This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by De Bernardi, B. Articles by Angelini, P. Search for Related Content PubMed PubMed Citation Articles by De Bernardi, B. Articles by Angelini, P. Social Bookmarking                            What's this?

Retrospective Study of Childhood Ganglioneuroma

Bruno De Bernardi, Claudio Gambini, Riccardo Haupt, Claudio Granata, Antonino Rizzo, Massimo Conte, Gian Paolo Tonini, Maurizio Bianchi, Maria Giuliano, Roberto Luksch, Arcangelo Prete, Elisabetta Viscardi, Alberto Garaventa, Angela Rita Sementa, Paolo Bruzzi, Paola Angelini

From the Departments of Hematology-Oncology and Surgery, and Services of Pathology, Radiology, and Statistics, Giannina Gaslini Children Hospital, and National Institute for Cancer Research, Genova; Department of Pediatrics, University of Bologna, Bologna; Department of Pediatrics, University of Napoli, Napoli; Department of Pediatrics, University of Torino, Torino; and the Division of Pediatric Oncology, National Cancer Institute, Milano, Italy

Corresponding author: Bruno De Bernardi, MD, Department of Pediatric Hematology-Oncology, Giannina Gaslini Children Hospital, Largo Gerolamo Gaslini 5, 16148 Genova, Italy; e-mail: brunodebernardi{at}ospedale-gaslini.ge.it

	ABSTRACT

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS Appendix REFERENCES

 
Purpose To review a historical cohort of childhood ganglioneuroma (GN), the benign representative of the peripheral neuroblastic tumor (PNT) family.

Patients and Methods Of 2,286 PNTs enrolled between 1979 and 2005, 146 (6.4%) were registered as GN. Histological revision was carried out on 76 tumors. Diagnosis was confirmed in 45, while 27 were reclassified as ganglioneuroblastoma intermixed (GNBI) and four were reclassified as other PNT subtypes.

Results GNs differed from other PNTs for sex, age, tumor site, stage, tumor markers, and scintigraphic results. Characteristics of 76 reviewed and 70 nonreviewed patients were comparable. Reviewed GN and GNBI patients were comparable except for homovanillic acid excretion, metaiodobenzylguanidine scintigraphy, and DNA content. Seven patients were only biopsied and 139 underwent surgery. Twenty-two patients suffered surgery-related complications, of which two were fatal and seven were severe. Radical tumor resection and surgery-related complication rates were comparable for GN, GNBI, and nonreviewed instances. Six patients developed tumor progression but survived. Two patients developed a late malignancy but survived. None of the 146 patients received chemotherapy. Of 146 patients, two died of surgery-related complications and 144 survived.

Conclusion Diagnosis was changed to GNBI for approximately one third of 76 reviewed tumors. Patients with confirmed GN, reclassified as GNBI, and nonreviewed histology presented with comparable clinical, biochemical, and biologic features. Surgical results, complication rate, number of progressions, and outcome were similar for the three groups. Surgery was associated with significant risk of complications. Survival was not influenced by extent of tumor resection. Aggressive surgical approach should not be recommended for childhood GN and GNBI.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS Appendix REFERENCES

 
Ganglioneuroma (GN) is the uncommon, benign representative of the peripheral neuroblastic tumors (PNTs),¹ that occur prevalently in childhood and include the malignant histotypes neuroblastoma and ganglioneuroblastoma nodular, and the stroma-rich ganglioneuroblastoma intermixed (GNBI).² The histological diagnosis of GN has always been controversial, especially for its distinction from GNBI. This was especially true before the introduction of the International Neuroblastoma Pathology Committee (INPC) criteria,³ which define GN as a schwannian stroma-dominant tumor, predominantly composed of ganglioneuromatous stroma with a minor component of scattered collections of differentiating neuroblasts and/or maturing or mature ganglion cells. Instead, GNBI is characterized by well-defined microscopic nests of neuroblastic cells in various stages of differentiation, intermixed or randomly distributed in a ganglioneuromatous tissue, usually in a background of abundant neuropil.³ However, the distinction between GN and GNBI remains somehow dependent on subjective interpretation. Moreover, instances diagnosed before the publication of the INPC classification may have been defined incorrectly by today's standards.

GN can be diagnosed de novo in healthy subjects or occasionally result from the spontaneous or chemotherapy-induced differentiation of a malignant PNT.² De novo GN differs from malignant PNTs in that it affects older children,⁴ produces normal or slightly elevated amounts of catecholamines,^4,5 and is often asymptomatic.^4,6,7 Symptoms result from the compressive effect of the tumor on neighboring tissues.^4,6 Surgical resection is the therapy of choice, although it can sometimes be challenging and risky, in particular when the great vessels are involved.^8,9 When deemed unresectable, the tumor may remain stable or grow slowly, sometimes attaining a size that may cause severe symptoms and thus require mandatory surgery.¹⁰ An additional reason for operating is that unresected GN may occasionally undergo transformation toward a malignant PNT^11,12 or other histotype.^13,14

The literature regarding childhood GN is scarce, even on relevant issues, such as surgical approach, clinical course, outcome,and histobiologic features. In addition, there are no published series in which histology of tumors have undergone revision according to the INPC classification. We herewith report the experience of the Italian Co-operative Neuroblastoma Group concerning a large number of patients registered as GN over a 27-year period.

	PATIENTS AND METHODS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS Appendix REFERENCES

 
The authors reviewed the records of children (ages, 0 to 18 years) with newly diagnosed PNT who were enrolled in the Italian Neuroblastoma Registry (INBR)¹⁵ between January 1, 1979, and December 31, 2005. Patients diagnosed as GN were identified through the INBR, and the related institutions were requested to provide follow-up data, together with clinical, biologic, and radiologic data, copy of the surgical report, details on surgery-related complications, if any, and copy of the original pathology report. When available, histology slides were reviewed by two independent pathologists according to the INPC classification.³ Disease extension was retrospectively defined following the International Neuroblastoma Staging System.¹⁶ Laboratory test results at diagnosis were categorized as being normal or abnormal on the basis of the following threshold values: 1,000 U per liter for lactate dehydrogenase (LDH); 150 ng/mL for ferritin; 100 ng/mL for neuron-specific enolase (NSE); 2.5 standard deviations of normal values by age for vanillylmandelic (VMA) and homovanillic acid (HVA) urinary excretion. MYCN oncogene amplification and chromosome 1p36 deletion were analyzed in a limited number of instances mostly by double color fluorescence in situ hybridization on interphase nuclei using tumor touch preparation.¹⁷ DNA index was assayed by flow cytometry.¹⁸

Results of surgery were defined as follows. Complete tumor resection was the excision of all visible tumor, even if residual microscopic tumor was revealed by histological examination. Near complete resection was tumor excision leaving minimal macroscopic residue. Incomplete resection was tumor excision leaving macroscopic gross residue. Finally, information regarding surgery-related complications or death was also collected and included any such event occurring within 60 days of the initial operation.¹⁹ Complications were classified according to the National Cancer Institute Common Toxicity Criteria.²⁰

Statistical Analysis
Descriptive statistics were reported as absolute frequencies and percentages for qualitative data, while medians and ranges were used to describe quantitative variables because of their non-normal distribution. Differences in the frequencies of each variable between registered GNs and other PNTs, as well as between histologically reviewed and nonreviewed instances, and patients histologically confirmed as GN and reclassified as GNBI, were evaluated by the ² test or Fisher's exact test for categoric variables, while the Mann-Whitney U test was used for continuous variables.

Follow-up was censored at the end of 2005. The Kaplan-Meier method was used to evaluate survival analyses and projected survival was reported together with the 95% CIs. With regards to the event-free survival analysis, only surgery-related death, tumor progression, or malignancy, whichever occurred first, were considered events. All statistical tests were two sided and P .05 was considered statistically significant. The statistical package Stata (release 9; Stata Corporation, College Station, TX) was used for all the analyses.

	RESULTS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS Appendix REFERENCES

 
During the 27-year study period, a total of 2,437 patients were registered in the INBR, of whom 151 were ineligible because of insufficient data (n = 40), diagnosis other than PNT (n = 32), previous antitumor treatment (n = 31), age 18 years (n = 25), and inadequate follow-up (n = 23). Of the remaining 2,286 instances, 2,140 were diagnosed with malignant PNT (93.6%) and 146 as GN (6.4%).

The main characteristics of the 146 patients registered as GN were compared with malignant PNTs and showed several significant differences (Table 1). In detail, GN patients were more frequently female (62.3% v 44.8%) and were diagnosed at an older median age (79 v 21 months); the tumor was more often in the thorax (42.4% v 16.6%) and less frequently in the abdomen (41.1% v 75.7%), and was always localized (100% v 49.5%). Differences in stage distribution persisted even when disseminated PNTs were excluded from the comparison. Moreover, GNs clearly differed biochemically from malignant PNTs, since they almost always had normal values of LDH (98.6% v 63.6%), ferritin (97.5% v 57.5%), and NSE (98% v 62.4%).

Histological Review
The original pathology report was obtained for all the 146 GN cases. However, we were only able to retrieve adequate histological material for INPC classification for 76 tumors, of which 45 were confirmed as GN (59.2%), while 27 were reclassified as GNBI (35.5%). Diagnosis of the remaining four patients was changed to ganglioneuroblastoma nodular (n = 3) and neuroblastoma differentiating (n = 1).

Comparison Between Histologically Reviewed and Nonreviewed Tumors
The 76 histologically reviewed tumors were compared with the 70 for which histological review was not possible (Table 2). No differences between the two groups were found with regards to features at diagnosis, except that nonreviewed patients were more often diagnosed during the early period of the study and were less likely to have abnormal HVA values.

Surgery. Biopsy alone was performed on three children. The remaining 42 underwent surgery, of whom 27 (64.3%) had complete tumor resection, eight had near complete tumor resection (19.0%), and 7 incomplete tumor resection (16.7%; Table 4). In two instances the tumor was multinodular and required two subsequent operations (online-only Fig 2). Complete tumor resection was performed on both occurrences of cervical location, and near complete resection was carried out in one of three occurrences of pelvic location. Complete resection was the most frequent type of surgery for both thoracic and abdominal tumors, but thoracic tumors were more likely to undergo incomplete resection (35% v 0%; P = .014). Unilateral nephrectomy was performed in one instance in order to obtain complete tumor resection.

Analysis of Patients Reclassified As GNBI
Clinical presentation. Of 27 children, sixteen were symptomatic (64%) with the most frequent symptoms being pain (n = 8) and respiratory distress (n = 5). Asymtpomatic infiltration of intervertebral foramina was documented in two children. One child was affected by type 1 neurofibromatosis.

Surgery. One patient underwent biopsy only. The remaining 26 underwent surgery and 21 had complete tumor resection (80.8%), three had near complete tumor resection (11.5%), and two had incomplete tumor resection (7.7%; Table 4). The complete resection rate was comparable to the rate of patients with confirmed GN (Table 3). In order to allow tumor resection to be performed, unilateral nephrectomy was carried out in two instances.

Surgery-relatedcomplications. Surgery-related complications arose in four patients (15.4%; Table 4). Among them, one was fatal (massive hemorrhage; Table 5; 10), two were severe (massive hemorrhage and multiple thromboses, respectively; Table 5; 11 and 12), and one was moderate (Table 5; 13). The frequency of severe complications was comparable to what was observed among confirmed GNs (Table 3).

Clinical course. Median follow-up was 63 months (range, 0 to 322 months). Progression occurred in two patients who had undergone an incomplete tumor resection and a biopsy, respectively. In the former patient the tumor was completely resected. In the latter patient the tumor was only biopsied and the tumor mass remained stable for several years.

Analysis of Nonreviewed Patients
Clinical presentation. The tumors were symptomatic in 38 (54.3%) of 70 patients with pain and respiratory distress being the most frequent symptoms (17 and seven instances, respectively). One patient had type 2 neurofibromatosis.

Surgery. Three patients underwent biopsy alone (4.3%). Among the remaining 67 patients, tumor resection was complete in 47 (70.2%), near complete in 12 (17.9%), and incomplete in 8 (11.9%; Table 4).

Surgery-related complications. Eleven surgery-related complications were reported (16.4%), of which five were severe and six were moderate (Table 4). Severe complications included brain hemorrhage and cardiocirculatory arrest (Table 5; 14), paraparesis and bladder dysfunction (Table 5; 15), aortic rupture (Table 5; 16 and 18), and rupture of other major arteries (Table 5; 17). The frequency of complications did not differ as compared with what was observed for reviewed patients (Table 2).

Clinical course. Median follow-up was 62 months (range, 0 to 320 months). Tumor progression was documented in three patients of whom two had near complete and one an incomplete tumor resection. The relapsed tumor underwent complete resection in one instance and near complete resection in the remaining two with residual tumor remaining stable for several years.

Patients' Outcome
Of 146 patients, two died of surgery-related complications and 144 are alive with a median follow-up of 7 years. The 144 alive patients include 97 alive disease free (two after progression) and 44 alive with stable tumor residue, of whom nine have persistent surgery-related sequelae (severe in one, moderate in eight). During the follow-up, two patients developed an associated malignancy in a site different from that of the original GN. Six patients developed local tumor progression that was resected in three instances and incompletely resected in the other instances, but ceased spontaneously to grow.

	DISCUSSION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS Appendix REFERENCES

 
In the context of the PNT family, neuroblastoma and ganglioneuroblastoma nodular are certainly malignant in nature, while GN is considered benign.² However, it is well known that GN may slowly grow and become symptomatic.^4,6,10 Few occurrences of late malignant changes have been reported.^11-14 In addition, GN must be distinguished from GNBI,³ whose clinical behavior is less well defined.

To our knowledge, our series of 146 childhood GNs registered over a 27-year period is the largest one published to date. In line with the few available reports^4,6 our patients differ from other PNTs for having older age at diagnosis, prevalence of thoracic tumor site and of normal values of urinary catecholamines, and LDH, NSE, and ferritin serum levels. These striking differences persisted even when the comparison of malignant PNTs only took into consideration the 45 histologically confirmed GNs.

Based on the premise that in previous GN series^4,6 tumor histology has not been revised according to the relatively recent INPC classification,³ and could thus include histotypes other than GN, we felt it necessary to ensure that the GN histology of our 146 patients was in agreement with those criteria. Understandably, given the length of the study period, we were able to retrieve valuable histological material for no more than half the occurrences, while for the remaining half we had to rely on the original reports. The characteristics at diagnosis of the reviewed and nonreviewed patients were quite similar, except that the nonreviewed patients had mainly been diagnosed in the early years of the study.

Revision of the histology was carried out by two experienced pathologists and showed that approximately one third of the reviewed patients had features that led to change diagnosis from GN to GNBI. In comparing patients with confirmed GN to those reclassified as GNBI, similar characteristics were found, except that GNBI patients more frequently had abnormal HVA urinary excretion, positive metaiodobenzylguanidine uptake, and aneuploid DNA index. These discrepancies, that may be explained by the subtle differences that make GN and GNBI two distinct entities, did not translate into differences in therapeutic behavior, number of tumor progressions. and outcome. We can thus conclude that, despite possessing distinct histological, biochemical, and biologic features, GN and GNBI tumors behave similarly and can both be considered the benign end of the PNT spectrum. Moreover, combining data on histologically reviewed GN and GNBI tumors, and comparing them to tumors that did not undergo histological review, also revealed strong similarities in both the presenting features and clinical course. Therefore, we felt it was reasonable to consider reviewed and nonreviewed patients as one single population.

The large majority of these occurrences underwent an attempt at surgical resection. Since GN can tightly adhere to, or encase major vascular structures,⁸ attempting resection may lead to severe, even life-threatening complications. Although the potential risks of operating on a GN are well known, reports on surgery-related complications, including blindness²¹ and neurological dysfunctions,²² are limited to few single case reports. In our series, surgical risks have emerged as a major problem. Indeed, two patients died of profuse bleeding after surgery, eight developed serious complications, and another 17 suffered moderate, but sometimes permanent complications. Overall, the surgery-related complication rate was 17.8%. In addition, to enable the tumor to be resected, three patients underwent elective nephrectomy. Complications occurred throughout the study period with the severe ones prevailing in the more recent years (data not shown), indicating the persisting tendency of surgeons and oncologists to resect a GN even in the presence of surgical risk factors documented by diagnostic imaging. Unlike the only other previously published large series,⁴ we did document some local tumor progressions, all occurring in patients who had undergone non radical tumor resection. In three of six occurrences, the mass was resected and did not recur. In the remaining three, the postsurgery residual tumor has remained stable for years.

No case of tumor residue undergoing malignant transformation after incomplete resection was recorded among our patients. However, in this regard, a longer follow-up is needed since similar events have occasionally been described decades after the diagnosis of GN.^11-14 Of note, two malignancies were observed during the follow-up of our patients, neither of whom had received chemo- or radiation therapy. The occurrence of a malignancy in 1.3% of our population is much higher than expected in the general population of comparable age.²³ The hypothesis that other factors besides chance alone may have played a role in the occurrence of these malignancies cannot be ruled out.

In summary, our study suggests that a proportion of patients originally described as GN would be reclassified as GNBI if submitted to INPC classification. However, in our experience both GN and GNBI displayed quite similar benign behavior. Additional reports on this issue are warranted. Tumor resection remains an option for these patients, considering that it may lead to serious complications when performed in presence of imaging-defined risk factors. We believe that the benign nature of GN (and GNBI) requires a more cautious surgical approach when surgical risk factors are identified. In such instances a watchful waiting policy should be established, with debulking surgery becoming justified when excessive growth has occurred or significant disturbances have arisen.

	AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS Appendix REFERENCES

 
The author(s) indicated no potential conflicts of interest.

	AUTHOR CONTRIBUTIONS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS Appendix REFERENCES

 
Conception and design: Bruno De Bernardi, Claudio Gambini, Riccardo Haupt

Provision of study materials or patients: Claudio Gambini, Claudio Granata, Antonino Rizzo, Massimo Conte, Gian Paolo Tonini, Maurizio Bianchi, Maria Giuliano, Roberto Luksch, Arcangelo Prete, Elisabetta Viscardi, Alberto Garaventa, Angela Rita Sementa, Paolo Bruzzi, Paola Angelini

Collection and assembly of data: Claudio Gambini, Riccardo Haupt, Claudio Granata, Maria Giuliano, Roberto Luksch

Data analysis and interpretation: Bruno De Bernardi, Riccardo Haupt, Claudio Granata, Antonino Rizzo, Gian Paolo Tonini

Manuscript writing: Bruno De Bernardi, Riccardo Haupt, Claudio Granata, Antonino Rizzo

Final approval of manuscript: Claudio Gambini, Claudio Granata, Antonino Rizzo, Massimo Conte, Arcangelo Prete, Paola Angelini

	Appendix

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS Appendix REFERENCES

 
Participating Italian institutions (with main investigators) are as follows: Giannina Gaslini Children Hospital, Genova (Bruno De Bernardi, Claudio Gambini, Alberto Garaventa, Claudio Granata, Angela Rita Sementa, Paola Angelini); Bambino Gesù Children Hospital, Roma (Alberto Donfrancesco, Renata Boldrini, Alessandro Jenkner, Aurora Castellano); Department of Pediatrics, University of Napoli (Maria Teresa Di Tullio, Maria Giuliano, Vittoria D'Onofrio); Department of Pediatrics, University of Torino (Maurizio Bianchi, Marco Forni); Department of Pediatrics, University of Padova (Modesto Carli, Elisabetta Viscardi, Emanuele SG D'Amore, Rita Alaggio); Division of Pediatric Oncology, National Cancer Institute, Milano (Roberto Luksch, Paola Collini); Department of Pediatrics, University of Bari (Alessandro Arcamone, Nicola Santoro); Department of Pediatrics, University of Bologna (Andrea Pession, Arcangelo Prete, Mirco Salfi); Department of Pediatrics, University of Pavia (Federico Bonetti, Marco Paulli, Pierluigi Parigi); Department of Pediatrics, University of Ancona (Paolo Pierani); Department of Pediatrics, University of Palermo (Maurizio Aricò, Paolo D'Angelo); Department of Pediatrics, University of Brescia (Katia Tettoni); Burlo Garofalo Children Hospital, Trieste (Paolo Zanazzo); Department of Pediatrics, University of Modena (Monica Cellini); Department of Pediatrics, University of Parma (Giancarlo Izzi); Department of Pediatrics, University of Catania (Andrea Di Cataldo, Gaetano Magro); Department of Pediatrics, University of Firenze (Angela Tamburini); Division of Pediatrics, Civic Hospital, Bergamo (Massimo Provenzi); Division of Pediatric Surgery, Civic Hospital, Vicenza (Maria Angelica Fabbro); Department of Pediatrics, University of Perugia (Augusto Amici); Department of Pediatrics, University of Siena (Antonio Acquaviva); and Department of Pediatrics, University of Cagliari (Anna Brigida Aru).

View larger version (44K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig A1. (A) Twelve-year-old girl suffering severe abdominal pain, vomiting and weight loss. Contrast-enhanced computed tomography (CT). A huge, solid abdominal mass that crosses the midline and displaces the great vessels and bowel loops. (B) Contrast-enhanced CT performed 6 years after surgery shows a small residual mass (black arrow) behind right renal artery and between aorta and inferior vena cava.

View larger version (40K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig A2. Magnetic resonance imaging for a 7-year-old girl. T1-weighted, fat-suppressed, gadolinium contrast-enhanced (A) axial and (B) sagittal images show a hyperintense, multinodular pelvic mass.

	ACKNOWLEDGMENTS

 
We thank Dr Francesca Bagnasco for statistical analyses; Dr Francesca Negri for DNA index analyses; Dr Maria Valeria Corrias, Dr Guido Pastore, and Dr Vito Pistoia for helpful criticism; Sara Calmanti for editing the manuscript; and Bernard C. Patrick, PhD, and Valerie Perricone for reviewing the text.

	NOTES

 
Supported in part by the Italian Neuroblastoma Foundation.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

	REFERENCES

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS Appendix REFERENCES

 
1. De Bernardi B, Milanaccio C, Occhi M: Neuroblastoma, in Sheaves R, Jenkins PJ, Wass JAH (eds): Clinical Endocrine Oncology. Oxford, United Kingdom, Blackwell Science, 1997, pp 306-311

2. Shimada H, Ambros IM, Dehner LP, et al: Terminology and morphologic criteria of neuroblastic tumors: Recommendations by the International Neuroblastoma Pathology Committee. Cancer 86:349-363, 1999[CrossRef][Medline]

3. Shimada H, Ambros IM, Dehner LP, et al: Terminology and morphologic criteria of neuroblastic tumors: Recommendations by the International Neuroblastoma Pathology Committee. Cancer 86:349-363, 1999[CrossRef][Medline]

4. Geoerger B, Hero B, Harms D, et al: Metabolic activity and clinical features of primary ganglioneuromas. Cancer 91:1905-1913, 2001[CrossRef][Medline]

5. Lucas K, Gula MJ, Knisely AS, et al: Catecholamine metabolites in ganglioneuroma. Med Pediatr Oncol 22:240-243, 1994[Medline]

6. Hayes FA, Green AA, Rao BN: Clinical manifestations of ganglioneuroma. Cancer 63:1211-1214, 1989[CrossRef][Medline]

7. Schulman H, Laufer L, Barki Y, et al: Ganglioneuroma: An ‘incidentaloma' of childhood. Eur Radiol 8:582-584, 1998[CrossRef][Medline]

8. Nelms JK, Diner EK, Lack EE, et al: Retroperitoneal ganglioneuroma encasing the celiac and superior mesenteric arteries. Scientific World J 4:974-977, 2004

9. Otal P, Mezghani S, Hassissene S, et al: Imaging of retroperitoneal ganglioneuroma. Eur Radiol 11:940-945, 2001[CrossRef][Medline]

10. Cronin EM, Coffey JC, Herlihy D, et al: Massive retroperitoneal ganglioneuroma presenting with small bowel obstruction 18 years following initial diagnosis. Ir J Med Sci 174:63-66, 2005[Medline]

11. Kulkarni AV, Bilbao JM, Cusimano MD, et al: Malignant transformation of ganglioneuroma into spinal neuroblastoma in an adult: Case report. J Neurosurg 88:324-327, 1998[Medline]

12. Moschovi M, Arvanitis D, Hadjigeorgi C, et al: Late malignant transformation of dormant ganglioneuroma? Med Pediatr Oncol 28:377-381, 1997[CrossRef][Medline]

13. Kimura S, Kawaguchi S, Wada T, et al: Rhabdomyosarcoma arising from a dormant dumbbell ganglioneuroma of the lumbar spine: A case report. Spine 27:513-517, 2002[CrossRef]

14. Drago G, Pasquier B, Pasquier D, et al: Malignant peripheral nerve sheath tumor arising in a "de novo" ganglioneuroma: A case report and review of the literature. Med Pediatr Oncol 28:216-222, 1997[CrossRef][Medline]

15. Conte M, Parodi S, De Bernardi B, et al: Neuroblastoma in adolescents: The Italian experience. Cancer 106:1409-1417, 2006[Medline]

16. Brodeur GM, Pritchard J, Berthold F, et al: Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol 11:1466-1477, 1993[Abstract/Free Full Text]

17. Coco S, Defferrari R, Scaruffi P, et al: Genome analysis and gene expression profiling of neuroblastoma and ganglioneuroblastoma reveal differences between neuroblastic and Schwannian stromal cells. J Pathol 207:346-357, 2005[CrossRef][Medline]

18. Hedley DW, Friedlander ML, Taylor IW: Application of DNA flow cytometry to paraffin-embedded archival material for the study of aneuploidy and its clinical significance. Cytometry 6:327-333, 1985[CrossRef][Medline]

19. Cecchetto G, Mosseri V, De Bernardi B, et al: Surgical risk factors in primary surgery for localized neuroblastoma: The LNESG1 study of the European International Society of Pediatric Oncology Neuroblastoma Group. J Clin Oncol 23:8483-8489, 2005[Abstract/Free Full Text]

20. National Cancer Institute: Common Terminology Criteria for Adverse Events Version 3.0 (v3.0): Cancer Therapy Evaluation Program. http://ctep.cancer.gov/reporting/ctc.html

21. Leuthardt R, Petralli C, Lütschg J, et al: Cortical blindness: An unusual complication after removal of a ganglioneuroma of the neck. Childs Nerv Syst 17:356-358, 2001[CrossRef][Medline]

22. Mosiello G, Gatti C, De Gennaro M, et al: Neurovesical dysfunction in children after treating pelvic neoplasms. BJU Int 92:289-292, 2003[CrossRef][Medline]

23. Parkin DM, Whelan SL, Ferlay J, et al: Cancer incidence in five continents. IARC Scientific Publications No. 155, Vol. VIII, Lyon, France, IARC, 2002

Submitted August 29, 2007; accepted December 4, 2007.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by De Bernardi, B. Articles by Angelini, P. Search for Related Content PubMed PubMed Citation Articles by De Bernardi, B. Articles by Angelini, P. Social Bookmarking                            What's this?