Reevaluation of Salivary Lymphadenoma: A Subgroup Identified as Warthin-like Mucoepidermoid Carcinoma Following Molecular Investigation for MAML2 Rearrangement

Abstract

Context.— Both salivary lymphadenomas (LADs) and Warthin-like mucoepidermoid carcinoma (MEC) contain components of epithelium and lymphoid stroma and their differential diagnosis can be difficult on the basis of morphology alone. Objective.— To clarify whether Warthin-like MEC was diagnosed as a LAD, and to compare their clinicopathologic features. Design.— A total of 16 LAD cases were analyzed for MAML2 rearrangement by using fluorescence in situ hybridization, and the clinical, histologic, immunohistochemical, and prognostic features were compared between MAML2 rearrangement–positive and MAML2 rearrangement–negative groups. Results.— Among the 16 cases investigated, 9 harbored a MAML2 rearrangement and were reclassified as Warthin-like MEC. The remaining 7 cases were classified as LADs with 1 nonsebaceous and 6 sebaceous cases. The patients with Warthin-like MEC had a wider age range (10–75 years) than the patients with LADs (36–68 years). Histologically, 2 of the 9 Warthin-like MECs (22.2%) showed focal invasion, whereas all the LADs had complete capsules. Warthin-like MECs exhibited a diverse epithelial cell morphology, including basaloid, glandular, cuboidal, epidermoid, with mucinous cells, although these cytologic features were seen only focally in some cases. Nonsebaceous LAD was composed of basaloid and glandular epithelial cells predominantly. In sebaceous LAD, the epithelial cells were composed of basaloid and large foamy sebaceous cells. In all cases, the stroma was composed mainly of lymphocytes accompanied by lymphoid follicles, although plasma cell infiltration could be much heavier in Warthin-like MEC. All the patients had a good outcome after a longer follow-up (3∼166 months). Conclusions.— Warthin-like MEC can be misdiagnosed as a LAD owing to overlap in clinicopathologic features of the 2 entities. Careful histologic evaluation and detection of MAML2 rearrangement can facilitate their differential diagnosis.

Warthin-Like Mucoepidermoid Carcinoma: A Morphological Spectrum – A Report of 3 Cases with Histological and Cytological Findings and Review of the Literature

“…Undoubtedly, MAML2 is the most important marker in the diagnosis of WL-MECs [1, 5-9, 11-18, 20-22]. Although cases of WT showing MAML2 rearrangement have been proposed [14, 23], these reports are not well accepted, may be because the histological features of these tumors have not been clearly defined [12, 14, 18, 23].…”

“…WL-MEC is more common in women and shows a younger age distribution than WT [7, 9, 19]. Its recognition is important clinicopathologically not only for correct identification of a malignant tumor but also to avoid aggressive treatment [7, 8].…”

“…Differential diagnosis of WL-MEC should include WT with mucinous and squamous metaplasia [1, 8, 15], lymphoepithelial cyst [4], and nonsebaceous lymphadenoma. Zang et al [9] evaluated MAML2 in 16 lymphadenoma cases and accepted 9 positive cases as WL-MEC. WTs with prominent squamous metaplasia [1] and some mucinous cells are at risk of being diagnosed as WL-MEC.…”

“…On the other hand, if oncocytic epithelium is not seen, the cytological diagnosis of WT should be avoided, where only squamoid epithelium and lymphoid cells on a cystic background are observed. In this scenario, the differential diagnosis will include lymphadenoma and other non-neoplastic and benign salivary gland lesions, such as lymphoepithelial cyst, in addition to WL-MEC if squamoid/oncocytoid differentiation is not clear [4, 9]. Due to the predominant cystic character of WL-MECs, the frequency of nonrepresentative sampling on FNA will be similar to that of WT and low-grade MECs.…”

“…The categorization of WL-MEC cases in the Milan System for Reporting Salivary Gland Cytology will change depending on where the case is standing morphologically and how adequately it is sampled. The cytological samples from WL-MECs may fall into each category; however, if the material is representative enough and contains few mucinous cells, it should be categorized at least as “salivary gland neoplasm of uncertain malignant potential-oncocytic/oncocytoid type” or “suspicious for malignancy.” Evaluation of MAML2 rearrangement in doubtful cases is of paramount importance, and the presence of mucinous/goblet-like cells in any combination should be alarming for WL-MEC [1, 4, 8, 9, 15, 16, 19].…”