Lymphoepithelial carcinoma in the body of the tongue: The rst case report

Lymphoepithelial carcinoma (LEC) of the tongue is a rare subtype of squamous cell carcinoma. Histologically, it is an undifferentiated carcinoma with rich lymphocyte and plasma cell inltration. The most common location for LEC in the head and neck is the salivary glands, and LEC of the oral cavity is extremely rare 1 . The rst case report of LEC in the body of the tongue is presented. In addition, a review of the literature was performed, and the relationship between LEC and Epstein-Barr virus infection was considered.


Introduction
Lymphoepithelial carcinoma (LEC) is a squamous cell carcinoma morphologically similar to nonkeratinizing nasopharyngeal carcinoma, undifferentiated subtype 1  HNLEC is a tumor diagnosed most commonly in the salivary glands, and only 17 cases in the oral cavity appear to have been reported so far. To the best of our knowledge, no case of LEC in the body of the tongue has been reported in the English literature. A case of LEC in the body of the tongue is presented, along with a review of the literature on oral LEC and a discussion of the relationship between oral LEC and EBV infection.

Case Report
An 82-year-old man with a previous history of alcohol and tobacco use and esophageal cancer 8 years earlier noticed a mass on the left edge of the tongue. Malignancy was suspected on examination of a biopsy specimen, and he was referred to our hospital. On clinical examination, a hard, slightly bulging mass with a smooth surface, approximately 2 × 1 cm 2 , was found (Fig. 1). The tumor was localized in the posterior edge of the left side of the tongue, and there was no cervical lymph node enlargement on computed tomography (CT) (Fig. 2). The nasal cavity, nasopharynx, and larynx appeared normal on endoscopy. The tumor was resected, and macroscopically, the excised tumor was a pale yellowish, solid mass, 1.7 × 1.0 × 1.2 cm 3 in size (Fig. 3). Histologically, the tumor cells showed proliferation of pale staining, cohesive epithelial cells with prominent surrounding and in ltrating lymphocytes (Fig. 4). The tumor cells contained large round vesicular nuclei with prominent nucleoli. On immunohistochemistry, the tumor cells were positive for cytokeratin AE1/AE3, p40, and p53. On in situ hybridization, the epithelial cells were negative for EBV-encoded small RNA (EBER) (Fig. 5). The diagnosis of LEC was made. After surgery, no recurrence was observed at the 7-month follow-up visit.

Discussion
LEC is a subset of poorly differentiated squamous cell carcinoma with intermingled lymphocytes. LEC outside of the nasopharynx is rare, and only 17 cases of oral LEC have been reported (Table 1). Oral LEC developed commonly in the minor salivary gland, lip, and palate. This is the rst report of LEC arising in the body of the tongue. The age of patients ranged from 11 to 82 years (average 55.5 years), and there was no sex predilection. All tumors were within 3 cm (range: 0.5 to 2.6 cm) in size. Six patients (37.5%) had metastases to the cervical lymph nodes. Although one patient who refused treatment died of tumor 34 months after diagnosis, the prognosis of patients with oral LEC was excellent.
Histologically, the present case showed proliferation of non-keratinized epithelial cells with massive in ltration of lymphocytes. On immunohistochemical examination, tumor cells were diffusely positive for cytokeratin AE1/AE3 and p40. These results con rm the character of the tumor cells as squamous epithelium.
Previous reports showed an association between EBV and oral LEC, especially in Asian cases. Of the 11 Asian cases, 9 were positive. In contrast, no cases in North and South America, Europe, and Africa showed an association with EBV. In the present case, the tumor cells were negative on EBER in situ hybridization.
The tumor cells of the present case showed overexpression of p53. This nding suggests that mutation of TP53 may play a key role in carcinogenesis of this tumor. In the previous studies, p53 status was studied in only 2 cases. One case with EBV showed p53 expression in only 25% of the tumor cells, suggesting wild type 3 . In contrast, one EBV-negative LEC showed overexpression of p53 on immunohistochemistry 4 . Although the number of cases is limited, there may be different mechanisms of tumorigenesis in oral LEC.
Lymph node metastasis was present in 6 of 18 cases, and it was more common in EBV-positive cases.
The EBV status of oral LEC may have some role in nodal metastasis.
In conclusion, the rst case of LEC in the body of the tongue was presented. This EBV-negative case might have been caused by TP53 mutation, another possible mechanism of tumorigenesis of oral LEC. To identify prognostic factors, study of additional cases is needed.

Declarations
Ethics approval and consent to participate Not applicable.