Ovarian involvement in neuroblastoma

A case of neuroblastoma involving the ovaries bilaterally at diagnosis is reported. A review of previous cases of neuroblastoma at Johns Hopkins Hospital revealed no previous occurrence of ovarian metastatic disease at diagnosis, but involvement in about one-third of cases at autopsy. This appears to be a more common site of metastatic disease than has been previously recognized. The significance of this site of metastases in neuroblastoma is unknown.     

Infantile neuroblastoma of the urinary bladder detected by hematuria

Malignant tumors of the urinary bladder in infants are extremely rare. Rhabdomyosarcoma is the most likely tumor in this site, whereas neuroblastoma of the urinary bladder is exceedingly uncommon and is not listed as a differential diagnosis for tumors of this site. We present a case of neuroblastoma arising from the dome of the bladder wall, detected by hematuria. Only six cases of neuroblastoma originating from the bladder, including the present case have been reported. Of the cases, five arose from the dome of the bladder wall. In this report, the differential diagnosis of bladder tumors in children is discussed. A diagnosis of neuroblastoma should be taken into consideration, especially in the case of tumors arising from the dome of the bladder wall despite an uncommon location.     

Diagnosis of neuroblastoma by electron microscopy of bone marrow aspirates.

Three patients are reported in whom the diagnosis of neuroblastoma was made following electron microscopy of a bone marrow aspirate. The ultrastructure of neuroblastoma cells is distinctive, and they can be distinguished by electron microscopy from cells of the other tumors with which neuroblastoma is often confused by light microscopy. The rapidity with which the diagnosis can be obtained through use of this procedure argues for its adoption in any patient in whom the diagnosis is suspected and who has tumor cells in bone marrow. Early initiation of appropriate therapy is made possible, and elaborate diagnostic procedures may be avoided.     

Lacking immunocytological GD2 expression in neuroblastoma: report of 3 cases

Immunocytological bone marrow assessment for contamination with neuroblastoma cells is based on their characteristic GD2 surface staining. Neuroblastoma without GD2 expression have been rarely and only after antibody therapy reported. Conventional cytology was performed using Pappenheim staining. For immunocytology, the APAAP method was utilized with the 14G2a anti-GD2 mouse monoclonal antibody. 7 x 10(5) cells on cytospin preparations were investigated. In 2003, 288 bone marrow samples from 191 neuroblastoma patients were investigated by cytology and immunocytology. Three cases demonstrated GD2 negativity on cytologically unambiguous neuroblastoma cells. Two female cases (94 and 37 months of age) with stage 4 neuroblastoma had GD2 expressing neuroblastoma cells in bone marrow at diagnosis. At 2nd relapse 25 and 23 months after diagnosis and 8 months and 12 months after anti-GD2 antibody treatment (ch14.18), the bone marrow infiltrating neuroblastoma cells lacked GD2 staining. The third patient, a 63-month-old girl with bone marrow replacement by neuroblastoma cells showed at diagnosis a mixture of GD2-unstained tumor clumps and very weakly stained neuroblastoma cells. Neuroblastoma cells may lack GD2 expression at diagnosis and at recurrence. This observation has diagnostic and therapeutic implications.     

131I-metaiodobenzylguanidine in the treatment of neuroblastoma at diagnosis

Radioactive metaiodobenzylguanidine (131I-MIBG) is taken up specifically by neuroblastoma cells and appears to represent a new treatment modality in patients with advanced neuroblastoma. Taking into account the fact that all patients so far treated were heavily pretreated and resistant to chemotherapy, the results obtained appear encouraging. In order to explore further the potential role of this new drug in untreated patients, we treated with 131I-MIBG a child with stage III neuroblastoma at diagnosis. We observed the complete disappearance of a large abdominal tumor mass after a relatively low dosage of 131I-MIBG, with minimal hematologic toxicity. No further treatment was given and, at present, the patient is alive with no evidence of disease 18 months from diagnosis. This child represents, to our knowledge, the only case of neuroblastoma thus far treated at diagnosis and the excellent response obtained suggests the need for further investigations of this therapy in untreated patients.     

Cystic fibrosis and neuroblastoma

Two cases of coexistent cystic fibrosis and infantile thoracic neuroblastoma are presented. In one patient, neuroblastoma was congenital, and diagnosis of cystic fibrosis was made at 3 months of age; in the other, the diagnosis of cystic fibrosis was made at 7 months of age, preceding that of neuroblastoma by 4 months. In both infants, surgical resection of the tumors have been successful. Recent advances in the genetic aspects of neuroblastoma, including translocation and activation of the oncogene N-myc, are discussed. Current recombinant DNA technology, which can identify translocation of N-myc and allow localization of the cystic fibrosis gene if the translocation occurs near the cystic fibrosis allele, is being applied to these cases.     

Significance of pleural effusion in neuroblastoma

BACKGROUND: Pleural effusion is uncommon at diagnosis of neuroblastoma in children. Because the presence of malignant cells in pleural fluid may significantly change the management and outcome of patients with neuroblastoma, we retrospectively analyzed a cohort of neuroblastoma patients who presented with pleural effusion at the time of diagnosis to determine the incidence, presentation, stage, treatment, and outcome of these patients. METHODS: We reviewed the presenting features of 295 patients with the diagnosis of neuroblastoma who received treatment at St. Jude Children's Research Hospital between 1991 and 2005. Patients were chosen for further analysis if pleural effusion had been identified on chest radiographs or computed tomography (CT) scans at diagnosis RESULTS: Thirty-one out of 295(10.5%) patients with neuroblastoma had pleural effusion identified at time of presentation. International neuroblastoma staging system (INSS) risk stratification was high risk in 29 cases and intermediate risk and low risk in 1 case each. The primary site of disease was abdomen in 26 patients; mediastinum in 5. We conducted cytologic analysis of pleural fluid of nine patients; the specimen of seven contained malignant cells. Eighteen of 31 patients died of progressive or recurrent disease. CONCLUSION: In patients with neuroblastoma, pleural effusion is usually associated with unfavorable biologic features and high-risk disease. Pleural fluid should be examined cytologically and at a time when the results would change the risk stratification. There was no statistically significant difference in the survival rate of the patients with high-risk neuroblastoma with or without malignant pleural effusion.     

Cystic metastatic cerebral neuroblastoma

Intracerebral neuroblastoma is an exceedingly rare manifestation of intracranial neuroblastoma and has been described as a solid lesion. Cystic metastatic intracerebral neuroblastoma has not been described. We report a case of histologically proven metastatic intracerebral neuroblastoma presenting in a cystic form 1 year after diagnosis and treatment of a solid intra-abdominal neuroblastoma. The imaging and clinical appearance of this case was indistinguishable from that of intracerebral cystic lesions caused by infection or inflammation. It has been suggested that, due to more aggressive treatment of neuroblastoma, patients are surviving longer and consequently intracranial involvement is becoming more frequent. It is important to be aware of this cystic manifestation of the disease.

     

Opsoclonus-myoclonus and anti-Hu positive limbic encephalitis in a patient with neuroblastoma

Opsoclonus-myoclonus syndrome (OMS) is seen in 2-3% of children with neuroblastoma and is believed to be caused by an autoimmune process elicited by the tumor. Although long-term neurologic sequelae are common in children with OMS, limbic encephalitis has not previously been reported. We report a child who developed limbic encephalitis associated with anti-Hu antibodies, 6 years after her initial diagnosis of neuroblastoma and OMS. This case demonstrates that patients with neuroblastoma and OMS are at risk for developing new paraneoplastic symptoms years after their original diagnosis and emphasizes the need for careful long-term follow-up.     

The laparoscopic approach of neuroblastoma

Neuroblastoma is one of the most common solid tumors, and the biopsy and excision of this tumor are often required as part of a planned multimodal treatment. In 1995, Holcomb and coworkers first reported endosurgical procedures for the diagnosis and treatment of pediatric malignancies; however, the usefulness of laparoscopic procedures for abdominal neuroblastoma is still unclear. Twenty-five laparoscopic biopsies for advanced abdominal neuroblastoma and nine laparoscopic excisions for localized abdominal neuroblastoma performed at Saitama Children's Medical Center were evaluated. The laparoscopic procedures significantly reduce the time to start postoperative feeding as well as the time to start postoperative chemotherapy and the duration of hospital stay. Also, the blood loss of laparoscopic excision of localized neuroblastoma was significantly little compared with that of open excision. Precise indications of laparoscopic procedure for the diagnosis and treatment of abdominal neuroblastoma provide better prognosis and quality of life for infants and children.     

Cystic neuroblastoma of the adrenal gland —A potential source of error in ultrasonic diagnosis

The ultrasonic findings in neuroblastoma of the adrenal gland are usually of a complex or echo producing mass. Cystic neuroblastoma of the adrenal gland is a rare entity. The ultrasonic findings in one such case are presented. The appearances were unusual in that the mass appeared totally transonic. A brief review of the literature concerning neuroblastoma is made and the differential diagnosis of similar ultrasonic masses is considered.     

PET-CT in detection of meningeal metastasis in neuroblastoma

Neoplastic meningitis is being recognized with increasing frequency in patients with cancer: the common causes being adenocarcinomas originating from the lung, stomach, breast, ovary, malignant melanoma, leukemia, lymphoma, Ewings sarcoma, rhabdomyosarcoma, retinoblastoma and primary CNS malignancies. Meningeal metastases, though rare can be seen in advanced stages of neuroblastoma. Recognition of meningeal metastases is crucial for successful diagnosis and prompt treatment of these patients. Here, we present two patients of neuroblastoma in whom positron emission tomography-computed tomography (PET-CT) examination resulted in detection of meningeal metastases at diagnosis; thus, emphasizing the need of inclusion of brain imaging in PET-CT protocol in all cases of advanced neuroblastoma.     

Three years of experience with random urinary homovanillic and vanillylmandelic acid levels in the diagnosis of neuroblastoma

During the last 3 years, random urine samples from 408 patients were tested for elevated homovanillic acid (HVA) and vanillylmandelic acid (VMA) levels to rule out the diagnosis of neuroblastoma. Thirty-seven of these patients had elevated HVA and/or VMA levels, and neuroblastoma was subsequently diagnosed. In three additional patients with negative test results (normal HVA and VMA levels), tumors were subsequently diagnosed (false-negative rate of 7.5%). Ten percent of the patients with neuroblastoma had normal HVA and 27.5% had normal VMA levels at the time of diagnosis. Only one patient (2.5%) with neuroblastoma had elevated VMA levels in the presence of normal HVA levels. More than 60% of the patients with neuroblastoma had urinary HVA and/or VMA levels higher than twice the upper limit of normal. No false-positive results were encountered. Age and stage distributions of the patients are shown, and the significance of the results is discussed.     

Clinical utility of fine needle aspiration in the diagnosis and management of neuroblastoma

Eleven fine needle aspiration (FNA) biopsies were performed in five children with neuroblastoma, including one patient with peripheral neuroectodermal tumor of the thoracopulmonary region (Askin tumor). Cytologic features in conjunction with immunocytochemistry and electron microscopy on the aspirated material enabled us to make a primary diagnosis in four of the five patients and diagnose local recurrence and metastatic disease in three patients. There were no false-positive or false-negative cytologic diagnoses; therefore, diagnostic accuracy was 100%. FNA is an extremely useful technique for the primary diagnosis and management of neuroblastoma and excludes other small cell malignancies of children. The results of this study and literature review demonstrate that FNA cytology coupled with ancillary techniques of immunocytochemistry and electron microscopy is a rapid, safe, minimally invasive procedure which can aid in the diagnosis and management of patients with neuroblastoma without resorting to more aggressive diagnostic procedures in selective cases.     

Ataxia and secretory diarrhea: two unusual paraneoplastic syndromes occurring concurrently in the same patient with ganglioneuroblastoma

The presence of rare paraneoplastic syndromes, the opsoclonus-myoclonus-ataxia syndrome (OMA), presumably caused by antineuronal antibody production, and diarrhea, caused by vasoactive intestinal peptide (VIP) secreted by neuroblastoma, may strongly signal the presence of neuroblastoma. The authors describe a child who presented with both syndromes concurrently; this has never been described previously in the same patient. However, diagnosis of neuroblastoma was delayed by a workup focused on the prolonged diarrhea rather than the ataxia. The diarrhea resolved after tumor resection, whereas OMA required further therapy. Increased awareness of VIP-secretory diarrhea, especially in an ataxic child, might contribute to an earlier diagnosis of neuroblastoma.     

Hemorrhagic intracranial parenchymal metastases from primary retroperitoneal neuroblastoma

An unusual case of parenchymal hemorrhagic metastases to the cerebrum and cerebellum in a child with retroperitoneal neuroblastoma is presented. While isolated parenchymal central nervous system (CNS) metastases have not typically been considered in association with neuroblastoma, review of the literature suggests an increased frequency of this manifestation, especially since 1980. Metastatic neuroblastoma should be included in the differential diagnosis of multiple hemorhagic parenchymal brain lesions in the pediatric population.     

Neuroblastoma with opsomyoclonus and turner syndrome

A neuroblastoma developed in a child with Turner’s syndrome (45, X), the second reported case of such an association. The initial symptom, opsomyoclonus, is associated with a better prognosis, as was evident in our case. The use of computed tomography is valuable in the diagnosis of occult neuroblastoma.     

Incidental neuroblastoma

The diagnosis of neuroblastoma in its early stage, especially in asymptomatic children, with the so-called incidentally diagnosed disease, may be associated with a good prognosis. The aim of this study is an attempt at analyzing this problem. Between 1 January 1993 and 30 April 1998, 40 children with newly diagnosed neuroblastoma started therapy at the authors' department. The disease was diagnosed incidentally in 5 (12.5%) patients. In no incidentally diagnosed child was stage IV disease detected, while in the remaining patients its incidence was 71%. All the children (median age 2 months) with incidental diagnosis have remained alive (median 39 months) in continuos remission without treatment. Among 35 children (median age 2 years and 7 months) with overt neuroblastoma, 18 died (median survival time 14.5 months). Seventeen patients have remained alive (median 45 months). The results show that children with incidentally diagnosed neuroblastoma are characterized by a more favorable prognosis than children with clinical disease.     

Thin-layer chromatography for diagnosis of secreting neuroblastoma

A thin-layer chromatographic technique for separation and identification of urinary phenolic acids is described. The method is simple enough to be used in the clinical laboratory and from it, an easy biochemical diagnosis of secreting neuroblastoma. The technique is also of interest for research in catabolism of catecholamines. Results obtained in 125 patients, including 8 patients with neuroblastoma are reported.