J Pathol Transl Med.  2023 May;57(3):158-165. 10.4132/jptm.2023.03.13.

Frequent apocrine changes in pleomorphic adenoma with malignant transformation: a possible pre-malignant step in ductal carcinoma ex pleomorphic adenoma

• Song JS
• Kim Y
• Lee YS
• Choi SH
• Nam SY
• Kim SY
• Cho KJ

• KMID: 2542282
• DOI: http://doi.org/10.4132/jptm.2023.03.13

Abstract

Background
The most common type of carcinoma ex pleomorphic adenoma (CPA) is histologically equivalent to salivary duct carcinoma, which has an apocrine phenotype. Invasive CPA is often accompanied by non-invasive or in situ carcinoma, an observation that suggests the presence of precursor lesions. The aim of this study was to identify candidate precursor lesions of CPA within pleomorphic adenoma (PA).
Methods
Eleven resected cases of CPA with residual PA and 17 cases of PA with atypical changes were subjected to immunohistochemistry (IHC) for p53, human epidermal growth factor receptor 2 (HER2), androgen receptor (AR), pleomorphic adenoma gene 1, gross cystic disease fluid protein-15 (GCDFP-15), and anti-mitochondrial antibody.
Results
Invasive or in situ carcinoma cells in all CPAs were positive for AR, GCDFP-15, and HER2. Atypical foci in PAs corresponded to either apocrine or oncocytic changes on the basis of their reactivity to AR, GCDFP-15, and anti-mitochondrial antibody. Atypical cells in PAs surrounding CPAs had an apocrine phenotype without HER2 expression.
Conclusions
Our study identified frequent apocrine changes in residual PAs in CPA cases, suggesting a possible precursor role of apocrine changes. We recommend the use of HER2 IHC in atypical PAs, and that clinicians take HER2 positivity into serious consideration.

Keyword

Carcinoma ex pleomorphic adenoma; Salivary duct carcinoma; Atypical pleomorphic adenoma; Apocrine changes

Figure

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  Fig. 1. Immunohistochemical results for carcinoma ex pleomorphic adenoma (left column), carcinoma in situ ex pleomorphic adenoma (middle column), and apocrine changes in residual pleomorphic adenoma (right column). All elements are positive for androgen receptor (AR), gross cystic disease fluid protein-15 (GCDFP-15), and anti-mitochondrial antibody (AM). The intensity of human epidermal growth factor receptor 2 (HER2) and p53 staining varies. Pleomorphic adenoma gene 1 (PLAG1) is negative in all cases.

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  Fig. 2. Atypical changes in pleomorphic adenoma can be divided into the apocrine type (left column) and oncocytic type (right column) according to the immunohistochemistry results for androgen receptor (AR) and gross cystic disease fluid protein-15 (GCDFP-15). Both types are positive for antimitochondrial antibody (AM). Faint focal staining for human epidermal growth factor receptor 2 (HER2) can be seen in five apocrine cases and one oncocytic type. In all cases, p53 is positive. Pleomorphic adenoma gene 1 (PLAG1) is expressed in most oncocytic cases, but rarely expressed in the apocrine type.

Reference

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