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

Infantile fibrosarcoma and congenital mesoblastic nephroma are tumors of infancy traditionally associated with the ETV6-NTRK3 gene fusion. However, a number of case reports have identified variant fusions in these tumors. In order to assess the frequency of variant NTRK3 fusions, and in particular whether the recently identified EML4-NTRK3 fusion is recurrent, 63 archival cases of infantile fibrosarcoma, congenital mesoblastic nephroma, mammary analog secretory carcinoma and secretory breast carcinoma (tumor types that are known to carry recurrent ETV6-NTRK3 fusions) were tested with NTRK3 break-apart FISH, EML4-NTRK3 dual fusion FISH, and targeted RNA sequencing. The EML4-NTRK3 fusion was identified in two cases of infantile fibrosarcoma (one of which was previously described), and in one case of congenital mesoblastic nephroma, demonstrating that the EML4-NTRK3 fusion is a recurrent genetic event in these related tumors. The growing spectrum of gene fusions associated with infantile fibrosarcoma and congenital mesoblastic nephroma along with the recent availability of targeted therapies directed toward inhibition of NTRK signaling argue for alternate testing strategies beyond ETV6 break-apart FISH. The use of either NTRK3 FISH or next-generation sequencing will expand the number of cases in which an oncogenic fusion is identified and facilitate optimal diagnosis and treatment for patients.

• MeSH
• dospělí MeSH
• fibrosarkom diagnóza   genetika   MeSH
• fúzní onkogenní proteiny genetika   MeSH
• genetické testování MeSH
• hybridizace in situ fluorescenční MeSH
• karcinom genetika   MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru genetika   MeSH
• mezoblastický nefrom vrozené   diagnóza   genetika   MeSH
• mladiství MeSH
• nádory ledvin vrozené   diagnóza   genetika   MeSH
• nádory prsu genetika   MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• protein ETS, translokační varianta 6 MeSH
• proteiny asociované s mikrotubuly genetika   MeSH
• proteiny buněčného cyklu genetika   MeSH
• protoonkogenní proteiny c-ets genetika   MeSH
• receptor DDR2 genetika   MeSH
• represorové proteiny genetika   MeSH
• sekvenční analýza RNA MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• serinové endopeptidasy genetika   MeSH
• Check Tag
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DDR2 protein, human MeSH Prohlížeč
• EML4 protein, human MeSH Prohlížeč
• fúzní onkogenní proteiny MeSH
• proteiny asociované s mikrotubuly MeSH
• proteiny buněčného cyklu MeSH
• protoonkogenní proteiny c-ets MeSH
• receptor DDR2 MeSH
• represorové proteiny MeSH
• serinové endopeptidasy 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