Ramón Ropero Toirac

Neuroblastoma – Molecular Basis for Diagnosis and Staging System

The origin of neuroblastoma was first described in Berlin, by Virchow in 1864, when he gave it the name “Glioma”. In 1891, Marchand observed similarities between this tumor and the ganglia of the Sympathetic Nervous System in its developmental phase, and Wright demonstrated that the cellular type of this tumor was similar to the one observed in the embryonic stage of the medulla of the adrenal glands. The name Neuroblastoma was proposed by James Homer Wright in 1910, while Morgan observed microscopically an adrenal tumor with fibrillar characteristics. In 1914, Herxheimer, using Bielschowsky’s method of silver staining, showed that the fibrillar structures were nerves fibers originating in the nerve cell proper, and not in the cells of the sheaths nerve as it has been noted in the case of a benign ganglioneuroma. Robertson indicated that any important series of these tumors of the neural crest were characterized by a variety of histological grades ranging from benign, with well differentiated cellular elements, to highly anaplastic forms. Rinscheid observed little fibrillar elements inside the tumor cells that were similar to those observed in normal neuroblasts. These findings were later confirmed by Murray and Stout in investigations done in vitro cultures of Neuroblastoma cells. Pepper described a supposed propensity for hepatic metastases (Pepper Metastases) in young children with Neuroblastoma, and Hutchison described a predilection for skeletal metastases(especially in the skull) from a primary Adrenal lesion in older children (Hutchinson metastases) In 1916, William Barlett, in Missouri, achieved the first successful tumor resection in a boy that survived for more than 15 years. Cushing and Worbach reported in 1922, in a 10 review, the progression of neuroblastoma to ganglioneuroblastoma. In 1928, Fill and Dresser used radiotherapy as treatment for neuroblastoma without success. Cytotoxic agents were introduced in 1940 without therapeutic results. In 1957, Mason published a report of a boy with neuroblastoma whose urine contained amine vasoconstrictors. This discovery contributed to the best understanding of neuroblastoma and its possible origin in the sympathetic nervous system [1].