TY - JOUR
T1 - A Subset of Salivary Intercalated Duct Lesions Harbors Recurrent CTNNB1 and HRAS Mutations
T2 - A Molecular Link to Basal Cell Adenoma and Epithelial-Myoepithelial Carcinoma?
AU - McLean, Anne C.
AU - Rooper, Lisa M.
AU - Gagan, Jeffrey
AU - Thompson, Lester D.R.
AU - Bishop, Justin A.
N1 - Funding Information:
This study was funded by the Jane B. and Edwin P. Jenevein M.D Endowment for Pathology at UT Southwestern Medical Center. No external funding was obtained for this study.
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Intercalated duct adenoma
KW - Intercalated duct hyperplasia
KW - Intercalated duct lesion
KW - Molecular diagnostics
KW - Salivary glands
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U2 - 10.1007/s12105-022-01513-x
DO - 10.1007/s12105-022-01513-x
M3 - Article
C2 - 36480093
AN - SCOPUS:85143665446
SN - 1936-055X
JO - Head and Neck Pathology
JF - Head and Neck Pathology
ER -