ETV6 Gene Rearrangements Characterize a Morphologically Distinct Subset of Sinonasal Low-grade Non–intestinal-type Adenocarcinoma: A Novel Translocation-associated Carcinoma Restricted to the Sinonasal Tract

Simon Andreasen; Alena Skálová; Abbas Agaimy; Justin A Bishop; Jan Laco; Ilmo Leivo; Alessandro Franchi; Stine R Larsen; Daiva Erentaite; Benedicte Parm Ulhøi; Christian von Buchwald; Linea C Melchior; Michal Michal; Katalin Kiss

doi:10.1097/PAS.0000000000000912

ETV6 Gene Rearrangements Characterize a Morphologically Distinct Subset of Sinonasal Low-grade Non–intestinal-type Adenocarcinoma: A Novel Translocation-associated Carcinoma Restricted to the Sinonasal Tract

Simon Andreasen, Alena Skálová, Abbas Agaimy, Justin A Bishop, Jan Laco, Ilmo Leivo, Alessandro Franchi, Stine R Larsen, Daiva Erentaite, Benedicte Parm Ulhøi, Christian von Buchwald, Linea C Melchior, Michal Michal, Katalin Kiss

Department of Clinical Medicine

32 Citations (Scopus)

Abstract

Low-grade sinonasal adenocarcinomas (low-grade SNACs) of the sinonasal tract comprise a poorly characterized and histologically heterogeneous group of tumors. We describe three cases of a histologically distinct variant of low-grade SNAC characterized by ETV6 gene rearrangements. The patients included 2 women (aged 32 and 88 y) and a man (aged 75 y); all were initially treated with surgery alone. Follow-up ranged from 9 to 170 months with one patient having 2 local recurrences and none experiencing distant or regional metastases. Tumors were composed of cytologically bland columnar and cuboidal eosinophilic tumor cells with basally located nuclei arranged in tubular and tubulotrabecular patterns. Immunohistochemically, CK7, DOG1, GCDFP-15, and SOX10 were positive in all cases, and vimentin was positive in 2 cases. Scattered single cells or small groups of tumor cells were S-100 positive. Only one case had weak, focal expression of GATA3, and mammaglobin was consistently negative. Two cases had ETV6-NTRK3 gene fusions, whereas ETV6 had an unknown fusion partner gene in one case. The highly similar morphology, immunohistochemical profile, and genetics of the presented cases are suggestive of a specific disease. Although translocation-associated adenocarcinomas in the sinonasal tract have previously been described exclusively as salivary-type carcinomas, we present the first type of carcinoma characterized by recurrent genetic rearrangements and distinct phenotype occurring exclusively in the sinonasal tract with no known major salivary gland counterpart. We provisionally designate this tumor ETV6-rearranged low-grade SNAC. Identification of additional cases is necessary to fully appreciate the morphologic and biological spectrum of this disease.

Original language	English
Journal	American Journal of Surgical Pathology
Volume	41
Issue number	11
Pages (from-to)	1552-1560
ISSN	0147-5185
DOIs	https://doi.org/10.1097/PAS.0000000000000912
Publication status	Published - Nov 2017

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Andreasen, S., Skálová, A., Agaimy, A., Bishop, J. A., Laco, J., Leivo, I., Franchi, A., Larsen, S. R., Erentaite, D., Ulhøi, B. P., von Buchwald, C., Melchior, L. C., Michal, M., & Kiss, K. (2017). ETV6 Gene Rearrangements Characterize a Morphologically Distinct Subset of Sinonasal Low-grade Non–intestinal-type Adenocarcinoma: A Novel Translocation-associated Carcinoma Restricted to the Sinonasal Tract. American Journal of Surgical Pathology, 41(11), 1552-1560. https://doi.org/10.1097/PAS.0000000000000912

ETV6 Gene Rearrangements Characterize a Morphologically Distinct Subset of Sinonasal Low-grade Non–intestinal-type Adenocarcinoma : A Novel Translocation-associated Carcinoma Restricted to the Sinonasal Tract. / Andreasen, Simon; Skálová, Alena; Agaimy, Abbas et al.

In: American Journal of Surgical Pathology, Vol. 41, No. 11, 11.2017, p. 1552-1560.

Research output: Contribution to journal › Journal article › Research › peer-review

Andreasen, S, Skálová, A, Agaimy, A, Bishop, JA, Laco, J, Leivo, I, Franchi, A, Larsen, SR, Erentaite, D, Ulhøi, BP, von Buchwald, C, Melchior, LC, Michal, M & Kiss, K 2017, 'ETV6 Gene Rearrangements Characterize a Morphologically Distinct Subset of Sinonasal Low-grade Non–intestinal-type Adenocarcinoma: A Novel Translocation-associated Carcinoma Restricted to the Sinonasal Tract', American Journal of Surgical Pathology, vol. 41, no. 11, pp. 1552-1560. https://doi.org/10.1097/PAS.0000000000000912

Andreasen S, Skálová A, Agaimy A, Bishop JA, Laco J, Leivo I et al. ETV6 Gene Rearrangements Characterize a Morphologically Distinct Subset of Sinonasal Low-grade Non–intestinal-type Adenocarcinoma: A Novel Translocation-associated Carcinoma Restricted to the Sinonasal Tract. American Journal of Surgical Pathology. 2017 Nov;41(11):1552-1560. doi: 10.1097/PAS.0000000000000912

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title = "ETV6 Gene Rearrangements Characterize a Morphologically Distinct Subset of Sinonasal Low-grade Non–intestinal-type Adenocarcinoma: A Novel Translocation-associated Carcinoma Restricted to the Sinonasal Tract",

abstract = "Low-grade sinonasal adenocarcinomas (low-grade SNACs) of the sinonasal tract comprise a poorly characterized and histologically heterogeneous group of tumors. We describe three cases of a histologically distinct variant of low-grade SNAC characterized by ETV6 gene rearrangements. The patients included 2 women (aged 32 and 88 y) and a man (aged 75 y); all were initially treated with surgery alone. Follow-up ranged from 9 to 170 months with one patient having 2 local recurrences and none experiencing distant or regional metastases. Tumors were composed of cytologically bland columnar and cuboidal eosinophilic tumor cells with basally located nuclei arranged in tubular and tubulotrabecular patterns. Immunohistochemically, CK7, DOG1, GCDFP-15, and SOX10 were positive in all cases, and vimentin was positive in 2 cases. Scattered single cells or small groups of tumor cells were S-100 positive. Only one case had weak, focal expression of GATA3, and mammaglobin was consistently negative. Two cases had ETV6-NTRK3 gene fusions, whereas ETV6 had an unknown fusion partner gene in one case. The highly similar morphology, immunohistochemical profile, and genetics of the presented cases are suggestive of a specific disease. Although translocation-associated adenocarcinomas in the sinonasal tract have previously been described exclusively as salivary-type carcinomas, we present the first type of carcinoma characterized by recurrent genetic rearrangements and distinct phenotype occurring exclusively in the sinonasal tract with no known major salivary gland counterpart. We provisionally designate this tumor ETV6-rearranged low-grade SNAC. Identification of additional cases is necessary to fully appreciate the morphologic and biological spectrum of this disease.",

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T2 - A Novel Translocation-associated Carcinoma Restricted to the Sinonasal Tract

AU - Andreasen, Simon

AU - Skálová, Alena

AU - Agaimy, Abbas

AU - Bishop, Justin A

AU - Laco, Jan

AU - Leivo, Ilmo

AU - Franchi, Alessandro

AU - Larsen, Stine R

AU - Erentaite, Daiva

AU - Ulhøi, Benedicte Parm

AU - von Buchwald, Christian

AU - Melchior, Linea C

AU - Michal, Michal

AU - Kiss, Katalin

PY - 2017/11

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N2 - Low-grade sinonasal adenocarcinomas (low-grade SNACs) of the sinonasal tract comprise a poorly characterized and histologically heterogeneous group of tumors. We describe three cases of a histologically distinct variant of low-grade SNAC characterized by ETV6 gene rearrangements. The patients included 2 women (aged 32 and 88 y) and a man (aged 75 y); all were initially treated with surgery alone. Follow-up ranged from 9 to 170 months with one patient having 2 local recurrences and none experiencing distant or regional metastases. Tumors were composed of cytologically bland columnar and cuboidal eosinophilic tumor cells with basally located nuclei arranged in tubular and tubulotrabecular patterns. Immunohistochemically, CK7, DOG1, GCDFP-15, and SOX10 were positive in all cases, and vimentin was positive in 2 cases. Scattered single cells or small groups of tumor cells were S-100 positive. Only one case had weak, focal expression of GATA3, and mammaglobin was consistently negative. Two cases had ETV6-NTRK3 gene fusions, whereas ETV6 had an unknown fusion partner gene in one case. The highly similar morphology, immunohistochemical profile, and genetics of the presented cases are suggestive of a specific disease. Although translocation-associated adenocarcinomas in the sinonasal tract have previously been described exclusively as salivary-type carcinomas, we present the first type of carcinoma characterized by recurrent genetic rearrangements and distinct phenotype occurring exclusively in the sinonasal tract with no known major salivary gland counterpart. We provisionally designate this tumor ETV6-rearranged low-grade SNAC. Identification of additional cases is necessary to fully appreciate the morphologic and biological spectrum of this disease.

AB - Low-grade sinonasal adenocarcinomas (low-grade SNACs) of the sinonasal tract comprise a poorly characterized and histologically heterogeneous group of tumors. We describe three cases of a histologically distinct variant of low-grade SNAC characterized by ETV6 gene rearrangements. The patients included 2 women (aged 32 and 88 y) and a man (aged 75 y); all were initially treated with surgery alone. Follow-up ranged from 9 to 170 months with one patient having 2 local recurrences and none experiencing distant or regional metastases. Tumors were composed of cytologically bland columnar and cuboidal eosinophilic tumor cells with basally located nuclei arranged in tubular and tubulotrabecular patterns. Immunohistochemically, CK7, DOG1, GCDFP-15, and SOX10 were positive in all cases, and vimentin was positive in 2 cases. Scattered single cells or small groups of tumor cells were S-100 positive. Only one case had weak, focal expression of GATA3, and mammaglobin was consistently negative. Two cases had ETV6-NTRK3 gene fusions, whereas ETV6 had an unknown fusion partner gene in one case. The highly similar morphology, immunohistochemical profile, and genetics of the presented cases are suggestive of a specific disease. Although translocation-associated adenocarcinomas in the sinonasal tract have previously been described exclusively as salivary-type carcinomas, we present the first type of carcinoma characterized by recurrent genetic rearrangements and distinct phenotype occurring exclusively in the sinonasal tract with no known major salivary gland counterpart. We provisionally designate this tumor ETV6-rearranged low-grade SNAC. Identification of additional cases is necessary to fully appreciate the morphologic and biological spectrum of this disease.

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DO - 10.1097/PAS.0000000000000912

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SN - 0147-5185

VL - 41

SP - 1552

EP - 1560

JO - American Journal of Surgical Pathology

JF - American Journal of Surgical Pathology

IS - 11

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