Congenital hemangioma in spondylocostal dysostosis: a novel association

Abstract Congenital hemangioma is a benign tumor caused by dysfunction in embryogenesis and vasculogenesis, which progresses during fetal life to manifest as fully developed at birth. Although hemangiomas are the most common tumor of infancy, rapidly involuting congenital hemangioma has not been described in spondylocostal dysostosis. I report the novel association of congenital hemangioma and spondylocostal dysostosis in a Mexican newborn female patient with neural tube defects. Given the embryological relationship between skin and nervous system, I surmise that this association is not coincidental. I also propose that these morphologic alterations be incorporated to the spondylocostal dysostosis phenotype and specifically looked for in other affected children, in order to provide appropriate medical management and genetic counseling.

Congenital hemangioma in spondylocostal dysostosis: a novel association.

Congenital hemangioma is a benign tumor caused by dysfunction in embryogenesis and vasculogenesis, which progresses during fetal life to manifest as fully developed at birth. Although hemangiomas are the most common tumor of infancy, rapidly involuting congenital hemangioma has not been described in spondylocostal dysostosis. I report the novel association of congenital hemangioma and spondylocostal dysostosis in a Mexican newborn female patient with neural tube defects. Given the embryological relationship between skin and nervous system, I surmise that this association is not coincidental. I also propose that these morphologic alterations be incorporated to the spondylocostal dysostosis phenotype and specifically looked for in other affected children, in order to provide appropriate medical management and genetic counseling.

The triad of nesidioblastosis, congenital neuroblastoma and glomerulocystic disease of the newborn: a case report.

Neuroblastoma is the most common malignant tumor of the newborn, comprising 20% of all malignancies encountered during the neonatal period. We herein report a newborn who was born after 29 weeks' gestation and died unexpectedly at the 12th hour of life with no response to vigorous cardiopulmonary resuscitation. Autopsy findings revealed a right pararenal mass; microscopic examination showed neuroblastoma. Although the pancreas was grossly normal, its microscopic sections revealed a reduced number of islets of Langerhans and dispersion of the islet cells throughout the exocrine cells of the pancreas, and immunocytochemistry for the pancreatic hormones confirmed the dispersion of the islet cells. Final pathologic interpretation thus concluded the presence of nesidioblastosis. Furthermore, microscopic examination of the kidney showed glomerulocystic disease. Although the association of congenital neuroblastoma and nesidioblastosis has recently been defined as a new complex, neurocristopathy, the triad of congenital neuroblastoma, nesidioblastosis and glomerulocystic disease of the newborn has not been reported previously. To our knowledge, our case is the first reported newborn presenting with this triad. In conclusion, the association of nesidioblastosis and/or renal glomerulocystic disease should be kept in mind when encountering a case of congenital neuroblastoma. However, whether the presence of glomerulocystic disease in association with those other neurocristopathic pathologies is a coincidental finding or shares a common pathophysiological mechanism remains to be determined.

"Vascular neurofibromatosis" and infantile gangrene.

An 11-year-old boy with slowly progressive gangrene caused by vasculopathy similar to that of neurofibromatosis (NF) type 1 (NF I; von Recklinghausen disease [NFvR]) and a newborn girl with idiopathic gangrene with vascular changes resembling those of NFvR prompted the analysis of all 105 propositi with NF (NF I and NF II) evaluated between January 2, 1982, and December 31, 1986, at the genetics clinic of University of South Florida. They were analyzed for renal hypertension, symptomatic ischemia, and known vascular changes. One additional 27-month-old boy with NFvR was found to have extensive vascular changes with renal hypertension. The vasculopathy indicated asymmetric over/undergrowth of cellular and extracellular components of the vascular wall and implied dysregulation of the paracrine growth mechanism. Immunocytochemical studies of affected vessels were done only in the 11-year-old boy and showed positive neuron-specific enolase, S-100 protein, and glial fibrillary acidic protein (GFAP) reactions indicative of Schwann cell involvement. The vascular changes in children with NFvR are mostly asymptomatic; however hypertension secondary to renal artery stenosis and/or Moya-moya disease have been reported infrequently. Our patients with vasculopathies provoked thoughts in regard to the so-called vascular NF, its place in current NF nomenclature and classification, relationship to fibromuscular dysplasia (FMD), and possible role in infantile gangrene.

Neurofibromatosis and associated neuroectodermal tumors: a congenital neurocristopathy.

The synchronous occurrence of neurofibromatosis and neuroblastoma has been labeled in the recent literature as a chance event. We report 2 cases of newborn infants with congenital neurofibromatosis and a similar midline pattern of multiple Schwann cell and neuroblastic tumors; other types of ectomesenchymal tumor differentiation are documented, along with supportive ultrastructural and immunohistochemical studies. The tumors may take an aggressive, fatal course despite maximal multimodality antitumor therapy. These 2 cases are reported, with additional literature review, to document a clinically recognizable neurocristopathy that links neuroblastic tumors and neurofibromatosis.

Diffuse, multicentric neurogenic tumors in two macerated fetuses: a possible intrauterine form of neurofibromatosis.

Two tiny macerated fetuses with a remarkably similar pattern of multicentric neurogenic neoplasms of both paravertebral autonomic structures and peripheral nerves are described. Maceration precluded further histologic classification of the neoplasms in either fetus. The first fetus had a Meckel's diverticulum, short attachment of the small bowel mesentery, pulmonary hypoplasia, and intrauterine growth retardation. The second had the sympus bipus variant of sirenomelia sequence. The multicentric neoplasms in these two fetuses are very similar to those previously described in a few neonates and one stillborn with well-documented or suspected neurofibromatosis. It is reasonable to hypothesize that these two fetuses may represent an early intrauterine expression of neurofibromatosis characterized by multicentric neurogenic neoplasms of autonomic structures and peripheral nerves. Detailed examination of early abortuses, especially those from families with neurofibromatosis, may help to confirm or disprove the hypothesis.

Morphology of transplacentally induced nervous system tumors in rats: some aspects of this model in neurooncology.

The morphology of 1136 single tumors of the nervous system induced by transplacental action of alkylating and related substances is analyzed. Tumors of the central nervous system are considered to yield the most representative model for the different stages of gliomas in humans. This and derived standardized models therefore are appropriate for studying open questions, especially as regards the treatment of human brain tumors.

Congenital malformations of the central nervous system and transplacental carcinogenesis: modification of ethylnitrosourea-induced brain tumors in rats by pretreatment with methylazoxymethanol.

X-irradiation of rat fetuses prior to exposing them transplacentally to the neurotropic carcinogen ethylnitrosourea (ENU) greatly reduces the frequency of offspring that develop neurogenic tumors. Since the tumor inhibition may have been related to the teratogenic effects of the irradiation of the fetal brain, it was of interest to learn whether another means of causing such brain damage would also interfere with the development of ENU-induced neurogenic tumors. For this purpose methylazoxymethanol (MAM), known to produce microencephaly, was used. Pregnant Sprague-Dawley rats were injected i.p. with 20 or 30 mg MAM/kg on the 15th day of gestation and 10 mg ENU/kg on the 16th or 20th day of gestation, or with either chemical alone. The offspring were observed during their life-span for the appearance of neurogenic tumors. MAM produced the expected microencephaly, but when administered alone caused no neurogenic tumors. ENU had no effect on brain size; and when administered alone produced high rates of offspring with neurogenic tumors (68 and 72% after treatment on the earlier and later day of gestation, respectively). The combined treatments resulted in significantly reduced frequencies of brain tumors, but did not modify the frequencies of non-brain tumors. The treatments caused relatively little or no excess pre- and postnatal mortality and for the most part had little effect on postnatal growth. Mean time of appearance of neurogenic tumors and mean number of neurogenic tumors per affected animal were unchanged by the dual treatments. There were no sex differences in tumor frequency, latency, or multiplicity. As noted, MAM reduced cerebral hemisphere size, but did not affect spinal cord size. The site of tumor inhibition by MAM thus appears to be correlated with the site of teratogenic damage. Nevertheless, various considerations led us to conclude that reduced number of target cells does not entirely explain the modifications in the frequency of tumors caused by MAM.

Chemical and viral agents in prenatal experimental carcinogenesis.

Malignant tumors are the second most common cause of death in children 0 to 15 years old. The typical organotropism of tumors in children is different than in adults aged 45-60 years. Due to the short induction periods, as well as the typical distribution of tumors, it is conceivable that various agents (chemicals, viruses) may induce carcinogenic effects during the prenatal life-span. It has been confirmed experimentally that certain chemicals, e.g., ethylnitrosourea, are potent prenatal carcinogens. Further, it is important to consider the especially high sensitivity of the fetus for chemical agents; this enhanced sensitivity is a major point of issue when discussing prenatal carcinogenesis. Results and conclusions obtained from prenatal carcinogenicity experiments should provide a basis for elucidating causes of cancer in children.