A 3-month-old boy is brought to the office by his mother for a routine checkup. He is found to have a right-sided white pupillary reflex. His father was diagnosed with a retinal neoplasm during childhood and had his left eye enucleated. This child is at the greatest risk of developing which of the following neoplasms?

Question

A 3-month-old boy is brought to the office by his mother for a routine checkup.  He is found to have a right-sided white pupillary reflex.  His father was diagnosed with a retinal neoplasm during childhood and had his left eye enucleated.  This child is at the greatest risk of developing which of the following neoplasms?

Quizplus · Accepted Answer

11ec160b_39eb_d1bd_9249_f7f08071b9e7_MD0001_00 Retinoblastoma is the most common ocular tumor of childhood. It usually presents with a white pupillary reflex (leukocoria) in children <5 years old. Approximately 60% of retinoblastomas are sporadic (usually unilateral), while 40% are familial (often, but not always, bilateral). Familial retinoblastoma occurs due to a germline mutation that affects the Rb tumor suppressor gene on chromosome 13; affected children carry one copy of the mutation in all their cells. However, there are two copies of the Rb gene (one allele from each parent), and malignancy does not occur while at least one copy of the gene is still functional. A somatic second mutation acquired early in life is the "second hit" that leads to retinoblastoma, as cells with two inactivated Rb genes proliferate uncontrollably and give rise to malignancy. Children with familial retinoblastoma often acquire other "second hit" mutations later in life, leading to additional tumors, usually sarcomas such as osteosarcoma. In contrast, patients with sporadic retinoblastoma are not at risk for other malignancies, as the chance of two acquired somatic mutations occuring multiple times in different cell lineages is very low. (Choice A) Patients with Down syndrome, ataxia-telangiectasia, and neurofibromatosis type 1 have an increased risk of development of acute lymphoblastic leukemia, which is not associated with familial retinoblastoma. (Choice B) Neuroblastoma is a common childhood cancer that arises from sympathetic nervous tissue, most commonly in the adrenals. Most cases are sporadic. (Choice C) Ewing sarcoma is an undifferentiated neoplasm of mesenchymal origin that most commonly occurs in the long and flat bones of children and adolescents. It occurs sporadically. (Choice E) Medulloblastoma is the most common malignant brain tumor of childhood, typically arising in the cerebellum. Educational objective: Familial retinoblastoma occurs as a result of mutations of each of the two Rb genes ("two hits"). These patients have an increased risk of secondary tumors, especially osteosarcomas, later in life.

A 3-Month-Old Boy Is Brought to the Office by His