MAML2 Rearrangements in Variant Forms of Mucoepidermoid Carcinoma

Abstract

Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy. Recent studies have shown that most MECs harbor gene fusions involving MAML2-an alteration that appears to be specific for MEC, a finding that could be diagnostically useful. While most cases of MEC are histologically straightforward, uncommon variants can cause considerable diagnostic difficulty. We present 2 variants of MEC for which MAML2 studies were crucial in establishing a diagnosis: a previously undescribed ciliated variant, and the recently described Warthin-like variant. All cases of ciliated and Warthin-like MEC were retrieved from the archives of The Johns Hopkins Hospital. Break-apart fluorescence in situ hybridization for MAML2 was performed on all cases. One ciliated MEC and 6 Warthin-like MECs were identified. The ciliated MEC presented as a 4.6 cm cystic lymph node metastasis originating from the tongue base in a 47-year-old woman. The Warthin-like MECs presented as parotid masses ranging in size from 1.2 to 3.3 (mean, 2.7 cm) in 4 women and 2 men. The ciliated MEC consisted of macrocystic spaces punctuated by tubulopapillary proliferations of squamoid cells and ciliated columnar cells. The Warthin-like MECs were comprised of cystic spaces lined by multilayered oncocytic to squamoid cells surrounded by a circumscribed cuff of lymphoid tissue with germinal centers. In these cases, the Warthin-like areas dominated the histologic picture. Conventional MEC, when present, represented a minor tumor component. MAML2 rearrangements were identified in all cases. Warthin-like MEC, and now a ciliated form of MEC, are newly described variants of a common salivary gland carcinoma. Unfamiliarity with these novel forms, unanticipated cellular features (eg, cilia), and morphologic overlap with mundane benign processes (eg, developmental ciliated cysts, Warthin tumor) or other carcinomas (eg, ciliated human papillomavirus-related carcinoma) may render these variants susceptible to misdiagnosis. These unusual variants appear to consistently harbor MAML2 fusions-a finding that establishes a clear link to conventional MEC and provides a valuable adjunct in establishing the diagnosis.

ATAC-Seq identifies regions of open chromatin in the bronchial lymph nodes of dairy calves experimentally challenged with bovine respiratory syncytial virus

“…These positional candidate genes are associated with various diseases or immune related functions. RDH14 is involved in retinol metabolism [ 43 ], increased expression of BAALC has been implicated in myeloid leukemogenesis [ 44 ], mutations in AZIN1 are associated with the progression of liver fibrosis during hepatitis C infection [ 45 ], DST is involved in the transport of herpes simplex virus 1 capsids to the nucleus of the host cell [ 46 ] and MAML2 is associated with risk of mucoepidermoid carcinoma [ 47 ].…”

MAML2 rearrangement as a useful diagnostic marker discriminating between Warthin tumour and Warthin-like mucoepidermoid carcinoma

“…Only newly reported cases of MEC with Warthin-like morphology were included in the analysis; thus, 7 studies reporting 20 cases were included (Table 1 [8][9][10][11][12][13][14]). Similarly, the PubMed database was searched using "Warthin MAML2" and "Warthin t(11;19)" queries (performed on 6 February 2019); subsequently, the reference lists of the included studies were also searched for further articles.…”

“…Originally, García et al reported a series of 12 oncocytic MECs in 2011 [8]. Among these, 5 were described as having Warthin-like histology (all such cases reported to date are summarized in Table 1 [8][9][10][11][12][13][14]) and harboured a mastermindlike transcriptional coactivator 2 (MAML2) rearrangement. This alteration occurs in > 50% of MECs and correlates with low-/intermediate-grade histology and a better prognosis [15].…”

“…Histopathological features are usually sufficient to obtain the definitive diagnosis; however, recently, Akaev et al reported a case of MEC with tumour-associated lymphoid proliferation indistinguishable from benign WT by histology and immunohistochemistry [13]. To date, all reported cases of Warthin-like MEC have been associated with MAML2 rearrangements; thus, the molecular test may provide the definitive answer [12]. On the other hand, it is still unclear whether "classic" WT may exceptionally harbour such translocations.…”

Effects of the MAML2 genetic variants in glioma susceptibility and prognosis

“…NOTCH signaling activation has been demonstrated to be involved in carcinogenesis, which plays a critical role in cell proliferation, metastasis and epithelial–mesenchymal transition in many diverse solid tumors including glioma [9,10]. Several studies have demonstrated MAML2 abnormal expression in various cancers, such as mucoepidermoid carcinoma, hidradenoma and breast cancer [11–13]. These studies have suggested that MAML2 might be involved in the tumorigenesis and progression of cancers.…”