Classification of head and neck tumors has evolved in recent decades including a widespread application of molecular testing in tumors of the salivary glands, sinonasal tract, oropharynx, nasopharynx, and soft tissue. Availability of new molecular techniques allowed for the definition of multiple novel tumor types unique to head and neck sites. Moreover, the expanding spectrum of immunohistochemical markers facilitates a rapid identification of diagnostic molecular abnormalities. As such, it is currently possible for head and neck pathologists to benefit from a molecularly defined classifications, while making diagnoses that are still based largely on histopathology and immunohistochemistry. This review highlights some principal molecular alterations in head and neck neoplasms presently available to assist pathologists in the practice of diagnosis, prognostication and prediction of response to treatment.

• Klíčová slova
• Head and neck, Molecular diagnostics, Next-generation sequencing, Salivary gland, Sinonasal tumor, Soft tissue,
• MeSH
• imunohistochemie MeSH
• lidé MeSH
• molekulární patologie * MeSH
• nádory hlavy a krku * diagnóza   genetika   MeSH
• patologové MeSH
• slinné žlázy MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

We report 2 cases of high-grade sinonasal adenocarcinoma with a distinct morphological and immunohistochemical phenotype. Albeit histologically different from secretory carcinoma of the salivary glands, both tumors presented here share an ETV6::NTRK3 fusion. The highly cellular tumors were composed of solid and dense cribriform nests, often with comedo-like necroses in the center, and minor areas with papillary, microcystic, and trabecular formations without secretions, mostly located at the periphery of the lesion. The cells displayed high-grade features, with enlarged, crowded, and often vesicular nuclei with conspicuous nucleoli and brisk mitotic activity. The tumor cells were immunonegative for mammaglobin while showing immunopositivity for p40/p63, S100, SOX10, and GATA3, as well as for cytokeratins 7, 18, and 19. For the first time, we describe 2 cases of primary high-grade non-intestinal type adenocarcinomas of the nasal cavity, distinct from secretory carcinoma by morphology and immunoprofile, harboring the ETV6::NTRK3 fusion.

• Klíčová slova
• ETV6::NTRK3, Nasal cavity, Salivary duct carcinoma, Secretory carcinoma, Sinonasal, non-intestinal-type adenocarcinoma,
• MeSH
• adenokarcinom * genetika   patologie   MeSH
• fúzní onkogenní proteiny genetika   MeSH
• imunohistochemie MeSH
• karcinom * genetika   patologie   MeSH
• lidé MeSH
• nádorové biomarkery genetika   MeSH
• nádory prsu MeSH
• nádory slinných žláz * genetika   patologie   MeSH
• protein ETS, translokační varianta 6 MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• fúzní onkogenní proteiny MeSH
• nádorové biomarkery MeSH
• NTRK3 protein, human MeSH Prohlížeč

We present a 72 years old male with a left nasal cavity (mammary analogue) secretory carcinoma (SC) which exhibited classical morphological features on light microscopical examination, diffuse strong S100 and mammoglobin positivity on immunohistochemistry, and ETV6-NTRK3 gene fusion on next generation sequencing (NGS) analysis. Unusual features of this tumor are expression of p63 and DOG1 on immunohistochemistry and the atypical junction between Exon 4 of the ETV6 gene and Exon 14 of the NTRK3 gene.

• Klíčová slova
• ETV6-NTRK3 fusion protein, human, Immunohistochemistry, Mammary analogue secretory carcinoma, Nasal cavity,
• MeSH
• anoctamin 1 biosyntéza   MeSH
• exony genetika   MeSH
• fúzní onkogenní proteiny genetika   MeSH
• lidé MeSH
• membránové proteiny biosyntéza   MeSH
• nádorové biomarkery analýza   MeSH
• nádorové proteiny biosyntéza   MeSH
• nádory nosu genetika   patologie   MeSH
• nosní dutina patologie   MeSH
• sekreční karcinom mamárního typu genetika   patologie   MeSH
• sekvenční analýza DNA MeSH
• senioři MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• ANO1 protein, human MeSH Prohlížeč
• anoctamin 1 MeSH
• CKAP4 protein, human MeSH Prohlížeč
• ETV6-NTRK3 fusion protein, human MeSH Prohlížeč
• fúzní onkogenní proteiny MeSH
• membránové proteiny MeSH
• nádorové biomarkery MeSH
• nádorové proteiny MeSH

This review concentrates on three salivary gland tumors that have been accepted in the recent literature as new neoplastic entities: mammary analog secretory carcinoma (MASC), sclerosing polycystic adenoma (SPA) and cribriform adenocarcinoma of tongue and other minor salivary glands (CAMSGs). MASC is a distinctive low-grade malignant salivary cancer that harbors a characteristic chromosomal translocation, t(12;15) (p13;q25) resulting in an ETV6-NTRK3 fusion. SPA is a rare lesion often mistaken histologically for low-grade salivary carcinoma. Previously thought to be a reactive fibroinflammatory process, but recent evidence of clonality, recurrences in up 30%, and dysplastic foci suggest it may be truly neoplastic. CAMSG is a distinct tumor entity that differs from polymorphous low-grade adenocarcinoma (PLGA) by location (ie, most often arising on the tongue), by prominent nuclear clearing, alterations of the PRKD gene family and clinical behavior with frequent metastases at the time of presentation of the primary tumor. Early metastatic disease seen in most cases of CAMSG associated with indolent behavior makes it a unique neoplasm among all low-grade salivary gland tumors. Salivary glands may give rise to a wide spectrum of different tumors. They are often diagnostically challenging as morphological features often overlap between different entities. Although conventional morphology in combination with immunohistochemical findings still provide the most important clues for diagnosis, recent advances in molecular pathology offer new diagnostic tools in investigating the differential diagnosis, as well as providing potentially valuable prognostic indicators. In the last two decades, several new salivary gland tumor entities have been described, namely MASC, SPA and CAMSGs.

• MeSH
• adenokarcinom diagnóza   genetika   patologie   MeSH
• adenom diagnóza   genetika   patologie   MeSH
• fúzní onkogenní proteiny genetika   MeSH
• lidé MeSH
• nádorové biomarkery genetika   MeSH
• nádory slinných žláz diagnóza   genetika   patologie   MeSH
• prognóza MeSH
• sekreční karcinom mamárního typu diagnóza   genetika   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• fúzní onkogenní proteiny MeSH
• nádorové biomarkery MeSH

Salivary gland hybrid tumour, first described in 1996, is a very rare neoplasm for which exact morphological criteria have not been universally agreed upon. In contrast, the concept of high-grade transformation (HGT) in salivary neoplasms has been widely accepted during the last decade, and the number of reported cases is rapidly increasing. A review of the literature revealed 38 cases of hybrid tumour reported in 22 publications. During approximately the same time period, well over 100 cases of HGT in salivary neoplasms have been reported. There are important histological similarities between hybrid tumours and salivary tumours with HGT. In the latter, containing one tumour component of low-grade malignancy and the other of high grade, the two tumour components are not entirely separated and appear to originate in the same area. Virtually, all cases reported as hybrid tumour had no clear lines of demarcation between the two tumour types. We are inclined to suggest that most of the 38 cases of hybrid tumours described in the literature would today better be called tumour with HGT rather than hybrid tumour. The relative proportion of the two components may vary, and the high-grade component is sometimes very small, which emphasises the importance of very generous sampling of the surgical specimen. The molecular genetic mechanisms responsible for HGT, including what used to be called hybrid tumour, remain largely unknown. Abnormalities of a few genes (including p53, C-MYC, cyclin D1, HER-2/neu) have been documented. As insufficient data exist on gene abnormalities in these lesions, conclusions as to whether or not they have a common origin and which mechanisms are involved in transformation cannot be drawn. Due to the small number of cases reported, many of which lack follow-up details; indicators of prognosis of hybrid tumours are not available, but their behaviour seems to be similar to that of tumours with HGT, i.e. an accelerated aggressive course. HGT of salivary gland neoplasms greatly influences macroscopic and microscopic evaluation of the specimen but also, given the high incidence of metastases and morbidity, carries significant treatment implications.

• Klíčová slova
• Dedifferentiation, High-grade transformation, Hybrid tumour, Salivary gland neoplasms, Salivary glands,
• MeSH
• dospělí MeSH
• geny myc genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorová transformace buněk patologie   MeSH
• nádory slinných žláz diagnóza   patologie   MeSH
• prognóza MeSH
• sekundární malignity diagnóza   patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stupeň nádoru MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Adenoid cystic carcinoma (AdCC) is among the most common malignant tumors of the salivary glands. It is characterized by a prolonged clinical course, with frequent local recurrences, late onset of metastases and fatal outcome. High-grade transformation (HGT) is an uncommon phenomenon among salivary carcinomas and is associated with increased tumor aggressiveness. In AdCC with high-grade transformation (AdCC-HGT), the clinical course deviates from the natural history of AdCC. It tends to be accelerated, with a high propensity for lymph node metastasis. In order to shed light on this rare event and, in particular, on treatment implications, we undertook this review: searching for all published cases of AdCC-HGT. We conclude that it is mandatory to perform elective neck dissection in patients with AdCC-HGT, due to the high risk of lymph node metastases associated with transformation.

• Klíčová slova
• Adenoid cystic carcinoma, Dedifferentiation, Fatal outcome, High-grade transformation, Local recurrence, Lymphatic metastasis, Neck dissection, Neoplasm recurrence, Salivary glands,
• MeSH
• adenoidně cystický karcinom mortalita   patologie   chirurgie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfatické metastázy patologie   MeSH
• lymfatické uzliny patologie   MeSH
• nádory slinných žláz mortalita   patologie   chirurgie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH