A 3-year-old boy was seen by their pediatrician for a “right eye deformity” which had been present since he was 1 year old. On clinical exam there is obvious leukocoria. He was born at 40 weeks gestation and has been healthy otherwise. No significant family history or other medical conditions. He has two healthy brothers. MRI of the orbits demonstrated a heterogeneous enhancing and calcified right intraocular mass. Enucleation specimen demonstrated an expansile whitish mass with calcifications growing into the vitreous space. The histologic specimen is illustrated in figures 1-7 (figure 7 is the optic nerve margin).
The correct answer is ...
Optic nerve involvement.
This is a case of retinoblastoma. It is the most common intraocular malignant tumor. These tumors arise from the neurosensory retina. There are a number of poor prognostic factors, but the most important is presence or absence of optic nerve involvement. The optic nerve should be inked by the surgeon and tumor at this margin is associated with categorization as a pT4, and these tumors have a very poor prognosis. Tumor at the retrolaminar aspect of the optic nerve margin leads to CNS involvement in approximately 90% of cases (Pathol Lab Med (2009) 133 (8): 1199–1202). The lamina cribrosa is the structure that helps to classify the tumor as prelaminar, laminar, or retrolaminar. The lamina cribrosa is a mesh-like collagenous structure in which unmyelinated retinal ganglion cells go from the retina and enter into the optic nerve. This patient had retrolaminar involvement and presented with CNS involvement around one year after initial diagnosis.
Earlier age at diagnosis is incorrect. Interestingly, grade increases with age at enucleation with retinoblastoma. So in summary, older children tend to have more poorly differentiated tumor. This is likely related to an accumulation of genetic mutations due to biallelic loss of retinoblastoma (J Pediatr Ophthalmol Strabismus. Jan-Feb 2008;45(1):22-5. doi: 10.3928/01913913-20080101-16).
Tumor grading has no bearing on prognosis is incorrect. Increasing degrees of anaplasia are associated with decreased overall survival and increased risk of mets (Am J Ophthalmol. 2015 Apr;159(4):764-76). Severe anaplasia/poor differentiation is characterized by very large hyperchromatic nuclei, extreme pleomorphism (angular, rhomboid, or fusiform), cell wrapping, numerous mitotic figures, and lack of resemblance to normal photoreceptors.
Absence of pineal gland involvement is incorrect. Children with pineal gland involvement points to a phenomenon called “trilateral retinoblastoma,” which can be seen in about 5% of patients with a germline mutation in the Rb gene. This means that a morphologically similar tumor as retinoblastoma develops within the brain, most commonly in the pineal gland, and is often diagnosed at the same time as retinoblastoma. This is because the pineal gland has embryologic/genetic overlap with cells of the retina and thus there is a predisposition of tumors in the pineal gland in those with a germline Rb mutation (Lancet Oncol. 2014 Sep;15(10):1157-67).
Casey Gleue, M.D.
Resident, Anatomic and Clinical Pathology
Jorge Trejo-Lopez, M.D.
Senior Associate Consultant, Anatomic Pathology
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science