Postoperative radiotherapy for T1/2N0M0 mucoepidermoid carcinoma positive for CRTC1/3‐MAML2 fusions

Abstract

Background The National Comprehensive Cancer Network (NCCN) guidelines recommend considering postoperative radiotherapy (PORT) for completely resected T1/2N0M0 salivary mucoepidermoid carcinomas when they show tumor spillage, perineural invasion, or intermediate/high‐grade histology. CRTC1/3‐MAML2 fusions have been associated with a favorable clinical outcome. Methods Forty‐seven T1/2N0M0 mucoepidermoid carcinoma cases positive for CRTC1/3‐MAML2 fusions were completely resected and were not treated with PORT. Results Pathologically, none of the cases showed tumor spillage or perineural invasion. Cases with intermediate/high‐grade histology numbered 9 (19%) to 26 (55%) with the currently used 3 different grading systems. During the follow‐up (median 60 months), locoregional tumor recurrence occurred in 4 cases, which were treated with surgery alone. At the last follow‐up (median 60 months; 7‐160), all patients were alive with no evidence of disease. Conclusion An excellent prognosis may be achieved without PORT in T1/2N0M0 mucoepidermoid carcinoma patients positive for CRTC1/3‐MAML2 fusions when the tumors are completely resected without tumor spillage.

Clinicopathological significance of EGFR pathway gene mutations and CRTC1/3–MAML2 fusions in salivary gland mucoepidermoid carcinoma

“…In addition, younger patients may be more likely to be treated less intensively. We recently showed that fusion‐positive MEC patients have an excellent prognosis without postoperative radiation therapy 42 . Whether it is necessary to submit MEC patients to postoperative radiotherapy should be critically considered, especially in the case of young individuals, as the therapy usually has several serious adverse effects.…”

Significance of Pretreatment Neutrophil-to-Lymphocyte Ratio in Mucoepidermoid Carcinoma of Pediatrics: A Multicenter Study

“…The prognostic significance of CRTC1/3-MAML2 fusion in MEC has been analyzed. Okumura et al (34) reported that in early-stage MEC patients positive for CRTC1/3-MAML2 fusions, an excellent prognosis may be achieved without adjuvant radiotherapy when the tumors are completely resected without tumor spillage. However, Birkeland et al (35) found a high rate of CRTC1/3-MAML2 gene fusions in a large cohort of MEC patients, but the authors did not note any correlation between fusion status and tumor grade or survival.…”

Das Mukoepidermoidkarzinom – Bedeutung der Molekularpathologie

“…Aus der t(11;19)(q21;p13)-Translokation resultiert eine CRTC1-MAML2-Transfusion, welche spezifisch für Mukoepidermoidkarzinome ist und in ca. 38-82 % aller Mukoepidermoidkarzinome nachzuweisen ist [11,12]. CRTC1 (auch MECT1, TORC1, WAMTP1) ist ein Koaktivator eines cAMP-response-binding elements (CREB), welcher eine Rolle in der Zelldifferenzierung und -proliferation spielt.…”

“…Interessanterweise konnte die p53-Mutation aber häufiger bei Fusionsprotein-negativen Mukoepidermoidkarzinomen festgestellt werden, hauptsächlich bei Intermediate-und High-grade-Mukoepidermoidkarzinomen. Bei Vorliegen einer p53-Mutation konnten auch insgesamt mehr Mutationen detektiert werden als bei Mukoepidermoidkarzinomen ohne p53-Mutation [12,17]. Diese Beobachtungen legen die Vermutung nahe, dass die p53-Mutation mit einem genetischen Switch in Verbindung zu bringen ist, durch welche ein Low-grade-in ein High-grade-Karzinom übergeht oder aber auch, dass p53 als eigenständiger Tumor- induktor bei Translokations-negativen Mukoepidermoidkarzinomen wirken könnte.…”

“…Da bei CRCT1-MAML2-negativen Mukoepidermoidkarzinomen eine schlechtere Prognose zu erwarten ist, wäre eine erweiterte Operation und/oder eine adjuvante Therapie eher in Betracht zu ziehen als bei CRCT1-MAML2-positiven Mukoepidermoidkarzinomen. So wurde in einer retrospektiven Untersuchung von Okumura et al 2017 festgestellt, dass Patienten mit einem R0-resezierten (ausschließlich Fusionsprotein-positiven) Mukoepidermoidkarzinom (T1/2 N0 M0) auch ohne adjuvante Radiotherapie eine gute Prognose haben [12].…”