Microscopically, both undifferentiated and differentiated elements may be present. Undifferentiated elements appear as collections of small, round cells with hyperchromatic nuclei; differentiated elements include Flexner-Wintersteiner rosettes, Homer Wright rosettes,  and fleurettes from photoreceptor differentiation. Genetic testing
Identifying the RB1 gene mutation that led to a childs retinoblastoma can be important in the clinical care of  the affected individual and in the care of (future) siblings and offspring. It may run in the family. Bilaterally affected individuals  and 13-15% of unilaterally affected individuals, are expected to show an RB1 mutation in blood. By identifying the RB1 mutation in the affected individual, (future) siblings, children, and other relatives can be tested for the mutation; if they do not carry the mutation, child relatives are not at risk of retinoblastoma, so need not undergo the trauma and expense of examinations under anaesthetic. For the 85% of unilaterally affected  patients found not to carry either of their eye tumor RB1 mutations  in blood, neither molecular  testing nor clinical surveillance of siblings is required. If  the  RB1 mutation of an affected individual is identified, amniotic cells in an at-risk pregnancy can be tested for the family  mutation;  any fetus that carries the mutation can be delivered early, allowing early treatment of any eye tumors, leading to better visual outcomes. For cases of unilateral retinoblastoma where no eye tumor  is available for testing, if no RB1 mutation is detected in blood after high-sensitivity molecular testing (i.e.
>93% RB1 mutation detection sensitivity),  the risk of a germline RB1 mutation is reduced to less than 1%, a level at which only clinic examination (and not examinations under anaesthetic) is recommended for the affected individual and their future offspring (National Retinoblastoma Strategy, Canadian Guidelines for Care). Imaging
Traditional ultrasound B scan can detect calcifications in the tumour while high-frequency ultrasound B scan is able to provide higher resolution than the traditional ultrasound and determine the proximity of the tumour with front portion of the eye. MRI scan can detect high-risk features such as optic nerve invasion; choroidal invasion, scleral invasion, and intracranial invasion. CT scan is generally avoided because radiation can stimulate the formation of more eye tumours in those with RB1 genetic mutation. Staging
In order to properly diagnose retinoblastoma, there must be guidelines to follow to properly classify the risk of the tumor. The Reese Ellsworth Classification System, by Dr. Algernon Reese and Dr. Robert Ellsworth, is universally used to determine the size, location, and multi-focality of the tumor. The system was originally used to decide the best treatment result by using external beam radiotherapy, as well as, the likeliness of salvaging the globe of the eye. Due to chemotherapy not being part of the Reese Ellsworth Classification System, there needed to be an updated classification system to foresee the treatment outcomes of chemotherapy. The International Classification for Intraocular Retinoblastoma is now the current system being used, and it was created by Murphree and associates.