The association between neuroblastoma and opsoclonus-myoclonus syndrome: a historical review.

An association between neuroblastoma and opsoclonus-myoclonus syndrome (OMS) was described as early as 1927 within the first report on the transformation of malignant neuroblastoma to a benign ganglioneuroma. It was not recognized at that time nor was it appreciated in the subsequent follow-up report on the same patient in 1959. Myoclonic encephalopathy of infancy, an alternative name for OMS, was described by a pediatric neurologist in 1962; however, its connection to neuroblastoma was not known. It was only in 1968 that the association between these two conditions was first reported. The neuroblastoma tumors associated with OMS are almost all small, stage I-II with no associated MYCN amplification or metastases. OMS occurs in 2-3% of patients with neuroblastoma, but neuroblastoma is found in as many as 50% of children who present with OMS. Nearly 100% of the children with neuroblastoma associated with OMS survive, and this has led to speculation that the OMS is a result of an autoimmune process, not metastases. Affected children are treated with steroids, ACTH, or intravenous immunoglobulin, but many have persistent neurologic and developmental deficits. Using the original case reported in 1927, we summarize a century of literature in this review on OMS and its association with neuroblastoma.

Neuroblastoma-remembering the three physicians who described it a century ago: James Homer Wright, William Pepper, and Robert Hutchison.

Neuroblastoma is often widespread at the time of diagnosis. Three physicians between 1900 and 1910 played an important role in the pathologic definition of neuroblastoma and its route of spread in relation to the age of the patient. These findings eventually led to the advances in treatment and decreased morbidity of today. In 1910 James Homer Wright was the first to recognize the tumor as being of primitive neural cell origin, calling it neuroblastoma and emphasizing the bundle of cells termed rosettes. While Wright recognized the neural nature of the tumor, the authors of previous reports had described its two distinct patterns of spread. In 1901 William Pepper published a series of infants with massive hepatic infiltration associated with adrenal tumors without spread to bone, and in 1907 Robert Grieve Hutchison reported his experience with a similar pathologic process in older infants and children who had orbital and skull metastases. Wright's valuable unifying concept served to tie together the descriptions of Pepper and Hutchison. A century later the names of these physicians should be remembered-Wright, who defined the adrenal tumor as of primitive neural origin, Pepper for his clinically accurate report of massive liver involvement in the infant, and Hutchison for describing the propensity of the tumor to spread to bone in older children.

Milestones in the development of pediatric hematopoietic stem cell transplantation--50 years of progress.

In the 1950s, the first infusions of hematopoietic stem cells were given as a form of treatment for childhood leukemia. This heralded the beginning of a field that has expanded to include the treatment of immune deficiencies, a variety of leukemias and solid tumors, and then genetic diseases. A number of milestones are highlighted, particularly in regard to the use of alternative sources of hematopoietic stem cells such as unrelated donors, peripheral blood stem cells and umbilical cord stem cells. In addition, newer techniques of using non-myeloablative preparative regimens helped to reduce the toxicity and long-term consequences of hematopoietic stem cell transplant. Many diseases now benefit from the replacement of the marrow stem cells and the provision of a new immune system and improved immune surveillance.

Neuroblastoma overview--1986.

Understanding of the biology of neuroblastoma has advanced dramatically in the last several decades. Misunderstood and misdiagnosed in the early years of this century, neuroblastoma is now the prototypic model for research in the molecular biology and genetics of the transformed cell. It is through these advances in knowledge of the malignant process, and of neuroblastoma itself, that exquisitely targeted therapies will shortly evolve. These include not only immunologic approaches through monoclonal antibodies, but also the exploitation of metabolic pathways. Radioactive meta-iodobenzylguanidine (MIBG) is among the most promising of the latter methods. It is deservedly undergoing clinical tests for its diagnostic and therapeutic applications in the management of neuroblastoma patients.