NSL is a rare benign tumor occurring most commonly in the salivary glands. The most common location is the parotid gland, and the second is submandibular gland. NSL may also occur in the thymic gland, albeit rarely. Weissferdt et al. documented two cases of sebaceous lymphadenoma in the thymus. In both of their cases, they were able to observe the non-sebaceous differentiation areas. In our this case, NSL was first confirmed in the thymus glands. The histopathological features present in our this case were similar to those described for non-sebaceous lymphadenoma of the salivary glands, mainly the presence of epithelial islands embedded in a lymphoid stroma containing germinal centers. These epithelial islands were distributed in the form of cystic or tubular structures. Besides, we were able to observe normal thymic tissue in the edge of the lesions confirming the tumor origin to thymus. Currently, the diagnostic criteria for NSL in the literature mainly include the following: (1) Solid, glandular, or cystic squamous epithelial nests without significant cytological atypia; (2) no sebaceous differentiation; (3) significant lymphoid infiltrate.
At present, the etiology and pathogenesis of NSL are not fully understood. The lymphocytic markers demonstrated a staining pattern consistent with reactive lymphoid hyperplasia in the stromal background. Some studies have suggested that lymphoid stromal components are lymphoid tissues associated with reactive tumors[1, 3, 16], but the histological origin of the epithelial component of tumors is unclear. Immunohistochemical studies supported the epithelial origin of these structures by showing positive staining for CK, CK18 and CK19. Studies have shown that CK19 is mainly distributed in luminal cells , but this pattern was not evident in our case. In addition, we found that the staining intensity of CK18 was higher in inner cells than outer cells. CK5/6, P63 was present in the periphery of epithelial component. The expression of CK5/6 in our case was the same as in previous studies. CK5/6 and P63 have been shown to be typically expressed in complex epithelial basal cells . These indicates that the epithelial component of the tumor is stratified ductal epithelium. Shaodong Yang et al.called it as “intercalated duct phenotype”. Expression of SMA is a marker of myoepithelial cell differentiation, but was not detected in our case. This suggests that no myoepithelial cells are involved in the tumor epithelium, a conclusion that is consistent with previous studies .
The differential diagnosis the present case included not only other salivary gland lesions, but also thymic epithelial neoplasm. In present case, we can see few mucous-secreting cell in lumen. Therefore, the most important differential diagnosis is mucoepidermoid carcinoma (MEC) among salivary gland-type lesions. Lack of cellular atypia and the presence of prominent lymphocytes containing germinal centers in the stroma set it apart from MEC. Among the thymic epithelial tumors, the most important differential diagnosis is lymphoepithelioma-like carcinoma. The absence of atypical and mitotic activity in the epithelial cells. The absence of invasive growth with desmoplastic stroma, and presence of distinct ductal differentiation in lymphadenoma can distinguish it from lymphoepithelial carcinoma. The second differential diagnosis is squamous cell carcinoma. There are two hallmarks for the diagnosis of thymic squamous cell carcinoma: the clear-cut cytological atypia in the large epithelial cells that are arranged in nests and cords, and the broad zone of fibrohyaline-stroma separating the tumour cell nests. Since this case occurred in the thymus, the thymoma must be retained in the differential diagnosis. In particular, micronodular thymoma with lymphoid stroma may be confused with a thymic lymphadenoma. However, in micronodular thymoma the epithelial nests are solid and do not show tubular or cystic structures. In addition, the epithelial nests in micronodular thymoma are usually formed by spindle cells, while in non-sebaceous lymphadenoma the epithelial nests are commonly of squamous type cells.
Briefly, we showed a rare case of primary thymic non-sebaceous lymphadenoma. To our knowledge, this is the first report case for non-sebaceous lymphadenoma occurred in thymus in the medical literature. So accurate understanding of the histopathologic diagnosis of this rare tumor is important to avoid unnecessary overtreatment.