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Head and Neck Pathology
Published in: Head and Neck Pathology 2/2023

08-12-2022 | Original Paper

A Subset of Salivary Intercalated Duct Lesions Harbors Recurrent CTNNB1 and HRAS Mutations: A Molecular Link to Basal Cell Adenoma and Epithelial-Myoepithelial Carcinoma?

Authors: Anne C. McLean, Lisa M. Rooper, Jeffrey Gagan, Lester D. R. Thompson, Justin A. Bishop

Published in: Head and Neck Pathology | Issue 2/2023

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Abstract

Background

Intercalated duct lesions (IDLs) are benign salivary gland proliferations that resemble normal intercalated ducts and are subdivided into hyperplastic, adenoma or hybrid types depending on circumscription. While IDLs were historically regarded as non-neoplastic, frequent association with basal cell adenoma (BCA) and epithelial-myoepithelial carcinoma (EMC) has raised the possibility that they are neoplastic precursors.

Methods

In this study, we performed β-catenin immunohistochemistry and targeted molecular analysis on IDLs to clarify their pathogenesis.

Results

We identified 15 IDLs from the parotid glands of eight men and six women with a median age of 65 years (range 42–85 years). These lesions included nine hyperplastic, three adenoma, and three hybrid types. Nuclear β-catenin localization was present in 7 of 13 lesions tested (54%). Next generation sequencing was successfully completed in 12 IDLs, of which seven (58%) had likely oncogenic mutations. These included three recurrent CTNNB1 mutations in hyperplastic (n = 2) and hybrid (n = 1) lesions and two recurrent HRAS hotspot mutations in adenomas.

Conclusion

Despite substantial heterogeneity, these findings confirm that a majority of IDLs are genuinely neoplastic, and some demonstrate molecular overlap with both BCA and EMC, supporting their theorized role as precursors to these tumors. Nevertheless, no oncogenic drivers were present in a significant subset of cases, suggesting that some IDLs may be truly reactive and hyperplastic. As such, IDL appear to represent a diverse morphologic and molecular spectrum that include both neoplastic and hyperplastic lesions. Reconsideration of the boundary between IDL and BCA in the future may be necessary to simplify classification.
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Metadata
Title
A Subset of Salivary Intercalated Duct Lesions Harbors Recurrent CTNNB1 and HRAS Mutations: A Molecular Link to Basal Cell Adenoma and Epithelial-Myoepithelial Carcinoma?
Authors
Anne C. McLean
Lisa M. Rooper
Jeffrey Gagan
Lester D. R. Thompson
Justin A. Bishop
Publication date
08-12-2022
Publisher
Springer US
Published in
Head and Neck Pathology / Issue 2/2023
Electronic ISSN: 1936-0568
DOI
https://doi.org/10.1007/s12105-022-01513-x

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