Case Descriptions/Results
Patient 1: 23 year old female with Gorham Stout Disease
This patient has an extensive LM in the lumbar spine and sacrum complicated by a L4/L5 nerve sheath-to-LM fistula causing a chronic cerebrospinal fluid leak and severe headaches.11 She failed treatment with interferon alpha and zoledronic acid, was treated with blood patches with transient relief, and also underwent glue embolization. She tried sirolimus for a year but had no benefit and developed hyperlipidemia so discontinued. Secondary to debilitating headaches, she had both ventricular-peritoneal and lumbar-peritoneal shunts placed. At age 22, she developed acutely worsening headaches, leading to multiple ED visits, and inability to attend school. Sequencing of a lytic bone biopsy demonstrated the EML4::ALK fusion.12 She was discussed at molecular tumor board, which recommended the ALK inhibitor alectinib based on its favorable side effect profile. She was started on 150 mg alectinib BID (starting dose for lung cancer is 600 mg BID). After 2 weeks, she noted decreased back swelling, which was present since infancy. However, her headaches continued and alectinib was increased to 300 mg BID. Subsequently, two shunt malfunctions were discovered and repaired and she continued on alectinib. Her headaches resolved, though it was unclear how much the alectinib verses the shunt revision contributed. She noted continued decreased swelling and pain in her back, which she attributed to alectinib and wanted to continue with the medication. After a year on alectinib, she is doing well and graduated from nursing school. MRI after 1 year of therapy demonstrated >50% reduction in soft tissue edema in the area of her LM (Fig. 1).
Patient 2: 10 year old female with GU lymphatic malformation
This patient presented at the age of 10 with a 1 month history of left labial swelling, purulent drainage, and difficulty wearing pants. She was diagnosed with an extensive LM with a concurrent abscess. After resolution of the infection, she was treated with sirolimus (goal trough 10-15 ng/mL) for >4 years. She suffered from frequent mouth sores yet had no radiographic or symptomatic response with almost continuous drainage from the lesion, pain, difficulty wearing clothing, and an inability to participate in physical activity. She stopped sirolimus and underwent sclerotherapy and labial debulking. Though her activity improved post-procedure, she continued to have pain and fluid drainage. Molecular testing of biopsy tissue showed an EML4::ALK fusion. With the goal of improved symptom control, alectinib, the ALK inhibitor with the best side effect profile, was prescribed. Despite multiple attempts, the only ALK inhibitor covered by insurance was crizotinib. Given this limitation, crizotinib was started at 250 mg BID, which is half the standard pediatric cancer starting dose for her BSA which was 1.99. Within 3 weeks of initiation, she had complete resolution of fluid drainage from the skin and pain, with no adverse effects. MRI at 3 months demonstrated over 20% reduction in the labial component of the malformation (Fig. 2) and she continues on therapy.