HMGA2-positive salivary gland neoplasms with prominent trabecular/canalicular morphology: a focus on carcinomas arising within this phenotype.

Abstract

Aims: Pleomorphic adenoma (PA) with a prominent trabecular/canalicular morphology has consistent HMGA2 protein expression, and association with HMGA2 fusions. We report our experience with this subtype, with emphasis on the carcinomas that can arise in this context.

Methods and results: A retro- and prospective review (2013-2024) of major salivary gland tumours with prominent trabecular/canalicular morphology was performed. Twenty-one parotid tumours met the criteria: 14 benign (66.7%), six carcinomas (28.6%), and one of uncertain behaviour (4.7%). HMGA2 immunohistochemistry (IHC) was performed on all cases. Next-generation sequencing was successfully performed on 18. Seven benign cases had a conventional PA component. In all cases, the tumour cells in these trabecular/canalicular areas demonstrated variable papillary thyroid carcinoma-like nuclear changes, including chromatin clearing, overcrowding, membrane irregularities, and intranuclear pseudoinclusions. Benign tumours were well-demarcated, whereas carcinomas demonstrated either a multinodular pattern of invasion or subtle infiltration. Two carcinomas showed increased cytologic atypia and architectural complexity and one had perineural invasion. By IHC, all were positive for HMGA2. In the trabecular/canalicular areas, there was consistent strong expression of CAM5.2, S-100, and SOX-10 and variable expression of p63 but negative p40. HMGA2 alterations were detected in 16 of 18 cases (89%). Follow-up was available on two carcinomas, with one being locally recurrent.

Conclusion: While most HMGA2-positive salivary gland neoplasms with a prominent trabecular/canalicular growth pattern are benign, they, like traditional PAs, may give rise to carcinomas that can locally recur. These carcinomas can be deceptively bland, subtly infiltrative, or have a multinodular pattern of invasion.