Recognizing the Central Nervous System as a Site of Pediatric Sarcoma Relapse: A 3-Patient Series

Background: Sarcomas are diverse malignancies derived from primitive mesenchymal cells that are difficult to diagnose and treat. Advances in local control techniques, chemotherapy regimens, and imaging modalities have led to improvements in both morbidity and mortality in pediatric patients. However, one-third of patients develop disease relapse. Previously, intracranial metastasis was thought to be rare. The incidence of sarcoma brain metastasis is thought to have increased and is associated with grim outcomes.

Case Information: Case 1 – A male Asian infant was born with a mass involving lower left extremity requiring through the knee amputation shortly after birth. Pathology confirmed infantile fibrosarcoma (IF). He was started an IF-based regimen after pulmonary biopsy confirmed metastatic disease. Two months after chemotherapy completion, 5.6 x 7.2 x 6.3 cm intracranial tumor was found with pathology confirming metastatic IF. Despite salvage chemotherapy and entrectinib, he continued to have increased neurological symptoms and died.

Case 2 - Ten-year-old Caucasian female presented with 8-month history of progressively enlarging right foot mass measuring 6.2 x 4.5 x 4.2 cm, consistent with Ewing Sarcoma upon biopsy. PET scan showed bilateral pulmonary metastatic disease with lymph node involvement. Chemotherapy and radiation therapy (XRT) were started. After completion of cycle 6, she had increased neurological symptoms and imaging showed 5 x 6 cm temporal mass with hemorrhage. Brain XRT, palliative chemotherapy, and Ruxolitnib were started; however, the patient subsequently died.

Case 3 – Six-year-old Hispanic female with large mass arising from right proximal humeral metaphysis with evidence of bilateral pulmonary metastasis. Biopsy confirmed metastatic osteosarcoma and chemotherapy was started. Although the patient was treated further with methotrexate, salvage chemotherapy, palliative XRT, and Pazopanib, she began to develop neurological symptoms over several weeks before passing.

Conclusions: We note this is the only report of IF brain metastasis, a rare report of sarcoma lymph node metastasis, and each patient was treated with an immunotherapy agent. Caregivers in cases 2 and 3 reported new-onset neurological manifestations prior to identification of new brain metastasis, indicating a lag in detection of new intracranial relapse in asymptomatic sarcoma patients. We suggest implementing a brief review of systems screening tool focused on concerning neurological manifestations to screen for brain metastasis.