Pattern of SOX9 expression in pleomorphic adenoma, carcinoma ex pleomorphic adenoma, and matrix-producing metaplastic carcinoma of the breast lends support to common biology.

In the salivary gland, the diagnosis of pleomorphic adenoma (PA) and carcinoma ex pleomorphic adenoma (CXPA) is not difficult, but when these entities occur in the breast, they produce challenges in diagnosis and in the differential diagnosis of mesenchymal/matrix-producing metaplastic carcinoma (MpMC). The study of these rare entities provides insight into the development of MpMC and potentially provides direction for therapeutic targets. Three cases of mammary CXPA were compared histologically and immunohistochemically with 35 cases of MpMC as well as 3 cases of PA. Evaluation of SOX9, a master regulator of chondrogenesis, was conducted in tissue sections of the tumors. All cases of CXPA of the breast were similar, demonstrating a nodule of tumor partially encased in a thick hyalinized sclerotic wall with central sclerosis. Well-defined ductular structures residing in a myxoid-chondroid stroma were identified. The malignant epithelial and myoepithelial components were distinctly more cellular than the central nidus of the PA and had peripheral expansion beyond the hyalinized pseudo-capsule of the tumor. In comparison, all MpMCs showed solid, bosselated equally distributed expansile hypercellular nests of cells within a dense myxoid and myxoid hyalinized stroma. Tumors showed a varying intensity of nuclear SOX9 staining in 100% of PA and CXPA and 31 (88.6%) MpMCs. Two of the four SOX9 negative MpMC cases showed osseous differentiation. SOX9 expression in tumors with heterologous mesenchymal differentiation can aid in establishing the diagnosis of PA, mammary CXPA, and chondroid MpMC.