Subsequent Primary Hematologic Malignancies in a 21-Year-Old Retinoblastoma Survivor: Case Report Study

Retinoblastoma (RB) is a malignant eye tumor that predominantly affects children. Although survival rates have improved significantly due to advancements in treatment, subsequent malignant neoplasms (SMNs) continue to be major causes of death in both heritable and non-heritable RB cases. These SMNs are often associated with mutations in the RB1 gene, as well as the effects of radiotherapy or chemotherapy. There are no previous reports of a nonhereditary RB survivor developing three sequential hematologic malignancies (AML, lymphoma, and ALL) over 20 years. Most secondary primary cancers (SPCs) in RB survivors are solid tumors, such as osteosarcoma, soft tissue sarcoma, and melanoma, with hematologic malignancies being far less common, especially as third or subsequent primary tumors.

We report a case of a 21-year-old Iranian male who developed multiple distinct hematologic malignancies following retinoblastoma treatment. Using NGS, Sanger sequencing, and bioinformatic analysis, the possibility of germline mutations was surveyed.

Germline changes associated with malignancies were examined using next-generation sequencing (NGS). There were no germline alterations discovered, suggesting no predisposition to develop cancer. Three pathogenic/likely pathogenic heterozygous variants were found in the patient by carrier screening. Absence of germline RB1 mutations or other hereditary cancer syndromes implicates treatment-related factors (chemotherapy/radiotherapy) as the primary driver of sequential malignancies. Nonhereditary retinoblastoma (RB) survivors have a lower risk of secondary malignancies (SMNs) compared to their hereditary counterparts. Chemotherapy, especially alkylating agents, increases the risk of secondary acute myelogenous leukemia (AML) and other leukemias and lymphomas due to its mutagenic effects and genetic factors. Although RB survivors rarely develop secondary cancers, the limited patient numbers and short follow-up periods may influence SPC risk assessments. Continuous monitoring and personalized follow-up care are crucial for managing long-term risks in these survivors. This research emphasizes the essential importance of ongoing monitoring and follow-up for survivors of retinoblastoma (RB) to identify and address secondary malignancies (SMNs), improve the management of long-term complications, and enhance both life expectancy and quality of life.