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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.

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.

Hamartoma of mature cardiac myocytes (HMCM) is a rare benign pseudoneoplastic myocardial lesion. We describe a case of 39-year-old Bulgarian woman living in the Czech Republic, who died because of rupture of anterior communicating artery aneurysm, and severe bronchopneumonia. An incidental finding at the autopsy was a whitish unencapsulated and not sharply demarcated tumor of the left ventricle and adjacent area of interventricular septum, which protruded above the plane of section. Microscopically the tumor consisted of various different forms of disorganized hypertrophic mature cardiac myocytes without vacuolization of cytoplasm, focally in a "herringbone" pattern. Dilated venules and thickened intramural coronary arteries, and intervening bands of connective tissue were present between cardiomyocytes in the tumor. Immunohistochemical staining of MIB1 for the detection of proliferative activity was completely negative. No inflammatory infiltration, adipose tissue or calcifications were present in the tumor.

Background: Patients with sensitive EGFR mutations are already being treated with first and second generation tyrosine kinase inhibitors (TKIs). However, resistance to these drugs occurs over time, and over half of all cases is caused by a mutation (T790M) in the EGFR kinase domain. Osimertinib offers a new treatment option that overcomes this problem. Unfortunately, resistance to this drug also develops after several months of treatment and is caused by another mutation (C797S) in EGFR., Case Report: Our case report provides evidence for the progressive development of EGFR-TKI resistance in a patient with a deletion of exon 19 in the EGFR gene. First, based on a mutation (T790M) identified after afatinib treatment and a subsequent mutation (C797S) mutation identified after osimertinib treatment. We mention overcoming this resistance (C797S) mutation by using 4th generation EGFR-TKI and other alternative procedures (chemotherapy, immunotherapy, and combinations of older EGFR-TKI generations). We also mention a rare case of peritoneal metastasis that occurred after previous treatment with osimertinib that we attempted to ameliorate by using erlotinib because the impaired condition of the patient did not allow treatment by chemotherapy. There are documented cases in which erlotinib has been successfully given to patients with peritoneal metastases and patients with the EGFR mutation C797S following progression to afatinib. This was not the case in our patient, probably because of the remaining EGFR mutation T790M., Conclusion: In our case report, erlotinib did not show efficacy after progression to osimetinib. Nowadays, chemotherapy is the only possible treatment in patients with good a performance status. The next-generation of TKIs are undergoing promising developments.Key words: EGFR - deletion on exon 19 - mutation T790M - mutation C797S - afatinib - osimertinibSubmitted: 12. 9. 2017Accepted: 12. 10. 2017 This project was supported by grant AZV 17-30 748A. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

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.

Goblet cell carcinoid (GCC) of the appendix is extremely rare, representing approximately 5% of all primary appendiceal neoplasms. Histologically there are three groups of GCC: group A (typical GCC), adenocarcinoma ex GCC signet ring cell type (group B), and adenocarcinoma ex GCC poorly differentiated carcinoma type (group C), which is the most aggressive. GCC metastasizes in 15-60% of cases, mainly to the ovaries, pelvis, abdominal cavity, ribs, vertebrae, and lymph nodes. Hematogenous metastasis to the liver or other parenchymal organs can occur, but this is very rare. The different organs metastases havent been described yet. The primary mode of treatment is radical surgical resection or debulking, followed by chemotherapy; however, patients with unresectable or recurrent GCC are candidates for systemic therapy. Here, we report a case of very aggressive GCC of the appendix, which had metastazed to the liver at the time of diagnosis and subsequently metastasized to the orbit.

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.

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.

The authors present two cases of Ewing-like sarcoma of the humerus and femur of a 12-year-old boy and a 28-year-old male, respectively. Identical morphology in both tumors consisted of multiple solid nests with a mosaic collection of small, round, uniform cells with clear cytoplasm and no apparent nuclear atypia. A monotonous structural arrangement, including both rich vascularity of bordering septae and significant admixtures of eosinophil leucocytes, resulted in a final organoid "neuroendocrine-like" pattern. Immunohistochemistry revealed diffuse strong CD10, CD99 and CD138 positivity. Detailed molecular analysis in both tumors confirmed translocation t(20;22) resulting in an EWSR1-NFATc2 fusion gene. Additionally, this translocation was accompanied by amplification of the proximal part of the genes and surrounding areas. Clinically, both neoplasms behaved aggressively and they were primarily chemoresistant. Four years later, the patient with the lesion in the humerus developed a massive local recurrence with a disruption of osteosynthesis. The last follow-up disclosed suspicious metastatic deposits in the lung. The boy with the femoral tumor underwent a total femoral prosthesis and there are no signs of local or systemic recurrence after 11 months of follow-up. The authors discuss the taxonomic placement of these rare examples of Ewing-like sarcoma family in the light of new molecular discoveries.

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 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.

Eight cases of ganglioneuroma were examined for a presence of perineural cell differentiation, using the immunohistochemical markers epithelial membrane antigen (EMA), claudin-1 and GLUT-1. The mean age of the patients was 42.3 years (range 26-68 years), six patients were females and two were males. Five tumors were located in the adrenal gland and 3 tumors in the retroperitoneum. Morphology of the tumors was typical, i.e., they were composed of neuroid spindle cell population and scattered mature appearing ganglion cells. Spindle cells positive for perineural cell markers claudin-1 and GLUT-1 were found in all lesions, at least focally. EMA+ cells were seen in 2 of 8 tumors. These perineural-type cells were often arranged in organoid fashion around the schwannoid bundles or around the vessels. Our findings indicate that perineural cell differentiation is commonly present in ganglioneuromas.