Epithelial-Myoepithelial Carcinoma with High Grade Transformation of Nasal Cavity

High grade transformation in epithelial-myoepithelial carcino¬ma is a recently defined entity with only a few cases reported in the literature. We present a 59 years old female patient with a polypoid lesion in nasal cavity, together with clinical com¬plaints as recurrent epistaxis and stuffiness. Histological and immunohistochemical examination of the surgically excised le¬sion revealed a diagnosis of epithelialmyoepithelial carcino¬ma with high grade transformation. Epithelial-myoepithelial carcinoma originates from salivary glands, mainly parotid gland. Other affected sites are submandibular gland and minor sali¬vary glands. Epithelialmyoepithelial carcinoma is characterized by double layered duct-like structures. Greater cytologi¬cal atypia, higher mitotic rate, presence of necrosis and loss of the biphasic ductlike structures are features of high grade transformation. Local recurrence and cervical lymph node me¬tastases are seen with low incidence in classical epithelial-myoepithelial carcinoma, whereas epithelial-myoepithelial carcinoma with high grade transformation has high tendency for lymph node and distant metastases.

High grade transformation (HGT) is defined as histological progression of low grade malignant neoplasm to highgrade, in which the original line of differentiation is no longer evident (2,6).Tumors with anaplasia have been called as either dedifferentiated epithelial-myoepithelial carcinoma or EMC with HGT (4).EMC with HGT is extremely rare; only a few cases are reported as high grade EMC arising in the nasal cavity (2,4).We report a case of EMC with HGT arising in nasal cavity in order to discuss clinical, radiological, histopatological and immunhistochemical features of this rare type of tumor.

CASE
A 59 years old female was admitted to our center with complaints of intermittent epistaxis and nasal obstruction for two months.In patient's nasal endoscopic examination, left inferior turbinate was hypertrophied and purple in color.Nasal septum and the middle turbinate were normal on endoscopic examination.No associated lymphadenopathy was observed in both sides of the neck.Axial and horizontal sections on tomography scan of the paranasal sinuses revealed a mass which fills the middle and lower nasal cavity, leading to minimal pushing to the nasal septum and medial maxillary wall and invading the inferior turbinate (Figure 1).Surgical excision was planned with a diagnosis of nasal polyp or angiofibroma according to the clinical and radiological findings.Therefore endoscopic view was not saved.Under general anesthesia, the inferior turbinate together with the mass was excised endoscopically.During operation middle turbinate and septal mucosa were normal.There was no complication after the operation.The histopathologic diagnosis was EMC with HGT.Follow-up for 4 months revealed no local recurrence or metastasis.Pathological findings; Grossly, the tumor was composed of fragmented, grayish polypoid nodule measuring 5x4x1 cm in diameter.On microscopic examination, the tumor was observed to be divided into lobules by fibrous stroma.The tumor was consisted of two components, including classical EMC and high grade EMC (Figure 2).The former component was composed of nests, duct-like and trabecular structures within a hyalinized background.Duct-like

Figure 1. Axial computed tomography (soft tissue window) of the paranasal sinus demonstrating a mass (arrow) that fills the lower nasal cavity
formations were lined with double layered epithelium.This epithelium was composed of a luminal layer with eosinophilic cuboidal epithelial cells, and a basal layer with polygonal -elongated cells.The tumor surface was covered with a single row of cuboidal or flattened epithelial cells.Linear PAS positive and diastase resistant material was seen in ductal lumens.The latter component was consisted of solid, cribriform and nested growth patterns with marked necrosis.Capsule of the tumor was invaded and surrounding soft tissues and bones were infiltrated.The number of mitoses was lower at classical EMC areas and higher at high grade areas, approximately 10 mitoses per 10 high power field were found.
Immunohistochemical staining was performed; epithelial cells were demonstrated by epithelial membrane antigen, and myoepithelial cells were stained for vimentin and smooth muscle actin.Myoepithelial cells and some luminal cells are positive for S-100.The tumor cells of classical component were diffusely positive for pancytokeratin.In high-grade component, the tumor cells showed patchy staining with pancytokeratin.Ki67 labeling index of classical EMC component was 5%, and index of high grade component was 25%.P53 was expressed in HGT component higher than classical component.
EMC forms a painless, slowly growing mass.Tumors of mi¬nor salivary glands have a tendency of forming ulcerated submucosal nodules with irregular margins (7,11).In four cases with EMC in the nasal cavity in the literature, tu¬mors were polypoid and arose from nasal septum or the inferior nasal turbinate as in our case (8).
EMC with HGT differs from classical EMC by greater cyto¬logical atypia, higher mitotic rate, presence of necrosis and loss of the biphasic duct-like structures.Additionally, bizarre, spindle, clear and plasmacytoid tumor cells may be observed in EMC with HGT (6).In our case, dedifferen¬tiated foci were seen adjacent to low grade areas.HGT in EMC can occur in the myoepithelial or ductal component.Yang et al. (2) reported that separating the high grade compo¬nent into ductal versus myoepithelial is subjective, un¬practical and less valuable as suggested by Roy et al.The authors and Roy at al. pro¬posed that these lessions be regarded as EMC with HGT (2).Baker et al. (9) have reported that in their case, p53 was overexpressed in high grade areas similar to case of Kusafuka et al.; and they reported Daa et al. found p53 staining in also typical EMC case in contrast.In our case, p53 was expressed more at high grade areas, but also low grade areas were stained as well.Ki-67 labeling index was higher in the high grade component, like p53 staining.
The differential diagnosis of EMC includes other salivary gland tumors which are composed of two types of cells: pleomorphic adenoma and adenoid cystic carcinoma (8).The pattern of cellular arrangement found in EMC excludes adenoid cystic carcinoma.The distribution of tumor cells in myxoid, hyalinised or condroid stroma is characteristic in pleomorphic adenoma.EMC differs by exhibiting greater epithelial cellularity with less stroma compared to pleomorphic adenoma (8).
EMC with HGT is more aggressive than classical EMC, with a high tendency for lymph node and distant metastases (2,6).A patient was reported which multiple pulmonary metastases 15 months after surgery (2).Baker et al. ( 9) noted a case with EMC with HGT in the nasal cavity represented recurrence at 15 months, bone metastases at 22 months in a report by Park et al.During follow up periods of 4 months after surgery, there was no local recurrence or distant metastasis in our patient.Although there is no defini¬tive treatment protocol, due to its rarity, some authors propose surgery with a safety margin, neck dissection and, radiotherapy and chemotherapy, because of it has more aggressive behavior and poorer prognosis than clas¬sical EMC (2,6).Although adjuvant radiotherapy may be appropriate, there are no data on optimal manage- ment because of rarity (9).We reported a case of EMC with HGT, because of its rarity.Presence of only a few reports with involvement of nasal cavity in literature was an ad¬ditional specificity of our case.
In conclusion, we must emphasize the need to recognize this variant of EMC with its aggressive behavior, which may be a reason to redirect surgeons to wide local excision of tumor.

Figure 2 .
Figure 2. Ductal formations in the classical EMC component (thick arrow) and proliferation of solidly arranged cells in the high grade component (thin arrow) (H&E, 100x)