MALAT1::PLAG1 Fusion in Pleomorphic Adenoma with Mucinous and Squamous Metaplasia: A Diagnostic Pitfall Mimicking Mucoepidermoid Carcinoma (ex Pleomorphic Adenoma)
7 affiliations
- 1Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH USA
- 2Department of Pathology, Faculty of Medicine in Pilsen and Faculty Hospital, Charles University, Pilsen, Czech Republic
- 3Bioptic Laboratory, Ltd., Pilsen, Czech Republic
- 4Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON Canada
- 5Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON Canada
- 6Faculty of Dentistry, University of Toronto, Toronto, ON USA
- 7Robert J. Tomsich Department of Pathology and Laboratory Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH L15 USA
Abstract
Purpose: Pleomorphic adenoma (PA), the most common salivary neoplasm, is capable of tremendous histologic diversity. Co-occurrence of squamous and mucinous differentiation in PA is a rare phenomenon generally considered within its histologic spectrum, though previously advocated by some as evidence of mucoepidermoid carcinoma (MEC) ex PA. Herein, we describe a multi-institutional series of MEC-like PA with squamous differentiation, mucous cells, cystic change, and MALAT1::PLAG1 fusion.
Materials and Methods: Retrospective multi-institutional review identified 5 PAs with MALAT1::PLAG1 fusion. Histopathologic and immunohistochemical slides were reviewed, as well as demographic, clinical, and molecular findings.
Results: Five MALAT1::PLAG1-rearranged PA occurred in the parotid gland of 3 female and 2 male patients (median age: 53 yrs, range: 47–58 yrs). Median tumor dimension was 2.5 cm (range: 1.4–3.4 cm). All tumors demonstrated characteristic histologic features of PA as well as areas of cystic squamous and mucinous differentiation resembling MEC (comprising 25–80% of the tumors). There was no capsular invasion or high-grade features. No canonical MEC driver alterations were identified by NGS. No recurrences were identified during available follow-up in 2 patients.
Conclusion: Cystic squamous and mucinous differentiation may occur in PA, representing a potential diagnostic pitfall both in small biopsy specimens, where it can be misdiagnosed as MEC, as well as in resection specimens where it should not be interpreted as MEC ex PA. Instead, apparent association of these histologic features with MALAT1::PLAG1 fusion suggests a novel genotype–phenotype correlation in PA. Adjunct molecular testing may be valuable in diagnostically challenging cases.
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BibTeX
@article{lu2026malat1plag1,
title = {{MALAT1::PLAG1 Fusion in Pleomorphic Adenoma with Mucinous and Squamous Metaplasia: A Diagnostic Pitfall Mimicking Mucoepidermoid Carcinoma (ex Pleomorphic Adenoma)}},
author = {Liang Lu and Martina Bradová and Elan Hahn and Iona Leong and Laura J. Tafe and Darcy A. Kerr and Ivan J. Stojanov},
journal = {Head and Neck Pathology},
year = {2026},
month = oct,
doi = {10.1007/s12105-026-01977-1},
url = {https://doi.org/10.1007/s12105-026-01977-1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - MALAT1::PLAG1 Fusion in Pleomorphic Adenoma with Mucinous and Squamous Metaplasia: A Diagnostic Pitfall Mimicking Mucoepidermoid Carcinoma (ex Pleomorphic Adenoma)
AU - Liang Lu
AU - Martina Bradová
AU - Elan Hahn
AU - Iona Leong
AU - Laura J. Tafe
AU - Darcy A. Kerr
AU - Ivan J. Stojanov
PY - 2026
DA - 2026/10/26
JO - Head and Neck Pathology
DO - 10.1007/s12105-026-01977-1
UR - https://doi.org/10.1007/s12105-026-01977-1
AB - Purpose: Pleomorphic adenoma (PA), the most common salivary neoplasm, is capable of tremendous histologic diversity. Co-occurrence of squamous and mucinous differentiation in PA is a rare phenomenon generally considered within its histologic spectrum, though previously advocated by some as evidence of mucoepidermoid carcinoma (MEC) ex PA. Herein, we describe a multi-institutional series of MEC-like PA with squamous differentiation, mucous cells, cystic change, and MALAT1::PLAG1 fusion. Materials and Methods: Retrospective multi-institutional review identified 5 PAs with MALAT1::PLAG1 fusion. Histopathologic and immunohistochemical slides were reviewed, as well as demographic, clinical, and molecular findings. Results: Five MALAT1::PLAG1-rearranged PA occurred in the parotid gland of 3 female and 2 male patients (median age: 53 yrs, range: 47–58 yrs). Median tumor dimension was 2.5 cm (range: 1.4–3.4 cm). All tumors demonstrated characteristic histologic features of PA as well as areas of cystic squamous and mucinous differentiation resembling MEC (comprising 25–80% of the tumors). There was no capsular invasion or high-grade features. No canonical MEC driver alterations were identified by NGS. No recurrences were identified during available follow-up in 2 patients. Conclusion: Cystic squamous and mucinous differentiation may occur in PA, representing a potential diagnostic pitfall both in small biopsy specimens, where it can be misdiagnosed as MEC, as well as in resection specimens where it should not be interpreted as MEC ex PA. Instead, apparent association of these histologic features with MALAT1::PLAG1 fusion suggests a novel genotype–phenotype correlation in PA. Adjunct molecular testing may be valuable in diagnostically challenging cases.
SN - 1936-055X
SN - 1936-0568
ER -