Author:
Skálová Alena,Taheri Touraj,Bradová Martina,Vaněček Tomáš,Franchi Alessandro,Slouka David,Kostlivý Tomáš,de Rezende Gisele,Michálek Jaroslav,Klubíčková Natálie,Ptáková Nicola,Nemcová Antónia,Michal Michal,Agaimy Abbas,Leivo Ilmo
Abstract
AbstractSMARCB1-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.
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Molecular Biology,General Medicine,Pathology and Forensic Medicine
Reference39 articles.
1. Agaimy A, Franchi A, Lund VJ, Skálová A, Bishop JA, Triantafyllou A, Andreasen S, Gnepp DR, Hellquist H, Thompson LDR, Rinaldo A, Ferlito A (2020) Sinonasal undifferentiated carcinoma (SNUC): from an entity to morphologic pattern and back again-a historical perspective. Adv Anat Pathol 27(2):51–60
2. Dogan S, Chute DJ, Xu B et al (2017) Frequent IDH2 R172 mutations in undifferentiated and poorly-differentiated sinonasal carcinomas. J Pathol 242(4):400–408
3. Mito JK, Bishop JA, Sadow PM et al (2018) Immunohistochemical detection and molecular characterization of IDH-mutant sinonasal undifferentiated carcinomas. Am J Surg Pathol 42(8):1067–1075
4. French CA (2010) NUT midline carcinoma. Cancer Genet Cytogenet 203(1):16–20
5. Bishop JA, Thompson LDR, Loney EL (eds) (2022) Chapter 2: nasal, paranasal, and skull base tumours. In: WHO classification of tumours editorial board. Head and neck tumours. [Internet; beta version ahead of print]. Lyon (France): International Agency for Research on Cancer; [cited 2023 May 8]. (WHO classification of tumours series, 5th ed.; vol. 9). Available from: https://tumourclassification.iarc.who.int/chapters/52/1