Retinoblastoma in Children

00:00 In this lecture, we will quickly review retinoblastoma in childhood; tumor of the eye.

00:07 Here is the characteristics of retinoblastoma.

00:11 It happens in one in 20,000 live births and thus there's about just over 300 cases every year in the United States and Canada.

00:20 So it's not that common, but it's a unique condition, so we'll discuss it.

00:25 Patients may have unilateral or bilateral retinoblastoma.

00:30 The unilateral disease is typically a spontaneous mutation in the Rb1 gene.

00:37 This is 70% of cases, and it typically presents between the age of two and five.

00:44 On the flipside, we can see bilateral disease.

00:48 This is a result of having inherited a mutation in the Rb1 gene and just getting a second hit.

00:57 This is 30% of cases and this presents in children under of year of age so they present a little bit earlier.

01:05 This is one of the typical, small blue round cell tumors, it's intraocular and it presents typically in infancy in patients who've inherited the disease.

01:16 It's associated with a genetic mutation of Rb1 or the retinoblastoma gene.

01:22 Rb1 is an important oncongenic tumor suppressor gene found on the 13th chromosome at 13q14.

01:33 Basically, a mutation in this gene causes cellular proliferation and cell cycle dysregulation, resulting in a clonal population of cells that can form tumors typically in the eye.

01:48 And it's associated with the development of other tumors as well.

01:51 Retinoblastoma can metastasize to other organs in the body.

01:56 So, this gene is something we think of in our typical two-hit hypothesis.

02:04 Remember, everyone has two copies of the retinoblastoma gene.

02:08 Here's a normal child who freakishly had one mutation in a cell population.

02:15 That population of cells then made a new set of clonal populations and then they have freakishly another mutation.

02:23 This is the more common type where they're not born with a mutation and this happens a little bit later in life because it takes more time to sort of - through absurdly bad luck have two hits on both genes.

02:37 This is to be compared with someone who has inherited this problem.

02:41 They've inherited one copy already not working, in this case, it's on dead sperm.

02:46 And then they only need one hit before they develop the tumor, so this would be more commonly in the 30% of children who have actually inherited the poor portion of the gene.

02:57 So how does it present? Well in infants or later in childhood, it's going to typically present with leukocoria.

03:05 Sometimes patients notice in a photograph that one eye is red and the other one isn't.

03:09 Often, it's picked up on routine screening by doctors.

03:13 So leukocoria is a white reflection in the pupil in infancy.

03:17 It can also be associated with strabismus because these patients may not be seeing very well and a decreased visual acuity.

03:25 They can also develop heterochromia of the iris as you can see here.

03:31 In general, these patients will get a CBC with differential which can be abnormal if there is bone metastasis of the lesion.

03:39 We will also get an LP to assess for spread into the CNS.

03:44 What are the radiologic findings? Well, we usually sedate the patients and do an ophthalmologic evaluation of both eyes under sedation.

03:54 We often will ultrasound the eyes to determine the extent of disease.

03:58 And we'll get a CT +/- an MRI of the orbits and brain to further characterize where this lesion is.

04:06 Lastly, we may get a bone scan if we're worried about boning metastasis as a way of determining if there are any.

04:14 So how do we treat this tumor? Well, we prefer if we can to do vision sparing techniques.

04:21 This will involve graduation, chemotherapy, surgery, photocoagulation, cryotherapy, and thermotherapy.

04:28 They were all a bunch of different ways the ophthalmologist can aggressively attack this disorder.

04:32 Unfortunately, there are times when we do have to do surgical enucleation of the eye and we will remove the affected eye.

04:41 This is usually in unilateral cases.

04:44 We don't do this typically in cases of bilateral disease because the risk is so profound that the other eye will be affected.

04:51 Complications are what you might expect from a germline mutation.

04:57 This is an inherited germline mutation, so in those minority of patients who have inherited, they absolutely have risk for other malignancies for the rest of their life.

05:07 Vision loss is from surgery or from disease and that we can expect.

05:11 Additionally, for those who have a secondary malignancy, there is a radiation risk of osteosarcoma and there can be also risk of skin cancer as well.

05:23 So that's a brief summary of retinoblastoma in childhood, thanks for your time.