Sebaceous Epithelial-Myoepithelial Carcinoma of the Salivary Gland: Clinicopathologic and Immunohistochemical Analysis of 6 Cases of a New Histologic Variant

Abstract

Epithelial-myoepithelial carcinoma (EMC) of the salivary glands is an uncommon, low-grade malignant tumor. A recent report demonstrates sebaceous differentiation in this tumor even though its significance has never been documented as a precise histologic variant. Six cases of EMC exhibiting sebaceous differentiation (sebaceous EMC) of the parotid gland were analyzed for their clinicopathologic features and immunohistochemical characteristics. In addition, primary salivary sebaceous carcinomas were also examined for comparison. In our series, the incidence of sebaceous EMC was 0.2% among 3012 cases of parotid gland tumors and 14.3% of all EMC cases. The 6 patients comprised 2 men and 4 women, age ranging from 77 to 93 years (mean, 83.7 y). Neither cervical lymph node nor distant organ metastases were found in any cases of sebaceous EMC and no patients died of disease, though local recurrences developed in 1 patient. Conversely, cervical lymph node metastasis was detected in 2 of 3 patients with sebaceous carcinoma, 1 of whom died of disease at 12 months. Histologically, all 6 tumors had an area of sebaceous differentiation admixed with features of bilayered ductal structures typical of EMC. A component of sebaceous differentiation was distributed diffusely in 4 tumors and focally in 2. Cytologic atypia of sebaceous EMCs was lesser than that of sebaceous carcinomas. Immunohistochemically, putative myoepithelial markers such as alpha-smooth muscle actin, calponin, p63, cytokeratin 14, S-100 protein, and vimentin were highly expressed in sebaceous EMC. However, the expression of the latter 4 markers was also observed in primary sebaceous carcinomas, whereas these tumors were all negative for alpha-smooth muscle actin and calponin. Positive immunoreactivity for epithelial membrane antigen, adipophilin, and perilipin confirmed sebaceous differentiation in EMC. These results indicate that sebaceous EMC is a low-grade malignancy, similar to conventional EMC. Our data also suggest that immunohistochemical examination of specific myoepithelial markers is helpful in distinguishing sebaceous EMC from sebaceous carcinoma, which may occasionally be associated with an aggressive clinical course.

Oncocytic and Apocrine Epithelial Myoepithelial Carcinoma: Novel Variants of a Challenging Tumor

“…Interestingly, unlike cutaneous sebaceous lesions, sebaceous elements in EMCa appear to be androgen receptor negative [2,13]. However, markers such as adipophilin and perilipin are still positive [14], and on frozen tissue, oil red O stains may highlight intracytoplasmic lipid vacuoles (Fig. 6f).…”

“…4f), hence the earlier descriptor of 'oncocytic-sebaceous' EMCa [2]. However, it has been noted that purely sebaceous EMCa exist [14], and anecdotally, oncocytic EMCa without sebaceous differentiation have been noted. The sebaceous elements vary, ranging from solid nests interspersed within myoepithelial rich areas to small intraductal proliferations transitioning from the oncocytic ductal epithelium.…”

“…Aside from these named variants, the myoepithelial cells in EMCa may show alterations such as 'ancient change' or spindled morphology with Verocay like palisading or squamous metaplasia (Fig. 3a) [2,[13][14][15]. The oncocytic and apocrine variants are the main focus of this review, but two important variants are summarized here.…”

Adipophilin expression in sebaceous tumors and other cutaneous lesions with clear cell histology: an immunohistochemical study of 117 cases

“…17 Additional studies have used these markers to confirm the lipid content in a variety of lesions from poorly differentiated sebaceous carcinomas arising in nevus sebaceus of Jadassohn to sebaceous epithelialmyoepithelial carcinomas of the salivary gland. [22][23][24] Other cutaneous lesions with clear cell histology may represent a differential diagnostic challenge with sebaceous lesions in routine hematoxylin and eosin staining, especially in the small biopsies of eyelid or periocular areas. 25 They include basal and squamous cell carcinomas that may have histologically focal or more diffuse clear cell differentiation.…”

My Journey into the World of Salivary Gland Sebaceous Neoplasms

“…These markers are well-characterized in sebaceous skin and eye tumors, with 95-100% of skin and eyelid sebaceous tumors staining with these markers in three recent studies [58,60,61]. However, in the salivary gland, these markers have only been studied in the sebaceous variant of epithelial myoepithelial carcinoma and in one sebaceous carcinoma of the tongue [62,63]. From the skin and eyelid data, one can extrapolate and conclude that these markers appear to be very sensitive markers for sebaceous differentiation and likely can be used to confirm sebaceous differentiation in a salivary gland tumor.…”