Primary thymic mucoepidermoid carcinoma with positive MAML2 gene rearrangement: a case report

Introduction

Thymic mucoepidermoid carcinoma (MEC) is an extremely rare malignant tumor, first reported in 1982 (1). It predominantly occurs in patients aged over 50 years, with a slight male predominance. Most cases are incidentally detected and present with no obvious symptoms, although some patients may present with chest tightness, chest pain, or shortness of breath, accompanied by systemic symptoms such as fever and weight loss (2).

Imaging studies typically reveal well-circumscribed cystic-solid masses with heterogeneous density, some of which show invasive features. Diagnosis primarily relies on histopathological examination, which demonstrates three characteristic cell types: mucous cells, intermediate cells, and epidermoid cells. According to the 2015 classification criteria of the World Health Organization (WHO), thymic MEC can be divided into low- and high-grade tumors. Low-grade tumors grow slowly with frequent cystic changes and mild cellular atypia, while high-grade tumors are predominantly solid with infiltrative growth and marked cellular atypia (3,4). Tumor grading plays a crucial role in prognosis assessment and treatment selection. We present a surgical case with a favorable prognosis to supplement this description. We present this article in accordance with the CARE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-1-591/rc).

Case presentation

A 28-year-old male, with no history of smoking or alcohol use, underwent chest computed tomography (CT) during a physical examination in 2022, revealing a right anterior mediastinal mass measuring approximately 60 mm × 11 mm. The patient was asymptomatic, and follow-up imaging was recommended. In 2023, a follow-up CT showed a slight increase in the size of the mass. A contrast-enhanced CT in August 2023 revealed a rounded, cystic-solid mass in the right anterior mediastinum, measuring approximately 61 mm × 32 mm, with mild peripheral enhancement. Magnetic resonance imaging (MRI) confirmed a predominantly cystic mass with multiple cystic lesions, totaling approximately 61 mm × 32 mm (Figure 1). Following preoperative evaluation, the patient underwent right anterior mediastinal tumor resection via single-port thoracoscopic-assisted surgery under general anesthesia in September 2023. Postoperative recovery was uneventful, and the patient was discharged on postoperative day 3. All procedures performed in this case were in accordance with the ethical standards of the Ethics Committee of The First Affiliated Hospital of Guangzhou Medical University (approval No. ES-2024-186-01) and with the Helsinki Declaration and its subsequent amendments. Oral informed consent was obtained from the patient for publication of this case report and accompanying images.

Figure 1 Imaging findings. (A,B) CT images demonstrate a round cystic-solid mass located on the right side of the anterior mediastinum midline. The lesion measures approximately 61 mm × 32 mm in its largest cross-section, with a well-defined boundary and regular shape indicated by the red arrows. (C,D) MRI images with red arrows indicate a primarily cystic round mass on the right side of the anterior mediastinum midline, exhibiting multiple cystic lesions with fusion changes. (E,F) CT images from the 1-year postoperative follow-up show no evidence of recurrence. CT, computed tomography; MRI, magnetic resonance imaging.

Postoperative pathology

Gross pathology showed a grayish-white to grayish-red anterior mediastinal mass, measuring approximately 8 cm × 7 cm × 2.5 cm, with a smooth, intact capsule. Sectioning revealed a multilocular cystic-solid structure measuring approximately 6.1 cm × 3.4 cm × 2.1 cm, containing dark brown material. The solid area appeared gray-yellow and firm. Microscopic examination indicated a low-grade primary MEC of the thymus, characterized by cystic changes. Cholesterol crystals and foreign body giant cell reactions were present in the cyst walls, and no vascular or nerve invasion was observed. Immunohistochemistry showed positivity for epithelial membrane antigen (EMA), cytokeratin (CK)19, p63/S-100, CK7, and cluster of differentiation (CD)5 (Figure 2), and negativity for carcinoembryonic antigen (CEA), glial fibrillary acidic protein (GFAP), and calponin. Ki-67 was approximately 5% positive, but other markers [thyroid transcription factor-1 (TTF-1), Napsin A, CK20, caudal type homeobox 2 (CDX2), Villin, and CD117] were negative. Special staining showed positivity for mucicarmine and Alcian blue (AB)-periodic acid-Schiff (PAS). The fluorescence in situ hybridization (FISH) analysis confirmed a mastermind-like transcriptional coactivator 2 (MAML2) gene rearrangement (Figure 3). The patient has been followed for over 1 year (Figure 1), with no recurrence or metastasis observed.

Figure 2 Immunohistochemical findings. Immunohistochemical results indicated positive staining for EMA, CK7, CK19, p63, CD5, and Ki-67 (immunohistochemical staining). Scale bar: 100 µm. CD, cluster of differentiation; CK, cytokeratin; EMA, epithelial membrane antigen.

Figure 3 Pathological findings. (A) Gross specimen of the surgically resected anterior mediastinal tumor, with a smooth and intact capsule surface; upon sectioning, a multilocular cystic-solid structure was observed, with dark brown contents in the cystic cavity and a grayish-yellow, firm texture in the solid area. (B,C) H&E staining showed cystic degeneration with a large amount of cholesterol crystal formation in the cyst wall, accompanied by a foreign body giant cell reaction; there was no evidence of vascular tumor thrombi or nerve bundle invasion [(B) scale bar: 100 µm; (C) scale bar: 50 µm]. (D,E) AB-PAS staining was positive, indicating intracellular mucin [(D) scale bar: 50 µm; (E) scale bar: 50 µm]. (F) FISH genetic testing showed the result for the MAML2 gene break-apart test was positive (scale bar: 50 µm). AB, Alcian blue; FISH, fluorescence in situ hybridization; H&E, hematoxylin and eosin; MAML2, mastermind-like transcriptional coactivator 2; PAS, periodic acid-Schiff.

Discussion

Clauditz et al. reported that MECs in the salivary glands, lungs, and other sites are strongly associated with recurrent t(11;19)(q21;p13) translocation (5). The translocation involves MEC translocated 1 (MECT1), located on 19p13, and MAML2, located on 11q21, which act on the Notch pathway (6). The resulting CRCT1-MAML2 fusion protein affects the Notch signaling pathway by activating cAMP/CREB transcription, inhibiting Notch and CREB signaling, and promoting tumorigenesis (7). The pathogenesis of thymic MEC remains unclear; however, in 2013, Roden et al. (8) first identified the MAML2 rearrangement in thymic MEC, noting that the MAML2 rearrangement is exclusive to thymic MEC and is not observed in moderately or poorly differentiated adenosquamous carcinoma, which suggests that the MAML2 rearrangement may help distinguish thymic MEC from squamous cell carcinoma and adenosquamous carcinoma (9). CRCT1-MAML2 gene fusion plays an essential role in the tumorigenesis of thymic MEC. However, not all thymic MECs exhibit the MAML2 rearrangement. Murase et al. examined 16 thymic MEC cases using FISH, of which 56% showed t(11;19)(q21;p13) CRCT1-MAML2 gene fusion (10). Additionally, YAP1-MAML2 and KMTP2A-MAML2 fusions detected in thymomas were negative in thymic MEC, providing a basis for distinguishing between thymic MEC and thymoma (11,12). The 2022 5^th edition of the WHO Classification of Head and Neck Tumors established the MAML2 rearrangement as a necessary criterion for diagnosing MEC (13).

Due to the rarity of thymic MEC, much of the literature consists of case reports, and no standardized treatment protocol exists. Surgical resection, including local lymph node removal, is the primary treatment for MEC. Mortality generally arises from local invasion or distant metastasis. Murase et al. reported a favorable prognosis in patients with CRCT1-MAML2 fusion, which was correlated with a lower primary tumor classification and tumor-node-metastasis stage, and no deaths during follow-up. In one case, a late-stage fusion-positive patient remained recurrence-free for 120 months post-resection without adjuvant therapy, underscoring the potential role of MAML2 status in treatment decisions (10). For high-grade or recurrent thymic MEC, radiotherapy and chemotherapy are recommended. Early chemo-radiotherapy may improve both the survival and quality of life of MEC patients.

Conclusions

In conclusion, this report detailed a rare case of primary thymic MEC, which lacked specific clinical or imaging features and required histopathology, immunohistochemistry, and molecular testing for diagnosis. MAML2 rearrangement is associated with a better prognosis, while high-grade and recurrent cases may be linked to poorer outcomes. Further research is required to clarify the pathogenesis of the disease and refine treatment approaches.

Acknowledgments

We thank the patient who participated in this study, as well as their family.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-1-591/rc

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-1-591/prf

Funding: This work was supported by the Joint Funds for the Guangdong Basic and Applied Basic Research Foundation, Guangdong Province (No. 2020A1515011293).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-1-591/coif). All authors report that this study was supported by the Joint Funds for the Guangdong Basic and Applied Basic Research Foundation, Guangdong Province (No. 2020A1515011293). The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this case were in accordance with the ethical standards of the Ethics Committee of The First Affiliated Hospital of Guangzhou Medical University (approval No. ES-2024-186-01) and with the Helsinki Declaration and its subsequent amendments. Oral informed consent was obtained from the patient for publication of this case report and accompanying images.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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(English Language Editor: L. Huleatt)