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.
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 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.
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.
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.
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.
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.
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.
Lymph nodes are routinely examined during the staging of malignant tumors, particularly those of epithelial origin. The assessment of metastatic involvement, especially of sentinel or regional lymph nodes, is absolutely crucial for the appropriate clinical management of patients. However, lymph nodes can also harbor other lesions that must be taken into consideration during differential diagnosis-not only reactive lymphadenopathy, but also less common findings, such as epithelial inclusions or heterotopic occurrence of certain tissues. In this paper we demonstrate the importance of such findings in two cases from our institution, accompanied by a brief review of the published literature focusing on the differential diagnosis of axillary lymph node lesions. We present case reports of findings in the axillary lymph nodes of two female patients with invasive breast carcinoma of NST type.
The existing HER2 immunohistochemistry testing is currently experiencing changes in its scoring caused by the recent clinical trials results, especially DESTINY Breast 04 and 06. These trials demonstrated that any detectable immunohistochemical positivity of HER2 protein on tumor cells is a predictor of response to the new antibody-drug conjugate trastuzumab deruxtecan. These studies introduced new terms "HER2 low" and later "HER2 ultralow" to distinguish subgroups within the original category "HER2 negative", which quickly became accepted in clinical practice. This article aims to explain these new terms and present Czech and international expert recommendations for testing and reporting of HER2 immunohistochemistry in relation to these new categories.
Breast cancer is the most common type of solid tumors in women. Breast cancer treatment at each stage of the disease is based on results describing genetic changes present in the tumor cells. Since breast cancer is not a homogeneous disease, its treatment approaches differ with respect to individual subgroups of breast cancer defined at the basic level by the expression of hormone receptors, HER2 receptor and Ki-67 marker. More recently described genetic changes in breast cancer cells significantly expand the treatment options, but on the other hand mean new challenges and demands in the further investigation of tumor samples. The following is a brief overview of prognostic and predictive markers used in breast cancer. The evaluation of these markers is in the hands of pathologists.
Traditional histopathological methods, such as hematoxylin and eosin staining and chromogenic immunohistochemistry, are still primarily used in clinical practice, however, they are limited in their ability to simultaneously detect multiple biomarkers and analyze spatial relationships between cell populations. These limitations are overcome by multiplex immunohistochemistry (mIHC) methods that allow detailed spatial analysis of formalin-fixed paraffin-embedded tissues with detection of multiple epitopes in a single sample. Detailed characterization of immune cell populations within tumor microenvironment has significantly contributed to the development of immunotherapeutic approaches, which have fundamentally transformed the prognosis of many advanced malignancies. Modern multiplex methods use both chromogenic and immunofluorescence detection and include sequential cyclic labeling or tyramine signal amplification techniques. Alternative approaches, such as the use of nucleotide-conjugated antibodies, allow highly specific detection and facilitate quantitative analysis, while mass spectrometry-based approaches enable the profiling of extensive biomarker panels. Despite significant technological advances, the integration of mIHC into routine clinical diagnostics remains challenging, primarily due to the need for standardization, antibody validation, advanced image data analysis integration, and the regulation of laboratory-developed tests. With the continued automation and digitization of pathology, wider use of mIHC in clinical practice can be expected, which could significantly contribute to the deeper characterization of tumors and improved therapy.
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.
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.
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.
Cholangiocellular carcinoma (cholangiocarcinoma, CCA) is a heterogeneous group of malignant epithelial tumors of the bile ducts, with varying classifications and molecular characteristics. CCA can arise in intrahepatic, perihilar, or extrahepatic bile ducts, with its incidence rising globally, particularly in Southeast Asia due to liver fluke infections. Other risk factors include primary sclerosing cholangitis, viral hepatitis, gallstones, congenital bile duct malformations, and cirrhosis. CCA is often diagnosed at advanced stages and has a poor prognosis. This article summarizes the complex classification systems of CCA and biliary precancerous lesions (biliary intraepithelial neoplasia, BilIN), focusing on morphology, molecular profiles, and clinical implications. It briefly addresses the differential diagnosis between CCA and BilIN, distinguishing intrahepatic from extrahepatic CCA, as well as differentiating CCA from hepatocellular carcinoma (HCC) and metastatic adenocarcinomas. Alongside selected literature, experiences from our institution using various immunohistochemical methods (CRP, S100P, IMP3) are presented, highlighting their relevance in routine practice. The majority of the article focuses on the molecular pathology of CCA, where mutation profiles differ according to anatomical subtypes. Intrahepatic CCA more frequently harbors mutations in IDH1/2, FGFR, and BAP1, while perihilar and extrahepatic CCAs are more likely to exhibit mutations in TP53, KRAS, and ERBB2. Alterations in FGFR2 and IDH1 are associated with better prognosis, while TP53 and KRAS mutations indicate worse outcomes. The article provides an overview of genetic alterations that are targetable with current oncological therapies, including FDA-approved inhibitors for FGFR2 (pemigatinib, futibatinib) and IDH1 (ivosidenib), along with inhibitors targeting BRAF, HER2, NTRK, and immunotherapies for MSI-high and TMB-high tumors. Intrahepatic CCA presents a broader spectrum of therapeutic targets, including rare fusions (ALK, RET), compared to perihilar and extrahepatic CCA, which share a poor prognosis and limited therapeutic options with pancreatic cancer. In this regard, intrahepatic CCA may become the "non-small cell lung cancer of gastrointestinal oncology."
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.
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.
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.
