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.