to bystander effects of the transplanted MSC.

Krukenberg tumor with yolk sac tumor differentiation.

An unusual case of bilateral Krukenberg tumor with foci of yolk sac tumor (YST) differentiation occurring in a 50-year-old patient is reported. The primary tumor was in the gastric antrum, and it showed morphology of poorly differentiated adenocarcinoma with diffuse and solid growth pattern. A component of typical YST was not found in the gastric primary and lymph node metastases, although some cells in these locations were positive for alpha-fetoprotein. In the ovarian metastases, YST element showed microcystic/reticular and solid patterns, whereas the adenocarcinoma component was of diffuse type with signet ring cells and with some undifferentiated areas. The case represents further example of the somatic cell-derived tumor with focal germ cell-type differentiation and the first report of YST differentiation in Krukenberg tumor.

Experimental hepatic uroporphyria induced by the diphenyl-ether herbicide fomesafen in male DBA/2 mice.

Hepatic uroporphyria can be readily induced by a variety of treatments in mice of the C57BL strains, whereas DBA/2 mice are almost completely resistant. However, feeding of the protoporphyrinogen oxidase-inhibiting herbicide fomesafen (0.25% in the diet for 18 weeks) induced hepatic uroporphyria in male DBA/2N mice (liver porphyrin content up to 150 nmol/g, control animals 1 nmol/g), whereas fomesafen-treated male C57BL/6N mice displayed only a slight elevation of liver porphyrins (approximately 5 nmol/g). The profile of accumulated hepatic porphyrins in fomesafen-treated DBA/2N mice resembled the well-characterised uroporphyria induced by polyhalogenated aromatic hydrocarbons, while histological examination confirmed the presence of uroporphyria-specific cytoplasmic inclusions in the hepatocytes. Uroporphyrinogen decarboxylase activity decreased to about 30% of control values in fomesafen-treated DBA/2N mice; microsomal methoxyresorufin O-dealkylase activity was slightly reduced. The amount of CYP1A1 and CYP1A2 mRNA, as determined by real-time PCR, was not significantly changed; mRNA encoding the housekeeping 5-aminolevulinic acid synthase was elevated 10-fold. Total liver iron was slightly increased. A similar uroporphyria was induced by the herbicide formulation Blazer, containing a structurally related herbicide acifluorfen, when fed to DBA/2N mice at a dose corresponding to 0.25% of acifluorfen in the diet. Since DBA/2 mice are almost completely resistant to all well-characterised porphyrogenic chemicals, the results suggest the possible existence of a yet unknown mechanism of uroporphyria induction, to which the DBA/2 mouse strain is more sensitive than the C57BL strain.