Dedifferentiated and undifferentiated ovarian carcinomas (DDOC/UDOC) are rare neoplasms defined by the presence of an undifferentiated carcinoma. In this study, we detailed the clinical, pathological, immunohistochemical, and molecular features of a series of DDOC/UDOC. We collected a multi-institutional cohort of 23 DDOC/UDOC and performed immunohistochemistry for core switch/sucrose nonfermentable (SWI/SNF) complex proteins (ARID1A, ARID1B, SMARCA4, and SMARCB1), mismatch repair (MMR) proteins, and p53. Array-based genome-wide DNA methylation and copy number variation analyses were performed on a subset of cases with comparison made to a previously reported cohort of undifferentiated endometrial carcinoma (UDEC), small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), and tubo-ovarian high-grade serous carcinoma (HGSC). The age of all 23 patients with DDOC/UDOC ranged between 22 and 71 years (with an average age of 50 years), and a majority of them presented with extraovarian disease (16/23). Clinical follow-up was available for 19 patients. Except for 2 patients, the remaining 17 patients died from disease, with rapid disease progression resulting in mortality within a year in stage II-IV settings (median disease-specific survival of 3 months). Eighteen of 22 cases with interpretable immunohistochemistry results showed loss of expression of core SWI/SNF protein(s) that are expected to result in SWI/SNF complex inactivation as 10 exhibited coloss of ARID1A and ARID1B, 7 loss of SMARCA4, and 1 loss of SMARCB1. Six of 23 cases were MMR-deficient. Two of 20 cases exhibited mutation-type p53 immunoreactivity. Methylation profiles showed coclustering of DDOC/UDOC with UDEC, which collectively were distinct from SCCOHT and HGSC. However, DDOC/UDOC showed an intermediate degree of copy number variation, which was slightly greater, compared with SCCOHT but much less compared with HGSC. Overall, DDOC/UDOC, like its endometrial counterpart, is highly aggressive and is characterized by frequent inactivation of core SWI/SNF complex proteins and MMR deficiency. Its molecular profile overlaps with UDEC while being distinct from SCCOHT and HGSC.

• MeSH
• dědičné nádorové syndromy * MeSH
• DNA-helikasy genetika   metabolismus   MeSH
• dospělí MeSH
• epiteliální ovariální karcinom MeSH
• jaderné proteiny genetika   MeSH
• karcinom * patologie   MeSH
• kolorektální nádory * MeSH
• lidé středního věku MeSH
• lidé MeSH
• malobuněčný karcinom * MeSH
• mladý dospělý MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• nádorový supresorový protein p53 genetika   MeSH
• nádory endometria * patologie   MeSH
• nádory mozku * MeSH
• nádory vaječníků * genetika   patologie   MeSH
• senioři MeSH
• transkripční faktory genetika   metabolismus   MeSH
• variabilita počtu kopií segmentů DNA MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

A 56-year-old female was referred to our service for management of a malignant salivary gland neoplasm with compromised margins that had been biopsied previously at another service. The patient reported a twenty-year history of a lesion in the oral cavity with progressive and exuberant growth over the past two years, associated with local pain and dyspnea. Physical examination revealed an erythematous, ulcerated, and hemorrhagic lesion measuring approximately 3 cm on the left soft palate and tonsillar pillar. Computed tomography revealed an expansile lesion in the topography of the left soft palate, growing predominantly toward the lumen of the nasopharynx and partially invading the left wall of this region. The patient underwent surgery and histopathologic examination revealed an infiltrative and aggressive epithelial neoplasia with large vacuolated and eosinophilic cytoplasm, vesicular nuclei, and prominent nucleoli. The neoplastic cells were arranged in a solid, microcystic, tubular, and follicular pattern with eosinophilic luminal secretion. Mitotic figures were frequent and all margins were affected by the neoplasia. Morphologic and immunohistochemical features supported the diagnosis of secretory carcinoma, and the patient is currently being followed for further therapeutic intervention.

• MeSH
• karcinom patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• malé slinné žlázy * patologie   MeSH
• nádory slinných žláz * patologie   diagnóza   MeSH
• počítačová rentgenová tomografie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• kazuistiky MeSH

V roce 2023 vydávaná 5. edice WHO klasifikace nádorů kůže doznala v sekci mezenchymálních nádorů několika změn, přičemž mezi nejvýznamnější, jako již tradičně, patří zařazení nově identifikovaných nádorových jednotek, kterými se tento přehledový článek bude zabývat především. Konkrétně se jedná o tři nové kožní mezenchymální tumory s melanocytární diferenciací a rearanžemi genů CRTC1::TRIM11, ACTIN::MITF a MITF::CREM. Dále byly nově zařazeny EWSR1::SMAD3- rearanžované fibroblastické tumory, superficiální CD34 pozitivní fibroblastické tumory a NTRK-rearanžované vřetenobuněčné neoplazie. Z dalších změn budou krátce zmíněny pouze ty nejvýznamnější.

The section on mesenchymal tumors in 5th edition of WHO classification of skin tumors has undergone several changes, the most important of which, as usual, is the inclusion of newly identified tumor entities, which will be the main focus of this review article. These specifically include three novel cutaneous mesenchymal tumors with melanocytic differentiation, and rearrangements of the CRTC1::TRIM11, ACTIN::MITF, and MITF::CREM genes. In addition, EWSR1::SMAD3-rearranged fibroblastic tumors, superficial CD34-positive fibroblastic tumors, and NTRK-rearranged spindle cell neoplasms were newly included. Of the other changes, only the most important ones will be briefly mentioned

• Klíčová slova
• mezenchymální nádory,
• MeSH
• antigeny CD34 analýza   MeSH
• diferenciální diagnóza MeSH
• fibroblasty asociované s nádorem klasifikace   patologie   MeSH
• karcinom klasifikace   patologie   MeSH
• melanocyty patologie   MeSH
• nádory kůže * genetika   klasifikace   patologie   MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

WHO klasifikace tyreoidálních nádorů vstupují do druhého půlstoletí vývoje 5. vydáním. Trvalý nárůst informací je v porovnání s předchozím 4. vydáním kla- sifikace především v úrovni molekulárně biologické. To změnilo pohled na velmi tradiční jednotky – preferovaný název pro polynodózní strumu je (s ohledem na monoklonální povahu některých uzlů) folikulární nodulární tyreoidální nemoc. Odstraněny byly i některé terminologické relikty – název onkocyty nahradil Hürthleho buňky. Folikulární adenom má nově podtyp s papilární úpravou (a chybějícími jadernými znaky papilárního karcinomu). V již vžité jednotce NIFTP jsou nově vymezeny podtypy menší než 10 mm a onkocytární. Všechny onkocytární tumory mají arbitrárně stanoven minimální podíl onkocytů na 75 %. Multi- disciplinární přístup k léčbě tyreopatií a stratifikace terapeutických postupů podle rizika přineslo zavedení gradingu do řady nozologických jednotek karcinomů papilárního, folikulárního, medulárního. Grading využívající počtu mitóz stanoví jejich kvantifikaci na 2 mm² místo dříve užívaných nejednotných zorných polí velkého zvětšení (HPF). Upřesnění nastalo na podkladě genetických poznatků i v řadě dalších, méně častých diagnóz (např. zařazení spinocelulárního karcino- mu mezi anaplastické). V kategorii vzácných nádorů jsou nově formulovány karcinomy salivárního typu se dvěma zástupci: mukoepidermoidním a sekretoric- kým karcinomem. Kribriformně morulárně upravený karcinom řazený dříve jako varianta karcinomu papilárního je nově oddělen na podkladě imunologického a genetického profilu do nově vzniklé kategorie nádorů nejisté histogeneze. Do této kategorie je zařazen rovněž sklerozující mukoepidermoidní karcinom s eo- zinofilií. Mikrokarcinom jako samostatná jednotka není v 5. vydání obsažen. Nádor menší než 10 mm musí být charakterizován příslušnými znaky odpovídající kategorie. Thyroblastom nahrazuje terminologicky maligní teratom Část nově stanovených diagnostických kritérií je uplatnitelná i ve FNAB diagnostice. Nově zavedený grading u některých nozologických jednotek může výjimeč- ně i změnit diagnózu (NIFTP/EFVPTC/ neinvazivní HG FVPTC), ale především ovlivní volbu terapeutických postupů.

The WHO classification of thyroid tumours enters its second half-century of development with the 5th edition. Compared to the previous 4th edition of the clas- sification, the permanent increase in information is mainly at the molecular biological level. This has changed the view of very traditional entities – the preferred name for polynodous goiter is (given the monoclonal nature of some nodules) follicular nodular thyroid disease. Some terminological relics have also been re- moved – Hürthle cells are definitively referred to as oncocytes. Follicular adenoma has a new subtype with papillary arrangement (and missing nuclear features of papillary carcinoma). In the already used NIFTP unit, subtypes smaller than 10 mm and oncocytic are newly defined. All oncocytic tumours have an arbitrarily set minimum proportion of oncocytes at 75 %. A multidisciplinary approach to the treatment of thyropathies and the stratification of therapeutic procedures according to risk brought about the introduction of grading into several nosological units of papillary, follicular, and medullary carcinomas. Grading using the number of mitoses determines their quantification at 2 mm² instead of the previously used non-uniform HPFs (high power fields of view). Clarification was made on the basis of genetic findings in a number of other, less frequent diagnoses (e.g. classification of squamous cell carcinoma among anaplastic). Among rare tumors a new category of salivary gland - type carcinomas is formulated with two representatives: mucoepidermoid and secretory carcinoma. Cribriform morular carcinoma previously classified as a variant of papillary carcinoma is newly separated on the basis of the immunological and genetic profile into the newly created category of tumors of uncertain histogenesis. This category also includes sclerosing mucoepidermoid carcinoma with eosinophilia. Microcarcino- ma as a separate entity is not included in the 5th edition. A tumor smaller than 10 mm must be characterized by the appropriate features of the corresponding category. Thyroblastoma replaces terminologically malignant teratoma from the previous classification. Part of the newly established diagnostic criteria is also applicable in FNAB diagnosis. The newly introduced grading in some nosological units can exceptionally change the diagnosis (NIFTP/EFVPTC/non-invasive HG FVPTC), but above all it will affect the choice of therapeutic procedures.

• MeSH
• folikulární adenokarcinom klasifikace   patologie   MeSH
• karcinom klasifikace   patologie   MeSH
• nádory štítné žlázy * klasifikace   patologie   MeSH
• stupeň nádoru klasifikace   metody   MeSH
• uzle štítné žlázy klasifikace   patologie   MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

Prostate cancer (PCa) is the second most common cancer. In this paper, the isolation and properties of exosomes as potential novel liquid biopsy markers for early PCa liquid biopsy diagnosis are investigated using two prostate human cell lines, i.e., benign (control) cell line RWPE1 and carcinoma cell line 22Rv1. Exosomes produced by both cell lines are characterised by various methods including nanoparticle-tracking analysis, dynamic light scattering, scanning electron microscopy and atomic force microscopy. In addition, surface plasmon resonance (SPR) is used to study three different receptors on the exosomal surface (CD63, CD81 and prostate-specific membrane antigen-PMSA), implementing monoclonal antibodies and identifying the type of glycans present on the surface of exosomes using lectins (glycan-recognising proteins). Electrochemical analysis is used to understand the interfacial properties of exosomes. The results indicate that cancerous exosomes are smaller, are produced at higher concentrations, and exhibit more nega tive zeta potential than the control exosomes. The SPR experiments confirm that negatively charged α-2,3- and α-2,6-sialic acid-containing glycans are found in greater abundance on carcinoma exosomes, whereas bisecting and branched glycans are more abundant in the control exosomes. The SPR results also show that a sandwich antibody/exosomes/lectins configuration could be constructed for effective glycoprofiling of exosomes as a novel liquid biopsy marker.

• MeSH
• exozómy * chemie   MeSH
• karcinom * metabolismus   patologie   MeSH
• lektiny analýza   metabolismus   MeSH
• lidé MeSH
• polysacharidy analýza   metabolismus   MeSH
• tekutá biopsie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Preferentially expressed antigen of melanoma (PRAME) is a cancer/testis antigen selectively expressed in somatic tissues and various solid malignant tumors and is associated with poor prognostic outcome. Our research aimed to comprehensively compare its expression in a large cohort of tubo-ovarian epithelial tumors and examine its correlation with our clinico-pathologic data, as well as to assess its potential use in diagnostics and therapy.We examined 485 cases of epithelial tubo-ovarian tumors including 107 clear cell carcinomas (CCC), 52 endometroid carcinomas (EC), 103 high grade serous carcinomas (HGSC), 119 low grade serous carcinomas (LGSC)/micropapillary variant of serous borderline tumors (mSBT), and 104 cases of mucinous carcinomas (MC)/mucinous borderline tumors (MBT). The immunohistochemical analysis was performed using TMAs.The highest levels of expression were seen in EC (60%), HGSC (62%), and CCC (56%), while expression in LGSC/mSBT (4%) and MC/MBT (2%) was rare. The clinico-pathologic correlations and survival analysis showed no prognostic significance.The results of our study showed that PRAME is neither prognostic nor a suitable ancillary marker in the differential diagnosis of tubo-ovarian epithelial tumors. Nevertheless, knowledge about the PRAME expression may be important concerning its potential predictive significance, because targeting PRAME as a potential therapeutic option is currently under investigation.

• MeSH
• antigeny nádorové MeSH
• karcinom * patologie   MeSH
• lidé MeSH
• melanom * MeSH
• nádorové biomarkery analýza   MeSH
• nádory cystické, mucinózní a serózní * MeSH
• nádory vaječníků * MeSH
• serózní cystadenokarcinom * patologie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Ameloblastic carcinoma and metastasising ameloblastoma are rare epithelial odontogenic tumours with aggressive features. Distinguishing between these two lesions is often clinically difficult but necessary to predict tumour behaviour or to plan future therapy. Here, we provide a brief review of the literature available on these two types of lesions and present a new case report of a young man with an ameloblastoma displaying metastatic features. We also use this case to illustrate the similarities and differences between these two types of tumours and the difficulties of their differential diagnosis. CASE PRESENTATION: Our histopathological analyses uncovered a metastasising tumour with features of ameloblastic carcinoma, which developed from the ameloblastoma. We profiled the gene expression of Wnt pathway members in ameloblastoma sample of this patient, because multiple molecules of this pathway are involved in the establishing of cell polarity, cell migration or for epithelial-mesenchymal transition during tumour metastasis to evaluate features of tumor behaviour. Indeed, we found upregulation of several cell migration-related genes in our patient. Moreover, we uncovered somatic mutation BRAF p.V600E with known pathological role in cancerogenesis and germline heterozygous FANCA p.S858R mutation, whose interpretation in this context has not been discussed yet. CONCLUSIONS: In conclusion, we have uncovered a unique case of ameloblastic carcinoma associated with an alteration of Wnt signalling and the presence of BRAF mutation. Development of harmful state of our patient might be also supported by the germline mutation in one FANCA allele, however this has to be confirmed by further analyses.

• MeSH
• ameloblastom * genetika   diagnóza   MeSH
• karcinom * patologie   MeSH
• lidé MeSH
• mutace MeSH
• odontogenní nádory * diagnóza   genetika   MeSH
• protoonkogenní proteiny B-raf genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

PURPOSE: To evaluate the effectiveness and toxicity of curative (chemo)radiotherapy in patients with metastatic carcinoma to cervical lymph nodes from an unknown primary. METHODS: Retrospective study of 90 consecutive patients, treated with curative radiotherapy from 2003 to 2018 (median age 59 years; current/former smokers 76%) was conducted. The distribution of nodal staging was as follows: N1: 12%, N2a: 21%, N2b: 43%, N2c: 10%, N3: 13%. In 62% of patients, neck dissection was performed before radiotherapy. Concomitant chemotherapy was given to 64% of patients. RESULTS: The median follow-up of surviving patients was 86 months. The median total radiotherapy dose achieved was 70 Gy. The 5‐ and 10-year locoregional control were 84% in both cases, while 5‐ and 10-year distant control were 90% and 89%, respectively. A primary tumor in the head and neck area was detected in only 2 patients. No patient had an initial failure in the pharyngeal axis or contralateral cervical nodes. The 5‐ and 10-year overall survival were 55% and 42%, respectively. Severe early toxicity occurred in 71%; severe late toxicity in 33% of patients. Multivariate analysis demonstrated N‐status (hazard ratio [HR] 2.424; 95% confidence interval [CI] 1.121-5.241; p = 0.024) and comorbidity scores assessed by ACE-27 (Adult Comorbidity Evaluation; HR 3.058; 95% CI 1.489-6.281; p = 0.002) as two independent prognostic factors for overall survival. CONCLUSION: The results of our work study demonstrate the high effectiveness of curative (chemo)radiotherapy on the pharyngeal axis and bilateral cervical nodes with long-term locoregional and distant control in 3/4 of the treated patients. N‐status and comorbidity scores were shown as strong prognostic factors influencing overall survival.

• MeSH
• dospělí MeSH
• karcinom * patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfatické metastázy patologie   MeSH
• lymfatické uzliny patologie   MeSH
• nádory hlavy a krku * patologie   MeSH
• nádory neznámé primární lokalizace * terapie   patologie   MeSH
• retrospektivní studie MeSH
• staging nádorů MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• Publikační typ
• časopisecké články 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.

• MeSH
• adenokarcinom * genetika   patologie   MeSH
• fúzní onkogenní proteiny genetika   MeSH
• imunohistochemie MeSH
• karcinom * genetika   patologie   MeSH
• lidé MeSH
• nádorové biomarkery genetika   MeSH
• nádory slinných žláz * genetika   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Epithelial ovarian cancer (EOC) is among the top five causes of cancer-related death in women, largely reflecting early, prediagnosis dissemination of malignant cells to the peritoneum. Despite improvements in medical therapies, particularly with the implementation of novel drugs targeting homologous recombination deficiency, the survival rates of patients with EOC remain low. Unlike other neoplasms, EOC remains relatively insensitive to immune checkpoint inhibitors, which is correlated with a tumor microenvironment (TME) characterized by poor infiltration by immune cells and active immunosuppression dominated by immune components with tumor-promoting properties, especially tumor-associated macrophages (TAMs). In recent years, TAMs have attracted interest as potential therapeutic targets by seeking to reverse the immunosuppression in the TME and enhance the clinical efficacy of immunotherapy. Here, we review the key biological features of TAMs that affect tumor progression and their relevance as potential targets for treating EOC. We especially focus on the therapies that might modulate the recruitment, polarization, survival, and functional properties of TAMs in the TME of EOC that can be harnessed to develop superior combinatorial regimens with immunotherapy for the clinical care of patients with EOC.

• MeSH
• epiteliální ovariální karcinom terapie   patologie   MeSH
• imunoterapie MeSH
• karcinom * patologie   MeSH
• lidé MeSH
• makrofágy spojené s nádory patologie   MeSH
• makrofágy MeSH
• nádorové mikroprostředí MeSH
• nádory vaječníků * MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH