REAH Dotaz Zobrazit nápovědu
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).
- Klíčová slova
- Atypical adenomatous lesions arising in REAH/seromucinous hamartoma, REAH, Respiratory adenomatoid hamartoma, Sebaceous differentiation, Seromucinous hamartoma,
- 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
Respiratory epithelial adenomatoid hamartoma (REAH) and seromucinous hamartoma (SH) are rare tumor-like lesions of the nasal cavity, paranasal sinuses, and nasopharynx. The pathogenesis of REAH/SH is still unclear. Neoplastic proliferation, chronic mechanical irritation, inflammation, or possible embryological tissue misplacement are speculated as possible mechanisms of their development. Low-grade tubulopapillary adenocarcinoma (LGTA) is a rare variant of nonsalivary, nonintestinal type sinonasal adenocarcinoma. The aim of this study was to evaluate the immunohistochemical and genetic profiles of 10 cases of REAH/SH, with serous, mucinous, and respiratory components evaluated separately and to compare these findings with the features of 9 cases of LGTA. All cases of REAH/SH and LGTA were analyzed immunohistochemically with a cocktail of mucin antigens (MUC1, MUC2, MUC4, MUC5AC, MUC6) and with epithelial (CK7, CK20, CDX2, SATB2) and myoepithelial markers (S100 protein, p63, SOX10). The next-generation sequencing assay was performed using FusionPlex Solid Tumor Kit (ArcherDx) in 10 cases of REAH/SH, and the EGFR-ZNF267 gene fusion was detected in 1 of them. Two female REAH/SH cases were assessed for the presence of clonality. Using the human androgen receptor assay, 1 case was proved to be clonal. The serous component of REAH/SH was positive for CK7/MUC1 and SOX10 similarly to LGTA. Although REAH/SH and LGTA are histopathologically and clinically separate entities, the overlap in their morphological and immunohistochemical profiles suggests that REAH/SH might be a precursor lesion of LGTA.
- Klíčová slova
- Low-grade tubulopapillary adenocarcinoma, Nasal cavity, REAH, Respiratory epithelial adenomatoid hamartoma, Seromucinous hamartoma, Sinonasal tract,
- MeSH
- adenokarcinom chemie diagnóza genetika patologie MeSH
- diagnostické techniky molekulární * MeSH
- diferenciální diagnóza MeSH
- dítě MeSH
- dospělí MeSH
- hamartom chemie diagnóza genetika patologie MeSH
- imunohistochemie * MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- nádorové biomarkery * analýza genetika MeSH
- nádory nosu chemie diagnóza genetika patologie MeSH
- nemoci nosohltanu diagnóza genetika metabolismus patologie MeSH
- nemoci nosu diagnóza genetika metabolismus patologie MeSH
- nosní sliznice chemie patologie MeSH
- prediktivní hodnota testů MeSH
- prekancerózy diagnóza genetika metabolismus patologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stupeň nádoru MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- nádorové biomarkery * MeSH
Respiratory epithelial adenomatoid hamartoma (REAH) is relatively new diagnosis, firstly described in WHO tumour classification in 2005. It is a benign lesion affecting nose and paranasal sinuses. Although REAH was considered a rare entity, it is recently more frequently revealed in histopathological exam in patients undergoing endoscopic surgery for nasal polyposis. There have been so far operated two patients with diagnosis of REAH in our department. Both were solitary lesions, and both were resected endoscopically. Definitive histopathological examination confirmed the finding of preoperative biopsy under local anesthesia. No recurrent disease has been observed. Considering quite frequent occurrence of REAH in patients with nasal polyposis and low awareness of the disease itself among ENT specialists, pathologists and radiologists it is still relatively underdiagnosed lesion. The possibility of misdiagnosis and confusion with other more serious diseases like inverted papilloma or low-grade adenocarcinoma is of clinical importance. It may lead to overtreatment and too aggressive surgical therapy.
- Klíčová slova
- benign sinonasal lesion, endoscopic endonasal surgery, respiratory epithelial adenomatoid hamartoma,
- MeSH
- diferenciální diagnóza MeSH
- endoskopie MeSH
- hamartom * MeSH
- lidé MeSH
- nosní dutina MeSH
- nosní polypy * MeSH
- paranazální dutiny * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
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
The pathology of reactive, dysplastic, and neoplastic sinonasal seromucinous glands is complex, and their contribution to tumorigenesis of sinonasal carcinomas remains controversial. In our practice, we have observed the presence of respiratory epithelial adenomatoid hamartomas (REAH) and seromucinous hamartomas (SH) associated with adenoid cystic carcinomas (AdCC) in a subset of cases. In many of these cases, genuine atypical features and dysplastic characteristics of the glands were noted at the interface of SH and AdCC. To investigate this phenomenon further, 88 sinonasal AdCC cases were selected from the authors' files and analyzed histologically, immunohistochemically, and genetically searching for MYB/MYBL1 and NFIB gene fusions. HPV testing was also performed. Univariate statistical analysis was conducted on our cohort. Thirty-one cases (35%) showed features of atypical sinonasal glands arising in SH (ASGSH) at the SH-AdCC interface, characterized by bilayered epithelium, architectural disarray, mild nuclear polymorphism, and atypia, sometimes with colloid-like material in the lumen. The MYB immunomarker was negative in 14 ASGSHs (with a positive internal control in AdCC cells), while only two cases showed faint and moderate to weak expression of the antibody in ASGSH glands. In 12 cases, the immunostaining of ASGSH could not be properly assessed, while AdCC cells were negative. The immunostaining was not performed in five cases. Our findings suggest that a subset of sinonasal AdCC may originate in a multistep dysplastic process within SH, consistent with an SH-ASGSH-AdCC progression sequence.
