Delayed Methotrexate Excretion Due to Sequestration in a Thymic Cyst

Background: High-Dose Methotrexate (HD-MTX) is extremely effective in childhood cancers; yet, it has many side effects due to its toxic potential. It is important that HD-MTX levels are continuously monitored. The normal timeframe for HD-MTX clearance is 2-3 days. In most patients, the levels should decline as the kidneys filter the medicine from the blood; however, prolonged excretion can result from HD-MTX accumulating in "third spaces'', for example pleural effusions or ascites. Case Information: A 16-year-old female patient was admitted for HD-MTX for osteosarcoma in 2019. During her first cycle of HDMTX, she experienced delayed clearance of MTX taking approximately 7.00 days, requiring prolonged hospitalization for drug level monitoring as well as monitoring for renal toxicity. Over the next two months, her clearance remained prolonged at 5.95 days and 7.08 days. Six weeks later, the patient presented to the clinic with chest pain. Upon evaluation, a CT angiogram revealed an elongated cystic structure in the superior mediastinum. The cyst was surgically removed. The patient cleared her next two scheduled HD-MTX treatments at 10- and 11-weeks post-diagnosis, in 2.66 and 2.93 days, respectively. Conclusions: This case study brings to light a rare occurrence of MTX sequestration within a pre-existing benign thymic cyst, leading to prolonged time to MTX clearance, prolonged hospitalization, and extended leucovorin rescue. It would be prudent to consider imaging patients with persistent delayed MTX excretion, looking for unusual areas where 3rd spacing may occur.