Porubský, Štefan

Thymic mucoepidermoid carcinoma (MEC) is a rare tumor, and its characteristics remain to be clarified. Here we investigated 20 cases of thymic MEC to systematically characterize its clinical, histopathologic, and molecular features. The median age of the patients was 56 years (range, 19 to 80 y), there was a slight male predilection (3:2), and 44% of the patients were asymptomatic at diagnosis. The median tumor size was 6.8 cm in diameter, 55% were pT1 tumors, and 50% were TNM stage I tumors. When 4 tumor grading systems for salivary MEC (Armed Forces Institutes of Pathology, Brandwein, modified Healey, and the Memorial Sloan-Kettering) were employed, low-grade, intermediate-grade, and high-grade tumors accounted for 35% to 70%, 5% to 25%, and 25% to 50%, respectively. Many histologic variants were noted, and 70% of the cases were classified as nonclassic variants. MAML2 rearrangement was detected in 56% of cases, and the fusion partner was CRTC1 in all cases. CRTC1-MAML2 fusion was associated with lower pT classification and lower TNM stage. The overall survival rate of all patients was 69% and 43% at 5 and 10 years, respectively. Worse overall survival was associated with higher pT stage, higher TNM stage, residual tumors, greater tumor size, high-grade tumor histology (Armed Forces Institutes of Pathology and Memorial Sloan-Kettering, but not the other 2), and with the absence of CRTC1-MAML2 fusion. Of note, none of the patients with CRTC1-MAML2 fusion-positive tumors died during the follow-up. In conclusion, the clinicopathologic and molecular findings of thymic MEC presented here are expected to contribute to the management of this rare tumor.

AimsIn thymic carcinomas, focal clear cell change is a frequent finding. In addition to a prominent, diffuse clear cell morphology, some of these carcinomas show an exuberant hyalinised extracellular matrix, and therefore probably represent a separate entity. However, a characteristic genomic alteration remains elusive. We hypothesised that, analogous to hyalinising clear cell carcinomas of the salivary gland, hyalinising clear cell carcinomas of the thymus might also harbour EWSR1 translocations.Methods and resultsWe identified nine archived cases of thymic carcinoma with focal clear cell features and two cases that showed remarkable hyalinised stroma and prominent, diffuse clear cell morphology. These two cases expressed p40 and were negative for Pax8, CD5, and CD117. Programmed death‐ligand 1 was highly positive in one case (70%), and negative in the other one. EWSR1 translocation was identified in both cases of hyalinising clear cell carcinoma, and was absent in all nine carcinomas that showed clear cell features without substantial hyalinisation. In one of the EWSR1‐translocated cases, a fusion between exon 13 and exon 6 of EWSR1 and ATF1, respectively was identified by next‐generation sequencing.ConclusionsThese findings suggest that the EWSR1 translocation and possibly the EWSR1–ATF1 fusion might be unifying genomic alterations for thymic clear cell carcinomas with prominent hyalinised stroma, for which we propose the term ‘hyalinising clear cell carcinoma of the thymus’. Because the immunophenotype is unspecific, testing for the EWSR1 translocation might be helpful in discriminating this entity from other thymic neoplasms or metastases, in particular those with clear cell change.