AIMS: Sinonasal adenosquamous carcinoma (ASC) is a rare tumour classified as a variant of squamous cell carcinoma, exhibiting both squamous and glandular differentiation. ASC has a poorer prognosis compared to sinonasal mucoepidermoid carcinoma (MEC), another uncommon tumour in this region. ASC is believed to originate from metaplastic squamous epithelium, though it may also arise from respiratory epithelium in respiratory epithelial adenomatoid hamartoma (REAH) or seromucinous glands in seromucinous hamartoma (SH). METHODS AND RESULTS: Five cases of sinonasal ASC were retrieved from our registry. Initially, they were classified as sinonasal MEC (n = 3), ASC (n = 2), and carcinoma ex REAH (n = 1). All cases showed adenosquamous malignant proliferation beneath the surface respiratory epithelium with occasional squamous metaplasia, except for one case that showed dysplasia. The respiratory epithelium exhibited an inverted growth pattern consistent with REAH/SH, and displayed atypical sinonasal glands (ASGSH) arising within seromucinous hamartoma. Next-generation sequencing (NGS) revealed multiple pathogenic mutations in two cases, and in case 4 GGA2::PRKCB and EYA2::SERINC3 gene fusions. One case was positive for high-risk HPV. None of the cases exhibited CRTC1/3::MAML2 gene fusion. CONCLUSION: The connection between ASGSH and ASC has not been described in the literature. There is a growing need for additional studies on the morphological, immunohistochemical, and genetic aspects of these tumours. SH/REAH may serve as precursor lesions in the progression of atypical sinonasal glands to malignancy, and their role in tumour development deserves further investigation.

• Klíčová slova
• EYA2, GGA2, PRKCB, SERINC3, HPV, adenosquamous carcinoma, genetic, mucoepidermoid carcinoma,
• MeSH
• adenoskvamózní karcinom * patologie   genetika   MeSH
• dospělí MeSH
• hamartom * patologie   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory vedlejších dutin nosních * patologie   genetika   MeSH
• respirační sliznice patologie   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Sclerosing mucoepidermoid carcinoma (SMEC) of the salivary glands is a rare variant of low-grade mucoepidermoid carcinoma with scanty cellular atypia characterized by marked fibrosis/sclerosis and a rich inflammatory infiltrate. Herein, we report 25 unpublished cases of SMEC, two of them with prominent eosinophilia (2/25; 8%) and three with abundant IgG4-positive plasma cells (3/25; 12%). In our series of salivary SMEC, molecular analysis using fluorescence in situ hybridization (FISH) and/or next-generation sequencing (NGS) provided evidence of MAML2 gene rearrangement in 18 cases of the 21 analyzable cases tested (86%), while this gene locus was intact in 3 cases (14%). This study focuses on the diagnostic criteria of salivary SMEC given its challenge of abundant collagenous stroma, minimal residual neoplastic areas, and inconspicuous mucous cells. Follow-up data of our cases indicate that salivary SMECs have favorable outcomes. Molecular analysis for MAML2 gene rearrangement suggests that SMECs of salivary glands represent a rare variant of conventional low-grade MECs of salivary glands. In contrast, SMECs of the thyroid gland are genetically distinct from salivary-type thyroid MECs.

• Klíčová slova
• MAML2 rearrangement, IgG4, Keloid-like stromal fibrosis, SMEC, Salivary gland, Sclerosing mucoepidermoid carcinoma, Sclerosis, Tissue eosinophilia,
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• časopisecké články MeSH

Branchioma is an uncommon benign neoplasm with an adult male predominance, typically occurring in the lower neck region. Different names have been used for this entity in the past (ectopic hamartomatous thymoma, branchial anlage mixed tumor, thymic anlage tumor, biphenotypic branchioma), but currently, the term branchioma has been widely accepted. Branchioma is composed of endodermal and mesodermal lineage derivatives, in particular epithelial islands, spindle cells, and mature adipose tissue without preexistent thymic tissue or evidence of thymic differentiation. Twenty-three branchiomas were evaluated morphologically. Eighteen cases with sufficient tissue were assessed by immunohistochemistry, next-generation sequencing (NGS) using the Illumina Oncology TS500 panel, and fluorescence in situ hybridization (FISH) using an RB1 dual-color probe. All cases showed a biphasic morphology of epithelial and spindle cells with intermingled fatty tissue. Carcinoma arising in branchioma was detected in three cases. The neoplastic cells showed strong AE1/3 immunolabeling (100%), while the spindle cells expressed CD34, p63, and SMA (100%); AR was detected in 40-100% of nuclei (mean, 47%) in 14 cases. Rb1 showed nuclear loss in ≥ 95% of neoplastic cells in 16 cases (89%), while two cases revealed retained expression in 10-20% of tumor cell nuclei. NGS revealed a variable spectrum of likely pathogenic variants (n = 5) or variants of unknown clinical significance (n = 6). Loss of Rb1 was detected by FISH in two cases. Recent developments support branchioma as a true neoplasm, most likely derived from the rudimental embryological structures of endoderm and mesoderm. Frequent Rb1 loss by immunohistochemistry and heterozygous deletion by FISH is a real pitfall and potential confusion with other Rb1-deficient head and neck neoplasms (i.e., spindle cell lipoma), especially in small biopsy specimens.

• Klíčová slova
• And neck, Branchioma, CD34, Ectopic hamartomatous thymoma, Head, RET, Retinoblastoma 1,
• MeSH
• branchiom * patologie   MeSH
• dospělí MeSH
• hybridizace in situ fluorescenční MeSH
• lidé MeSH
• molekulární biologie MeSH
• nádory brzlíku * MeSH
• nádory glandulární a epitelové * MeSH
• nádory měkkých tkání * patologie   MeSH
• nádory sítnice * MeSH
• retinoblastom * genetika   patologie   MeSH
• thymom * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Branchioma (previously called ectopic hamartomatous thymoma, branchial anlage mixed tumor, or thymic anlage tumor) is a rare lower neck lesion with an adult male predominance and an uncertain histogenesis. Except for 4 cases, all branchiomas described in the literature were benign. Recently, HRAS mutation was detected in one case, but still little is known about the molecular genetic background of this rare entity. We herein report the histological, immunohistochemical, and molecular genetic analysis of a branchioma with a nested/organoid (neuroendocrine-like) morphology in a 78-year-old man. Histology revealed classical branchioma areas merging with nested/organoid cellular component lacking conventional features of malignancy. Immunohistochemistry was positive for high-molecular-weight cytokeratins. CD34 was expressed in the spindle cell component. Moreover, the tumor cells showed near-complete loss of retinoblastoma (RB1) expression (<1% of cells positive). All neuroendocrine markers (synaptophysin, chromogranin, and INSM1) were negative. Next-generation sequencing (TSO500 Panel) revealed 5 pathogenic/likely pathogenic mutations including 1 mutation in KRAS and 2 different mutations in each of MSH6 and PTEN. FISH and DNA sequencing were negative for RB1 gene alterations. To our knowledge, this is the first report of a branchioma showing misleading nested/organoid morphology and the first report on Rb1 immunodeficiency in this entity, in addition to multiple gene mutations revealed by NGS.

• Klíčová slova
• Androgen receptor, Branchioma, CD34, Ectopic hamartomatous thymoma, Head and neck, Neuroendocrine carcinoma-like, RB1 gene, Retinoblastoma,
• MeSH
• branchiom * patologie   MeSH
• lidé MeSH
• nádory brzlíku MeSH
• nádory glandulární a epitelové MeSH
• nádory měkkých tkání * MeSH
• nádory sítnice * MeSH
• organoidy patologie   MeSH
• represorové proteiny MeSH
• retinoblastom * genetika   patologie   MeSH
• senioři MeSH
• thymom MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• INSM1 protein, human MeSH Prohlížeč
• represorové proteiny MeSH

The salivary gland section in the 5th edition of the World Health Organization Classification of Head and Neck Tumours includes a description of several new entities. In addition, numerous tumor variants were described and new concepts proposed, most of which have been based on recent molecular discoveries. However, there are still some controversial issues that remain to be resolved, and some of them are discussed in this review.

• Klíčová slova
• Carcinosarcoma, Intraductal carcinoma, Intraductal papillary mucinous neoplasms, Mucinous adenocarcinoma, Oncocytic carcinoma, Salivary gland, World health organization classification,
• MeSH
• lidé MeSH
• nádory hlavy a krku * MeSH
• nádory slinných žláz * patologie   MeSH
• slinné žlázy patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• New Orleans MeSH

This review gives a brief history of the development of head and neck pathology in Europe from a humble beginning in the 1930s to the explosive activities the last 15 years. During the decades before the introduction of immunohistochemistry in the 1980s, head and neck pathology grew as a subspeciality in many European countries. In the late 1940s, the Institute of Laryngology and Otology with its own pathology laboratory was founded in London, and in 1964 the World Health Organization (WHO) International Reference Centre for the Histological Classification of Salivary Tumours was established at the Bland-Sutton Institute of Pathology, also in London. International collaboration, and very much so in Europe, led to the publication of the first WHO Classification of Salivary Gland Tumours in 1972. In the 1960s, a salivary gland register was organised in Hamburg and in Cologne the microlaryngoscopy was invented enabling microscopic endoscopic examination and rather shortly afterwards a carbon dioxide laser attached to the microscope became established and laryngeal lesions could be treated by laser vaporisation. During the last three decades, the use of immunohistochemistry supplemented with cytogenetic and refined molecular techniques has greatly facilitated the pathological diagnostics of head and neck lesions and has had a huge impact on research. Collaboration between different European centres has drastically increased partly due to establishment of scientific societies such as the Head and Neck Working Group (HNWG) within the European Society of Pathology and the International Head and Neck Scientific Group (IHNSG). A very large number of European pathologists have contributed to the 2nd, 3rd and 4th WHO books, and are involved in the upcoming 5th edition. Accredited educational meetings and courses are nowadays regularly arranged in Europe. Numerous textbooks on head and neck pathology have been written and edited by European pathologists. The increased collaboration has created larger series of tumours for research and new entities, mainly defined by their genetic abnormalities, are continuously emerging from Europe, particularly regarding salivary gland neoplasms and "undifferentiated" sinonasal tumours. These findings have led to a better and more precise classification and open the possibilities for new treatment strategies.

• Klíčová slova
• Cancer, Head and neck pathology, History of European head and neck pathology, Laryngeal neoplasms, Salivary neoplasms, Sinonasal neoplasms,
• MeSH
• lidé MeSH
• nádory hlavy a krku * diagnóza   MeSH
• nádory slinných žláz * MeSH
• slinné žlázy MeSH
• Světová zdravotnická organizace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• Evropa MeSH

The salivary gland section in the 5th edition of the World Health Organization Classification of Head and Neck Tumours 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 mutations 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). 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. 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 variant of PAC is still controversial. Poorly differentiated carcinomas and oncocytic carcinomas are discussed in the category "Salivary carcinoma not otherwise specified (NOS) and emerging entities". 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.

• Klíčová slova
• Classification, Gene fusion, Neoplasm, Salivary gland, WHO, World Health Organization,
• MeSH
• adenokarcinom * patologie   MeSH
• adenom * genetika   patologie   MeSH
• lidé MeSH
• mucinózní adenokarcinom * MeSH
• nádorové biomarkery genetika   MeSH
• nádory slinných žláz * genetika   patologie   MeSH
• slinné žlázy patologie   MeSH
• Světová zdravotnická organizace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• nádorové biomarkery MeSH

Salivary gland carcinomas represent a heterogeneous group of poorly characterized head and neck tumors. The purpose of this study was to evaluate ALK gene and protein aberrations in a large, well-characterized cohort of these tumors. A total of 182 salivary gland carcinomas were tested for anaplastic lymphoma kinase (ALK) positivity by immunohistochemistry (IHC) using the cut-off of 10% positive cells. ALK positive tumors were subjected to FISH analysis and followed by hybrid capture-based next generation sequencing (NGS). Of the 182 tumors, 8 were ALK positive by IHC. Further analysis using hybrid capture NGS analysis revealed a novel MYO18A (Exon1-40)-ALK (exon 20-29) gene fusion in one case of intraductal carcinoma. Additional genomic analyses resulted in the detection of inactivating mutations in BRAF and TP53, as well as amplifications of ERBB2 and ALK. ALK rearrangements are a rare entity in salivary gland carcinomas. We identified a potentially targetable novel ALK fusion in an intraductal carcinoma of minor salivary glands.

• Klíčová slova
• Anaplastic lymphoma kinase, FISH, Immunohistochemistry, Intraductal carcinoma, Next generation sequencing, Salivary gland carcinoma,
• MeSH
• amplifikace genu MeSH
• anaplastická lymfomová kináza genetika   MeSH
• dítě MeSH
• dospělí MeSH
• fúze genů MeSH
• hybridizace in situ fluorescenční MeSH
• imunohistochemie MeSH
• intraduktální neinfiltrující karcinom enzymologie   genetika   patologie   MeSH
• karcinom enzymologie   genetika   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádorové biomarkery genetika   MeSH
• nádory slinných žláz enzymologie   genetika   patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ALK protein, human MeSH Prohlížeč
• anaplastická lymfomová kináza MeSH
• nádorové biomarkery MeSH

Diagnosis of salivary gland neoplasms is often challenging due to their high morphological diversity and overlaps. Several recurrent molecular alterations have been described recently, which can serve as powerful diagnostic tools and potential therapeutic targets (e.g. NTRK or RET fusions). However, current sequential molecular testing can be expensive and time consuming. In order to facilitate the diagnosis of salivary gland neoplasms, we designed an all-in-one RNA-based next generation sequencing panel suitable for the detection of mutations, fusions and gene expression levels (including NR4A3) of 27 genes involved in salivary gland neoplasms. Here we present the validation of the "SalvGlandDx" panel on FFPE histological specimen including fine needle aspiration (FNA) cell block material, against the standard methods currently used at our institution. In a second part we describe selected unique cases in which the SalvGlandDx panel allowed proper diagnosis and new insights into special molecular characteristics of selected salivary gland tumors. We characterize a unique salivary gland adenocarcinoma harboring a ZCCHC7-NTRK2 fusion, a highly uncommon spindle cell and pseudoangiomatoid adenoid-cystic carcinoma with MYBL1-NFIB fusion, and a purely oncocytic mucoepidermoid carcinoma, whereas diagnosis could be made by detection of a CRTC3-MAML2 rearrangement on the cell block specimen of the FNA. Further, a rare case of a SS18-ZBTB7A rearranged low-grade adenocarcinoma previously described as potential spectrum of microsecretory adenocarcinoma, is reported. In addition, features of six cases within the spectrum of polymorphous adenocarcinoma / cribriform adenocarcinoma of salivary gland including PRKD1 p.E710D mutations and novel fusions involving PRKAR2A-PRKD1, SNX9-PRKD1 and ATL2-PRKD3, are described.

• Klíčová slova
• Biopsy, Comprehensive, FNA, Molecular, Salivary gland neoplasm, Testing,
• MeSH
• biopsie MeSH
• fúzní onkogenní proteiny genetika   metabolismus   MeSH
• hybridizace in situ fluorescenční MeSH
• imunohistochemie metody   MeSH
• lidé MeSH
• mutace MeSH
• nádorové biomarkery * MeSH
• nádorové buněčné linie MeSH
• nádory slinných žláz diagnóza   farmakoterapie   genetika   MeSH
• staging nádorů MeSH
• stanovení celkové genové exprese * metody   MeSH
• stupeň nádoru MeSH
• vysoce účinné nukleotidové sekvenování * metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fúzní onkogenní proteiny MeSH
• nádorové biomarkery * MeSH