Ganglioneuromas in Childhood: Hacettepe Experience With 70 Cases.

BACKGROUND: Ganglioneuromas (GNs) are rare benign peripheral neuroblastic tumors (PNTs). We shared our institutional experience with childhood GNs. METHODS: Records of the children with PNTs between January 1995 and December 2021 were reviewed, and cases with histopathological diagnoses of GN were identified. Clinical, laboratory, radiological, and histopathological findings, image-defined risk factors (IDRFs), procedures, and overall outcomes were recorded. RESULTS: Of 668 cases with PNTs, 70 (10.4%) had GNs. The median age was 7.4 years (range, 2.6-15.7 years) (girls/boys, 41/29). Common presenting complaints were abdominal pain and cough; 33/70 cases (47.1%) were diagnosed incidentally. Primary tumors were in the abdomen in 41/70, the thorax in 25/70, the neck in 3 cases, and the pelvis in one. The median tumor size was 6.5 cm (range, 1.4-17). Fifty cases (71.4%) were staged as INRG-L1; 20 cases with IDRFs (15 single, five >1) were staged as INRG-L2. Complete and partial tumor resections were performed in 58/70 and 6/70 cases, while 6 had no resection. The overall complication rate was 17.1% (11/64). At a median follow-up of 9 years, five were lost to follow-up; 65 were alive. One patient with gross residue underwent total resection due to progression 13 years after the surgery, and one in the unresected group was lost to follow-up. Ten other cases without a complete resection experienced no tumor progression. CONCLUSIONS: Ganglioneuromas are benign PNTs, and most are free of IDRFs. Even without complete resection, long-term outcomes are excellent. Guidelines should be devised considering the high surgical complication rates and benign course of GNs. LEVEL OF EVIDENCE: Case series, IV.

Epidemiological and clinical characteristics of children with peripheral neuroblastic tumors: a study on a Moroccan population.

PURPOSE: Peripheral neuroblastic tumors are the most common extracranial cancers found in children, and they are characterized by a diverse spectrum of clinical manifestations and heterogeneous behaviors. This study aimed to investigate the epidemiological and clinical characteristics of children with peripheral neuroblastic tumors admitted to the Department of Pediatric Hematology and Oncology of the Hospital August 20 in Casablanca. METHODS: The medical files of 48 children with peripheral neuroblastic tumors addressed to our department between February 2018 and February 2023 were reviewed. The clinical and demographic characteristics of patients were analyzed by the Statistical Package for the Social Sciences (SPSS), survival curves were obtained by Kaplan-Meier technique, and we assigned the tumor stage to patients based on the International Neuroblastoma Risk Group Staging System (INRGSS). RESULTS: The median age of diagnosis was 30 months (1-174), with a ratio F/M of 1.28. 93.75% of patients had neuroblastoma, and the rest had ganglioneuroma. About 64.6% of patients had at their initial presentations stage M of peripheral neuroblastic tumors. The adrenal region made up 71% of the primary tumor site. The bone was one of the most prevalent metastatic sites (54.2%). The five-year overall survival rate was 35.4%. CONCLUSION: Overall, this study revealed a high stage of peripheral neuroblastic tumors in the majority of the diagnosed patients in our Department of Pediatric Hematology and Oncology. Moreover, the heterogeneity of peripheral neuroblastic tumors makes clinical recognition difficult and, in general, too late.

Adrenal ganglioneuromas: a retrospective multicentric study of 104 cases from the COMETE network.

OBJECTIVE: Adrenal ganglioneuromas are rare, differentiated, neuroblastic tumors that originate from the peripheral sympathetic nervous system. Because of their rarity, information is limited, derived from small cases series. Our objective was to characterize this tumor and provide help for its management. METHODS: A retrospective multicenter analysis of adrenal ganglioneuromas from 20 French centers belonging to the COMETE network and one Belgian center. RESULTS: Among the 104 cases identified, 59.6% were women (n = 62/104), median age at diagnosis was 29 years, with 24 pediatric cases. 60.6% (n = 63/104) were incidentalomas. Ganglioneuromas were non-secreting tumors in 90.8% of cases (n = 89/98), whereas the preoperative hormonal evaluation was indeterminate for 9.2% of patients (n = 9/98). CT imaging, performed on 96 patients, revealed large tumors (median diameter of 50 mm) with a non-contrast density > 10 Hounsfield units in 98.1% (n = 52/53) and calcifications in 64.6% of cases (n = 31/48). Increased uptake on 123I-MIBG scintigraphy and 18F-FDG-PET/CT was observed in 26.7% (n = 8/30) and 42.2% (n = 19/45) of the tumors, respectively. All 104 patients underwent surgery. No recurrence was observed among the 42 patients who had an imaging follow-up (mean 29.6 months, median 18 months (4-156)). CONCLUSION: Adrenal ganglioneuromas are large tumors, mostly nonfunctioning, without benign imaging features. Although the duration of follow-up was limited in our series, no recurrence was identified. A review of the literature confirms the absence of postoperative recurrence. Based on all available data, in the absence of special circumstances (genetic form, uncertain histological diagnosis), long-term follow-up is not necessary after complete surgery for patients with an adrenal ganglioneuroma.

A nationwide survey of adrenal incidentalomas in Japan: the first report of clinical and epidemiological features.

The aim of this study was to reveal clear epidemiologic and clinical characteristics of incidentally discovered adrenal masses, termed adrenal incidentalomas (AIs), and to establish appropriate managemental and therapeutic regimens in Japan. This study had been originally carried out as a project of a research proposed on behalf of the Japanese Ministry of Health, Labour and Welfare, from 1999 to 2004. This nationwide multicenter study on AIs included 3,672 cases with clinically diagnosed AIs, involving 1,874 males and 1,738 females, with mean age 58.1 ± 13.0 years (mean ± SD). In the present study, we focused on the investigation of the real prevalence of various adrenal disorders with AI. The mean nodule size of AI based on computed tomography was 3.0 ± 2.0 cm. Compared to non-functioning adenomas (NFAs), tumor diameters were significantly larger in adrenocortical carcinomas (ACCs), pheochromocytomas, cortisol-producing adenomas (CPAs), myelolipomas, metastatic tumors, cysts, and ganglioneuromas (p < 0.01). Endocrinological evaluations demonstrated that 50.8% of total AIs were non-functioning adenomas, while 10.5%, including 3.6% with subclinical Cushing's syndrome, were reported as CPAs, 8.5% as pheochromocytomas, and 5.1% as aldosterone-producing adenomas. ACCs were accounted for 1.4% (50 cases) among our series of AIs. In conclusion, while almost 50 % of AIs are non-functional adenomas, we must be particularly careful as AIs include pheochromocytomas or adrenal carcinomas, because they may be asymptomatic. To our knowledge, this is the first and the largest investigation of AI, thus providing basic information for the establishment of clinical guidelines for the management of AI.

Gangliocytomas of the sellar region: A challenging diagnosis.

Gangliocytoma of the sellar region are extremely rare and often coexist with pituitary adenoma. Aim of this review is to collect all the cases reported in literature and to summarize the most recent literature evidences on the subject. A systematic review was performed through PubMed searching for articles describing gangliocytoma of the sellar region in the adult population, up to September 2015. An analysis of epidemiological data, clinical presentation, histochemical and radiological features and follow-up data was performed. A total of 55 articles were included in our analysis, reporting 129 cases of gangliocytoma of the sellar region. One case identified in our institution was also included. 85% of cases presented in association with pituitary adenomas. A female prevalence was evident. Patients presented most frequently with symptoms of hyperprolactinemia (44%) or visual disturbances (47%) when the sellar gangliocytoma was isolated, or with acromegalic manifestations (67%) when the gangliocytoma was associated with a pituitary adenoma. Immunohistochemistry showed a higher prevalence of mixed GH-PRL adenomas in association with sellar gangliocytomas, followed by GH adenomas. A purely intrasellar localization was found in about 25% of cases and a suprasellar extension in 30% of cases. A more extensive infiltration was present in about 40% of cases. A complete resection was obtained in 56% of collision lesions. The follow-up period was variable but endocrine remission was reported in 81% of cases of associated gangliocytoma and pituitary adenoma. Sellar gangliocytomas are rare lesions and an association with pituitary adenomas should always be searched. Mixed GH PRL adenomas are most frequently isolated. Collision lesions seem to have a behavior similar to isolated adenoma but a more important aggressiveness should be excluded at a molecular level. Further studies will allow advancements in clarifying the pathogenesis of this association.

Temporal clustering of neuroblastic tumours in children and young adults from Northern England.

BACKGROUND: The aetiology of neuroblastic tumours is unclear with both genetic and environmental factors implicated. The possibility that an infectious agent may be involved has been suggested. 'Temporal clustering' occurs if cases display an irregular temporal distribution and may indicate the involvement of an agent that exhibits epidemicity. We tested for the presence and nature of temporal clustering using population-based data from northern England. METHODS: We extracted all cases of neuroblastic tumours diagnosed in children and young adults aged 0-24 years during 1968-2011 from the Northern Region Young Persons' Malignant Disease Registry. This is a population-based registry, covering a population of approximately 900,000 young persons, and includes all cases resident in northern England at the time of diagnosis. Tests for temporal clustering were applied using a modified version of the Potthoff-Whittinghill method. Estimates of extra-Poisson variation (ß) and standard errors (SEs) were obtained. RESULTS: 227 cases of neuroblastic tumours were diagnosed during the study period. All the analyses between fortnights and between months found significant extra-Poisson variation, with ß = 0.846 (SE = 0.310, P = 0.004) for the analysis between fortnights within months. Restricting the analyses to the 76 cases diagnosed at ages less than 18 months showed significant extra-Poisson variation between fortnights within months (ß = 1.532, SE = 0.866, P = 0.038), but not between months. In contrast, analyses of cases aged 18 months to 24 years showed significant extra-Poisson variation between quarters within years, as well as over shorter timescales. CONCLUSIONS: Transient environmental agents may be involved in the aetiology of neuroblastic tumours. The initiating factor might be a geographically-widespread agent that occurs in 'mini-epidemics'.

Adrenal ganglioneuroma: features and outcomes of 27 cases at a referral cancer centre.

BACKGROUND: Adrenal ganglioneuroma (AGN) is a rare neurogenic tumour that can mimic other adrenal neoplasms. Limited information, mostly derived from small cases series, is available for AGN. METHODS: A retrospective review for AGNs seen at a tertiary referral centre describing important features to distinguish AGN from other adrenal neoplasms. RESULTS: Of 53 ganglioneuromas, 27 were AGNs. Median age was 31 years (range, 1·7-64 years) and median tumour size was 8 cm (range, 1·5-20 cm). Seventeen AGNs (63%) were detected incidentally and nine patients (33%) presented with abdominal/back discomfort. Catecholamine levels, available for 21 patients, were normal. On computed tomography (CT), most AGNs were homogenous and well circumscribed with a median density of 32·5 Hounsfield units (HU) on unenhanced CT; 40 HU on postcontrast venous phase; and 66·5 HU on delayed postcontrast phase. On magnetic resonance imaging (MRI), AGNs had hypo-intense signal on T1-weighted images with heterogeneous hyperintense signal on T2-weighted images. In four patients, there was no tumour growth during median follow-up of 48 months (range, 21-60 months). One patient had malignant peripheral nerve sheath tumour arising from AGN. Thirteen patients with resected AGN had no recurrence during a median follow-up of 50 months (range, 2-135 months). CONCLUSIONS: We herein describe the largest AGN series reported to date. Isolated AGNs do not produce catecholamines and have CT imaging characteristics that can help in distinguishing them from other adrenal and para-adrenal neoplasms. The natural history of AGNs is usually benign, although local extra-adrenal extension or malignant transformation can rarely occur.

Adrenal ganglioneuromas: a 10-year experience in a Chinese population.

BACKGROUND: Adrenal ganglioneuroma (GN) is extremely rare. The present study is to describe the largest series of this adrenal tumor treated in a single medical center to our knowledge. METHODS: Clinical details, radiologic, laboratory, and pathologic findings as well as follow-up data were analyzed retrospectively in 17 patients with incidentally discovered adrenal GN who received operative resection at a tertiary referral hospital in eastern China between June 1999 and June 2009. RESULTS: The mean age of the 17 GN patients was 39.2 years (range, 7-72; male:female ratio, 1:2.4), of whom 13 patients had unilateral GN on the right side, and the remaining 4 on the left side. None of the 17 tumors was hormonally active. Only 6 of the 17 GN cases were diagnosed as benign nerve cell tumors by computed tomography or magnetic resonance imaging before operation. Treatment consisted of open unilateral adrenalectomy in 9 patients and laparoscopy in 8 patients. The mean pathologic size of the adrenal GNs was 6.3 +/- 3.1 cm (range, 1.0-13.0). Ultrastructural examination provided additional support for confirming the diagnosis. CONCLUSION: Although there have been some clues for radiologic diagnosis of adrenal GN, pre-operative mis- and maldiagnosis are not infrequent. We recommend that complete operative resection should be considered once malignancy cannot be excluded by pre-operative evaluation. Laparoscopic adrenalectomy is a reasonable option at least for tumors < or =7 cm.

Laparoscopic resection of large adrenal ganglioneuroma.

We report on a 23-year-old woman with a right adrenal tumor 13 cm in diameter who was treated by laparoscopy. The patient was asymptomatic, and the tumor was incidentally diagnosed on abdominal ultrasonography. A subsequent computed tomography (CT) of the abdomen confirmed a 12 x 7 x 8-cm homogenous mass of the right adrenal. Magnetic resonance imaging (MRI) showed a solid mass measuring 13 x 7 x 7.5 cm arising from the right adrenal. Laparoscopic complete excision of the mass was accomplished through a transabdominal lateral approach. The postoperative period was uneventful, and the patient was discharged on the second postoperative day. Histology was consistent with an adrenal ganglioneuroma. Two years later, there is no evidence of recurrence on abdominal CT scan.

Genetic epidemiology of neuroblastoma: a study of 426 cases at the Institut Gustave-Roussy in France.

BACKGROUND: Genetic susceptibility to neuroblastoma (NB) is now highly probable and the likelihood that it may also confer a higher risk of other cancer types has been suggested. The aim of this study was to estimate the fraction of inherited cases and penetrance associated with a carrier status, and to investigate the hypothesis that susceptibility cancer genes might be non-specific. PROCEDURE: The family history of 426 children treated for NB at the Institut Gustave Roussy was obtained. The excess of relatives affected by NB or early-onset cancer (EOC) was sought using the standardized incidence ratio (SIR). The risk of NB among sibs was estimated taking into account the age of patients' sibs. Estimation of penetrance in hereditary cases and of the proportion of sporadic cases was obtained using segregation analysis of proband sibships. RESULTS: There was a positive family history of NB or ganglioneuroma in 5 of the 426 cases (1.2%). A highly significant excess of NB was found among relatives (SIR=11.4, 95% CI: 3.7-26.5). The excess of EOC (SIR=1.22, 95% CI=0.92-1.58) was non-significant, but it was of borderline significance among first-degree relatives (SIR=1.70, 95% CI=0.99-2.72). The risk of NB among sibs was estimated at 0.2% (95% CI=0.004-1.0%). Penetrance in hereditary cases was estimated at 11.4% and the proportion of inherited cases, 3.5%. CONCLUSIONS: The genetic factors heightening susceptibility to NB are most probably dominantly inherited with low penetrance and are involved in only a very small fraction of NB patients. The overall risk in sibs is very low and this should reassure parents with regard to their other children. We found some arguments for the existence of non-specific genetic susceptibility, which would slightly in crease the probability of developing any cancer.

Epidemiology of neuroblastoma: analysis of a single institution.

BACKGROUND: Neuroblastoma is the fourth most frequent cancer among all pediatric neoplasms Epidemiological studies may shed more light on the disease and aid in improving treatment of patients with neuroblastoma. PATIENTS AND METHODS: Epidemiology data are presented for 333 children with neuroblastoma or ganglioneuroblastoma and 11 children with ganglioneuroma who were treated at the Institute of Mother and Child in Warsaw, Poland, from 1962 to 1996. RESULTS: Analysis of the stage of the disease, age, sex and survival of children with neuroblastoma demonstrated comparable distribution of good and intermediate stages versus the stages with a poor prognosis. CONCLUSION: Comprehensive analysis of epidemiological data on the stage of cancer, age, sex and survival in patients with neuroblastoma provides a basis for better prognosis of the disease and cost-efficient treatment.

[Histopathologic differentiation of tumors derived from neuroblastic cells in children depending on age]. / Zróznicowanie histologiczne guzów grupy neuroblastoma u dzieci w zaleznosci od wieku.

The histopathology of 224 tumours of neuroblastic origin was analysed in relation to the age of patients. Maturing neuroblastomas (NBS) dominated in infants, where as in the most numerous group of children 1-5 years of age, prevalence of neuroblastomas without any signs of maturation was noted. In children over 5 years of age a high incidence of tumours with evident maturation was noted (ganglioneuroblastomas and ganglioneuromas). The prevalence of maturing neuroblastomas in infants correlate well with an advantageous clinical course of neuroblastomas at this age.

Coexistence of an adrenocortical carcinoma with an abdominal ganglioneuroma in a child.

We report a 3-year, 5-month-old boy with an adrenocortical carcinoma. These tumours are rare and highly malignant in childhood. In most cases they are functional, secreting adrenocortical hormones. In this case there was a misleading coexistence with a second abdominal neoplasm, which was a ganglioneuroma; this is a rare benign tumour arising from the sympathetic nervous system. The imaging investigations and their findings are discussed and correlated with pathology.

[Primary mediastinal tumors in children--comparison with mediastinal tumors in adults].

During the past 43 years, 628 patients with a primary mediastinal tumor underwent surgical operation in our institution. Of those patients, 106 patients (16.9%) were children of 15 yr of age or less and 522 patients (83.1%) were adults. 47 (44.3%) of the 106 children had neurogenic tumors, while 21 patients (19.8%) had a teratoma. 189 (36.2%) of the 522 adults had thymoma and 89 patients (17.1%) had teratoma. In the 106 children there were 71 benign tumor patients (66.9%) and 35 malignant tumor patients (33.1%). There were 277 (53.1%) benign and 245 (46.95) malignant tumors in the 522 adults. The adults had significantly more malignant tumors than the children (p < 0.01). In our series of malignant mediastinal tumors in children, 14 patients (13.3%) had a lymphoma and 11 patients (10.5%) had a neuroblastoma. On the other hand, in the adults, 127 patients (24.3%) had a thymoma and 66 patients (12.6%) had a lymphoma. Regarding benign mediastinal tumors, in children, 30 patients (28.5%) had a ganglioneuroma and 19 patients (18.0%) had a teratoma. In the adults, 68 patients (13.0%) had a teratoma and 62 patients (11.9%) had a thymoma. In the clinical manifestation, 51 child patients (48.1%) and 191 adult patients (36.6%) were asymptomatic. As symptoms due to compression or direct invasion to adjacent structures, dyspnea was seen in 16 child patients (15.1%), and chest pain occurred in 59 adult patients (11.3%). Dyspnea was significantly more common in children than in in adults (p < 0.01). Emergency operations were performed in children more than in adults.

Mass screening in Japan increased the detection of infants with neuroblastoma without a decrease in cases in older children.

Analysis of data from the Kanto-Ko-Shin-Etsu Branch of the Japan Children's Cancer Registry revealed that mass screening for neuroblastoma increased the detection of cases in infants younger than 1 year from about 25% before screening to about 50%, and the percentage of neuroblastomas among all pediatric cancers almost doubled, from approximately 10% to 19.3%. However, when the cases found on screening were subtracted, the numbers after the onset of mass screening were similar to those before screening. It is likely that neuroblastoma mass screening has identified a unique type of tumor, which may not be recognized without mass screening, rather than that it has contributed to the earlier diagnosis of tumors in older children.