(P 444) TWO CASES OF BRAIN METASTASES OF CD99 POSITIVE SMALL ROUND BLUE CELL TUMORS

Objective: CD99 positive small round blue cell tumors (Ewing sarcoma) can occur in and metastasize to essentially all parts of the body, highlighting our lack of understanding of the cell of origin. While locations such as the lung and bone are common, we describe 2 cases of brain metastases of CD99 positive small round blue cell tumors. We review 3 large pediatric case series to highlight the rarity and propose an area of future investigation.

Methods: The charts of 2 patients treated at the authors’ institution were reviewed. A literature search was conducted using PubMed.

Results: Case 1 was an African American patient who presented with widely metastatic CD99 positive, WT-1 negative small round blue cell tumor. EWSR1 break apart was negative. Initial brain MRI was normal. The disease responded to vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide/etoposide (VDC/IE) and radiotherapy. The patient’s disease progressed 7 months off therapy. The patient received 13 cycles of vincristine, irinotecan, and temozolomide (VIT) with disease stabilization until brain metastases were detected on scan for changes in personality and headaches. Radiotherapy followed by cabozantinib was administered. The systemic disease stabilized with only minimal growth of brain metastases for 1 year until progression of systemic disease. Therapy was discontinued; the patient died 6 months later, 4 years after diagnosis.

Case 2 was a Caucasian patient who presented with a localized distal femur CD99 positive small round blue cell tumor with EWSR1-ERG translocation. The patient received 16 cycles of VDC/IE with surgery and radiotherapy. Fifteen months off therapy, a pulmonary relapse was treated with 16 cycles of VIT with good response and resection of disease. Three months later, recurrence was identified in the same lobe of the lung. The patient received 13 cycles of vincristine, topotecan, and cyclophosphamide, with good response, and resection. Three months later, a third pulmonary recurrence was discovered in the same lobe. The patient underwent 2 cycles of high dose ifosfamide, with good response, and a complete lobectomy. While recovering, 2 intraparenchymal brain metastases were discovered on imaging for altered mental status. The patient received radiotherapy and soon thereafter developed progressive systemic disease. Palliative radiotherapy and cabozantinib were administered. The patient died of progressive systemic disease 2 months after brain metastases, 5 ½ years after diagnosis.

Conclusion: Intraparenchymal brain metastases not associated with direct extension from bone metastases are rare in Ewing sarcoma. From three of the largest pediatric series, 27 out of 885 Ewing sarcoma patients experienced brain metastases (3%). All but one patient died with a reported median survival of 2.7 months from diagnosis of brain metastases. Brain was the only site of metastatic disease in only 3 cases, all from the oldest report. Translocation data is not reported, so the effect, if any, of translocations cannot be determined. Neither of our 2 cases had an EWSR1-FLI translocation, which highlights the need to continue to evaluate the differences in clinical behavior of CD99 positive small round cell sarcomas with various translocations to determine if specific translocations have higher incidence of brain metastases. This data may help inform monitoring strategies and treatment if a subset of patients with systemic metastases are at increased risk of metastases to the brain.

References
Parasuraman S, et.al. “Brain Metastases in Pediatric Ewing Sarcoma and Rhabdomyosarcoma: The St. Jude Children’s Research Hospital Experience.” J Pediatr Hematol Oncol 1999:21;370-377.
Paulino AC, et.al. “Brain Metastasis in Children with Sarcoma, Neuroblastoma, and Wilms’ Tumor.” Int J Radiation Oncology Biol. Phys. 2003:57;177-183.
Trigg ME, et.al. “The Frequency of Isolated CNS Involvement in Ewing’s Sarcoma.” Cancer 1982:49;2404-2409.