Primary differentiated neuroblastoma of the orbit

A 49-year-old woman had a 12-year history of a localized left orbital tumor that required five subtotal excisions, orbital radiotherapy, and finally an exenteration. The last procedure was performed after visual function had deteriorated and in order to prevent spread of the tumor into a surrounding compartment. The biopsy specimens from the first four surgeries showed a stroma-free spindle cell tumor with benign cytologic features and no mitotic activity, which exhibited palisading of nuclei, imbrication of delicate cytoplasmic processes (neuropil), true perivascular rosettes with cytoplasmic processes oriented perpendicular to vessel walls, and Wright rosettes. The biopsy after radiotherapy and the exenteration specimen contained more polyhedral (gemistocytoid) tumor cells with abundant eosinophilic cytoplasm and tapering cell processes; nuclear pleomorphism without mitotic activity was also seen. Electron microscopy showed the presence of neurosecretory dense-core granules in the perikaryon region of the tumor cells and in the myriad interweaving cytoplasmic processes (neurites); neither Nissl substance nor synapses were identified. Immunohistochemical staining for neuron-specific enolase was positive, but glial fibrillary acidic protein stained negative. This previously undescribed orbital tumor is interpreted as a primary differentiated neuroblastoma without evidence of ganglion cell differentiation that exhibited locally aggressive behavior. The distinctions between neuroblastic and neuroendocrine tumors are discussed.