MYCN Amplified Relapse Following Resolution of MYCN Nonamplified 4S Neuroblastoma With Placental Involvement: A Case Report and Review of the Literature.

Congenital neuroblastoma with placental involvement is exceptionally rare, but mortality is high. Detailed examination of placenta including MYCN amplification and segmental chromosomal aberrations should be performed in all suspected cases, as it is noninvasive and readily available. Maternal dissemination has not been reported. In this manuscript, we describe an infant with placental diagnosis of MYCN nonamplified congenital neuroblastoma. This is the first report of a recurrence of congenital 4S neuroblastoma following resolution in which MYCN amplification is only detected in the recurrence. Germline sequencing using a large comprehensive cancer panel did not reveal variants in candidate cancer predisposition genes.

Neuroblastoma in a Neonate: A Case Report.

Neuroblastoma represents approximately 6 to 10 percent of childhood cancers, yet is one of the most common solid tumors observed in neonates; approximately 700 cases are reported in the United States each year. Neuroblastoma occurs secondary to oncogene mutations that cause abnormal proliferation of neural crest cells and tumor formation anywhere along the spinal cord. Visible manifestations include a blueberry rash and subcutaneous skin nodules. Common histologic findings include multifocal, small, round, blue cell tumors. Cytogenetics testing differentiates aggressive versus nonaggressive forms of neuroblastoma. Treatment ranges from supportive care to surgery and chemotherapy; targeted molecular therapies and immunotherapy offer opportunity to individualize treatment. Morbidity and mortality are contingent upon age at diagnosis and genetic abnormalities. Neonatal clinicians must establish and maintain active knowledge of the current science pertaining to this neoplasm to assist in early identification and timely initiation of medical management. This article presents a case report and comprehensive discussion of the state of the science on metastatic familial (congenital) neuroblastoma.

Fatal Congenital Retroperitoneal Neuroblastoma Diagnosed by Fetal Magnetic Resonance Imaging.

Congenital extra-adrenal neuroblastoma is a rare condition, which typically has a favorable prognosis. We present a unique case of extra-adrenal retroperitoneal neuroblastoma diagnosed by fetal magnetic resonance imaging, which ultimately leads to fetal hydrops and neonatal death.

Refractory Chylous Ascites Secondary to Neuroblastoma.

BACKGROUND: Neonatal ascites is a complex condition that often poses a diagnostic dilemma for the clinician. We present a case of neonatal ascites secondary to neuroblastoma. CASE PRESENTATION: Our neonatal patient had congenital and recurrent chylous ascites despite multiple postnatal paracenteses, which resolved with complete resection of a retroperitoneal neoplasm. CONCLUSION: Congenital neuroblastoma may present with chylous ascites, probably due to disruption of the lymphatic vasculature.

Fetal neck tumors - antenatal and intrapartum management.

In this review article we describe the ante- and perinatal management of fetal neck tumors. Although there are rare congenital anomalies, the clinical consequences for the fetus may be fatal and include airways obstruction, heart insufficiency, pulmonary hypoplasia and cosmetic effect. The right management allows to decrease the fetal and neonatal mortality and morbidity associated with the disease. It includes intrauterine therapy in some cases, mostly in a goitrus hypothyroidism of the fetus, but firstly, an assessment of the fetal airways patency with a subsequent, eventual Ex-Utero Intrapartum Treatment (EXIT).

Congenital Adrenal Neuroblastoma With and Without Cystic Change: Differentiating Features With an Emphasis on the of Value of Ultrasound.

OBJECTIVE: The purpose of this study was to compare the features of congenital adrenal neuroblastomas with and without cystic changes and to emphasize the value of ultrasound in the diagnostic evaluation of cystic congenital adrenal neuroblastoma. MATERIALS AND METHODS: A total of 41 patients with surgically confirmed congenital adrenal neuroblastoma were enrolled. We divided the patients into two groups according to presence or absence of cystic change in the tumor, as determined from the initial ultrasound findings. Clinical and laboratory findings, disease stage, and patient outcome were investigated with a statistical comparison between the two groups. The imaging findings for cystic congenital adrenal neuroblastoma were reviewed to compare the additional diagnostic value of CT and MRI when paired with ultrasound. RESULTS: There were 22 patients (54%) in the group without cystic changes and 19 patients (46%) in the group with cystic changes. Prenatal detection and absence of metastasis were significantly more common in the cystic group than in the noncystic group (p < 0.05). Sensitivities of tumor marker levels were also significantly lower in the cystic group. Patient outcome was excellent, and there was no significant difference between the groups. With regard to imaging of cystic congenital adrenal neuroblastoma, in the 15 cases in which CT or MRI was paired with ultrasound, no additional diagnostic information was discerned with CT or MRI. CONCLUSION: Nearly one-half of congenital adrenal neuroblastomas are cystic, and these tumors have clinical and laboratory features that distinguish them from noncystic congenital adrenal neuroblastoma. Diagnostic tests, including CT, MRI, and assessment of tumor markers, have low diagnostic value in the evaluation of cystic congenital adrenal neuroblastoma.

Congenital neuroblastoma with symptoms of epidural compression at birth.

The occurrence of congenital neuroblastoma presenting at birth with symptoms of epidural compression secondary to spinal canal invasion is rare. Almost all cases reported in the literature have survived from the tumor but suffer severe sequelae, with the exception of the 2 most recently described whose birth was anticipated. The 3 cases of this article have been followed for a minimum of 5 years with the aim to describe their definitive late complications. In none of these cases had the routine ultrasound scan performed in third trimester of pregnancy discovered a tumor mass, nor had it shown abnormal fetal movements. All had leg hypotonia detected on the first day of life. In all, both primary and intraspinal tumors responded well to chemotherapy. All survive with motor deficit and severe bladder dysfunction despite early physiotherapy. Scoliosis has developed in the case with the longest follow-up. The description of these patients enforces the importance of early diagnosis of tumor masses in late pregnancy. Neonatologists should be aware of this rare clinical entity and take it into account in the differential diagnosis with other conditions of early-onset hypotonia. On the other hand, obstetric sonologists should be aware of the possibility to detect such rare tumors in late pregnancy, as anticipation of delivery may reduce the risk of late sequelae.

Congenital neuroblastoma in a neonate with isotretinoin embryopathy.

We describe a neonate with isotretinoin embryopathy and an incidental finding of congenital neuroblastoma. Diffuse liver metastases led to the decision to provide oncologic therapy followed by tumor resection. Despite the possible need for chronic care related to the comorbidities of the isotretinoin embryopathy and oncologic management, the patient remains disease-free. Because of the uncertain etiology of neuroblastoma, it remains unclear whether exposure to isotretinoin during embryogenesis and fetal development had an oncogenic effect on this patient.

Management of cervicomediastinal neuroblastoma presenting with life-threatening tracheal obstruction in infancy.

The authors report on 3 infants below 6 months of age at diagnosis, with cervicomediastinal neuroblastoma who presented with life-threatening tracheal obstruction as an oncologic emergency. These neuroblastomas were characterized by favorable biology and chemoresistance. All initially grew rapidly before spontaneously regressing. Nerve injuries occurred in all patients as a result of tumor location. Maintenance of the airway until the expected spontaneous regression was a critical component in the management of these patients.

Long-term follow-up of the "wait and see" approach to localized perinatal adrenal neuroblastoma.

BACKGROUND: Evidence-based guidelines for the management of localized perinatal adrenal neuroblastoma are not yet available. We describe our preliminary experience managing this tumor with a "wait and see" policy. METHODS: A single-center prospective study (February 2002 to December 2009) was conducted with 12 consecutive patients in whom an adrenal mass was detected antenatally or within the first 3 months of life. Diagnostic workup included the following investigations: measurement of urine catecholamine metabolites, imaging studies (ultrasonography, magnetic resonance imaging, or computed tomography), metaiodobenzylguanidine scintigraphy, and/or core needle biopsy. RESULTS: The male/female ratio was 1.4:1.0. Median tumor size at presentation was 29 mm (range 10-50 mm). Eight lesions were detected antenatally. Ten lesions were diagnosed as localized neuroblastoma. Of these ten lesions, four were excised because of parental preference (n = 2), tumor enlargement (n = 1) or tumor persistence (n = 1). The remaining six patients underwent watchful clinical observation, which showed progressive tumor shrinkage and complete regression within 10-39 months (median 12.5 months). The final two lesions were small predominantly cystic lesions without a clear-cut diagnosis. They were managed noninvasively. At an overall median follow-up of 109 months (range 30-122 months), all patients are alive and disease-free, although one patient progressed to stage 4 disease despite early excision of the primary tumor. CONCLUSIONS: Spontaneous regression of localized perinatal adrenal neuroblastoma occurs often, and a "wait and see" strategy seems justified in these small infants. Patients with enlarging or stable lesions that have persisted for several months may benefit from surgery, although prompt excision may not prevent tumor progression.

Congenital neuroblastoma: an autopsy report.

Neuroblastoma (NB) is the foremost malignant neoplasm of the fetus and neonate. It has a distinct biologic behavior and varied clinical manifestations. The perinatal tumors are most frequently associated with a favorable outcome. We describe an autopsy case of a 2-day-old baby with congenital NB of the left adrenal with extensive metastatic deposits in the liver. Despite the tumor having a favorable histology, it proved to be fatal with death occurring on the second day of life.

Germline gain-of-function mutations of ALK disrupt central nervous system development.

Neuroblastoma (NB) is a frequent embryonal tumor of sympathetic ganglia and adrenals with extremely variable outcome. Recently, somatic amplification and gain-of-function mutations of the anaplastic lymphoma receptor tyrosine kinase (ALK) gene, either somatic or germline, were identified in a significant proportion of NB cases. Here we report a novel syndromic presentation associating congenital NB with severe encephalopathy and abnormal shape of the brainstem on brain MRI in two unrelated sporadic cases harboring de novo, germline, heterozygous ALK gene mutations. Both mutations are gain-of-function mutations that have been reported in NB and NB cell lines. These observations further illustrate the role of oncogenes in both tumour predisposition and normal development, and shed light on the pleiotropic and activity-dependent role of ALK in humans. More generally, missing germline mutations relative to the spectrum of somatic mutations reported for a given oncogene may be a reflection of severe effects during embryonic development, and may prompt mutation screening in patients with extreme phenotypes.

Clinical features and surgical outcome of a suprarenal mass detected before birth.

PURPOSE: With the widespread use of the obstetrical ultrasound, identification of a fetal suprarenal mass has become more common. Most of these masses prove to be congenital neuroblastomas (CNB), but the diagnosis is often confused with other benign lesions and the postnatal management remains to be controversial. METHODS: The medical records of 18 patients that underwent primary surgical excision for an antenatally detected suprarenal mass, between January 1995 and April 2009, were reviewed. The clinical, radiological, surgical, and pathological data were collected. Staging evaluation was performed after histological confirmation of the CNB. RESULTS: There were 13 cases of CNB, 1 adrenal cyst, 2 adrenal hemorrhages, and 2 pulmonary sequestrations. The differential diagnosis was impossible before surgery. Most of the CNBs were stage I (N = 11), with 1 stage IV and 1 stage IV-S. Four patients (3 stage I and 1 stage IV-S) had more than one copy of N-myc gene. The stage I patients were cured by surgery alone, and stage IV patients underwent nine cycles of adjuvant chemotherapy and currently have no evidence of disease. The five benign lesions were cured with excision alone. There were no postoperative complications. CONCLUSION: For early diagnosis and treatment, surgical excision should be considered as the primary therapy for an antenatally detected suprarenal mass. The surgery can be safely performed during the neonatal period and provides a cure in most cases.

Congenital Neuroblastoma.

Neuroblastoma is the most common extracranial solid tumor diagnosed during childhood and gives rise to various heterogeneous tumors along the sympathoadrenal axis. Congenital neuroblastoma accounts for 5% of total neuroblastoma cases diagnosed annually, with the majority of cases diagnosed in the first month after birth. Interestingly, neonates demonstrate a unique disease trajectory compared with children older than 1 year of age. This article will provide information on the pathogenesis and variable clinical presentation of congenital neuroblastoma, along with the biological prognostic factors that predict long-term outcomes in affected neonates.

Congenital stage 1 neuroblastoma evolved into stage 4s.

A newborn with a prenatally detected adrenal mass underwent complete resection of a stage 1 favorable histology neuroblastoma (NB) without MYC-N amplification. Two months later, the infant presented with a local recurrence and multiple hepatic metastases. Close follow-up without therapy was adopted for stage 4s NB. Enlarging tumor lesions were seen until the child was 8 months old, followed by later decrease in size. At 36 months of follow-up, the child is alive and disease-free. We describe this case of NB and its abnormally short evolution from stage 1 to stage 4s, despite initial surgery. Its spontaneous regression may help us understand the natural history of congenital NB.

The observation of congenital retroperitoneal large size neuroblastoma.

The article represents current literature data on epidemiological, clinical-morphological features and diagnostic criteria of neuroblastoma. The case of large congenital neuroblastoma with multiple metastases in the newborn child is presented. The histological picture and immunohistochemical profile of the tumor allowed us to consider this type of neuroblastoma as the least differentiated variant (subtype, "neuroblastoma rich in Schwann stroma"), with rapid progression and metastasizing started before the birth of the child.

[Acute shock secondary to congenital neuroblastoma: Neonatal case report]. / Shock agudo secundario a un neuroblastoma congénito: Caso clmico neonatal.

Congenital neuroblastoma is the most frequent malignant solid tumor in the neonatal period. The clinical presentation is usually either by prenatal diagnosis or by palpation of an abdominal mass. Staging allows classifying it according to risk groups with a different prognosis and treatment. In the neonatal period, it is characterized by a high rate of spontaneous regression and good prognosis (disease-free survival at 5 years greater than 90 %). We present a clinical case of congenital neuroblastoma whose presentation, shock and hypertension, was only described on a previous occasion. Antihypertensive treatment along with systemic chemotherapy produced clinical control and patient improvement.

El neuroblastoma congénito es el tumor sólido maligno más frecuente en el período neonatal. La forma de presentación suele ser por diagnóstico prenatal o por una masa abdominal. Su estadificación permite clasificarlo en grupos de riesgo con pronóstico y tratamiento diferentes. En el período neonatal, se caracteriza por la alta tasa de regresión espontánea y el buen pronóstico (supervivencia libre de enfermedad a los 5 años superior al 90 %). Se presenta un caso clínico de neuroblastoma congénito cuya forma de presentación, shock e hipertensión, solo estaba descrita en otra ocasión antes. El tratamiento antihipertensivo, junto con la quimioterapia sistémica, produjo el control clínico y la mejoría del paciente.