Advanced stage tumors are usually treated initially with neoadjuvant chemotherapy followed 3-4 months later by surgery. Chemotherapy shrinks the tumor and makes it firmer, reducing the risk of rupture and hemorrhage during surgery. The histologic changes in the tumor induced by chemotherapy/radiation therapy include extensive necrosis, hemorrhage, hemosiderin deposition, fibrosis, and calcification along with varying degrees of tumor maturation. This image shows maturation to ganglioneuroblastoma following chemotherapy. The differentiating neuroblasts have moderate to abundant acidophilic or amphophilic cytoplasm and an enlarged eccentric vesicular nucleus with a single prominent nucleolus. There is abundant neuropil in the background.