Epithelial-Myoepithelial Carcinoma of Parotid Gland: A Cytological Challenge with Histological Correlation

Case: We present the case of an 86-year-old female who presented clinically with a bulky lesion behind her right ear. Fine needle aspiration cytology with immunocytochemistry has been performed and the patient was diagnosed with a biphasic neoplasm, epithelial-myoepithelial, highly suggestive of EMC. She underwent a wide surgical excision and diagnostic was confirmed by histological examinations, which showed a tumor composed of ducts with double cell lining surrounded by a basement membrane in a sclerotic stroma. Immunohistochemistry was carried on to highlight the biphasic cell pattern. The patient is free of disease after 20 months of surgical procedure.


Introduction
Epithelial-Myoepithelial Carcinoma (EMC) is a rare malignant salivary gland tumor which chiefly occurs in the parotid gland, representing about 1% of all neoplasm of salivary gland [1]. Donath et al. [2] in 1972 introduced the term EMC by noting the myoepithelial component as an integral part of the tumor. EMC occurs mainly in the parotid gland, but it has been also described in the submandibular gland, in the minor salivary glands and extra oral areas [3][4][5][6]. It is more commonly seen in females, with a peak incidence in the seventh decade [7]. We report a case of EMC in an 86 year old female who complained of a bulky mass on her right parotid. A cytological and histological correlation was made.

Case Report
An 86 year old female with a history of painless longstanding bulky lesion over her right parotid gland. Since, last 5 months to date she noted a fast growing. Cervical adenopathy and her right facial nerve function were unaffected. Ultrasonography and computed tomography of the head and neck revealed a non-homogeneously solid mass measuring 6.5 × 4.5 cm in her right parotid gland with a skin protuberance, an external jugular vein displacement and possibility of a sternocleidomastoid muscle infiltration. There wasn´t evidence of jaw affectation. The tumor's interface with the parotid gland was clearly defined. Clinically and radiologically the tumor suggested a malignant neoplasm. The patient underwent Fine Needle Aspiration Cutting sections from formalin fixed tumour did show a poorly circumscribed greyish mass, arranged in a globular pattern with a haemorrhagic core, measuring 6 cm in higher diameter (Figure 2b). Histopathology sections displayed a normal parotid structure and a uniform nesting arrangement of tumor cells being separated by a thin fibrous connective tissue capsule (Figure 3a). There were two cell types, an outer layer of clear myoepithelial cells and an inner layer of cuboidal eosinophilic duct-like cells. These cells were further enveloped on outside by a well defined basement membrane material (Figure 3b). There wasn´t evidence of nuclear atypia but some mitotic figures were seen.
Immunohistochemistry assay was also made. Epithelial cells were strongly positive for cytokeratin 8 ( Figure 3c) and CD 117 (Figure 3f). Myoephitelial cells did stain with smooth muscle actin ( Figure 3d) and P-63 (Figure 3e). S100 was also positive in myoephitelial cells showing nuclear and cytoplasmatic staining. Both groups of cells were negative for GFAP and PSA. Ki-67 was up to 20% mainly in the myoepithelial component. Thus, the final diagnosis of EMC of the right parotid gland was made. Since the surgery the patient has done well, without evidence of either local recurrence or metastases.

Discussion
Firstly described by Donath et al. in 1972 [2], EMC wasn't included in the World Health Organization classification of salivary gland tumors until 1991 [8]. Higher incidence is in older persons with a female predominance, and affect principally the parotid gland, more than the others salivary glands [7]. Furthermore, most patients tend to present an asymptomatic enlarging mass from weeks to months, whereas others exhibited signs of malignancy such as pain or facial paralysis.
Although radiological signs can approach to the malignancy, EMC is a pathological challenge particularly when the diagnostic is not suspected. In cytology smears differential diagnosis must be done with myoepithelioma, pleomorphic adenoma, monomorphic adenoma, adenoid cystic carcinoma and polymorphous low grade adenocarcinoma. Klijanienko et al. have published a quantitative differential diagnosis of EMC on cytology smears taking into account both , stroma and cells features, such as papillary formations, clear cells, cuboidal/basal cells, plasma-shape myoepithelial cells, squamous cells, cellular atypia, chondromixoid stroma, mucoid stroma, hyaline deposits and crystalloids. Sometimes these characteristics are overlapping between one tumor and another, however up to 84,6% of EMC are diagnosed as suspicious/malignant as this authors demonstrated. In the other hand, only 7.7% of cases were diagnosed as a benign tumor such as pleomorphic adenoma. Finally, they conclude that failure to  distinguish between these entities is not dramatic, because all of them lead to surgical excision [9].
In the way to improve our knowledge about salivary gland tumors, we could find in the English literature that Seethala et al. recently published a frequent positivity (69,2%) of c-kit (CD117) in EMC [10]. However, Andreadis et al. [11] have lately demonstrated that CD117 was also expressed in a wide group of malignant salivary gland tumors, such as adenoid cystic carcinoma, acinar cell carcinoma and basal cell adenocarcinoma. By the way, they have also seen a CD117 expression in benign salivary gland pathology, for example inflammatory disease.
In order to differentiate EMC from others malignancies, is important to take into account that biphasic nature (epithelial and myoepithelial) is the most relevant finding. This pattern can be present in smears, but it´s better seen in histology and is characterized by a tubular or ductal structures composed of basal myoepithelial and luminal epithelial cells, these latest look like normal intercalated salivary gland ducts. We confirmed the double-cell pattern on smear and on histology sections. In the former, immunocytochemistry displayed a strong positivity for CD117 ( Figure 1c Although PSA is considered highly specific marker for prostate carcinoma, several authors have demonstrated focal immunostaining for PSA in pleomorphic adenoma, mucoepidermoid carcinoma, and ductal carcinoma of salivary gland [12]. Aberrant expression of PSA was recently described by Venetia et al. in one case of dedifferentiated EMC [13]. In the present case PSA was negative.
In conclusion, we remark the biphasic pattern of EMC as a cytological strategy to orientate the diagnosis of this exceedingly rare malignant salivary gland tumor; however, non-specific antibodies can help us to make a good diagnostic approach, although they may be useful. Our patient is free of disease since surgery.