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Background: Ganglioneuroblastoma intermixed (GNBi) and ganglioneuroma (GN) represent benign variants of peripheral neuroblastic tumours. While historically surgical resection was recommended, watchful active observation has become the accepted management for a subset of patients., Objectives: To review clinical features, biology, natural history and management of a retrospective UK CCLG study cohort of GN and GNBi, and compare outcomes of patients treated with surgical resection or watchful active observation., Methods: Retrospective review of histologically confirmed non-metastatic GN and GNBi diagnosed between 1990 and 2020., Results: A total of 259 patients were identified (163 GN, 93 GNBi, median age 62 months). In all 201 (78%) had initial surgery and 58 (22%) were observed. Overall survival was 98%. Twenty-one of 58 observed (36%) required subsequent surgery due to progressive tumour growth (52%). Gross total resection (GTR) was achieved in 79% of patients with a 19% complication rate. GTR was obtained in a similar proportion of patients having initial surgery (65%) and delayed surgery (76%). Patients obtaining GTR were more likely to have complete symptom(s) control (43% vs. 24%). In 45 cases (39%), surgical pathology was different from pathology at biopsy, and in 14 (12%) the pathology changed from GN/GNBi to neuroblastoma/GNB nodular., Conclusion: Watchful active observation can be a safe approach, with surgical resection reserved for symptomatic patients. However, a small proportion of patients in the observation group had their diagnosis revised to malignant at surgery. Careful assessment of surgical risk and expected benefits, after considering an initial period of observation, will allow clinicians to make optimal decisions for patients and their families., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Background: Adult- and adolescent-onset neuroblastomas are rare, with no established therapy. In addition, rare pheochromocytomas may harbor neuroblastic components. This study was designed to collect epidemiological, diagnostic and therapeutic data in order to better define the characteristics of malignant peripheral neuroblastic tumors (MPNT) and composite pheochromocytomas (CP) with MPNT., Procedure: Fifty-nine adults and adolescents (aged over 15 years) diagnosed with a peripheral or composite neuroblastic tumor, who were treated in one of 17 institutions between 2000 and 2020, were retrospectively studied., Results: Eighteen patients with neuroblastoma (NB) or ganglioneuroblastoma (GNB) had locoregional disease, and 28 patients had metastatic stage 4 NB. Among the 13 patients with CP, 12 had locoregional disease. Fifty-eight percent of the population were adolescents and young adults under 24 years of age. The probability of 5-year event-free survival (EFS) was 40% (confidence interval: 27%-53%)., Conclusions: Outcomes were better for patients with localized tumor than for patients with metastases. For patients with localized tumor, in terms of survival, surgical treatment was the best therapeutic option. Multimodal treatment with chemotherapy, surgery, radiotherapy, and immunotherapy-based maintenance allowed long-term survival for some patients. Adolescent- and adult-onset neuroblastoma appeared to have specific characteristics associated with poorer outcomes compared to pediatric neuroblastoma. Nevertheless, complete disease control improved survival. The presence of a neuroblastic component in pheochromocytoma should be considered when making therapeutic management decisions. The development of specific tools/resources (Tumor Referral Board, Registry, biology, and trials with new agents or strategies) may help to improve outcomes for patients., (© 2024 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Peripheral neuroblastic tumors (neuroblastoma, ganglioneuroblastoma and ganglioneuroma) are heterogeneous and their diverse and wide range of clinical behaviors (spontaneous regression, tumor maturation and aggressive progression) are closely associated with genetic/molecular properties of the individual tumors. The International Neuroblastoma Pathology Classification, a biologically relevant and prognostically significant morphology classification distinguishing the favorable histology (FH) and unfavorable histology (UH) groups in this disease, predicts survival probabilities of the patients with the highest hazard ratio. The recent advance of neuroblastoma research with precision medicine approaches demonstrates that tumors in the UH group are also heterogeneous and four distinct subgroups-MYC, TERT, ALT and null-are identified. Among them, the first three subgroups are collectively named extremely unfavorable histology (EUH) tumors because of their highly aggressive clinical behavior. As indicated by their names, these EUH tumors are individually defined by their potential targets detected molecularly and immunohistochemically, such as MYC-family protein overexpression, TERT overexpression and ATRX (or DAXX) loss. In the latter half on this paper, the current status of therapeutic targeting of these EUH tumors is discussed for the future development of effective treatments of the patients.

Chronic abdominal pain is a very common complaint in the population of children and adolescents. In most cases, the usual cause are functional gastrointestinal disorders. However, in a few percent of children, the reason for persistent chronic stomach pain are organic diseases occurring in the gastrointestinal tract, as well as parenteral diseases, including uro-genital tract abnormalities, inflammation of the lower respiratory tract and cancer processes. Among organic causes, in addition to those commonly encountered, such as: intolerances and food allergies, gastroesophageal reflux disease, chronic gastritis or duodenitis, or urinary tract infections, the diagnosis should also include very rare causes, for example, neoplastic diseases, among them tumors of the abdominal cavity. In the case described in the present article, a 6-year-old girl with chronic abdominal pain, symptoms of gastro-oesophageal reflux and constipation, and previously diagnosed food allergy and lactose intolerance, was referred for widening the diagnosics due to the occurrence of alarm symptoms. The nodule revealed in the chest X-ray, in CT scan, turned out to be a paravertebral tumor with the specific features of neuroblastoma. After a macroscopically complete tumor resection based on the result of histopathological examination, the diagnosis of ganglineuroblastoma was established. The presence of alarm symptoms in anamnesis and physical examination in children with abdominal pain suggests a higher probability of the organic origin of the disease and should always lead to extended diagnostics. Ganglioneuroblastoma is a very rare disease, in most cases is located primarily in the abdominal cavity, and the most common associated symptom is abdominal pain.

Rationale: Intracranial ganglioneuroblastoma represents a rare subtype of primitive neuroectodermal tumor. Here, we report a hippocampal ganglioneuroblastoma and a literature review of cerebral anglioneuroblastoma is carried out., Patient Concerns: We report a 16-year-old male patient presenting with absence seizure and high-infiltration hippocampal ganglioneuroblastoma., Interventions: Magnetic resonance imaging (MRI) indicates a space-occupying lesion with a well-defined margin in the right temporal lobe and hippocampus. However, hyper-signal on flair and diffusion-weighted imaging (DWI) with a low apparent diffusion coefficient (ADC) value is detected, which prompts high tumoral invasiveness., Interventions: A total resection of tumor and subsequent chemotherapy combing with radiotherapy is performed., Outcomes: For a follow-up period of 60 months, no evidence of recurrence and further seizures are detected., Lessons: High-infiltration hippocampal ganglioneuroblastoma is a rare event. MRI examination often showed features of low-grade gliomas, while hyper-signal lesion on DWI with a low ADC value can be detected. Complete resection combined with fractionated radiotherapy and chemotherapy was the optimal treatment for cerebral ganglioneuroblastoma., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Purpose  We explored the diagnostic value of diffusion-weighted MRI (DWI) for tumor characterization, differentiation and therapy monitoring in pediatric patients with extracranial neuroblastic tumors. Materials and Methods  All 29 patients (14 girls, median age: 3 years) with neuroblastoma (NB, n = 19), ganglioneuroblastoma (GNB, n = 4) and ganglioneuroma (GN, n = 6) who had had at least one in-house DWI examination since 2005 were identified and retrospectively analyzed. Two independent blinded readers measured ADC values (unit: 10-3 mm 2 /s) and signal intensity ratios (SIRs) of the primary tumor and, if applicable, of the tumor after chemotherapy, metastases and tumor relapse. Results  The pre-treatment ADC was 0.90 ± 0.23 in NB/GNB and 1.70 ± 0.36 in GN without overlap between the two entities for both readers, 0.67 ± 0.14 in metastases and 0.72 ± 0.18 in tumor relapse. With chemotherapy, mean ADC increased to 1.54 ± 0.33 in NB/GNB and to 1.23 ± 0.27 in metastases (p < 0.05). The median SIRs of various tumor lesions vs. liver, vs. muscle tissue and vs. adjacent tissue were significantly higher on DWI (range: 2.4 - 9.9) than on ce-T1w (range: 1.0 - 1.8, all p < 0.05). The coefficient of variation (CV) was ≤ 8.0 % for ADC and ≤ 16.4 % for signal intensity data. Conclusion  Based on mean ADC, DWI distinguishes between NB/GNB and GN with high certainty and provides plausible quantitative data on tumor response to therapy. Lesion conspicuity, as measured by SIR, is superior on DWI, compared to ce-T1w. DWI as a noninvasive, radiation-free and widely available imaging technique should be an integral part of MR imaging for neuroblastic tumors and should undergo prospective evaluation in multicenter studies. Key Points   · DWI reliably distinguishes neuroblastoma/ganglioneuroblastoma from ganglioneuroma, based on the mean ADC.. · DWI provides plausible quantitative data on tumor response to chemotherapy.. · DWI offers highly superior lesion conspicuity compared to contrast-enhanced T1w imaging.. · DWI should be considered a standard for imaging neuroblastic tumors.. Citation Format · Neubauer H, Li M, Müller VR et al. Diagnostic Value of Diffusion-Weighted MRI for Tumor Characterization, Differentiation and Monitoring in Pediatric Patients with Neuroblastic Tumors. Fortschr Röntgenstr 2017; 189: 640 - 650., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

We report a patient with stage 3 ganglioneuroblastoma who initially presented with clinical and laboratory features consistent with mucopolysaccharidosis including coarse facial features, developmental delay, and an elevated quantitative urine glycosaminoglycan (GAG) level. All mucopolysaccharidosis features resolved following successful treatment of neuroblastoma. High GAG levels have been documented in the pediatric oncology literature, yet not as a potential marker of malignancy or other target for clinical utility. This patient prompts further investigation into the relationship between neuroblastoma and elevated GAG levels.

Background: Ganglioneuroma (GN) and ganglioneuroblastoma intermixed (GNBI) are mature variants of neuroblastic tumors (NT). It is still discussed whether incomplete resection of GN/GNBI impairs the outcome of patients., Methods: Clinical characteristics and outcome of localized GN/GNBI were retrospectively compared to localized neuroblastoma (NB) and ganglioneuroblastoma-nodular (GNBN) registered in the German neuroblastoma trials between 2000 and 2010., Results: Of 808 consecutive localized NT, 162 (20 %) were classified as GN and 55 (7 %) as GNBI. GN/GNBI patients presented more often with stage 1 disease (68 % vs. 37 %, p < 0.001), less frequently with adrenal tumors (31 % vs. 43 %, p = 0.001) and positive mIBG-uptake (34 % vs. 90 %, p < 0.001), and had less often elevated urine catecholamine metabolites (homovanillic acid 39 % vs. 62 %, p < 0.001, vanillylmandelic acid 27 % vs. 64 %, p < 0.001). Median age at diagnosis increased with grade of differentiation (NB/GNBN: 9; GNBI: 61; GN-maturing: 71; GN-mature: 125 months, p < 0.001). Complete tumor resection was achieved at diagnosis in 70 % of 162 GN and 67 % of 55 GNBI, and after 4 to 32 months of observation in 4 GN (2 %) and 5 GNBI (9 %). Eleven patients received chemotherapy without substantial effect. Fifty-five residual tumors (42 GN, 13 GNBI) are currently under observation (median: 44 months). Five patients (3 GN, 2 GNBI) showed local progression; all had tumor residuals > 2 cm. No progression occurred after subtotal resection. Two patients died of treatment, none of tumor progression., Conclusions: GN/GNBI account for one quarter of localized NT and differ from immature tumors in their clinical features. Chemotherapy is not effective. Subtotal resection appears to be a sufficient treatment., Trial Registration: ClinicalTrials.gov identifiers - NB97 (NCT00017225; registered June 6, 2001); NB2004 (NCT00410631; registered December 11, 2006).

Background: Neuroblastoma in the adult is rare. No established therapeutic guidelines exist for these patients and the literature on this issue is scant and contradictory., Materials and Methods: Between 1986 and 2011, 21 adults (18 to 38 y; median, 23) diagnosed with neuroblastoma were referred to our hospital. Three of the 21 were classified as neuroblastoma, not otherwise specified, 13 as neuroblastoma, schwannian stroma-poor, and 5 as ganglioneuroblastoma, nodular. Nine patients had a resectable (stage 1/2) and 6 an unresectable primary tumor (stage 3); 6 had disseminated disease (stage 4)., Results: Of 9 stage 1/2 patients, 6 underwent surgery alone (2 survive, 4 died), 2 received adjuvant chemotherapy (both survive), and 1 received radiation therapy (alive). Four of the 6 stage 3 patients received chemotherapy and died, 1 underwent partial tumor resection only and died, and 1 received radiation therapy after partial tumor resection and is alive. The 6 stage 4 patients received chemotherapy with/without radiotherapy, and all died. Event-free survival at 10 years was 33.3% for stage 1/2, 16.7% for stage 3, and 0% for stage 4 patients. The 10-year overall and event-free survival rates were 39.8% and 19.1%, respectively., Conclusions: The outcome of neuroblastoma in adults is poorer than in younger patients at all stages. The clinical course seems modestly influenced by therapy.

We describe a 4-year-old girl with acute onset headaches and transient blindness who underwent surgical intervention, chemotherapy, and radiotherapy for an intracranial mass. This mass was pathologically confirmed as a primary intracranial ganglioneuroblastoma, a rare finding in the pediatric population. The literature on pediatric primary intracranial ganglioneuroblastoma is reviewed., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Neuroblastomas and ganglioneuroblastomas (NB/GNB) are malignant tumors that rarely occur in adults. Their disease progression and appropriate treatment are unclear., Methods: All adults (age ≥18 years) were evaluated for histologically confirmed NB/GNB within our institution. Data were collected via chart review and direct patient contact., Results: From 1980 to 2009, a total of 15 adult patients with NB/GNB were evaluated: six men (mean age 23 years, range 19-33 years) and nine women (mean 34 years, range 20-66 years). Their overall average age at diagnosis was 30 years. Tumor-related symptoms occurred in ten patients: Pain (abdominal 3, back 2, pelvic 1, groin 1) was more common than a mass (abdominal 2) or dysmenorrhea (1). Five patients had tumors found incidentally by computed tomography (4) or chest radiography (1). Primary tumor origins were in the pelvis (4), mediastinum (3), abdomen (2), adrenal gland (2), retroperitoneum (2), and mixed locations (2). Altogether, 12 patients underwent surgical resection (biopsy in 3; resections of R0 in 5, R1 in 3, R2 in 4). Ten underwent chemotherapy. Histology showed four GNBs and 11 NBs. Five patients with stage I disease survived a mean of 21 years (range 10-40 years). Two are alive today. Three stage III patients died at 2, 6, and 9 years after diagnosis (mean 5.7 years). Six of seven patients (one was lost to follow-up) with initial stage IV neuroblastoma died within 5 years (mean 2.7 years). NB and GNB patients had similar survivals., Conclusions: Adult-onset NB/GNB is rare. Symptoms appear to occur later when incurable stage IV disease is detected. Complete surgical resection can lead to long-term, disease-free survival in stage I patients.

We conducted an observation program of neuroblastoma in infants, detected by mass screening at 6 months of age; we followed up with them for 15 years. No recurrence was observed after disappearance of tumors, and persistent tumors showed no malignant transformation or metastasis. Histology of the resected tumors showed age-related differentiation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The most common malignant neurogenic tumors in children are neuroblastic tumors, classified as ganglioneuroblastoma or neuroblastoma. Ganglioneuroblastomas usually occur at the sympathetic ganglia in the mediastinum, whereas neuroblastomas occur in the abdominal cavity. We describe a case of large posterior mediastinal ganglioneuroblastoma extending from the aortic arch to the left renal hilum in a 17-year-old boy. Despite chemotherapy, post-treatment computed tomography showed disease progression. The patient underwent a thoracolaparotomy incision and excision of the tumor. These malignant mediastinal tumors can potentially grow to a very large size. If alternative treatment has failed, resection can be accomplished with relative safety., (© The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

We report the case of a 3-year-old girl with a mediastinal mass, severe anemia, leukocytosis and neutropenia, in whom, after initial suspicion of metastatic neuroblastoma, a final diagnosis of concurrent ganglioneuroblastoma and acute lymphoblastic leukemia was made. The mediastinal tumor was surgically excised and the child subsequently underwent chemotherapy for acute lymphoblastic leukemia. The patient remains in complete remission from both diseases 4 years after the diagnosis and 24 months after completion of all treatment. The simultaneous occurrence of 2 different neoplasms in a child is very infrequent, and no comparable cases are reported in the literature.

Most vasoactive intestinal peptide (VIP)-producing tumours are from epithelial origin. Tumours derived from the sympathetic nervous system can produce VIP as well. We report here the case of a Verner-Morrison syndrome in a 40-year-old woman revealing a metastatic ganglioneuroblastoma. The diarrhea resolved after the resection of primary tumour and liver metastases. Neuroblastic tumours occur extremely rarely in adults. Thus, the management of these tumours is poorly defined in adults.

Ganglioneuroblastic differentiation in malignant melanomas is an exceedingly rare event. Although there has been a single report of this occurrence in a metastatic melanoma, divergent ganglioneuroblastic differentiation has not been documented previously in a primary cutaneous lesion of melanoma. The present report describes an unusual case of invasive melanoma arising on the lower leg of a 61-year-old woman. The 16.9-mm thick tumor showed extensive ganglioneuroblastic differentiation, which was confirmed both immunohistochemically and ultrastructurally. Although the prognostic significance of this observation remains uncertain, the unique case reaffirms the potential morphologic diversity of melanomas and suggests a shared histogenetic origin from a common neural crest derivative.

Introduction: The neuroblastoma (NB) is one of the most common pediatric malignant neoplasms. The most commonly used tumor markers in the diagnosis and follow-up of this tumor are the serum neuron-specific enolase (NSE), ferritin and lactic dehydrogenase and urinary vanillymandelic and homovanillic acid. The common imaging modalities are CT, MRI and 123I or 131I-meta-iodobenzylguanidine scintigraphy., Aim: The aim of this study is to assess the value of 123I-meta-iodobenzylguanidine (MIBG) scintigraphy and serum determinations of NSE and ferritin in the diagnosis and evolution of NB patients., Material and Methods: 20 patients (8 female, 12 male) whose ages ranged from 2 months to 9 years with a mean age of 2.64 years diagnosed of NB. 47 123I-MIBG scans, 47 NSE determinations and 47 ferritin ones were selected., Results: At the time of diagnosis, 100% of the 123I-MIBG scans were positive. 65% of NSE determinations presented clearly pathological levels and 15% were very near to the cut-off point. Only 45% of the ferritin levels were increased. The differences between the lesions visible by 123I-MIBG scanning before and 3 months after treatment as well as NSE and ferritin levels were studied. When the Student's T test was applied, we found statistically significant pre and post-treatment differences in 123I-MIBG scanning and NSE. In the case of ferritin, there was no statistical significance in spite of the decrease in the values. The direct correlation and Spearman correlation between laboratory data and 123I-MIBG scanning as well as correlation between NSE and ferritin were also studied. There was a good correlation between 123I-MIBG and NSE and between NSE and ferritin. We have also studied the data in 7 relapses., Conclusions: 123I-MIBG scintigraphy and serum determination of NSE are two successful diagnostic tools for the diagnosis and evolution of NB patients.

Background: Gangliosicle GD2 is abundant on human neuroblastoma (NB). Monoclonal antibody 3F8 targeted to GD2 may have imaging and therapeutic potential. Antigen-negative clones can escape immune-mediated attack leading to clinical resistance or recurrence., Procedure: Among 95 evaluable patients treated intravenously with 3F8 (94 Stage 4, 1 Stage 3), 66 received nonradiolabeled 3F8, 11 received 131-iodine-labeled-3F8 (8-28 mCi/kg) with autologous bone marrow rescue, and 18 received both forms of treatment. Prior to treatment, 90 patients tested positive for GD2 reactivity by bone marrow immunofluorescence (n = 68), tumor immunohistochemistry (n = 20), or diagnostic radioimmunoscintigraphy (n = 2)., Results: Of 62 patients who had refractory or recurrent neuroblastoma following 3F8 treatment, 61 (98%) tested positive for GD2 reactivity by bone marrow immunofluorescence (n = 51) or tumor immunohistochemistry (n = 10). The sole tumor that lost GD2 expression underwent phenotypic transformation into a pheochromocytoma-like tumor., Conclusions: The persistence of GD2 expression in refractory or recurrent NB suggests that complete antigen loss is an uncommon event and cannot account for treatment failure.

Background: Only ten cases of the rare occurrence of a malignant peripheral nerve-sheath tumor (MPNST) arising in a ganglioneuroma either de novo or at a site of previous irradiation have been reported., Patients and Methods: We present two children who at the age of 19 months and 6 months were diagnosed with a cervicothoracic ganglioneuroblastoma and a retroperitoneal neuroblastoma, respectively. They both received radiation therapy as part of the treatment of their disease., Results: Following a 12-year interval, MPNST arose inside a benign ganglioneuroma in both patients. We illustrate the imaging findings in these two cases and review the cases reported in the literature to increase awareness of this association among radiologists.

A 2-year-old male with neurofibromatosis who had a Wilms tumor of the right kidney and an ipsilateral adrenal ganglioneuroblastoma is reported. Both tumors were completely removed and no recurrence occurred for 4 years after completion of the therapy. In a review of the literature, the prognosis of neurofibromatosis with these embryonal tumors is not satisfactory due to development of secondary tumors and disseminated metastases of the tumors. The synchronous occurrence of Wilms tumor and neuroblastoma in neurofibromatosis is extremely rare and this may be the first report in the world.

Purpose: A retrospective study was conducted to investigate the relationship between CD44 expression in neuroblastoma and related tumors and other known prognostic indicators., Materials and Methods: Immunostaining of CD44 was done on surgical specimens of 55 cases (42 patients) of neuroblastoma (NB) and ganglioneuroblastoma (GNB) and nine cases of ganglioneuroma. The percentage of positive tumor cells was scored semiquantitatively (0-4+) by two observers. CD44 expression was then correlated with survival, age, stage, and N-myc amplification., Results: Fifty-seven percent of the patients with NB or GNB had heterogeneous positive staining (2-4+) on their diagnostic specimens. Twenty-four percent of the patients had no staining for CD44, and 19% had 1+ staining. In the 17 cases with N-myc analysis, an inverse relationship was demonstrated between N-myc and CD44 expression by univariate analysis. Lack of expression of CD44 was highly associated with poor survival (p = 0.0002). When assessing the joint effects of age, stage, and CD44 in multivariate analysis, the effect of CD44 remains significant (p = 0.028) and appears to be independent of age and stage., Conclusion: Our data suggest a relationship between CD44 and N-myc amplification. Absence or low expression of CD44 correlates with poor survival and may be a biologic marker of tumor aggressiveness. CD44 appears to be an independent prognostic marker and deserves continued investigation in prospective studies of neuroblastoma.

Infants with neuroblastoma are known to have a better prognosis than older children. In Japan in 1985, mass screening for neuroblastoma in infants aged 6 months was introduced. With this policy, there has been an increase in the number of patients seen with neuroblastoma between 6 and 11 months of age. In a previous report the authors described the management and prognosis of infants with disease detected by mass screening, but there is still little information regarding the strategies of management for infants with neuroblastoma aged less than 6 months. The authors analyzed the data regarding 27 patients aged less than 6 months registered in their region (population 15 million) from 1985 to 1992, and compared it with that of the previous 8-year period. In the younger age group, there was a significantly higher rate of advanced disease stages (III and IV). In spite of the variation in treatment related to the choice of individual institutions, infants with stages I, II, and III disease had a good outcome, suggesting that aggressive chemotherapy is not necessary unless poor prognostic factors are present. One patient with stage IV disease died of disseminated disease and one with stage IVs and 22 copies of N-myc oncogene also died of tumor relapse in spite of aggressive chemotherapy. It is therefore concluded that the prognosis in infants with stage IV and IVs neuroblastoma under the age of 6 months is not as good as had previously been believed, and that such patients, therefore, require special consideration.

Since 1985, a nationwide program of mass screening (MS) for neuroblastoma has been underway for 6-month-old infants throughout Japan. As a result, the number of patients with stage I or II disease has obviously increased, and this has resulted in overall improvement of the prognosis for neuroblastoma. Some cases detected by MS were already in an advanced stage and have also had a good prognosis. In such cases, no definitive treatment protocol has been developed. Therefore, the authors investigated (1) the clinical and biological features of the advanced neuroblastoma cases detected by MS and (2) the best way to deal with such cases. The authors analyzed 94 cases of advanced-stage neuroblastoma registered in the Kyushu area (population, 15 million) between 1985 and 1990. Eighteen cases (16 stage III, 2 stage IV) were found by MS, and the others (23 stage III, 53 stage IV) were diagnosed clinically. The following results were obtained: (1) No N-myc amplifications were observed in cases detected by MS, whereas 16 of the 45 examined patients in the non-MS group had high amplifications of N-myc. (2) With regard to Shimada's classification, DNA content, and S-100 protein positivity, most of the advanced tumors found by MS showed characteristics indicating a good prognosis. (3) The 5-year survival rate for the non-MS group is less than 25%, whereas all of the patients whose tumors were detected by MS are alive, even after undergoing mild chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)