Ewing’s Sarcoma as Second Malignant Neoplasm after Retinoblastoma: A Case Report

Abstract

Objectives: To report a case of a child with the hereditary form of unilateral retinoblastoma (RB), who developed Ewing’s sarcoma of the right fibula 3 years after the enucleation of the right eye. Case Presentation and Intervention: The child was diagnosed as a case of RB of the right eye at the age of 9 months. He was fully investigated and found to have locally advanced RB with bone marrow involvement (Reese-Ellsworth stage IVA). Enucleation was recommended to the family, but they refused. The patient received chemotherapy and diode laser thermotherapy in Kuwait and the UK. He had a local relapse after 11 months and subsequently underwent enucleation of the right eye. After 3 years, he was investigated for a small swelling in his right lower leg. After extensive investigations, it was reported as Ewing’s sarcoma. He was treated with chemotherapy, surgery (complete excision of the fibula) and high-dose chemotherapy followed by autologous stem cell transplantation. The child is now nearly 2 years after completing the treatment and is disease free. Conclusions: This case confirms the increased risk of a second malignant neoplasm (SMN) in children with hereditary RB. These children need a very close follow-up for the early diagnosis of SMNs or even subsequent malignancies.

Ewing’s sarcoma as second malignancy following a short latency in unilateral retinoblastoma

“…Previously, six cases of Ewing’s sarcoma in patients with a prior history of bilateral [1, 6, 8, 16] and two cases of unilateral [6, 12] retinoblastoma have been reported. Here, we present a case of a child with unilateral RB who developed Ewing’s sarcoma of the right humerus 2 years after enucleation of the left eye, and a review of the pertinent literature.…”

Germline Mutations in Predisposition Genes in Pediatric Cancer

“…Although Ewing's sarcoma has been recognized as a second cancer in children who have been treated for retinoblastoma, [22][23][24][25] it has not, to our knowledge, been associated with other cancer-predisposition syndromes. 26 We found that six patients with Ewing's sarcoma had pathogenic germline mutations in TP53 (in four patients), PMS2 (in one), or RET (in one), although we cannot state with certainty that each mutation had a bearing on the patient's cancer.…”

“…org/ site). These genes were classified into three categories: tumorsuppressor genes (58 genes), 9 tyrosine kinase genes (23), and other cancer genes (395). Our analyses of the genes in these three categories focused on known hotspot-activating mutations in genes encoding kinases and on truncation mutations in genes encoding tumor-suppressor proteins and in other cancer genes.…”

Is There a Predisposition Gene for Ewing's Sarcoma?

“…Finally, several authors have reported on the association of Ewing's sarcoma after diagnoses and treatment for retinoblastoma [75, 76]. Spunt et al [42] published on a cohort of 6 Ewing's patients diagnosed after treatment for various cancers including lymphoma, leukemia, Wilms tumor, and retinoblastoma.…”