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The character of the tumor microenvironment is a relevant prognostic and predictive biomarker across a wide range of malignancies. The composition, density, and functional capacity of tumor-infiltrating immune cells are especially crucial for selecting suitable immunotherapy. Head and neck squamous cell carcinomas are considered immunologically hot tumors, with high numbers of tumor-infiltrating effector and regulatory T cells. Higher T cell counts, along with a better prognosis, were observed in patients with head and neck squamous cell carcinomas associated with human papillomavirus infection. The immune profile of smoking-associated tumors was more variable, with higher numbers of suppressive myeloid cells and a substantial variability in T cell numbers between the patients. Nevertheless, the high density of cytotoxic T cells was a stronger prognostic factor for head and neck squamous cell carcinoma patients than HPV status alone. Thus, prognostic markers based on knowledge of the tumor microenvironment and tumor-infiltrating immune cells could significantly improve patient stratification for immunotherapeutic and de-escalation treatment protocols.

Salivary gland tumors represent a  rare and morphologically heterogeneous group of neoplasms, which represents a  significant diagnostic challenge for histopathologists. Diagnosis is based primarily on morphological evaluation, but immunohistochemical methods are often a necessary complementary tool. However, due to immunophenotype overlap between different tumor entities, even immunohistochemistry may not always allow an unambiguous diagnosis. In recent years, characteristic genomic alterations, particularly gene fusions, have been identified in a number of salivary gland tumors. These alterations are tightly tumor type specific, and their detection may be crucial in diagnostically difficult cases. In addition, selected genetic changes may have prognostic and/ or potential therapeutic significance in the era of personalized medicine. The aim of this review article is to summarize current knowledge in this area.

The World Health Organization (WHO) recently published the 5th edition of head and neck tumors. This edition describes both existing entities and a group of emerging entities, along with updates regarding taxonomy and detailed characteristics of tumors and tumor-like lesions. Sinonasal tumors and skull base tumors represent a heterogeneous group of tumors with significant histological variability and overlap in imaging methods. An important change in the 5th edition of the WHO classification is the relocation of recurrent soft tissue, hematolymphoid, and neuroectodermal tumors into a separate chapter, meaning they are no longer repeated in other chapters as they were previously. Only those tumors that are unique to the sinonasal area remain classified in this chapter. In this review article, we will primarily provide a brief overview of all 24 diagnostic entities, allowing readers to gain a concise understanding. We will focus in detail on the new entities of SWItch/Sucrose Non-Fermentable complex-deficient sinonasal carcinomas and human papillomavirus-related multiphenotypic sinonasal carcinoma. In another review article in this issue, we detailed IDH-mutated sinonasal malignancies; therefore, we will exclude them from this overview and concentrate on DEK::AFF2 carcinomas, currently classified as sinonasal undifferentiated carcinomas or non-keratinizing squamous cell carcinomas, respectively.

Claudin 18.2 (CLDN18.2) represents one of the newest biomarkers expected to enter routine testing in the near future and expanding the spectrum of available predictive markers. It is currently a clinically relevant predictor for adenocarcinomas of the stomach and the gastroesophageal junction, although its use will likely extend also to other diagnoses. The aim of this report is to provide an overview of selected aspects of CLDN18.2 expression testing, including the choice of appropriate tissue, the issue of tumor heterogeneity, antibodies suitable for testing and their evaluation, where such testing can be performed, and the prospects for the future.

Winter sports such as skiing, snowboarding, and sledding rank among the most popular recreational activities in developed countries, yet they also represent a  significant source of traumatic injuries, including fatal cases. The combination of high speeds, altered stability, hard surfaces, the movement of other participants, and the presence of mechanized equipment on slopes creates a  high-risk environment for injuries. Despite technological advancements in protective gear, the incidence of severe injuries remains alarmingly high, with head and spinal injuries predominating in terms of severity. The article analyzes two case reports of fatal injuries in minor individuals (aged 8 and 9) during recreational skiing. Although the injury mechanisms differed, both cases share a common factor - non-adherence to the principles of safe conduct on ski slopes. The study emphasizes the importance of continuous education, the individual responsibility of each slope participant, the selection of appropriate safety equipment, and adherence to safe conduct rules. A multidisciplinary analysis of these tragic events underscores the need for intensive prevention, interdisciplinary cooperation, and awareness-raising activities aimed at minimizing risks not only in children's but also in adult skiing.

The review article describes the most important news in head and neck pathology, that were published in the period 2021-2025, and that are only marginally mentioned or not mentioned at all in the WHO Classification of Head and Neck Tumors 2024, the 5th edition. The article focuses solely on the pathology of the salivary glands and sinonasal tract and deals only with malignant tumors. Regarding salivary gland pathology; palisading adenocarcinoma, microcribriform adenocarcinoma, mucoacinar carcinoma, mucoepidermoid carcinoma devoid of morphologically distinct squamous cell differentiation, metatypical adenoid cystic carcinoma, adenoid cystic carcinoma with striking tubular hypereosinophilia, and new proposals for a  grading system for acinic cell carcinoma and secretory carcinoma are discussed. Regarding pathology of the sinonasal tract; olfactory carcinoma and IDH2-mutated sinonasal carcinoma are mentioned.

In the present case report, the authors describe the deaths of two individuals-an 85-year-old female and her 56-year-old son - both discovered within a shared household, exhibiting advanced postmortem changes. The fatalities occurred in a confined apartment environment. The decedents had been residing under conditions of extreme environmental neglect, characterized by prolonged accumulation of domestic waste and an almost complete absence of interaction with the external community. Postmortem examinations revealed morphological indicators consistent with hypothermia, including pale postmortem lividity, frostbite lesions, and Visnevsky's spots within the gastric mucosa. The terminal causes of death in both cases were determined to be combined cardiovascular and respiratory failure secondary to hypothermia. Relevant comorbidities were identified: in the female, predominantly chronic cardiac and hepatic pathology; in the male, marked malnutrition. In both individuals, ethanol was detected in postmortem blood specimens at concentrations consistent with endogenous production during the late stages of decomposition. In both cases, different degrees of development of hypothermia-related Visnevsky spots were observed, which the authors explain by different reserve capacities of the organism.

Castleman disease is a rare and heterogeneous lymphoproliferative disorder with variable clinical presentation. The plasma cell variant, particularly when associated with Epstein-Barr virus (EBV), is uncommon and diagnostically challenging. We present a complex and long-lasting case of EBV-associated plasma cell variant Castleman disease with fluctuating systemic symptoms, multiorgan involvement, and delayed definitive diagnosis. A 35year old man (born 1974) first presented in 2009 with high-grade fever, diarrhea, elevated inflammatory markers, hepatomegaly and biochemical signs of liver injury. Initial findings were attributed to rotavirus infection. Over the following years, he developed recurrent episodes of fever, night sweats, fatigue, arthralgias, hepatosplenomegaly, lymphadenopathy, and progressive laboratory abnormalities including persistent elevation of CRP, leukocytosis, hyperfibrinogenemia and polyclonal hypergammaglobulinemia. Extensive diagnostic workup repeatedly ruled out infectious, rheumatologic and malignant causes. Imaging eventually demonstrated retroperitoneal lymphadenopathy, hepatosplenomegaly, spinal lesions (Th5- Th8), narrowing and occlusion of the inferior vena cava, and multiorgan inflammatory changes. Multiple biopsies (lymph nodes, spleen, liver, pancreas, bone lesions) initially showed only nonspecific reactive changes. Repeated PET/CT scans revealed multifocal FDG-avid lesions of low to moderate metabolic activity. In 2023, after multidisciplinary reassessment, lymph node tissue demonstrated EBV positivity in the absence of peripheral viremia, leading to a diagnosis of EBV-associated plasma cell variant Castleman disease. The patient was initiated on targeted therapy. During the third-line treatment, a sustained clinical and laboratory remission was achieved. This case illustrates the diagnostic complexity of EBV-associated plasma cell variant Castleman disease, especially when presenting with longstanding systemic inflammation, nonspecific multiorgan involvement, and repeatedly inconclusive histopathology. Early consideration of Castleman disease in chronic inflammatory syndromes with lymphadenopathy may reduce diagnostic delay and improve outcome.

Classification of diffuse large B-cell lymphoma (DLBCL) according to cell-of-origin (COO) distinguishes two main biological subtypes: activated B-cell-like (ABC) and germinal center B-cell-like (GCB). Although this distinction reflects different pathogenetic mechanisms, its prognostic impact diminishes in the context of evolving therapeutic strategies. Molecular subtyping of DLBCL, which is based on the spectrum of affected genes and aims to personalize treatment approaches, is currently gaining importance. In the study, we applied targeted gene expression profiling (GEP) using a custom Lympho-qPCR panel, enabling rapid and practically applicable ABC/GCB classification together with risk stratification of patients. RNA isolated from a cohort of 89 DLBCL tissue samples was analyzed using three GEP-based classification models. Model A compared the expression profile with immunohistochemical (IHC) COO determination and showed the expected lower correlation (62 %). Model B employed the expression scores of selected genes to predict COO regardless of IHC classification. Model C was developed as a new IHC-independent prognostic tool allowing patient stratification based on expected survival. Patients identified as high-risk by Model C had significantly worse outcomes, regardless of existing clinical prognostic indicators. In patients with early progression, parallel DNA sequencing analysis (integrative LYNX panel) confirmed complex chromosomal aberrations and defects in BCL2, TP53 and CDKN2A/B. Our results demonstrate that targeted GEP testing represents a robust, rapid, and clinically applicable method for COO determination and risk stratification in DLBCL patients. In the near future, the predictive value of ABC/GCB classification is expected to increase in relation to novel targeted therapeutic regimens. Integration of transcriptomic and genetic data will be essential for independent and individualized risk assessment in the molecular diagnostics of DLBCL.

Lymphocytic myocarditis is the most common form of inflammatory myocardial disease. However, its histopathological diagnosis has been burdened by considerable subjectivity until recently. In 2025, the Society for Cardiovascular Pathology (SCVP) and the Association for European Cardiovascular Pathology (AECVP) published a two-part document entitled the "Seaport Criteria," which introduces new diagnostic approaches for endomyocardial biopsies and nonbiopsy specimens - surgical and autopsy material. This article summarizes the key elements of these documents, including practical recommendations for routine histopathological diagnosis.

Castleman disease (CD) is a  mesmerising group of disorders mainly affecting lymph nodes sharing some morphological features but with heterogeneous aetiology, clinical presentation and therapeutic approaches. Morphologically, hyaline-vascular (or hypervascular), plasmacytic, and mixed types of changes are distinguished. Confirmation of the diagnosis and subtype of Castleman disease involves meeting or excluding several clinical criteria and therefore requires close cooperation with a clinician. Unicentric Castleman disease involves usually a solitary enlarged lymph node with mild symptoms and excision surgery is often curative. Multicentric forms of Castleman disease affect multiple groups of lymph nodes and are associated with varying degrees of systemic clinical symptoms. Multicentric Castleman disease is either idiopathic or associated with human herpesvirus 8 infection or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes). Idiopathic multicentric Castleman disease is further divided into a variant associated with TAFRO syndrome (thrombocytopenia, anasarca, fever, reticulin fibrosis / renal dysfunction, and organomegaly), idiopathic plasmacytic lymphadenopathy type, and not otherwise specified variant. The treatment of multicentric forms of Castleman disease is complex and depends on etiological factors, including biological therapy, chemotherapy, or interleukin-6 activity inhibition. The aim of this educational text is to present the current view of Castleman disease and provide a comprehensive description of the morphological changes and clinical characteristics of the individual subtypes of Castleman disease.

Differentiating reactive lymphadenopathies in the context of autoimmune disease from Idiopathic Multicentric Castleman Disease (iMCD) poses a significant diagnostic challenge. Castleman-like histological features have been described in various autoimmune disorders, necessitating a strict and comprehensive integration of clinical and laboratory findings to reach the correct diagnosis. Although the Castleman Disease Collaborative Network (CDCN) consensus guidelines list several autoimmune conditions as exclusion criteria for an iMCD diagnosis, mixed connective tissue disease (MCTD) is not currently among them. We report the case of a  77-year-old woman presenting with fatigue, Raynaud's  phenomenon, sclerodactyly, mild generalized lymphadenopathy, in whom the lymph node biopsy revealed a Castleman-like histology. The absence of systemic inflammatory symptoms and the presence of high-titer anti-U1- RNP antibodies were, however, inconsistent with iMCD, favouring the diagnosis of a reactive Castleman-like lymphadenitis secondary to MCTD. This report highlights that Castleman-like lymphadenopathy can occur in MCTD, closely mimicking iMCD. Therefore, in patients with autoimmune diseases not explicitly listed among the CDCN exclusion criteria, comprehensive clinicopathological integration is essential to avoid misdiagnosis and potentially inappropriate antiIL-6-based therapy.

The salivary gland section in the 5th edition of the World Health Organization classification of head and neck tumors features a description and inclusion of several new entities, including sclerosing polycystic adenoma, keratocystoma, intercalated duct adenoma, and striated duct adenoma among the benign neoplasms; and microsecretory adenocarcinoma and sclerosing microcystic adenocarcinoma as the new malignant entities. The new entry also includes mucinous adenocarcinoma subdivided into papillary, colloid, signet ring, and mixed subtypes with recurrent AKT1 E17K mutation across patterns suggesting that mucin-producing salivary adenocarcinomas represent a histologically diverse single entity that may be related to salivary intraductal papillary mucinous neoplasm (IPMN). Cribriform adenocarcinoma of salivary gland origin (CASG) now represents a distinctive subtype of polymorphous adenocarcinoma (PAC). PAC is defined as a clinically, histologically and molecularly heterogeneous disease group. Whether CASG is a different diagnostic category or a subtype of PAC is still controversial. New defining genomic alterations have been characterized in many salivary gland tumors. In particular, they include gene fusions, which have shown to be tightly tumor-type specific, and thus valuable for use in diagnostically challenging cases. The recurrent molecular alterations were included in the definition of mucoepidermoid carcinoma, adenoid cystic carcinoma, secretory carcinoma, polymorphous adenocarcinoma, hyalinizing clear cell carcinoma, mucinous adenocarcinoma, and microsecretory adenocarcinoma. Importantly, the number of entities in the salivary chapter has been reduced by omitting tumors or lesions if they do not occur exclusively or predominantly in salivary glands, including hemangioma, lipoma, nodular fasciitis and hematolymphoid tumors. They are now discussed in detail elsewhere in the book.

Stenosis of the bile ducts is a relatively common disease arising from benign or more often malignant causes. As a result of stenosis, bile flow is interrupted, obstructive jaundice in some cases leads to inflammation of the bile ducts. The decision on the etiology of stenosis is crucial and is made on the basis of a summary of the clinical picture and the findings of laboratory and imaging examinations. Endoscopy plays a crucial role in the diagnosis of stenosis. Endoscopic retrograde cholangiography and endoscopic ultrasonography allow not only to macroscopically evaluate the stenosis, but also to obtain a tissue sample for cytological or histological examination. Given that the majority of patients with tumor stenosis require a definitive diagnosis for their subsequent treatment, histopathological diagnosis is absolutely essential. Cholangioscopy currently provides the most accurate assessment of the nature of the stenosis. The still limited sensitivity of imaging examinations could be increased in the future by artificial intelligence methods.

Papillary breast lesions represent a morphologically and biologically diverse group of entities that include benign intraductal papillomas, papillomas with atypical ductal hyperplasia, with ductal or lobular carcinoma in situ, papillary ductal carcinoma in situ, encapsulated papillary carcinoma (with or without invasion), solid papillary carcinoma, and invasive papillary carcinoma. Accurate classification is often challenging particularly in core needle biopsies, and even in excision specimens can pose difficulties, especially for less experienced pathologists. This review summarizes the essential histological and immunohistochemical features of each lesion and highlights key diagnostic pitfalls and helpful clues in their differential diagnosis. While genetic testing is not routinely required for diagnostic purposes, recent studies have identified more or less distinct molecular alterations across the spectrum of papillary lesions. These findings may support future refinements in classification and understanding of these tumors.

In this article, we describe the course and diagnosis of pulmonary alveolar proteinosis (PAP) based on two cases from our practice. The first case is a 52-yearold woman, the second a 34-year-old man. Both referred patients were examined by a pulmonologist for interstitial lung disease, in the first case also with transition to pulmonary fibrosis. As part of the differential diagnosis, these patients were hospitalized at the NÚTPCHaHCH in Vyšné Hágy. Chest X-ray showed diffuse bilateral lung infiltrates, in the first patient locally confluent. Chest CT showed parenchymal involvement of the lungs with bilateral ground-glass opacities with thickened interlobular septa (crazy paving). Bronchoscopic examination was performed in both patients with bronchoalveolar lavage, which had a characteristic milky-glazed appearance. Videothoracoscopic lung biopsy was additionally indicated and histopathologically there were pulmonary alveolar proteinosis confirmed. Therapeutically, the patients underwent large volume lung lavage, with clinical condition improvement, including radiological findings improvement. We point out the basic pillars of the diagnosis of pulmonary alveolar proteinosis, which are the pattern of pulmonary involvement in the radiographic and CT (or HRCT) images, the characteristic appearance of the bronchoalveolar lavage fluid, and additionally also the histopathologic pattern of pulmonary involvement in this disease. We emphasize the need for centralized management of patients with lung diseases, which is particularly urgent in cases of rare diseases, where it provides rapid availability of all relevant diagnostic and therapeutic options, including large-volume lung lavage.

The biliary tree comprises a three-dimensional network of intrahepatic and extrahepatic ducts lined by biliary epithelium (cholangiocytes). The bile ducts and cholangiocytes may be affected by a broad spectrum of disorders collectively referred to as cholangiopathies. These conditions are classified based on anatomical aspects (predominantly affecting small or large bile ducts), aetiopathogenesis (immune-mediated, toxic and drug-induced, ischaemic, infectious, genetically determined, or neoplastic), and the predominant morphological pattern of injury (inflammatory or non-inflammatory). While abnormalities in medium-sized and large bile ducts are typically detected using radiological methods, the diagnosis of small duct cholangiopathies continues to rely primarily on histopathological evaluation of liver tissue. This review summarises the key morphological features of the most clinically significant cholangiopathies, focusing on histopathological changes observed in liver biopsy.

With the advancing digitalization of pathology, the application of machine learning and artificial intelligence methods is becoming increasingly important. Research and development in this field are progressing rapidly, but the clinical implementation of learning systems still lags behind. The aim of this text is to provide an overview of the process of developing and deploying learning systems in digital pathology. We begin by describing the fundamental characteristics of data produced in digital pathology. Specifically, we discuss scanners and sample scanning, data storage and transmission, quality control, and preparation for processing by learning systems, with a particular focus on annotations. Our goal is to present current approaches to addressing technical challenges while also highlighting potential pitfalls in processing digital pathology data. In the first part of the text, we also outline existing software solutions for viewing scanned samples and implementing diagnostic procedures that incorporate learning systems. In the second part of the text, we describe common tasks in digital pathology and outline typical approaches to solving them. Here, we explain the necessary modifications to standard machine learning methods for processing large scans and discuss specific diagnostic applications. Finally, we provide a brief overview of the potential future development of learning systems in digital pathology. We illustrate the transition to large foundational models and introduce the topic of virtual staining of samples. We hope that this text will contribute to a better understanding of the rapidly evolving field of machine learning in digital pathology and, in turn, facilitate the faster adoption of learning-based methods in this domain.

Cytological examination of extrahepatic bile ducts represents a challenging diagnostic field, often limited by sample quality and cellularity. Despite the availability of detailed classifications and cellular morphology descriptions, distinguishing benign from malignant lesions remains difficult in clinical practice. This paper reviews the current WHO classification system for pancreatobiliary cytopathology, with a focus on diagnostic categories specific to extrahepatic bile ducts. It discusses typical cytomorphological features, differential diagnoses, and the use of ancillary techniques such as immunohistochemistry and FISH, which may enhance diagnostic sensitivity and specificity. The importance of clinical context and interdisciplinary collaboration in cytological interpretation is emphasized.