Human retinoblastoma: a morphological study of apoptotic, leukocytic, and vascular elements

Retinoblastoma (Rb), derived from retinal neuroepithelial progenitor cells, is the most common intraocular malignancy of childhood. This study examined 10 human Rb biopsy specimens with light and electron microscopy for histopathological features not previously described in detail, including cell death, leukocytic infiltration, and the tumor vasculature. Rb is a solid well-vascularized tumor with regions of viable tumor cells surrounding vessels, interspersed with zones of necrosis; apoptotic cells were seen in all specimens. Mononuclear phagocyte series (MPS) cells and lymphocytes often colocalized, adjacent to tumor vessels, and MPS cells frequently invested the perivascular space. Lymphocytes were rarely seen within areas of viable tumor. Tumor vessels at early stages of formation resembled normal developing retinal vessels. While junctions were often seen between endothelial calls, disruption of these junctions and endothelial fenestrae was sometimes evident. Müller cells and astrocytes extended processes around tumor cells and blood vessels, and contributed to the formation of the vascular glia limitans, which in some mature vessels was disrupted and discontinuous. Overall, this study provides further morphological details of cell death within Rb, particularly apoptotic involution, and describes the presence of a vascular-associated leukocytic infiltration in Rb. Evidence of compromise of the normal blood-retinal barrier (BRB) within the Rb tumor vessels is presented.