**Abstract**

Retinoblastoma (RB) is the most common intraocular tumor in children. It arises from the nuclear layer of the retina, with different growth patterns: endophytic, exophytic, and mixed. Retinoblastoma also has characteristic histopathological appearance with areas of viable tumor, necrosis, and calcifications. The tumor differentiation can be determined by the presence of rosettes—Flexner-Wintersteiner rosettes as well as fleurettes—and tends to become less differentiated with age. Histopathological risk factors are used as prognostic indicators and will be discussed in this chapter together with the typical tissue diagnostic features. These will include optic nerve/choroidal invasion, extraocular extension, and anterior segment involvement. Other prognostic factors with less impact will be discussed as well including the amount of necrosis, mitotic figures, and grading of anaplasia. Furthermore, we will briefly discuss different regression patterns and posttreatment findings in enucleated globes.

**Keywords:** retinoblastoma, pathological prognostic indicators, optic nerve invasion, choroidal invasion, pathological classification

## **1. Introduction**

Retinoblastoma was first ever described by Petras Pawius from Amsterdam in 1597, and it wasn't until 1809 when James Wardrop of Edinburgh established its origination from the retina and recommended enucleation as a primary treatment method for saving lives [1–3]. Nine years later, the first case of fungus hematodes, old name of retinoblastoma, was reported in the American literature [2, 4]. In the following three decades when the microscope was introduced, Virchow, the wellknown pathologist, claimed that this tumor is a glioma as it arises from glial cells [2, 5]. Nevertheless, both the pathologist Simon Flexner (1891) and ophthalmologist Hugo Wintersteiner (1897) believed independently that this tumor is actually a neuroepithelioma due to the presence of cellular rosettes harboring a central lumen histologically. In fact, the Flexner-Wintersteiner rosettes that are diagnostic for retinoblastoma are named after these two physicians [2, 6, 7]. Later in the nineteenth century, the American pathologist Verhoeff confirmed that undifferentiated retinal cells are the original nidus of this tumor; thus, he called it retinoblastoma. This term was first adopted by the American Ophthalmology Society in 1926, and it has been in use since then [2, 8].
