During the Retina Subspecialty Day Oncology Section (Ret08) on Friday, Carol L. Shields, MD, discussed some of her research findings in retinoblastoma and how you don’t need to be a geneticist to make accurate retinoblastoma predictions.
Somatic vs. germline. Retinoblastoma is one of the most common malignancies affecting children and can stem from either a somatic or germline mutation. Knowing the type of mutation is critical for appropriate clinical management. Whereas somatic mutations are not heritable and do not involve the risk of pinealoblastoma or secondary cancers, germline mutations can be passed down from generation to generation. They also put patients at much higher risk for developing multifocal tumors and additional malignancies down the road.
Genetic testing is recommended. DNA testing is the only way to definitively determine whether you are dealing with somatic or germline retinoblastoma. However, as Dr. Shields noted, there are features on clinical exam that can be used to reliably determine the most likely type of disease.
Age and location are key. Most cases of germline retinoblastoma involve both eyes and feature multifocal tumors, so any child presenting with these traits—especially with a family history of retinoblastoma—can be assumed to have a germline mutation. It gets trickier in cases of unilateral, unifocal disease, which can stem from either type of mutation. In these cases, Dr. Shields recommends looking at the child’s age and the location of the tumor.
The youngest children are at the greatest risk. In a 2019 study involving 482 children with solitary, unilateral retinoblastoma, Dr. Shields found that younger age at diagnosis was significantly associated with a greater risk of germline retinoblastoma: 61% of children 0-3 months of age had germline retinoblastoma (vs somatic retinoblastoma), compared with only 22% in children aged 9-12 months. The percentage of germline mutation–affected children fell to 17% in the 1-2–year age group and 8% in the 2-3–year age group.1
Macular involvement also points to a germline mutation. In addition, a 2022 study found tumor location to be an independent risk factor for germline retinoblastoma. A solitary tumor in the macula was twice as likely to be associated with a germline mutation than with a somatic mutation.2
Recognizing these features could help provide quicker and easier diagnosis of children with germline retinoblastoma. For example, a child 3 months old or younger presenting with unilateral, single retinoblastoma located in the macula? Germline retinoblastoma is a pretty good bet. —Lauren Jarem, MS
1 Shields C et al. J Pediatr Ophthalmol Strabismus. 2021;58(6):355-364.
2 Dockery P et al. Br J Ophthalmol. Published Nov. 22, 2022.
Financial disclosures: Carol L. Shields, MD: Aura Biosciences, Inc.: C; Immunocore, Inc.: C; Interveen, Inc: C; iOnctura, Inc: C.
Disclosure key: C = Consultant/Advisor; E = Employee; EE = Employee, executive role; EO = Owner of company; I = Independent contractor; L = Lecture fees/Speakers bureau; P = Patents/Royalty; PS = Equity/Stock holder, private corporation; S = Grant support; SO = Stock options, public or private corporation; US = Equity/Stock holder, public corporation. For definitions of each category, see aao.org/eyenet/disclosures.
Read more news about Subspecialty Day and AAO 2023.