Two benign adenomatous lesions are commonly recognized within the sinonasal tract, namely respiratory epithelial adenomatoid hamartoma (REAH) and seromucinous hamartoma (SH). We present 10 hitherto unrecognized benign polypoid nasal and sinonasal tumoriform lesions having in average 3.6 cm in largest dimension, which are histogenetically related to SH and REAH. In addition to typical structures of REAH and SH, these lesions contained an additional characteristic and slightly atypical adenomatous component, which we termed atypical sinonasal glands arising in SH (ASGSH). ASGSH often produced deep red colored secretion with peripheral clearing similar to that seen in thyroid follicles. In contrast to SH, ASGSH was endowed by both secretory and myoepithelial layers and had mostly angulated shapes with snout-like protrusions into the lumens. Both layers were formed by an irregular, disorganized, and often incomplete cell lining, which had slightly atypical cytological features without mitoses. In 3 cases, ASGSHs revealed sebaceous differentiation, and in 3 cases the stroma produced a well-differentiated cartilage. Neoplastic nature of ASGSH was supported by finding of various mutations as revealed by next generation sequencing in five cases. In two cases each, we found identical mutations in BRAF gene (Val600Glu), and RET gene (Arg912Trp), respectively and in one case FAT1 gene alteration (Pro1665Leu).
- MeSH
- adenom patologie genetika MeSH
- dospělí MeSH
- hamartom * patologie genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace MeSH
- nádory nosu patologie genetika MeSH
- nádory vedlejších dutin nosních patologie genetika MeSH
- respirační sliznice patologie MeSH
- senioři nad 80 let MeSH
- senioři 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
SMARCB1-deficient sinonasal adenocarcinoma is a rare variant of SWI/SNF-deficient malignancies with SMARCB1 loss and adenocarcinoma features. More than 200 high-grade epithelial sinonasal malignancies were retrieved. A total of 14 cases exhibited complete SMARCB1 (INI1) loss and glandular differentiation. SMARCA2 and SMARCA4 were normal, except for one case with a loss of SMARCA2. Next-generation sequencing (NGS) and/or fluorescence in situ hybridization (FISH) revealed an alteration in the SMARCB1 gene in 9/13 cases, while 2/13 were negative. Two tumors harbored SMARCB1 mutations in c.157C > T p.(Arg53Ter) and c.842G > A p.(Trp281Ter). One harbored ARID1B mutations in c.1469G > A p.(Trp490Ter) and MGA c.3724C > T p.(Arg1242Ter). Seven tumors had a SMARCB1 deletion. One carried an ESR1 mutation in c.644-2A > T, and another carried a POLE mutation in c.352_374del p.(Ser118GlyfsTer78). One case had a PAX3 mutation in c.44del p.(Gly15AlafsTer95). Histomorphology of SMARCB1-deficient adenocarcinoma was oncocytoid/rhabdoid and glandular, solid, or trabecular in 9/14 cases. Two had basaloid/blue cytoplasm and one showed focal signet ring cells. Yolk sac tumor-like differentiation with Schiller-Duval-like bodies was seen in 6/14 cases, with 2 cases showing exclusively reticular-microcystic yolk sac pattern. Follow-up of a maximum of 26 months (median 10 months) was available for 8/14 patients. Distant metastasis to the lung, liver, mediastinum, bone, and/or retroperitoneum was seen in 4/8 cases. Locoregional failure was seen in 75% of patients, with 6/8 local recurrences and 3 cervical lymph node metastases. At the last follow-up, 5 of 8 (62%) patients had died of their disease 2 to 20 months after diagnosis (median 8.2 months), and 3 were alive with the disease. The original diagnosis was usually high-grade non-intestinal-type adenocarcinoma or high-grade myoepithelial carcinoma. A correct diagnosis of these aggressive tumors could lead to improved targeted therapies with potentially better overall disease-specific survival.
- MeSH
- adenokarcinom * genetika patologie MeSH
- diferenciální diagnóza MeSH
- DNA vazebné proteiny genetika nedostatek MeSH
- dospělí MeSH
- gen SMARCB1 * nedostatek genetika MeSH
- hybridizace in situ fluorescenční MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace * MeSH
- myoepiteliální nádor * genetika patologie MeSH
- nádorové biomarkery genetika MeSH
- nádory vedlejších dutin nosních * genetika patologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stupeň nádoru MeSH
- transkripční faktory * genetika nedostatek MeSH
- vysoce účinné nukleotidové sekvenování 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
OBJECTIVE: One of the possible risks of sinonasal malignancy is its possible spread in the orbit. However, there is no clear consensus among the different departments as to whether it is necessary to exenterate the orbit in limited tumorous infiltration of periorbital fat. The purpose of the study was to demonstrate that periorbital infiltration and periorbital fat invasion without involvement of deeper orbital tissues are not the indication of orbital exenteration. MATERIALS AND METHODS: Retrospective analysis was performed over a 17-year period of patients undergoing surgical treatment for sinonasal malignancy with histologically verified periorbital infiltration or deeper invasion into the orbit. A total of 32 patients were included in the study. For each group, the following data were analysed: sex, age, preoperative imaging studies, histological findings, site of origin, stage, surgical reconstruction, oncological treatment, survival, cause of death, number of recurrences in the orbit and functional status of preserved eyes. RESULTS: Based on our criteria for orbital exenteration, orbital preservation was feasible in 18 patients. Orbital exenteration was performed in 14 patients with deeper tumor infiltration. There was a statistically insignificant difference in survival between the two groups. The 5-year overall survival (OS) was 44% for the orbital preservation group (only 2 patients died from local tumor recurrence) and 34% for the orbital exenteration group. The groups did not differ in other observed factors other than the extent of orbital infiltration. In 11 (61.1%) patients, vision was without significant change after radiation therapy. In 2 (11.1%) patients, visual function was impaired due to diplopia. 5 (27.8%) patients had severely impaired vision due to optic nerve atrophy after radiation therapy. CONCLUSIONS: Our results show a relatively high survival rate in the group of patients with orbital preservation with a high chance of vision preservation, which justifies our approach to orbital preservation even in some tumors with periorbital infiltration.
- MeSH
- dospělí MeSH
- eviscerace orbity MeSH
- invazivní růst nádoru * MeSH
- léčba šetřící orgány metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory orbity * patologie chirurgie MeSH
- nádory vedlejších dutin nosních * patologie chirurgie MeSH
- orbita patologie MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- staging nádorů 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
Classification of tumors of the head and neck has evolved in recent decades including a widespread application of molecular testing in tumors of the sinonasal tract, salivary glands, and soft tissues with a predilection for the head and neck. The availability of new molecular techniques has allowed for the definition of multiple novel tumor types unique to head and neck sites. Moreover, an expanding spectrum of immunohistochemical markers specific to genetic alterations facilitates rapid identification of diagnostic molecular abnormalities. As such, it is currently possible for head and neck pathologists to benefit from a molecularly defined tumor classification while making diagnoses that are still based largely on histopathology and immunohistochemistry. This review covers the principal molecular alterations in sinonasal malignancies, such as alterations in DEK, AFF2, NUTM1, IDH1-2, and SWI/SNF genes in particular, that are important from a practical standpoint for diagnosis, prognosis, and prediction of response to treatment.
We report a case of a 67-year-old male patient with a sinonasal tumor that showed areas of classic biphenotypic sinonasal sarcoma (BSNS) which in some sections sharply transitioned into high-grade rhabdomyosarcoma. Immunohistochemically, the conventional BSNS parts showed S100 protein, SMA, PAX7, and focal MyoD1 expression, whereas desmin and myogenin were negative. In contrast, the cells in high-grade areas expressed desmin, MyoD1, myogenin, and PAX7, while being negative for S100 protein and SMA. Using the Archer FusionPlex assay, the classical PAX3::MAML3 gene fusion was detected. FISH for PAX3 and MAML3 confirmed a break of these genes in both components. Despite aggressive therapy, the tumor progression resulted in the patient's death. The herein presented case, together with 2 previously published cases of BSNS with high-grade transformation, helps to better understand this novel phenomenon. Although the risk for such transformation appears low, it has important clinical and diagnostic implications which are discussed.
- MeSH
- alveolární rhabdomyosarkom * MeSH
- desmin MeSH
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- myogenin MeSH
- nádorové biomarkery genetika MeSH
- nádory měkkých tkání * genetika MeSH
- nádory vedlejších dutin nosních * patologie MeSH
- proteiny S100 MeSH
- rhabdomyosarkom * genetika MeSH
- sarkom * genetika MeSH
- trans-aktivátory MeSH
- transkripční faktor PAX3 genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Mucosal malignant melanoma (MMM) is a rare and aggressive tumor. Despite effective local therapies, tumor recurrence and metastasis remain frequent. The genetics of MMM remain incompletely understood. This study is aimed to identify actionable genetic alterations by next-generation sequencing. Fifteen MMM samples were analyzed by next-generation and Sanger sequencing. Gene copy number alterations were analyzed by MLPA. Mutation status was correlated with pERK, pAKT, and Ki-67 expression and follow-up data. Inactivating mutations and intragenic deletions in neurofibromatosis type-1 (NF1) were identified in 3 and 2 cases, respectively, (in total 5/15, 33%) and activating mutations in NRAS and KRAS (3/15, 20%) cases. Other mutated genes included CDKN2A, APC, ATM, MITF, FGFR1, and FGFR2. BRAF and KIT mutations were not observed. Cases with NF1 alterations tended to have worse overall survival. The mutational status was not associated with pERK, pAKT, or Ki-67 immunostaining. MMM carries frequent gene mutations activating the MAPK pathway, similar to cutaneous melanoma. In contrast, NF1 is the most frequently affected gene. Intragenic NF1 deletions have not been described before and may go undetected by sequencing studies. This finding is clinically relevant as NF1-mutated melanomas have worse survival and could benefit from therapy with immune checkpoint and MEK inhibitors.
- MeSH
- delece genu * MeSH
- fenotyp MeSH
- genetická predispozice k nemoci MeSH
- lidé MeSH
- melanom genetika mortalita sekundární terapie MeSH
- mutační analýza DNA MeSH
- nádorové biomarkery genetika MeSH
- nádory vedlejších dutin nosních genetika mortalita patologie terapie MeSH
- neurofibromin 1 genetika MeSH
- nosní sliznice patologie MeSH
- prognóza MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Sinonasal mucosal melanoma is a rare tumor arising within the nasal cavity, paranasal sinuses, or nasopharynx (sinonasal tract). This study evaluated 90 cases diagnosed in 29 males and 61 females with median age 68 years. Most tumors involved the nasal cavity and had an epithelioid morphology. Spectrum of research techniques used in this analysis includes targeted-DNA and -RNA next-generation sequencing, Sanger sequencing, fluorescence in situ hybridization and immunohistochemistry. Sinonasal melanomas were commonly driven by RAS (38/90, 42%), especially NRAS (n = 36) mutations and rarely (4/90, 4%) displayed BRAF pathogenic variants. BRAF/RAS mutants were more frequent among paranasal sinuses (10/14, 71%) than nasal (26/64, 41%) tumors. BRAF/RAS-wild type tumors occasionally harbored alterations of the key components and regulators of Ras-MAPK signaling pathway: NF1 mutations (1/17, 6%) or NF1 locus deletions (1/25, 4%), SPRED1 (3/25, 12%), PIK3CA (3/50, 6%), PTEN (4/50, 8%) and mTOR (1/50, 2%) mutations. These mutations often occurred in a mutually exclusive manner. In several tumors some of which were NRAS mutants, TP53 was deleted (6/48, 13%) and/or mutated (5/90, 6%). Variable nuclear accumulation of TP53, mirrored by elevated nuclear MDM2 expression was seen in >50% of cases. Furthermore, sinonasal melanomas (n = 7) including RAS/BRAF-wild type tumors (n = 5) harbored alterations of the key components and regulators of canonical WNT-pathway: APC (4/90, 4%), CTNNB1 (3/90, 3%) and AMER1 (1/90, 1%). Both, TERT promoter mutations (5/53, 9%) and fusions (2/40, 5%) were identified. The latter occurred in BRAF/RAS-wild type tumors. No oncogenic fusion gene transcripts previously reported in cutaneous melanomas were detected. Eight tumors including 7 BRAF/RAS-wild type cases expressed ADCK4::NUMBL cis-fusion transcripts. In summary, this study documented mutational activation of NRAS and other key components and regulators of Ras-MAPK signaling pathway such as SPRED1 in a majority of sinonasal melanomas.
- MeSH
- fosfatidylinositol-3-kinasy třídy I genetika MeSH
- hybridizace in situ fluorescenční MeSH
- lidé MeSH
- melanom * genetika patologie MeSH
- molekulární biologie MeSH
- mutace MeSH
- mutační analýza DNA MeSH
- nádory vedlejších dutin nosních * genetika patologie MeSH
- paranazální dutiny * patologie MeSH
- protoonkogenní proteiny B-raf genetika MeSH
- RNA MeSH
- senioři MeSH
- signální transdukce MeSH
- TOR serin-threoninkinasy genetika MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
The field of head and neck pathology was just developing 50 years ago but has certainly come a long way in a relatively short time. Thousands of developments in diagnostic criteria, tumor classification, malignancy staging, immunohistochemistry application, and molecular testing have been made during this time, with an exponential increase in literature on the topics over the past few decades: There were 3506 articles published on head and neck topics in the decade between 1969 and 1978 (PubMed source), with a staggering 89266 manuscripts published in the most recent decade. It is daunting and impossible to narrow the more than 162000 publications in this field and suggest only a few topics of significance. However, the breakthrough in this anatomic discipline has been achieved in 3 major sites: oropharyngeal carcinoma, salivary gland neoplasms, and sinonasal tract tumors. This review will highlight selected topics in these anatomic sites in which the most profound changes in diagnosis have occurred, focusing on the information that helps to guide daily routine practice of surgical pathology.
- MeSH
- dějiny 20. století MeSH
- dějiny 21. století MeSH
- lidé MeSH
- nádorové biomarkery analýza dějiny MeSH
- nádory hlavy a krku chemie dějiny patologie virologie MeSH
- nádory orofaryngu chemie dějiny patologie virologie MeSH
- nádory slinných žláz chemie dějiny patologie virologie MeSH
- nádory vedlejších dutin nosních chemie dějiny patologie virologie MeSH
- Papillomaviridae izolace a purifikace MeSH
- patologie dějiny trendy MeSH
- rozšiřování inovací MeSH
- staging nádorů MeSH
- Check Tag
- dějiny 20. století MeSH
- dějiny 21. století MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- historické články MeSH
- přehledy MeSH
Cíl studie: V rámci této studie jsme využili metody kvantitativní real-time PCR pro sledování úrovně relativní exprese miR-145-5p, miR-484 a miR-99a-5p v souboru HPV pozitivních a HPV negativních vzorků sinonasálního dlaždicobuněčného karcinomu. Typ studie: původní práce.Název a sídlo pracoviště: Ústav klinické biochemie a diagnostiky, Lékařská fakulta v Hradci Králové, Univerzita Karlova a Fakultní nemocnice Hradec Králové, Sokolská 581, 500 05 Hradec Králové.Materiál a metody: Metoda kvantitativní real-time PCR s TaqManTM Advanced miRNA Assays byla použita pro sledování relativní exprese vybraných mikroRNA (miR-145-5p, miR-484 a miR-99a-5p) v unikátním souboru vzorků fixovaných ve formalínu a archivovaných v parafinu získaných od 46 pacientů se sinonasálním dlaždicobuněčných karcinomem. Statistická analýza (Studentův t-test, jednofaktorová analýza rozptylu a regresní analýza) byla provedena s cílem porovnat úroveň relativní exprese mikroRNA se zaznamenanými klinickopatologickými daty jako je HPV status.Výsledky: Naše výsledky ukazují statisticky významnou downregulaci miR-145-5p (P < 0,001 a Fold change = -2,78) ve vzorcích sinonasálního skvamózního karcinomu. Přítomnost HPV infekce korelovala s mírou exprese všech tří studovaných mikroRNA. Exprese miR-145-5p byla nižší u HPV negativních vzorků (P = 0,019), miR-99a-5p byla upregulována u HPV pozitivních vzorků (P = 0,058) a miR-484 byla downregulována u HPV pozitivních vzorků (P = 0,016). Pacienti, kteří byli zařazeni do kategorie kuřáci nebo bývalí kuřáci, vykazovali downregulaci miR-99a-5p (P = 0,060). Perineurální šíření bylo spojeno s významnou downregulací miR-99a-5p (P = 0,0055). Významná downregulace miR-145-5p byla spojena s angioinvazí (P = 0,037) a regionálním šířením (P = 0,076).Závěr: V rámci naší studie jsme nalezli spojitost mezi expresí studovaných mikroRNA a přítomností HPV infekce v nádorových vzorcích. Naše výsledky naznačují, že miR-145-5p, miR-484 a miR-99a jsou součástí patogeneze HPV. Avšak přesná role miRNA spojených s HPV infekcí ve vývoji sinonasálních karcinomů není dosud známá.
Objective: In the present study, we used quantitative real-time PCR to investigate relative expression values of miR-145-5p, miR-484 and miR-99a-5p in HPV positive and HPV negative samples of sinonasal squamous cell carcinoma. Design: Original Article. Settings: Institute of Clinical Biochemistry and Diagnostics, Charles University, Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Sokolská 581, 500 05 Hradec Králové Materials and Methods: Quantitative real-time PCR with TaqManTM Advanced miRNA Assays was used to investigate relative expression values of selected microRNAs (miR-145-5p, miR-484 and miR-99a-5p) in a unique set of formalin-fixed paraffin-embedded tissue samples obtained from 46 patients with sinonasal squamous cell carcinoma. Statistical analysis (Student‘s t-test, one-way analysis of variance and regression analysis) was performed to compare relative expression miRNA values and recorded clinicopathological data such as HPV status. Results: Our results show statistically significant downregulation of miR-145-5p (P < 0.001 and Fold change = -2.78) in sinonasal squamous cell carcinoma samples. The presence of HPV infection correlated with the expression levels of all three studied miRNAs. The expression of miR-145-5p was lower in HPV negative samples (P = 0.019), miR-99a-5p was upregulated in HPV positive samples (P = 0.058) and miR-484 was downregulated in HPV positive samples (P = 0.016). Patients with recorded history of smoking or currents smokers showed downregulation of miR-99a-5p (P = 0.060). Perineural invasion was linked to significant downregulation of miR-99a-5p (P = 0.0055). Distinctive downregulation of miR-145-5p was linked to vascular invasion (P = 0.037) and regional recurrence (P = 0.076). Conclusion: We have found correlation between studied miRNA expression and presence of HPV infection in the patient samples. Our results suggest that miR-145, miR-484 and miR-99a are involved in HPV pathogenesis. However, the actual pathway of HPV related miRNA involvement in sinonasal tumor development is not yet known.
- Klíčová slova
- sinonasální karcinom,
- MeSH
- dlaždicobuněčné karcinomy hlavy a krku * patologie virologie MeSH
- infekce papilomavirem komplikace MeSH
- klinická studie jako téma MeSH
- lidé MeSH
- mikro RNA MeSH
- nádory vedlejších dutin nosních patologie virologie MeSH
- Papillomaviridae * izolace a purifikace MeSH
- Check Tag
- lidé MeSH
