Some pleomorphic adenomas of the breast share PLAG1 rearrangements with the analogous tumour of the salivary glands

Abstract

Some pleomorphic adenomas of the breast share PLAG1 rearrangements with the analogous tumour of the salivary glands Aims: Pleomorphic adenoma (PA) of the breast, and especially its malignant transformation, is extremely rare and represents a diagnostic pitfall. Molecular alterations in this entity have not been investigated. We aimed to examine the clinicopathological features of our breast PAs and perform molecular analysis. Methods and results: Seven cases of breast PA, including two cases of carcinoma ex PA, were analysed. PLAG1 and HMGA2 gene rearrangements were assayed by fluorescence in-situ hybridisation (FISH) and RNA sequencing (RNA-Seq), respectively. Reverse transcription-polymerase chain reaction (RT-PCR) and Sanger sequencing were used to verify RNA sequencing results. All seven cases of breast PA occurred in women. The histological features were similar to the analogous tumour in salivary glands, including a dual epithelial-myoepithelial component and negativity of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) by immunohistochemistry. Of the two cases with carcinoma ex PA, one demonstrated minimal invasion and one was extensively invasive. PLAG1 rearrangements were identified in two cases (28.6%), but no rearrangements of HMG2A were found. A novel fusion product in PAs, TRPS1-PLAG1, was identified in one case. No patients had recurrence or metastasis with a follow-up period of 6-158 months. Conclusions: Breast PA is rare, but it is an important differential diagnosis of breast pathology with the potential to develop carcinoma ex PA. We report a novel TRPS1-PLAG1 fusion gene in breast PA.

Breast lesions with myoepithelial phenotype

“…Recently, it has been demonstrated that some breast PA can harbour PLAG1 rearrangements (comprising a novel fusion gene TRPS1‐PLAG1), similar to the salivary gland counterpart. In breast PA, no HMG2A rearrangements have been detected 51 …”

“…HG‐AdCC (Figure 8) is a very rare condition, characterised by the appearance of a high‐grade type of carcinoma arising in AdCC 51 . At variance with the diagnosis of SB‐AdCC, the high‐grade transformation should be considered when carcinomatous elements with divergent differentiation appear.…”

“…In breast PA, no HMG2A rearrangements have been detected. 51 The prognosis is usually good. Diaz et al 52 reported 10 cases, treated with surgical excision alone, that did not show recurrences or metastases, 4.9 years after diagnosis.…”

“…HG-AdCC (Figure 8) is a very rare condition, characterised by the appearance of a high-grade type of carcinoma arising in AdCC. 51 At variance with the diagnosis of SB-AdCC, the high-grade transformation should be considered when carcinomatous elements with divergent differentiation appear. The case reported by Noske et al 70 showed areas of metaplastic carcinoma and areas of melanomatous differentiation; Cabibi et al 71 reported the association between AdCC and small cell carcinoma with neuroendocrine differentiation; the case illustrated by Cima et al 56 showed the features of carcinoma of no special type (NST), with strong ER expression appearing in an ER/PRnegative AdCC.…”

Unusual Clinical Morphology of Bilateral Pleomorphic Adenoma with Unilateral Cystic Degeneration; a Consequence of Delay in Consent for Treatment: A Case Report

“…Pleomorphic adenomas are benign tumours of the salivary glands found much more commonly in the major salivary glands with incidence of up to ninety percent in the parotid gland, while 10% appear in minor salivary glands [1]. Other reported uncommon sites of pleomorphic adenoma include the submandibular gland [2], nasolacrimal duct [3], lacrimal gland [4], trachea [5], epiglottis [6], and the breast [7]. They are also found incidentally as rigid, unilateral, painless masses, growing gradually [1].…”