{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T17:12:30Z","timestamp":1766509950043,"version":"3.48.0"},"reference-count":37,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Reports"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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\u2010heritable 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\u2009years. 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case<\/jats:title>\n                    <jats:p>We report a case of a 21\u2010year\u2010old 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Germline changes associated with malignancies were examined using next\u2010generation 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\u2010related 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\u2010up periods may influence SPC risk assessments. Continuous monitoring and personalized follow\u2010up care are crucial for managing long\u2010term risks in these survivors. This research emphasizes the essential importance of ongoing monitoring and follow\u2010up for survivors of retinoblastoma (RB) to identify and address secondary malignancies (SMNs), improve the management of long\u2010term complications, and enhance both life expectancy and quality of life.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cnr2.70411","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T10:53:00Z","timestamp":1764240780000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Subsequent Primary Hematologic Malignancies in a 21\u2010Year\u2010Old Retinoblastoma Survivor: Case Report Study"],"prefix":"10.1002","volume":"8","author":[{"given":"Elham","family":"Karimi","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, School of Medicine Tehran University of Medical Sciences  Tehran 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