Search Results (5)

Variants in the RB1 gene are associated with retinoblastoma (RB) development, and their presence in germline cells considerably increases the risk of subsequent malignant neoplasms (SMNs) in RB survivors. We report a female patient with bilateral RB who developed two SMNs in less than ten years, with a de novo pathogenic nonsense variant in RB1 [NM_000321.3:c.306T>A, p.(Cys102*)] in heterozygosity. The updated literature review of similar cases of SMN in patients with a previous diagnosis of RB reveals a wide range in both the type of subsequent malignancy and the age at which these SMNs develop. In addition, we identified only three cases with two SMNs following RB diagnosis, with at least one of these being an EWS. This case broadens the clinical and genetic landscape of RB, demonstrates the importance of a multidisciplinary approach in these patients, and highlights genetic diagnosis as a mandatory feature for management. Full article

Retinoblastoma (RB) is the most common ocular neoplasm in children, whose development depends on two mutational events that occur in both alleles of the retinoblastoma susceptibility gene (RB1). Regarding the nature of these mutational events, RB can be classified as hereditary if the first event is a germline mutation and the second one is a somatic mutation in retina cells or nonhereditary if both mutational events occur in somatic cells. Although the rate of survival of RB is significantly elevated, the incidence of second malignant neoplasms (SMNs) is a concern, since SMNs are the main cause of death in these patients. Effectively, RB patients present a higher risk of SMN incidence compared to other oncology patients. Furthermore, evidence confirms that hereditary RB survivors are at a higher risk for SMNs than nonhereditary RB survivors. Over the decades, some studies have been performed to better understand this subject, evaluating the risk of the development of SMNs in RB patients. Furthermore, this risk seems to increase with the use of ionizing radiation in some therapeutic approaches commonly used in the treatment of RB. This review aims to clarify the effect of ionizing radiation in RB patients and to understand the association between the risk of SMN incidence in patients that underwent radiation therapy, especially in hereditary RB individuals. Full article

Hereditary retinoblastoma survivors have substantially increased risk of subsequent malignant neoplasms (SMNs). The risk of benign neoplasms, a substantial cause of morbidity, is unclear. We calculated the cumulative incidence of developing benign tumors at 60 years following retinoblastoma diagnosis among 1128 hereditary (i.e., bilateral retinoblastoma or unilateral with family history, mutation testing was not available) and 924 nonhereditary retinoblastoma survivors diagnosed during 1914–2006 at two US medical centers with follow-up through 2016. Using Cox proportional hazards regression, we compared benign tumor risk by hereditary status and evaluated the association between benign tumors and SMNs. There were 100 benign tumors among 73 hereditary survivors (cumulative incidence = 17.6%; 95% confidence interval [CI] = 12.9–22.8%) and 22 benign tumors among 16 nonhereditary survivors (cumulative incidence = 3.9%; 95%CI = 2.2–6.4%), corresponding to 4.9-fold (95%CI = 2.8–8.4) increased risk for hereditary survivors. The cumulative incidence after hereditary retinoblastoma was highest for lipoma among males (14.0%; 95%CI = 7.7–22.1%) and leiomyoma among females (8.9%; 95%CI = 5.2–13.8%). Among hereditary survivors, having a prior SMN was associated with 3.5-fold (95%CI = 2.0–6.1) increased risk of developing a benign tumor; the reciprocal risk for developing an SMN after a benign tumor was 1.8 (95%CI = 1.1–2.9). These large-scale, long-term data demonstrate an increased risk for benign tumors after hereditary versus nonhereditary retinoblastoma. If confirmed, the association between benign tumors and SMNs among hereditary patients may have implications for long-term surveillance. Full article

Retinoblastoma (Rb) is a pediatric malignant eye tumor. Subsequent malignant neoplasms (SMNs) and trilateral Rb (TRb) are the leading cause of death in heritable Rb patients in developed countries. The high rate of SMNs in heritable Rb patients is attributed to the presence of a mutation in the RB1 tumor suppressor gene. In addition, Rb therapy choices also influence SMN incidence in this patient group. The incidence rates and age of occurrence for the most frequent SMNs and TRb will be discussed. In addition, the impact of genetic predisposition and Rb treatments on the development of SMNs will be evaluated. Furthermore, screening and other prevention methods will be reviewed. Full article

Retinoblastoma (Rb) is a malignant tumor of the developing retina that affects children before the age of five years in association with inherited or early germline mutations of the RB1 gene. The genetic predisposition is also a driver for other primary malignancies, which have become the leading cause of death in retinoblastoma survivors. Other malignancies can occur as a consequence of radiotherapy. We describe a patient with retinoblastoma in which we detected a novel RB1 c.2548C > T, p.(Gln850Ter) and a synchronous MET c.3029C > T, p.(Thr1010Ile) mutation as well. After presenting with bilateral retinoblastoma, the patient developed at least four different manifestations of two independent osteosarcomas. Our goal was to identify all germline and somatic genetic alterations in available tissue samples from different time periods and to reconstruct their clonal relations using next generation sequencing (NGS). We also used structural and functional prediction of the mutant RB and MET proteins to find interactions between the defected proteins with potential causative role in the development of this unique form of retinoblastoma. Both histopathology and NGS findings supported the independent nature of a chondroblastic osteosarcoma of the irradiated facial bone followed by an osteoblastic sarcoma of the leg (tibia). Full article