Fine‐needle aspiration cytology of the apocrine variant of epithelial‐myoepithelial carcinoma

Abstract Epithelial‐myoepithelial carcinoma (EMCa) is a rare neoplasm that most frequently afflicts the parotid gland. Histologically, a dual layer of inner, luminal epithelial cells and outer myoepithelial cells with associated background hyalinization characterize these tumors. Several variants of EMCa have been described, including the more recent description of the apocrine variant. We present here a case of a 71‐year‐old male with a parotid mass diagnosed on FNA as an apocrine epithelial‐myoepithelial carcinoma. To our knowledge, this is the first case report describing the cytomorphologic features of apocrine EMCa on FNA smears.


| INTRODUCTION
The name epithelial-myoepithelial carcinoma (EMCa) was coined by Donath et al. in 1972 but this neoplasm was likely previously reported under other names. 1 EMCa is a biphasic malignant tumor composed of epithelial and myoepithelial cells. The epithelial cells are luminal and resemble intercalated ductal cells, which is the theorized origin of this tumor. 2 EMCa is a rare neoplasm comprising approximately 1-2% of salivary gland neoplasms. 1,3 These tumors tend to arise in the sixth to seventh decade with a slight predominance in females. It most commonly affects the major salivary glands, with the parotid gland being most common overall, but other reported sites include the upper and lower respiratory tract and palate. 1,[3][4][5] This tumor is considered a low-grade malignancy due to its rare spread to lymph nodes or distant sites and overall portends a favorable prognosis with 5-year and 10-year survivals of 94% and 82%, respectively, as reported by Seethala et al. 6,7 However, recurrences are seen in up to 50% of cases. 4 One of the rare variants of classic EMCa is the apocrine variant, which was recently described by Seethala et al. 7 Herein, we report a case of apocrine EMCa presenting as a parotid mass and diagnosed on FNA. To our knowledge, this is the first case report describing the cytomorphologic features of apocrine EMCa on FNA smears.  Figure 9). Immunohistochemical stain for S100 highlighted the myoepitheial cells with sparing of the apocrine epithelial ductal cells ( Figure 10). The overall findings were consistent with apocrine epithelial-myoepithelial carcinoma with myoepithelial anaplasia, which is a variant of classic EMCa with a higher recurrence rate than the classic type. 8

| DISCUSSION
Cytologically, classic EMCa is a tumor with a high false-negative rate due to its variable morphology and similarity to more common salivary gland lesions. 9,10 FNA will show a cellular smear with a biphasic popu-  Recently, an apocrine variant of EMCa has been described by Seethala et al. 7 This variant is morphologically similar to the oncocytic variant of EMCa, which was first described by Savera et al. 11 and tends to occur in patients that are a decade older than classic EMCa.
Both variants combined make up approximately 8% of EMCa cases. 6,7 Morphologically, both the apocrine and oncocytic variants maintain Based on the cytomorphologic features in our case, including the biphasic population with numerous apocrine cells admixed with a second population of basaloid cells within background hyaline stroma, the main differential diagnosis to consider was cellular pleomorphic adenoma with oncocytic/apocrine change. However, the absence of a chondromyxoid stroma and the presence of a distinct myoepithelial layer within the lesion that does not seem to blend into the background stroma made this diagnosis less likely.
Other potential but a less likely entity to consider in the differential diagnosis is salivary duct carcinoma. Apparently, the apocrine component of apocrine EMCa can be confused with the salivary duct carcinoma neoplastic epithelial cells, which tend to have abundant granular cytoplasm that may appear oncocytoid. 15 To further complicate this issue, rare hybrid cases of EMCa and salivary duct carcinoma have been reported. 12 Additionally, salivary duct carcinoma arising in a pleomorphic adenoma should also be considered as a possible mimicker, which makes the presence of a distinct myoepithelial layer critical. 8 Salivary duct carcinoma in situ should be distinguished from EMCa especially as both have a p63-positive basal cell layer. However, in salivary duct carcinoma in situ, p63 highlights only the residual native basal layer; whereas apocrine EMCa has p63 positivity in both the luminal and basal layer. 8 Oncocytoma and oncocytic carcinoma aspirates show oncocytes that are indistinguishable from those of oncocytic/apocrine EMCa.
However, the absence of p63-positive myoepithelial cells and the presence of atypia, necrosis, or increased mitotic activity usually points to oncocytic carcinoma. Adenoid cystic carcinoma is also an important diagnostic consideration to keep in mind for oncocytic/apocrine EMCa due to their overlapping morphologic features and the common presence of hyaline stroma. However, the degree of cellular atypia in EMCa is milder than the cytologically atypical adenoid cystic carcinoma. 13

| CONCLUSION
To our knowledge, there have been no cases reported so far on the cytomorphologic features of the apocrine variant of EMCa diagnosed by FNA. Being a rare entity, apocrine EMCa can be diagnostically challenging when its first presented on cytology smears. Careful cytomorphologic evaluation and a thorough immunohistochemical workup play a vital role in establishing this rare but challenging diagnosis.