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Volume 39, Issue 1, 2025

Online ISSN: 3042-3511

ISSN: 3042-3503

Volume 39 , Issue 1, (2025)

Published: 31.03.2025.

Open Access

Welcome to Issue 39, No. 1 – the first of our two annual publications for this year. Inside, you'll find a curated selection of articles. Start your year with the essential knowledge and perspectives offered in this timely edition

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01.04.2018.

Abstracts

The von Meyenburg complex

Introduction: Hamartomas of the bile duct named von Meyenburg complex are benign liver lesions consisting of dilated bile duct structures with a surrounding fibrous stroma. Their incidence is age-dependent and they are observed about 1% in children and 5%-6% in adults. Von Meyenburg complexes are infrequently observed lesions, characterized by multiple small nodular lesions located below the Glisson’s capsule, and ranging from 0.1 to 1.0 centimeters in diameter. Von Meyenburg complex of the liver are usually detected during laparotomy or autopsies an incidental finding. Multilocular occurrence is possible although they are rarely spread throughout the whole liver, as it was observed in our patient. They are normally asymptomatic, and are incidental findings in asymptomatic patients. They may be found in normal liver tissue, but also in association with Caroli’s syndrome, congenital hepatic fibrosis, autosomal dominant polycystic renal diseas, cholangiocarcinomas and cholangitis. Cholangiocarcinoma which arise from these lesions are usually lower stage and better differentiations than other type of cholangiocarcinoma. The sonographic findings of von Meyenburg complex are variable, including multiple, small, hyperechogenic images, with poorly delimited margins, or even hypoechogenic images with a “target” pattern with a hyperechogenic center and a hypoechogenic periphery, and well delimited margins. A magnetic resonance cholangiography is the best imaging examination of hamartomas of the bile duct, which can distinguish the different forms of dilatation of the bile duct. Histology of von Meyenburg complexes consists of a variable number of dilated small bile ducts, embedded in a fibrous, sometimes hyalinizing stroma. Microscopically, they are characterized by cystic dilatations of the bile duct or clusters of mature bile duct of various sizes, peri-ductal glands, and encompassed by fibrous stroma. The ductules are lined by small cuboidal or flattened cells, with round to oval nuclei. Bile duct hamartomas contain cysts that are more irregularly shaped then normal ducts, and they may also contain eosinophilic debris or inspissated bile. Case report: A 68-year-old male patient with multiple hepatic lesion which ultrasonic and MSCT appearance suggestive of multiple liver metastases was accepted for surgical exploration and liver biopsy. The patient had one mounts symptoms of vomits and weight loss. During surgery numerous whitish irregular lesions of various sizes scattered in the hepatic surface imitating metastatic deposits were noted trough both liver lobe and trough all liver quadrants. Explorations of the rest of abdominal cavity not found any pathological changes or peritoneal carcinomatosis. Liver biopsy was done and taken three samples for analysis. Tissue was brown-yellow-gray color and medium-firm consistency. Histological analysis demonstrated multiple lesions composed of biliary ducts incorporated in fibrotic tissue (Figure 1).There are usually cystic dilatations of some intrahepatic biliary ducts with irregular shape lined with uniform epithelium (Figure 2). The epithel of biliary ducts in von Meyenburg complex were immunohistochemicaly Epithelial Membrane Antigen positive, Pan-Cytokeratin positive, Cytokeratin 7 negative, Cytokeratin 5/6 negative and Carcinoembryonic antigene negative. Also present were signs of cholestasis with small lakes of bile.Conclusion: Von Meyenburg complexes are an important differential diagnosis of liver metastases. Differential diagnosis of liver metastases also includes other benign liver lesions, including hemangiomas, adenomas or infectious lesions e.g. miliary tuberculosis. As the existence of liver metastases is crucial for therapeutic decision making in malignant diseases, this differential diagnosis must be carefully clarified. Since VMC are usually less than 5 mm in size, they can escape preoperative radiologic diagnostics. The macroscopic appearance of von Meyenburg complexes can mimic liver metastasis as demonstrated in our reported patients.

Filip Vukmirovic, Ljiljana Vuckovic, Mileta Golubovic

01.04.2018.

Abstracts

Diagnostic challenges in pulmonary pathology: between morphology and immunohistochemistry

Aim: The aim of this paper is to point out the importance and the role of immunohistochemistry in diagnosing rare benign epithelial tumours of the lung and a very similar malignant tumour of well-differentiated lepidic adenocarcinoma. Introduction: In pulmonary pathology diagnostic dilemmas are frequent. One of the most complex challenges is to differentiate between benign tumours of pneumocytes and other forms of similar tumours. In particular, it is difficult to differentiate between the tumours of the same or similar histogenetic origin and morphological characteristics. However, dilemmas can also be related to whether a tumour has benign or malignant potential. In order to be able to have proper diagnostics, we need to have a detailed insight in the morphological and immunohistochemical features of these tumours. One of the best KRATKI KURSEVI APSTRAKTI 85 MATERIA MEDICA • Vol. 34 • Issue 1, suplement 1 • april 2018. examples of this are two very rare and morphologically very similar benign epithelial tumours: sclerosing pneumocytoma (according to the 2015 World Health Organisation Classification of Lung Tumours; new terms changed or entities added since 2004; the 2004 World Health Organisation Classification called it sclerosing haemangioma)1 and alveolar adenoma on the one hand; and well-differentiated lepidic adenocarcinoma on the other hand. These are most often cited as the most problematic in terms of their differential diagnostics. When it comes to first two tumours, as it can be concluded from their original names, they were considered to be the tumours of completely different histogenetic origin. However, their immunohistochemical profile and all current data show that they have identical structure and origin. Immunohistochemical diagnostics enabled the demystification of neoplastic processes, as is the case with rare benign tumours of pneumocytes. This diagnostics can also point out the biological potential and help differentiate between benign and malign tumours. Additional dilemma is posed by the fact that sclerosing pneumocytoma may even give metastases into regional lymph nodes, which do not affect disease prognosis 2,3. Histopathological differential diagnosis includes, apart for the above mentioned, other benign epithelial tumors, hemangioma, primary and metastatic carcinoma4. Materials and methods: We analysed two very rare and morphologically very similar benign epithelial tumours, (sclerosing pneumocytoma and alveolar adenoma) and welldifferentiated lepidic adenocarcinoma. It was also performed their immunohistochemical analysis using the following markers: Cytokeratin 7 (CK7), Thyroid transcription factor 1 (TTF-1), Epithelial membrane antigen (EMA), Pan-cytokeratin (CK), Carcinoembryonic Antigen (CEA), FVIII, Ki67 and p53. Results: The first tumour, at the microscopic level, showed sclerosing and haemorrhagic arrangement, with ectatic spaces filled by blood and solid areas and papillary-like formations. Basic cell population was epithelial cells, dominantly with eosinophilic and partially with granular cytoplasm. The nucleus was in the centre, round, without prominent nucleoli and mitoses. Stroma was moderately pronounced and centrally it was denser and composed of bundles of oval and spindle-shaped fibroblasts. Some of the cavities within the tumour had wide, cavernous space, lined with endothelium-like attenuated cells. Mainly in the middle part of the tumour, we could see the areas of hyalinisation of connective tissue. The tumour borders were expansive. The tumour did not infiltrate the pleura. On the final histopathological slides, the second tumour had a microcystic appearance. In central parts there was pale amorphous, homogenous content. Spaces were lined with cylindrical cells containing acidophilic and clear cytoplasm. Stroma was scarcely developed and sometimes with more pronounced parts and composed of groups of elongated spindle-like fibrocytes and fibroblasts. Immunohistochemical analysis of both tumours showed very similar reactivity: Ck7, TTF-1, EMA and CK showed diffuse positivity, k67 showed low proliferation index <1%. Cea in the major part of sclerosing pneumocytoma was negative and focally individual cells had reactivity, while alveolar adenoma was negative in its entirety. P53 and FVIII in both cases showed negative results. After all analyses, the definitive diagnosis of the first tumour is pneumocytoma and for the second one alveolar adenoma. The third tumour showed similar morphology as the previous two. At the microscopic hematoxylin eosin stain, it was dominantly composed of alveolar-adenoid formations. Tumour cells were bulky, cubic or polygonal; foamy, pale acidophilic, with homogenous cytoplasm and hyperchromatic roundish nuclei without prominent nucleoli. The immunohistochemical analysis of the third tumour showed positive reactivity with Ck7, TTF-1, CK, Cea, EMA, k67 proliferation index > 32%, while p53 proliferation index ≥1%, while the FVIII had a negative result. Final diagnosis for this tumour is well-differentiated lepidic adenocarcinoma. Conclusion: Due to almost identical histopathological and immunohistochemical characteristic, there may be a diagnostic dilemma: are these two separate tumours or this is the same tumour. Taking into consideration that sclerosing pneumocytoma give positive epithelial immunohistochemical reaction, their earlier name is wrong. Previous examples are good indicators of how we should adapt the names of tumours to their real nature and this is a good recommendation in terms of how we should organise future classifications. All of the above mentioned points to the fact that with these tumours it is necessary to have immunohistochemical evaluation and that we have to introduce new immunohistochemical predictive and prognostic markers. It is necessary to determine the cut off values for proliferative markers.

Mileta Golubovic, Ljiljana Vuckovic, Filip Vukmirovic

01.12.2017.

Review paper

Pathohistological aspects of pulmonary Langerhans cell histiocytosis

Milana Panjković, Mirjana Miladinović, Ljiljana Vučković, Tanja Lakić, Aleksandra Ilić, Aleksandra Lovrenski

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