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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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Contents
01.04.2018.
Abstracts
Benign lymphadenitis imitating malignant lymphoma
Aim: The aim of this study is to present a case of benign lymphadenitis that cytologically was interpreted as suspicios for malignant lymphoma. Introduction: This study represents a case of a patient with cervical lymph node swelling in which the cyto-diagnosis performed by fine needle aspiration cytology was suspicious for lymphoma. The correct diagnosis was assessed by subsequent histology after the removal of the enlarged cervical lymph node. Material and Methods: For cytologic study the material was obtained by fine needle aspiration biopsy and syringe washings, air-dried smears and alcohol-fixed smears, which were prepared and appropriately stained by PAP and May Gruenwald-Giemsa stains. For correct diagnosis an extirpated lymph node was properly fixed and processed with routine haematoxylin eosin staining as well as with an additional immunohistochemical analyses. Results: The cyto-histologic features were characterized by a polymorphous population of cells, germinal center cells with large nuclei, a few epithelioid-type cells and histiocytes with intracellular inclusions The cytological diagnosis implied suspicion for malignant lymphoma probably of Hodgkin type. Histologic features revealed a reactive lymph node architecture that immunohistochemically revealed the diagnosis of Toxoplasma lymphadenitis. Serologic testing for toxoplasma in other institution revealed elevated titres that established the histopathological diagnosis. Conclusion: Lymphadenitis due to Toxoplasma infection is common and should be considered in the diagnosis of unexplained lymphadenopathy at all sites, especially the cervical region. Serologic confirmation should be recommended for all suspected cases and unlike in this case, fine needle aspiration cytodiagnosis can eliminate the need for hospitalization and surgery.
Djengis Jasar, Katerina Kubelka-Sabit, Vanja Filipovski
01.04.2018.
Abstracts
Introducing new terminology in mixed colorectal tumors
Aim: To review current terminology of mixed exocrine and endocrine tumors of the large intestine. Introduction: Previous classification of colorectal tumors contained category called “mixed adenoneuroendocrine carcinoma” (MANEC) which encompassed neoplasms of the large intestine with features of both adenocarcinoma and a neuroendocrine carcinoma. Indeed, the vast majority of the mixed colorectal tumors have these two malignant components. However, this designation is no more suitable as other combinations of neuroendocrine and non-neuroendocrine tumors are recognised. Material and Metods: A detailed review of the literature on classification of mixed neuroendocrine-nonneuroendocrine tumors has been done. Results: The nonneuroendocrine component in a mixed colorectal tumor can be either exocrine or squamous and can be either benign or malignant. The histological grade of the nonneuroendocrine component may also vary. Therefore in several recent papers a new term has been coined “mixed neuroendocrine-nonneuroendocrine neoplasms” (MiNENs) in order to convey all possible combinations of the two components. According to the histologically estimated malignant potential, MiNENs are further subdivided into three categories low grade, intermediate grade and high grade. Conclusion: The new terminology is much more comprehensible than the previous ones and ensures a more accurate assessment of biological behaviour of the mixed colorectal tumors thus avoiding overtreatment of clinically innocent lesions.
Nenad Solajic
01.04.2018.
Abstracts
Between fjords and cytology
The Norvegian University of Science and Technology is the largest educational institution in Norway. It was founded in 1760 as the Trondheim Academy. The Faculty of Medicine and Health Sciences is part of the St Olav’s Hospital in Trondheim, and being there, as participant of the Annual Cytology Tutorial of the European Federation of Cytology Societies, was an outstanding experience. Colleagues from all over the world had the opportunity to meet and learn from experts in various fields of cytology. Particularly, differences between conventional and Thin Prep Pap smears, as well as immunocytochemistry of air-dried smears were thoroughly discussed.
Zorana Vukasinovic Bokun
01.04.2018.
Abstracts
Learning Pathology in the “R’n’R Capital of the World
The presentation will reflect on a one-month period of education that the author spent with the Cleveland Clinic soft tissue pathology team. Cleveland is a US city in the state of Ohio. One of its nicknames is
“The Rock and Roll Capital of the world”, due to the fact that the term R’n’R was coined in the 1950s by
a Cleveland-based disc jockey Alan Freed. The city hosts the Rock and Roll Hall of Fame, established in
1983. It is also home to the Cleveland Clinic, a multispecialty academic hospital currently ranked as the
#2 hospital by U.S. News & World Report1. In 2014, Cleveland Clinic had a total revenue of $11.63 billion, making it the #2 hospital in US on the Becker’s Hospital Review revenue list2. The author spent one
month on a UICC ICRETT fellowship in November 2016 with the Cleveland Clinic soft tissue pathology
team. The main strength of the soft tissue team is the presence of several internationally known experts
with diverse interests within the field of soft tissue and beyond, with team philosophy highlighting the
synergy of team work and individual reputation. Among various topics that were covered during the
one-month fellowship, certainly one of the most interesting was differentiation among different fibrohistiocytic neoplasms. Fibrohistiocytic tumors are among the most frequent soft tissue tumors and they
are most commonly encountered in the skin. “Fibrohistiocytic” is in fact a merely descriptive term for
cells that resemble both normal fibroblasts and histiocytes, and not a true line of differentiation3. Like
other soft tissue tumors, fibrohistiocytic neoplasms are divided into benign, intermediate and malignant
categories. In presentation, the author will reflect on the key points in the pathology diagnosis within this
category of tumors, and these are:
- being able to give a common denominator to numerous variants of benign fibrous histiocytoma
- awareness of the pitfalls in the diagnosis of dermatofibrosarcoma protuberans
- discrimination of malignant fibrohistiocytic skin-based tumors from other, more adverse cutaneous
malignancies.
Zlatko Marušić
01.04.2018.
Abstracts
What have I learned about lung transplantation?
Lung transplantation remains the definitive treatment for end-stage lung diseases and an option when
medical and surgical care has been exhausted. The first human single lung transplant was performed in
1963, and the patient, survived for 18 days. From 1963 to 1978, multiple attempts at lung transplantation
failed because of rejection and problems with anastomotic bronchial healing. It was only after the invention of the heart-lung machine, coupled with the development of immunosuppressive drugs, that organs
such as the lungs could be transplanted with a reasonable chance of patient recovery. The first clinically
successful long-term single lung transplant was performed in 1983, and since then over 25,000 lung transplants performed worldwide.
Aleksandra Lovrenski
01.04.2018.
Abstracts
Vulvar Paget disease and Fish tank granuloma -diagnostic challenge
The skin is the largest organ in our body.Receiving information from the environment allows the role barrier between the human organism and the environment. The histological structure of the skin is variable depending on the part of the organism. The diseases of skin also vary depending on the region. The reason is the local immune status and the external physical, chemical and microbiological environment. The histopathological diagnosis of skin lesions request detailed clinical information. On the other side the histopathological diagnosis of skin lesions provides information on local disease , as well as potential other associated pathological conditions.˝ Extramammary Paget‘s vulvar disease is rare. The pathology of the skin of the vulva is specific both for specific localization, as well as for specific friction and microbiological flora. It is clinically presented as erythematosus or eczematous lesion. It can be local or extensive. Histopathologically, it is characterized by relatively large glandular atypical Paget cells, which are pathognomonic for this disease. These cells have abundant cytoplasm that is granular or vacuolated. Tumor cells are typically localized individually or in groups in the basal and parabasal layers. Immunochemical analyzes are necessary in the diagnosis of Paget‘s disease. The main reason is that Paget‘s disease can be a primary skin disease or associated with non-cutaneous carcinoma primarily of the urothelial or rectal carcinoma . Therefore, it is necessary to recommend that a detailed clinical trial of a patient be conducted in all diagnosed cases of vulvar Paget‘s disease. Mycobacterium marinum is etiological factor of Fish tank granuloma.This Mycobacterium more often causes diseases of fish, both marine and river fish. The humans become infected with Mycobacterium marinuim after contact with skin after micro/trauma Infection is usually localized to the skin.In immunocompromised patients the infection may disseminate or spread to the subcutis and bone. After incubation of few weeks after infection the lesion appear as solitary nodules or plaques.In some cases the disease progresses like suppurative ulcers. Histopathologically there is a wider range of histopathological presentations. Most often you can see abscess, necrosis of wheat and fatty tissue. However, granuloma inflammation is a key morphological substrate. After granuloma inflammation, fibrosis occurs. Since the microscopic image may be somewhat non-specific, clinical data are of great importance for the diagnosis. Multidisciplinarity in the final diagnosis includes microbiological confirmation of the presence of Mycobacterium marinum.
Biserka Vukomanovic-Djurdjevic
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
01.04.2018.
Poster session
Mediastinal metastasis of extraneural ependymoma: case report
Aim: The aim of this case was a correct diagnosis of mediastinal tumor in a 41-years old female patient. Introduction: The rarity of primary extraneural ependymomas, its great variations in morphology and rare occurrence of metastasis, increase chances of misdiagnosis. Case report: Macroscopic examination of received specimen was performed, followed by histological and immunohistochemical analysis of the tissue samples. In presented case, onset of the disease was 14 years ago, when after right salpingo-oophorectomy, patient was diagnosed with malignant mesothelioma. In following years patient had multiple and extensive surgical procedures, resulting in different patohistological diagnosis, and after seven years, a diagnosis of extraneural ependymoma was established. Later on, patient was surgically treated in several medical centers across the region, again with different patohistological diagnosis. At present, tumor metastasized to mediastinum, presenting as grey to brown, multicystic formation, with cysts filed with clear serous fluid or red-brown hemorrhagic fluid. Inner surface of the cysts had smooth to partly papillary appearance. Tumor cells exhibited several architectural paterns (solid, pseudorosette or rosette formations, papillary and pseudopapilary structures), and immunophenotype specific for extraneural ependymoma (GFAP, ER, PR positive, calretinin, WT-1, S100, synaptophysin, chromogranin, CK7 and pan-cytokeratin negative). Conclusion: This case demonstrates an important principle in tumor pathology. Neoplasms may occur in unusual and unexpected primary and metastatic sites. Pathologists need to be familiar with histologic features of a wide range of neoplasms and not just the appearance of neoplasms within their own limited subspecialty area.
Bojana Andrejic Visnjic, Zivka Eri, Dejan Vuckovic, Aleksandra Lovrenski, Dragana Tegeltija, Golub Samardzija
01.04.2018.
Abstracts
Differential diagnosis of benign spindle cell pancreatic lesions: report of two cases
Introduction: Pancreatic lesions, made of spindle cells, are a heterogeneous group of lesions, ranging from reactive, inflammatory changes to tumors. Differentiation of an individual lesion is difficult and requires the use of additional analytical methods (histochemical, immunohistochemical and molecular), and a comparison of morphological characteristics with other characteristics of the changes (radiologic and laboratory characteristics). We will present two cases of benign spindle cell lesions of the pancreas, with reference to the differential diagnosis. Material and Metods: The first patient was a female, aged 51 years, with a change localized in the pancreatic head, diameter of 9.5 cm. The second patient was a male, aged 35 years, with a change in the pancreatic tail, with maximum diameter of 5.5 cm. Results: In a female patient, the lesion was an inflammatory myofibroblastic pancreatic tumor, built of fascicles of mostly spindle cells (fibroblasts/myofibroblasts). The cells had uniform, elongated, spindle nuclei and eosinophilic cytoplasm. They were arranged in short fascicles that occasionally made storiformn formations. Mitotic activity of spindle cells was low (0 - 2 mitosis/ HPF 10, FD 0.65). In the stroma, there was a mixed inflammatory infiltrate, consisting of lymphocytes, plasma cells, histiocytes, eosinophils and neutrophils. In between, there were fascicles of collagen, together with the parts of the pancreas (excretory ducts, lobules, acini, and parts of the endocrine pancreas) (Figure 1). Immunohistochemically, spindle cells showed a diffuse immunohistochemical positivity to: Vimentin, SMA and Desmin. Negative immunohistochemical reaction was showed to S-100, p53, CDX2 and ALK-1.
Radoslav Gajanin
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