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.
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.
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.
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.
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.
The Czech Republic is one of the countries with the highest incidence of endometrial cancer in the world. In June 2023, the Women's Cancer Committee of the International Federation of Gynaecology and Obstetrics (FIGO) introduced a new staging system for endometrial cancer, FIGO 2023, which replaced the 2009 version. The FIGO 2023 staging system differs significantly from the previous version by incorporating the result of molecular classification of the tumour and some histopathological parameters - histological type of tumour, tumour grade and presence of substantial lymphovascular invasion - into the definitions of stage I and stage II. For stage I and II tumours, specific separate stages are reserved when the molecular profile of POLEmut or TP53mut is detected. Stages III and IV have also been modified, but the result of the molecular classification of the tumour and other histopathological parameters do not influence the staging. However, the molecular classification result should be reported for all stages. These changes have further strengthened the role of the pathologist in staging. The changes, which are partly based on the recommendations of the three European professional societies ESGO/ESTRO/ESP for the diagnosis and treatment of endometrial cancer, better reflect the biological behaviour of the tumour and significantly refine the prognosis of the patient at a given stage. On the other hand, the FIGO 2023 staging system is quite complex and requires expensive tests, which may pose a problem for its routine use in a global context. The implementation of the FIGO 2023 endometrial cancer staging system in daily practice requires the full involvement of all stakeholders.
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.
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.
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.
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.
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.
X-ray microtomography (microCT) represents a modern high-resolution imaging technology enabling detailed analysis of the tissue. It offers a unique perspective on three-dimensional architecture, bridging the gap between macroscopic and histological imaging. In anatomical pathology, microCT is particularly utilized for morphometric tumor analysis, evaluation of surgical specimen resection margins, and detection of metastases in lymph nodes. The combination of microCT with traditional histopathological techniques, and with digital 3D reconstructions, opens new avenues for analyzing complex pathological processes. Although this method is currently used in research, its clinical potential is significant. Key advantages include non-invasive imaging and the ability to be integrated with digital pathology and artificial intelligence tools. Current limitations include the need for sample contrast enhancement, the monochromatic nature of the images, and high radiation exposure. Advances in technological development, however, may overcome these barriers and enable the broader adoption of microCT in routine clinical diagnostics. This article explores the diagnostic potential of microCT in pathology, highlighting its applications, advantages, and limitations, while offering insights into current capabilities and future perspectives of this technology.
Adult granulosa cell tumor is a predominant malignant tumor among ovarian sex cord-stromal tumors, representing approximately 3-5% of all ovarian malignancies and being known for its risk of recurrence with high mortality rate. We present a unique case of a 71-year-old woman with, to our knowledge, the first documented instance of a recurrent AGCT arising concurrently with a mature ovarian teratoma, confirmed through both immunohistochemistry and molecular biological analysis. The tumor in both the primary and recurrent lesion harbored a missense FOXL2 mutation typical for adult granulosa cell tumor. TP53, TSC2 and RB1 mutations were present only in the recurrent tumor, indicating secondary mutations acquired during progression.
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.
This case report describes a 71-year-old male patient in whom a solitary fibrous tumor (SFT) of the pancreatic tail was incidentally discovered during staging of chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL). The patient also had a history of excised malignant melanoma. SFT is a mesenchymal neoplasm characterized by NAB2::STAT6 gene fusion, STAT6 and CD34 immunohistochemical positivity, and unclear biological behavior. In this case, the tumor was a firm, well-circumscribed spindle cell lesion without cytologic atypia, necrosis, or significant mitotic activity, showing strong diffuse STAT6 and CD34 expression. According to WHO classification criteria, it was classified as a low-risk SFT with respect to metastatic potential. The diagnosis of SFT is based on characteristic morphology and nuclear expression of STAT6, which helps distinguish it from a broad spectrum of CD34-positive mesenchymal lesions. The article discusses relevant differential diagnoses and highlights the molecular basis of SFT, including the prognostic implications of different NAB2::STAT6 fusion variants and the association of TERT promoter mutations with more aggressive behavior. Although pancreatic SFT is rare, similar cases have been reported in the literature. From a clinical standpoint, accurate risk stratification for recurrence or metastasis is essential. Several scoring systems have been proposed and validated, including the one adopted in the WHO classification, which considers tumor size, mitotic rate, necrosis, and patient age. In this case, the tumor was completely resected, and the patient has remained disease-free with no signs of SFT recurrence or B-CLL/SLL progression more than six months after surgery.
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.
Dysplastic gangliocytoma of the cerebellum, also known as Lhermitte-Duclos disease (LDD), is a rare lesion of the posterior cranial fossa, classified among glioneuronal and neuronal tumors of the CNS, WHO grade 1. It typically has a characteristic radiological appearance on magnetic resonance imaging in the form of "tiger stripes" on T2-weighted images. In adults, LDD is often associated with Cowden syndrome and PTEN gene mutations. Our case report presents a 51-year-old patient with a somewhat atypical finding on magnetic resonance imaging, where histopathological examination surprisingly revealed dysplastic gangliocytoma of the cerebellum with a PTEN gene mutation, subsequently confirmed to be of germline origin. The patient was then examined for other manifestations of Cowden syndrome and is being followed up in a specialized clinic, with cascade genetic testing also conducted in her family.