Epithelial-myoepithelial carcinoma of salivary gland

Epithelial-myoepithelial carcinomas are uncommon low grade carcinomas of salivary glands are composed in varying portions of ductal cells and clear myoepithelial cells. They may be placed on the spectrum between pure epithelial clear cell carcinoma and pure myoepithelial clear cell carcinoma. They are probably related to adenoid cystic carcinoma as so-called "hybrid" carcinomas. Epithelial-myoepithelial carcinomas constituted 1.1% of all epithelial salivary gland tumours reviewed by the AFIP2.

Synonyms

Prior to the description by Donath in 197214, such tumours were variously reported as adenomyoepithelioma, clear cell adenoma, tubular solid adenoma, monomorphic clear cell tumour, glycogen-rich adenoma, glycogen-rich carcinoma, and clear cell carcinoma.

Epidemiology

Most series show a female predominance of 2:1.

Clinical features

This is usually a tumour of the parotid gland4. Rare sites include submandibular gland10, palate13, sinonasal tract5,8, larynx9, trachea, bronchus7 and lung6 , breast and lacrimal gland.

Macroscopic appearance

The tumour is well circumscribed and may be encapsulated13. Some are multinodular13. Less often, the tumour is infiltrative13. It is usually grey-white to tan-white. Haemorrhage and necrosis are uncommon. Some tumours are cystic13.

Histopathology

There is a dual population of ductal and myoepithelial cells. In some cases, the ductal component is sparse4. The ductal cells have eosinophilic cytoplasm and uniform round nuclei. The ducts may contain PAS-positive, mucicarmine-negative eosinophilic proteinaceous material, which may form calcific deposits13. In some cases, the epithelial cells are clear columnar or mucinous, or show squamous or sebaceous metaplasia13.

The ductal cells are surrounded by large polygonal clear cells containing large amounts of glycogen. The clear cells may sometimes by spindled. A spindle cell myoepithelial component may show "Verocay" palisading of nuclei or "ancient" nuclear change13. Aggregates of cells are often surrounded by hyalinised basement membrane, giving an organoid pattern. When cysts are present, papillary epithelial projections into the cysts are seen. Perineural or angiolymphatic invasion is sometimes seen4,13. In 20% of cases, the myoepithelial cells lack clearing of the cytoplasm15.

Nuclear atypia is variable, usually mild to moderate. Mitoses are present, particularly in the myoepithelial component13.

Variants:

• An oncocytic variant, with oncocytic epithelial or myoepithelial cells, has been described13. The tubules are larger than those of typical epithelial-myoepithelial carcinomas and there may be papillary growth. Sebaceous differentiation is common. Pagetoid spread into an excretory duct has been reported.

• Double clear epithelial-myoepithelial carcinoma has both clear epithelial and clear myoepithelial cell components. The epithelial component predominates, with large calibre ducts and may be cribriform or solid. They tend to show intraluminal calcification and pagetoid spread13.

• Rarely, epithelial-myoepithelial carcinomas arises ex pleomorphic adenoma.

• Rare high grade or dedifferentiated epithelial-myoepithelial carcinomas occur13. The dedifferentiated component makes up a variable proportion of the tumour. These areas have mitotic rates of about 10/10HPF in the epithelial component, lower in the myoepithelial cells. There may be extensive necrosis.

• Epithelial-myoepithelial carcinoma with myoepithelial anaplasia shows predominance of the myoepithelial component, with areas of severe nuclear atypia arising by gradual transition from the typical myoepithelial component and accounting for more than 20% of the myoepithelial cells15.

• Epithelial-myoepithelial carcinoma with ancient change: there are scattered enlarged hyperchromatic nuclei with smudged chromatin, against a background of non-bizarre nuclei and with a low mitotic rate, distinguishing it from dedifferentiated epithelial-myoepithelial carcinomas.

Immunohistochemistry

Ultrastructure

Confirms the dual population12 with a myoepithelial cell component11.

Differential diagnosis

Encapsulated / minimally invasive epithelial-myoepithelial carcinoma:

• • Pleomorphic adenoma: shows myxochondroid stroma not seen in epithelial-myoepithelial tumours. The myoepithelial cells are not large and optically clear.

• Hyalinising clear cell carcinoma: occurs in minor salivary glands and lacks ductal or myoepithelial differentiation

• Mucoepidermoid carcinoma: lacks a biphasic pattern

• Acinic cell tumour: lacks a biphasic pattern

• Adenoid cystic carcinoma: bcl-2 and CD117 are not useful in this differential.

Oncocytic variant:

• • Oncocytoma, which lacks a biphasic pattern

  • Oncocytic papillary cystadenoma / cystadenocarcinoma

• Metastatic renal cell carcinoma: lacks a biphasic pattern

Prognosis

Five and ten year disease-free survival of 94% and 82% have been reported13. There is a 30-50% local recurrence rate3,4,13. with a median disease free interval of 11.3 years13. Recurrence and metastases may occur more than 20 years after first presentation. Metastases to local lymph nodes are seen in 18% of cases and distal metastases to lung, kidney and brain in 8% of cases, resulting in a similar mortality rate. Nuclear atypia in more than 20% of cells3, necrosis13, positive margins13, angiolymphatic invasion13 and aneuploidy3 may indicate a worse prognosis. Dedifferentiated epithelial-myoepithelial carcinoma has a poor prognosis15.

References

Diagnostic histopathology of tumors. Edited by CDM Fletcher. 2nd edition. Churchill Livingstone. Page 277.

1 Perez-Ordonez B. Selected topics in salivary gland tumour pathology. Current Diagnostic Pathology 2003;9:355-365.

2 Eliis GL, Auclair PL. Malignant epithelial tumours in: Tumors of the Salivary Glands. Armed Forces Institute of Pathology, Washington DC. Atlas of Tumor Pathology, 3rd Edition, 1996;15-373.

3 Fonseca, I. and J. Soares (1993). "Epithelial-myoepithelial carcinoma of the salivary glands. A study of 22 cases." Virchows Arch A Pathol Anat Histopathol 422(5): 389-96.

4 Brocheriou, C., M. Auriol, et al. (1991). "[Epithelial-myoepithelial carcinoma of the salivary glands. Study of 15 cases and review of the literature]." Ann Pathol 11(5-6): 316-25.

5 Harada, H., S. I. Kashiwagi, et al. (1996). "Epithelial-myoepithelial carcinoma--report of a case arising in the nasal cavity." J Laryngol Otol 110(4): 397-400.

6 Wilson, R. W. and C. A. Moran (1997). "Epithelial-myoepithelial carcinoma of the lung: immunohistochemical and ultrastructural observations and review of the literature." Hum Pathol 28(5): 631-5.

7 Ryska, A., Z. Kerekes, et al. (1998). "Epithelial-myoepithelial carcinoma of the bronchus." Pathol Res Pract 194(6): 431-5; discussion 436-8.

8 Jin, X. L., C. N. Ding, et al. (1999). "Epithelial-myoepithelial carcinoma arising in the nasal cavity: a case report and review of literature." Pathology 31(2): 148-51.

9 Mikaelian, D. O., R. B. Contrucci, et al. (1986). "Epithelial-myoepithelial carcinoma of the subglottic region: a case presentation and review of the literature." Otolaryngol Head Neck Surg 95(1): 104-6.

10 Simpson, R. H., T. J. Clarke, et al. (1991). "Epithelial-myoepithelial carcinoma of salivary glands." J Clin Pathol 44(5): 419-23.

11 Luna, M. A., N. G. Ordonez, et al. (1985). "Salivary epithelial-myoepithelial carcinomas of intercalated ducts: a clinical, electron microscopic, and immunocytochemical study." Oral Surg Oral Med Oral Pathol 59(5): 482-90.

12 Corio, R. L., J. J. Sciubba, et al. (1982). "Epithelial-myoepithelial carcinoma of intercalated duct origin. A clinicopathologic and ultrastructural assessment of sixteen cases." Oral Surg Oral Med Oral Pathol 53(3): 280-7.

13 Seethala RR, Barnes EL,Hunt JL Epithelial-myoepithelial carcinoma: a review of the clinicopathologic spectrum and immunophenotypic characteristics in 61 tumors of the salivary glands and upper aerodigestive tract. Am J Surg Pathol 2007; 31:44-57

14 Donath K, Seifert G,Schmitz R [Diagnosis and ultrastructure of the tubular carcinoma of salivary gland ducts. Epithelial-myoepithelial carcinoma of the intercalated ducts]. Virchows Arch A Pathol Pathol Anat 1972; 356:16-31

15 Cheuk W,Chan JK. Advances in salivary gland pathology. Histopathology 2007; 51:1-20

16 Meer S,Altini M. CK7+/CK20- immunoexpression profile is typical of salivary gland neoplasia. Histopathology 2007; 51:26-32

This page last revised 4.8.2007.

©SMUHT/PW Bishop