MAML2 Rearrangements in Thymic Mucoepidermoid Carcinomas
Anja C Roden, Michele Erickson-Johnson, Eunhee S Yi, Joaquin J Garcia. Mayo Clinic, Rochester, MN
Background: Mucoepidermoid carcinoma (MEC) is a rare histologic subtype of thymic carcinoma and composed of epidermoid, intermediate and mucous cells. High grade MECs mainly consist of the epidermoid component and could be challenging to differentiate from squamous cell carcinoma. Substantial evidence from several anatomic sites including lung and head and neck has demonstrated a strong association between MEC and t(11;19)(q21;p13). The most common genes involved in this translocation are Mucoepidermoid Carcinoma Translocated 1 (MECT1) on chromosome 19p13 and a member of the MasterMind-Like gene family, MAML2, on chromosome 11q21. Although this translocation is often considered a disease-defining event for MEC, the incidence of this finding in the context of thymic MEC has not been explored. In this study we evaluate the diagnostic utility of detecting MAML2 rearrangement by fluorescence in situ hybridization (FISH) in thymic MEC along with unequivocal examples of squamous cell carcinoma and adenosquamous cell carcinoma cases in order to evaluate its role in diagnosis and in understanding molecular pathogenesis.
Design: FISH was employed to detect MAML2 rearrangements using a MAML2 - 11q21 break apart probe (BAP) that consisted of bacterial artificial chromosomes (BAC) flanking the 5' and 3' sides of MAML2. 5' BACs were labeled in SpectrumOrange and consisted of RP11-1056O10, CTD-2325K3, and RP11-8N17. 3' BACs were labeled in SpectrumGreen and consisted of CTD-2252L1, RP11-123F20, RP11-7D4, and CTD-254417. At least 100 interphase tumor cell nuclei were evaluated per case. Identifying a split signal in more than 10% of tumor cells was considered positive.
Results: FISH for MAML2 rearrangement was performed on low and intermediate-grade thymic MEC (n=1, each), poorly differentiated thymic squamous cell carcinoma (n=7) and thymic adenosquamous cell carcinoma (n=1). The two cases of low and intermediate-grade thymic MEC (38 yo male, 4.0 cm tumor; 68 yo female, 8.0 cm tumor, respectively) were positive for MAML2 rearrangement. All other tested cases were negative.
Conclusions: FISH for MAML2 rearrangement is likely a useful tool in the evaluation of thymic malignancies; specifically, distinguishing MEC from squamous cell carcinoma and adenosquamous cell carcinoma. These findings suggest that thymic MEC are not only histologically but also biologically related to MECs of the head & neck. Larger studies of thymic MEC are necessary to confirm our findings and to assess whether MAML2 translocation status bears prognostic significance as well.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 289, Wednesday Afternoon