Residency Program - Case of the Month

Answer

Lymphoepithelial carcinoma

Discussion

Lymphoepithelial carcinomas are rare, and comprise 0.4% of salivary gland carcinomas¹. They are morphologically similar to nasopharyngeal carcinoma (the undifferentiated, nonkeratinizing subtype), but occur outside of the nasopharynx. According to the WHO (2005) Pathology of Head and Neck Tumors, lymphoepithelial carcinoma is a malignant epithelial tumor of the nasal cavity and paranasal sinuses that can be defined as “a poorly differentiated squamous cell carcinoma or histologically undifferentiated carcinoma accompanied by a prominent reactive lymphoplasmacytic infiltrate, morphologically similar to nasopharyngeal carcinoma”². Lymphoepithelial carcinoma typically affects adult males (3:1) between the ages of 50-70 most commonly located in Southeast Asia. There is a well-documented association with the Epstein-Barr virus, although the occurrence of EBV positivity is more commonly found in nasopharyngeal carcinoma². Lymphoepithelial carcinoma is most commonly located in the nasal cavity and paranasal sinuses, but can also be found in tonsils, oropharynx, and oral mucosa⁴. Cases occurring in the parotid gland and sublingual gland have also been reported¹.

Clinical features depend on tumor location, and include epistaxis, nasal obstruction, or an indolent mass. When invasion occurs, particularly of the adjacent bony structures, abnormalities of the cranial nerves may also be noted.

Some studies in the literature have found that the presence of metastasis or local invasion depends on the location of the primary tumor. It appears the oral and oropharyngeal LECs have a 70.0% tendency to metastasize and 16.6% tendency spread locally, whereas nasal and paranasal LECs rarely metastasize, but 60% spread locally⁴.

Immunohistochemistry shows positive staining for pancytokeratin markers in the tumor cells. The background inflammatory infiltrate typically shows CD45 positivity.

The differential diagnosis of lymphoepithelial carcinoma includes:

• Sinonasal undifferentiated carcinoma (SNUC): Unlike lymphoepithelial carcinoma, SNUC are characterized by a high mitotic index, frequent necrosis, and nuclear pleomorphism.
• Others: large cell neuroendocrine tumors, malignant melanoma, non-Hodgkin lymphoma, malignant lymphoma, and chronic inflammatory conditions.

Treatment ideally consists of surgical resection with wide local excision in combination with adjuvant radiation and/or chemotherapy. The five year survival rate ranges from 50-90% depending on the degree of local invasion, the presence of metastasis, positive margins, or disease recurrence¹.

References

1. Roy, Moubayed, Ayad. Lymphoepithelial Carcinoma of the Sublingual Gland: Case Report and Review of the Literature. J Oral Maxillofac Surg. 2015 May 8.
2. Barnes, L., Eveson, J.W., Reichart, P., Sidransky, D. Pathology and Genetics of Head and Neck Tumours. Third edition. Who Classification of Tumors, Volume 9. IARC.
3. Wenig.. Lymphoepithelial-like carcinomas of the head and neck. Semin Diagn Pathol. 2015 Jan;32(1):74-86.
4. Rytkönen A, Hirvikoski PP, Salo TA. Lymphoepithelial carcinoma: two case reports and a systematic review of oral and sinonasal cases. Head Neck Pathol. 2011 Dec;5(4):327-34.