Volume 81, Issue 1 pp. 44-54

Original Article

Endometrial neuroendocrine carcinoma and undifferentiated carcinoma are distinct entities with overlap in neuroendocrine marker expression

Basile Tessier-Cloutier,

Basile Tessier-Cloutier

orcid.org/0000-0001-8739-3879

Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada

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Eun-Young Kang,

Eun-Young Kang

Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada

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Deepu Alex,

Deepu Alex

Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada

Department of Pathology and Laboratory Medicine, BC Cancer, Vancouver, BC, Canada

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Colin J R Stewart,

Colin J R Stewart

Department of Histopathology, King Edward Memorial Hospital and School for Women's and Infants' Health, University of Western Australia, Perth, WA, Australia

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W Glenn McCluggage,

W Glenn McCluggage

orcid.org/0000-0001-9178-4370

Department of Pathology, Belfast Health and Social Care Trust, Belfast, UK

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Martin Köbel,

Martin Köbel

orcid.org/0000-0002-6615-2037

Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada

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Cheng-Han Lee,

Corresponding Author

Cheng-Han Lee

[email protected]

orcid.org/0000-0003-2094-1222

Department of Laboratory Medicine and Pathology, Royal Alexandra Hospital, Edmonton, AB, Canada

Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada

Address for correspondence: Cheng-Han Lee, MD-PhD, FRCPC, Department of Laboratory Medicine and Pathology, University of Alberta, 5–142E, Katz Building, 114th St and 87th Ave, Edmonton, T6G 2E1 AB, Canada. e-mail: [email protected]Search for more papers by this author

Basile Tessier-Cloutier,

Basile Tessier-Cloutier

orcid.org/0000-0001-8739-3879

Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada

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Eun-Young Kang,

Eun-Young Kang

Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada

Search for more papers by this author

Deepu Alex,

Deepu Alex

Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada

Department of Pathology and Laboratory Medicine, BC Cancer, Vancouver, BC, Canada

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Colin J R Stewart,

Colin J R Stewart

Department of Histopathology, King Edward Memorial Hospital and School for Women's and Infants' Health, University of Western Australia, Perth, WA, Australia

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W Glenn McCluggage,

W Glenn McCluggage

orcid.org/0000-0001-9178-4370

Department of Pathology, Belfast Health and Social Care Trust, Belfast, UK

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Martin Köbel,

Martin Köbel

orcid.org/0000-0002-6615-2037

Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada

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Cheng-Han Lee,

Corresponding Author

Cheng-Han Lee

[email protected]

orcid.org/0000-0003-2094-1222

Department of Laboratory Medicine and Pathology, Royal Alexandra Hospital, Edmonton, AB, Canada

Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada

First published: 08 April 2022

https://doi.org/10.1111/his.14639

Citations: 4

B.C.-T. and E.-T.K. contributed equally to this work.

M.K. and C.-H.L. are the senior authors.

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Abstract

Aims

Dedifferentiated endometrial carcinomas (DDECs)/undifferentiated endometrial carcinomas (UDECs) frequently harbour genomic activation of switch/sucrose non-fermentable (SWI/SNF)-complex proteins, and can show histological overlap with neuroendocrine carcinoma (NEC). The aim of this study was to compare the extent of the expression of neuroendocrine markers, SWI/SNF proteins and mismatch repair (MMR) proteins in DDEC/UDEC and NEC.

Methods and results

The extent of expression of synaptophysin, chromogranin, CD56, ARID1A, ARID1B, SMARCA4, SMARCB1 and MMR proteins was evaluated by immunohistochemistry on 44 SWI/SNF-deficient DDECs/UDECs and 15 NECs. Thirty-three of 44 (75%) DDECs/UDECs showed expression of at least one neuroendocrine marker, with 18 of 44 (41%) expressing two or more neuroendocrine markers, whereas all 15 NECs showed expression of at least one neuroendocrine marker, with 14 of 15 (93%) expressing two or more neuroendocrine markers. Neuroendocrine marker expression in DDECs/UDECs was typically focal when present, with average extents of 17%, 4% and 8% for synaptophysin, chromogranin and CD56 in the positive cases, respectively, in contrast to 73%, 40% and 62% in the positive NEC cases, respectively. All 15 NECs showed intact expression of SWI/SNF-complex proteins, except for one that showed isolated loss of ARID1A. Thirty-eight of 44 DDECs/UDECs were MMR-abnormal (34 with loss of MLH1 and PMS2, and four with loss of PMS2 alone), whereas all NECs retained MMR protein expression.

Conclusions

Our study demonstrates frequent but typically focal neuroendocrine marker expression in SWI/SNF-deficient DDECs/UDECs, whereas NECs typically express two or more neuroendocrine markers, with diffuse expression of at least one marker. ARID1B, SMARCA4 and SMARCB1 immunohistochemistry can be used to aid in the differentiation between DDEC/UDEC and NEC.

Graphical Abstract

Conflicts of interest

The authors have no conflicts of interest to declare.

Open Research

Data availability statement

Data available on request from the authors

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Citing Literature

Volume81, Issue1

July 2022

Pages 44-54