Case Presentation
A 15-month-old previously healthy male presented with a slowly enlarging, firm right-hand mass, first noticed at around 6-months of age. After visits to multiple specialists across many institutions, he was diagnosed by biopsy with low grade myopericytoid-ovoid sarcoma infiltrating around digits revealing a novelERC1- unaligned-ALK fusion. ALK-fusion sarcoma fusion partners known to date are depicted in Figure 1. Histologically, the tumor had a vascular staghorn and bland, up to moderately cellular lipofibromatosis-like infiltrative appearance into skeletal muscle and adipose tissue (Figure 2) and was focally positive for S100 protein, negative for CD34 and SOX10. Metastatic workup, including chest CT and full body MRI, which revealed a 3 mm non-specific stable pulmonary nodule, was considered negative. Other than increasingly restricted range of motion and painless stiffness due to tumor bulk, the patient was asymptomatic and met developmental and growth milestones.
Initial MRI imaging of the right hand revealed a homogenous enhancing mass 5.6 x 4 x 5.1 cm within the hand at the level of the metacarpal bones, interdigitating around and remodeling adjacent bones without destruction (Figure 3A). The radiologic presentation was initially considered a vascular malformation, due to the prominent vessels that correspond to the myopericytic staghorn vascular appearance by morphology. Surgical resection, likely curative, would require distal forearm amputation, based on orthopedic and plastic surgical expertise. Consensus was reached across multiple disciplines and institutions to trial enteral neoadjuvant crizotinib and determine tumor responsiveness while limiting long-term morbidity. Due to our patients age and size, emergency use authorization was granted by the FDA through Pfizer and approved by our institutional review board, for single patient use to access the oral crizotinib liquid formulation being employed as part of the Children’s Oncology Group ANBL 1531 trial. Due to taste intolerance, a gastrostomy tube was placed for drug administration. Initial MRI was obtained approximately 5 months prior to treatment initiation with repeat baseline imaging 5 days after stating crizotinib. Treatment response was monitored via MRI at 3, 7, 10, and 16 months after drug initiation. Marked tumor regression and return to normal use and function was noted at the 3- and 7-month checkpoints, with complete radiographic resolution at 10- and 16-months of treatment.
Although targeted dosing for crizotinib is 215 mg/m2/dose BID, our patient’s chronic mild neutropenia limited dosing to approximately 140 mg/m2/dose BID. Since gastrostomy tube insertion, he tolerated all doses as scheduled except for a brief hold and dose readjustment for one early episode of grade IV neutropenia, and individual doses held due to sedation for MRIs. Side effects were otherwise limited to intermittent mild neutropenia and occasional constipation. Toxicity was monitored with routine ophthalmology evaluations and serial EKGs to track QT/QTc intervals. Crizotinib was electively discontinued after 16 months, 6 months following his complete response. Tumor resection was not attempted at the completion of therapy because there was no remaining radiologic or clinical tumor (Figure 3B). Radiographic monitoring at 1, 6, and 8 months after discontinuation of crizotinib demonstrated complete radiologic resolution of the mass.