Lymphoepithelial Carcinoma of Salivary Gland EBV-association in Endemic versus Non-Endemic Patients: A Report of 16 Cases

Abstract

Lymphoepithelial carcinoma of salivary glands (LECSG) are rare neoplasms, reported in endemic populations (southeastern Chinese) with a strong Epstein-Barr virus (EBV) association. A retrospective series comparing EBV status within an ethnically diverse population (endemic vs. non-endemic patients) has not been reported. Sixteen LECSG were equally distributed between males (n = 8) and females (n = 8) with a median age of 54 years (range 18 to 85 years) at initial diagnosis. Ten patients were white, 4 Asian, and 2 black. The patients typically presented with swelling or mass for an average of 11.6 months. Tumors affected only major salivary glands: parotid (n = 13); submandibular (n = 3). Tumors were an average of 2.9 cm (range 1.5 to 5.8 cm). Nine of 16 (56%) patients had cervical lymph node metastases at presentation. No patients had nasopharyngeal or oropharyngeal tumors. Microscopically, the tumors were widely infiltrative, characterized by large polygonal to spindled cells arranged in a syncytial, lattice-like network in a background of lymphoplasmacytic cells. The neoplastic cells showed an open-vesicular nuclear chromatin to a more basaloid-morphology, the latter showing hyperchromatic nuclei and less cytoplasm, while nearly all of the cases had associated lymphoepithelial lesions/sialadenitis. By in situ hybridization, 8 of 16 cases had a strong, diffuse EBER expression (4 of 4 Asians; 4 of 12 non-Asians), while with immunohistochemistry all cases tested were pan-cytokeratin, CK5/6 and p63 reactive; none of the cases tested were p16 reactive. All patients were managed with wide or radical excision, 4 with concurrent chemoradiation, and 6 with radiation alone. Distant metastasis (lung, brain, and bone) developed in 2 patients. Overall follow-up (mean 3.8 years) revealed 12 patients alive and 2 dead, none with evidence of disease (mean 4.3 years); one white male alive with disease at 1.9 years, and one Asian female dead of disease at 4.2 years; both of these latter patients had Group IV stage disease. High stage (Group IV) patients had a shorter mean survival than lower stage patients: 3.1 versus 4.8 years, respectively. In conclusion, LECSG are uncommon primary neoplasms. Concurrent lymphoepithelial lesions may help suggest a primary tumor. The tumors, irrespective of race or ethnicity, may express EBER. There is an overall good survival, perhaps better for EBV-negative patients and for those with lower stage disease.

Keywords: EBER; Ethnic groups; Immunohistochemistry; Lymphoepithelial carcinoma; Salivary glands.

Fig. 1

a A left parotid gland well defined hyperintense mass (arrow) on T2 weighted coronal MR, fat suppressed image. b There is a fish-flesh pale cut surface to a mass replacing much of the parotid gland

Fig. 2

a Broad sheets and nests of neoplastic cells invade into the parotid gland as large islands (10x). b Smaller islands of epithelial cells associated with sclerosis and tumor necrosis (20x). c Infiltration of the neoplastic cells into the adjacent adipose tissue (100x). d Perineural invasion by the neoplastic cells (400x)

Fig. 3

a Squamous metaplasia of a duct, with an associated lymphoepithelial lesion showing an intimate relationship between the lymphoid elements and the epithelium, but without atypia (400x). b Numerous foreign-body type giant cells are seen at the advancing edge of the tumor, representing a granulomatous reaction (400x)

Fig. 4

a The neoplastic cells are difficult to identify as they blend with the lymphoid stroma (400x). b Islands of interconnecting neoplastic cells (200x). c A sheet-like distribution of syncytial neoplastic cells (400x). d A jigsaw puzzle-like architecture with prominent sclerotic stroma (100x)

Fig. 5

a Syncytium of pleomorphic cells with high nuclear to cytoplasmic ratio (400x). b Focal areas of squamous differentiation and adjacent tumor necrosis (400x). c Pleomorphic tumor cells showing prominent nucleoli within vesicular nuclei (400x). d Tumor cell spindling was noted in a few cases (400x)

Fig. 6

a There is a strong, diffuse, membranous and cytoplasmic reaction with CK5/6 (100x). b There is a wispy, lattice-like cytoplasmic reaction with AE1/AE3 (400x). c The nuclei of the neoplastic cells are strongly reactive with p63 (400x). d A strong, diffuse, nuclear reaction in all of the neoplastic epithelial cells with EBER ISH (200x)