Thymus-like phenotype in benign lymphoepithelial neoplasms of salivary glands: clinicopathological and molecular characterization and reappraisal of relationship to non-sebaceous lymphadenoma

Agaimy A, Laco J, Schubart C, Stöhr R, Tögel L, Ihrler S

Publication Language: English

Publication Type: Journal article

Journal

Virchows Archiv Springer Verlag (Germany)

Abstract

Benign lymphoepithelial tumors of salivary glands had been restricted to sebaceous and non-sebaceous (NSLA) lymphadenomas. However, salivary neoplasms recapitulating carcinoma showing thymus-like elements (CASTLE) have been the subject of recent case reports. We reviewed clinicopathological, immunohistochemical, and molecular findings in 20 salivary gland tumors with thymus-like phenotype (18 histologically benign and two with malignant component). Original diagnoses were NSLA (n = 11) and unclassified thymus-like lymphoepithelial neoplasms (n = 9). Patients were 13 males and 7 females aged 28 to 83 years (median, 61). All tumors originated in the parotid with a median tumor size of 2.7 cm. A cystic component was noted in eight cases (40%). Histologically, the tumors were composed of large squamoid cells with indistinct cell borders, forming large irregular branching and anastomosing aggregates within lymphoid stroma with Hassall corpuscle-like structures and intraepithelial sprinkling of lymphocytes. All tumors were diffusely positive for p63/p40 and CK5/CK14. CD5 and CD117 were expressed in 13/20 (65%) and 15/19 (79%) cases, respectively. The malignant component in two cases showed lower CD5/CD117 expression. Targeted DNA sequencing revealed pathogenic/likely pathogenic CYLD mutations in 4/7 cases (57%). One case each had a mutation in TAF1 + WISP3, DNMT3A, and BCOR. Targeted RNA sequencing revealed a YAP1::MAML2 fusion in 1/7 cases. This is the first systematic study addressing the concept of thymus-like phenotype in benign lymphoepithelial salivary gland tumors, showing that the majority of NSLAs (65%) belong to this poorly characterized category. Frequent CYLD mutations in these histologically distinct tumors represent a novel addition to the spectrum of CYLD-mutated salivary neoplasms.

Authors with CRIS profile

Abbas Agaimy Institute of Pathology Christoph Schubart Institute of Pathology Robert Stöhr Institute of Pathology Lars Tögel Institute of Pathology

Involved external institutions

Univerzita Karlova v Praze / Charles University in Prague Dermpath München

How to cite

APA:

Agaimy, A., Laco, J., Schubart, C., Stöhr, R., Tögel, L., & Ihrler, S. (2025). Thymus-like phenotype in benign lymphoepithelial neoplasms of salivary glands: clinicopathological and molecular characterization and reappraisal of relationship to non-sebaceous lymphadenoma. Virchows Archiv. https://doi.org/10.1007/s00428-025-04234-y

MLA:

Agaimy, Abbas, et al. "Thymus-like phenotype in benign lymphoepithelial neoplasms of salivary glands: clinicopathological and molecular characterization and reappraisal of relationship to non-sebaceous lymphadenoma." Virchows Archiv (2025).

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