Second primary tumors in patients with retinoblastoma a review of the literature

Abstract

Purpose: The aim of this survey was to review the different studies regarding the occurrence of second primary tumors (s PT) among survivors of retinoblastoma. Methods: Ovid (Medline, Current contents life, Psychlit, Embase) was searched for the years 1966 -1995 using the mesh headings: 'retinoblastoma', 'second primary neoplasms', and 'multiple primary neoplasms'. The inclusion criteria were: the study should involve 50 patients or more and should not be limited to one specific SPT. A checklist with criteria regarding the study design and the results was applied to each study. Results: Eleven studies were identified which met the inclusion criteria. Thirtyfive different types of S P T (Ntotal=z43) were reported. Most of them were osteosarcomas (37.0%), followed by melanomas (7.4%), soft-tissue sarcomas (6.9%), brain tumors (4.5%), fibrosarcomas (3.3%), chondrosarcomas (3.3%), and sarcomas (3.3%). Less frequently reported were leukemias (2.4%), sebaceous cell carcinomas (1.6%), and non-Hodgkin lymphomas (1.6). Pineoblastoma, which in fact is a trilateral retinoblastoma and not an S P T , was found in 2.4%. Despite the differences, all 11 studies showed a higher incidence of S P T compared to the general population. Only 4 studies were judged to be free from selection bias, reporting a cumulative incidence of S P T of 8.4% 18 years after diagnosis, 15.7% at the age of 20 years, 19% at the age of 35 years, and a relative risk of 15.4 for s P T, respectively. Conclusion: s P T is a serious problem for the survivors of hereditary retinoblastoma and its importance shoud be recognized in (genetic) counseling of patients.

A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment

“…99 Individuals with hereditary retinoblastoma can also have an increased risk for pinealoblastoma, 100 osteosarcomas, sarcoma (especially radiogenic), and melanoma. 101,102 Referral should be considered for any individual who has a personal history of or first-degree relative with a retinoblastoma.…”

Release of cell cycle constraints in mouse melanocytes by overexpressed mutant E2F1E132, but not by deletion of p16INK4A or p21WAF1/CIP1

“…Inherited mutations in Rb predispose humans to melanoma since retinoblastoma patients and their relatives display an increased risk to develop melanomas as well as other tumors (see for example Bataille et al, 1995;Moll et al, 1997. However, inactivating mutations in Rb are rare in melanomas Horowitz et al, 1990).…”

Developmental defects and tumor predisposition in Rb mutant mice

“…RB is also mutated in sporadic retinoblastoma, lung, breast, prostate and bladder cancer (Harbour et al, 1988;Lee et al, 1988;Horowitz et al, 1990;Knudson, 1993;Bookstein, 1994;Miyamoto et al, 1995). Whereas in inherited retinoblastoma, patients show an increased predisposition to second primary tumors such as osteosarcoma, melanoma and brain tumors (Moll et al, 1997) they are not at higher risk for developing other types of cancer (Eng et al, 1993). This indicates that in the majority of sporadic cancers RB loss is not the rate-limiting step in the disease.…”