Ganglioneuroma Research Articles

Large Adrenal Ganglioneuroma

We herein report the case of a 41-year-old male patient with an incidentally identified large adrenal ganglioneuroma (GN). His endocrine examinations were normal except for one episode of elevated urinary dopamine and noradrenaline levels. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) showed a large solid tumor with calcifications and a slightly lobular edge in the right adrenal gland. We performed open tumor excision and diagnosed it as adrenal ganglioneuroma. Adrenal GN is a rare benign tumor, and its hormonal activity and imaging characteristics are occasionally very similar to those of other adrenal tumors. Therefore, it needs careful evaluation by endocrine examinations and multiple imaging procedures to rule out other types of tumors.

CT and MRI manifestations of the intrathoracic ganglioneuroma

Objective To evaluate CT and MRI findings of the intrathoracic ganglioneuroma and to improve its diagnosis and differential diagnosis ability.Methods Clinical,CT( n = 14),MRI (n = 6) and pathology manifestations of 20 patients with the intrathoracic ganglioneuroma were retrospectively analyzed.All 20 cases had chest CT and MRI plain scanning and multiphase enhance scanning before operation.Results Seventeen of 20 lesions were located in posterior mediastinum,2 in pleura side and 1 in right thorax cavity.The CT value of the plain scans ranged from 20 to 40 HU ( mean 30.5 HU),Tubercle calcification were detected in four masses,one case with fat density was showed on CT scanning.After injecting contrast media,CT value ranged from 0 to 12 HU (mean 6.2 HU) in artery phase,ranging from 10 to 20 HU ( mean 14.3 HU) in delay phase.Five of 6 cases of MRI signals were homogeneously low intensity on T1 WI,1 case with fat signal was imhomogeneously low intensity on T1WI.Six cases were imhomogeneously high intensity on T2WI.A whorled appearance was visualized in one tumor on T2WI.The post-contrast enhancement MR images was slight enhancement imhomogeneously in artery phase and gradual increasing enhancement in delay phase.Conclusion On CT and MR imaging,no enhancement or slight enhancement in artery phase and gradual increasing enhancement in delay phase are characteristic manifestations of ganglioneuroma in the thorax. Key words: Thorax; Ganglioneuroma; Tomography, X-ray computed; Magnetic resonance imaging

Diagnosis and treatment for adrenal ganglioneuroma

To evaluate the clinical characteristics,diagnosis and treatment for adrenal ganglioneuroma. Thirty cases of adrenal ganglioneuroma at our hospital from 1999 to 2010 were reviewed. Their clinical, radiological, laboratory and pathologic findings as well as follow-up data were analyzed retrospectively. There were 12 males and 18 females with an age range of 7 - 63 (23.8 ± 11.4) years old. Tumor size ranged from 2.5 cm to 15 cm. Fourteen (46.7%) cases were found incidentally without any overt symptom. And the presenting symptoms and signs of the others were paroxysmal headache and palpitation (n = 7, 23.3%), hypertension (n = 5, 16.7%) and flank or abdominal pain (n = 4, 13.3%). All cases underwent open or laproscopic operations and their diagnosis of adrenal ganglioneuroma was confirmed pathologically. An oval or crescentic well-defined mass, low or intermediate attenuation on CT (computed tomography) scan was found in most cases. Tumors partially or completely surrounded major blood vessels in 9 cases while 7 cases had discrete punctuate calcification. The 24-hours urinary catecholamine and urinary free cortisol output were within a normal range. Seventeen cases underwent a (99)Tc-octreotide scan and negative results were found in 15 cases. Seven cases had a (131)I-Metaiodobenzylguanidine ((131)I-MIBG) scan and all results were negative. Twenty-one cases were diagnosed empirically as adrenal ganglioneuroma. One case was found pre-operatively with multiple bone metastases. Among all cases, either open operation (n = 11) or retroperitoneal laparoscopic excision (n = 19) was performed successfully. All recovered smoothly. One patient with pre-operative bone metastasis developed progression. No recurrence was detected after a follow-up period of 1 - 11 years. Mostly benign in nature, adrenal ganglioneuromas is often found incidentally without specific clinic symptoms. A relatively accurate preoperative diagnosis can be made on the basis of a detailed history and the relevant imaging and laboratory results. Surgical resection of tumor is a preferred choice with a fairy good prognosis.

Brain lipid–binding protein: a marker of differentiation in neuroblastic tumors

Purpose Neuroblastoma (NB), ganglioneuroblastoma (GNB), and ganglioneuroma (GN) are neuroblastic tumours (NT) of sympathetic nervous system origin. Brain lipid-binding protein (BLBP) has potential morphogenic activity during nervous system development but has not been studied in these tumours. We analyzed the expression of BLBP in NT according to histological subtypes and extent of differentiation. Methods Thirty cases of NT (10 each of NB, intermixed GNB, and GN) were identified from the histopathology archive of a single center. Tissue sections were obtained from representative paraffin blocks and immunohistochemistry for BLBP performed. Results Brain lipid-binding protein was not expressed in any NB case. In all cases of GN, BLBP was strongly expressed in the cytoplasm of mature ganglion cells but negative in Schwannian stroma. In the intermixed GNB, there was similar strong BLBP immunoreactivity in the cytoplasm of fully differentiated and differentiating ganglion cells but no BLBP expression in immature neuroblasts. Conclusion Brain lipid-binding protein is strongly expressed in mature and maturing ganglion cells in NT (GN and GNB), whereas it is absent in poorly differentiated neuroblasts of GNB and NB. Cytoplasmic expression of BLBP in NT increases as the cells undergo neural differentiation and is therefore associated with the extent of tumour differentiation and favorable histology.

Abstract 4347: Anaplastic lymphoma kinase (ALK) expression is an independent prognostic factor in neuroblastoma patients and correlates well with ALK inhibitor response in vitro

Abstract Introduction: ALK mutations are one of the most common genetic aberrations occurring in 3-11% of the neuroblastoma (NBL) patients and are considered oncogenic. We determined the role of ALK protein levels on survival of NBL patients. Secondly, we tested in vitro responsiveness to ALK inhibitors in NBL cell lines with and without ALK mutation. Results: Formalin-Fixed, Paraffin-Embedded material of 71 NBL, 12 ganglioneuroblastoma (GNBL) and 20 ganglioneuroma (GN) patients was stained for total ALK protein by immunohistochemistry (IHC). The percentage of ALK positive cells in IHC was stratified in 4 Ccategories; Category 1 (n=40): < 20% ALK-positive cells, category 2 (n=25): 20-50% ALK positive cells, category 3 (n=25): 50-75% ALK positive cells, and category 4 (n=13): 75-100% ALK positive cells. These categories correlate significantly with overall survival in the spectrum of NBL, GNBL and GN (p=0.002, Logrank test). ALK mutations were identified in 2/63 NBL (3.2%) and 2/11 GNBL (18.2%) patients by sequencing. Importantly, in NBL and GNBL patients, ALK protein expression remains a significant factor in a multivariate model (Cox Proportional Hazard model) including the COG risk stratification (p<0.000), which encompasses stage and NMYC status (see table). Further, we studied the role of ALK levels in the response to ALK inhibitors in vitro in NBL cell lines. ALK inhibitor response (TAE684) correlates well with ALK protein levels (r=−0.813, p=0.001). ALK point mutated cell lines show higher ALK levels and a better ALK inhibitor response (LC50 values 14.9 fold lower, p=0.004) than WT and amplified cell lines. In conclusion: ALK protein expression is an independent predictor of overall survival in NBL patients and ALK inhibitor response in vitro. ICH staining with ALK antibody is reliable and correlates well with prognosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4347. doi:10.1158/1538-7445.AM2011-4347

Correlation between typing of peripheral neuroblastic tumors and prognosis: a clinicopathologic study of 135 cases

To study the clinicopathologic characteristics of peripheral neuroblastic tumors and to investigate the prognostic significance of International Neuroblastoma Pathology Classification (INPC). One hundred and thirty-five cases of peripheral neuroblastic tumors encountered in Shanghai Children's Medical Center were enrolled into the study. All the cases were classified according to INPC and International Neuroblastoma Staging System (INSS). The follow-up data were analyzed. The consensus diagnoses of the 135 cases were as follows: 80 cases (59.2%) of neuroblastoma, 24 cases (17.8%) of ganglioneuroblastoma, intermixed, 17 cases (12.6%) of ganglioneuroma and 14 cases (10.4%) of ganglioneuroblastoma, nodular. The cases were subdivided into 2 subgroups: favorable histology (number = 90, 66.7%) and unfavorable histology (number = 45, 33.3%). According to INSS, the number of cases in stages I, II, III and IV was 22 (16.3%), 24 (17.8%), 34 (25.2%) and 55 (40.7%), respectively. The survival of peripheral neuroblastic tumors correlated with histologic diagnosis, INPC and INSS (P < 0.05). Diagnostic categorization of peripheral neuroblastic tumors according to INPC is of prognostic value.

Bilateral and symmetric ganglioneuromas of the cervical spine:a case report

患者男,46岁,右手乏力1年并双下肢步态不稳2个月余,于2010年3月29 日来我院就诊.体检:步态不稳,四肢无肌萎缩,右上肢肌力Ⅲ级,肌张力正常,右手对指试验、Hoffmann征(+);左上肢及双下肢肌力及肌张力正常;双膝反射正常,病理征未引出。

The role of WT1 gene in neuroblastoma

Background/Purpose The oncogenic properties of the Wilms' tumor gene ( WT1) have recently been reported in various malignancies. However, the role of WT1 in pediatric tumors is unclear. To elucidate the role of WT1 in the development of neuroblastoma (NB), we examined the WT1 expression in NB and the effect of WT1 suppression on NB cell proliferation. Methods We examined the expression of the WT1 protein in 20 NBs and 5 ganglioneuromas (GNs) by performing immunohistochemical analysis. We determined WT1 messenger RNA expression in 22 NBs, 5 GNs, and 4 NB cell lines by real-time reverse transcription polymerase chain reaction. We studied the effects of WT1 suppression on cell proliferation using small interfering RNA against WT1. Results Expression of WT1 was higher in mature ganglionic cells, and in the immunohistochemical analysis, the WT1 positivity for GNs was significantly higher than that for NBs ( P < .01). The level of WT1 messenger RNA expression did not correlate with histologic grade, clinical stage, and prognosis of the tumor. Knockdown of WT1 gene promoted the proliferation of NB69 cells ( P < .01). Conclusions The WT1 may govern cell differentiation and suppress cell proliferation in NB. The WT1 does not act as an oncogene, but it may participate in the maturation of NB.

Adrenal Ganglioneuroma With Lymph Node Deposits: A Rare Benign Tumor

Ganglioneuromas are rare, benign tumors arising from primordial neural crest cells. We report a case of a seven-year-old girl presenting with a history of pain in the left side of the abdomen since one year. A provisional diagnosis of a non-functioning adrenal tumor was made on the basis of radiological scans and endocrine profile. The specimen was excised along with a lymph node. The specimen showed a grey white lesion measuring 2.5 x 2.5 cm. Sections from the lesion and the lymph node showed a benign tumor with spindle cells in intersecting fascicles and ganglion cells in clusters. A final diagnosis of benign ganglioneuroma was thus made. Adrenal gland ganglioneuromas with lymph node deposits represent a spontaneous differentiation from neuroblastoma in which the lymph node deposit has also matured. Representation of this entity in literature is important to alert the histopathologist for the diagnosis of a benign tumor in the primary and metastatic site. doi:10.4021/jnr56e

Adrenal Ganglioneuroma with Multifocal Retroperitoneal Extension: A Challenging Diagnosis

A ganglioneuroma (GN) is the rarest and most benign of the neuroblastic tumors and originates from neural crest cells wherever sympathetic nervous tissue exists, such as in the retroperitoneum and adrenal gland. The diagnosis can be very challenging, given the rarity and asymptomatic presentation of this neoplasia, and can be achieved only by means of histological evaluation. Although benign, a few cases of metastatic GNs have been reported in the literature. The prognosis, however, seems to be excellent after surgical resection. We describe a rare case of multifocal retroperitoneal GN, diagnosed incidentally in a 46-year-old woman, with para-aortic and adrenal localizations. After intraoperative pathological diagnosis was made, complete excision of all the visible masses was performed. The postoperative period was uneventful and she was recurrence free 3 months after surgery. To our knowledge, this is the first case report of a multifocal retroperitoneal GN. Among the broad differential diagnoses of adrenal incidentalomas, an adrenal location of neuroblastic tumors should not be forgotten.

Loss of mitochondria in ganglioneuromas

A shift in cellular energy production from oxidative phosphorylation (OXPHOS) to glycolysis, even under aerobic conditions, is called the Warburg effect. To elucidate changes of the mitochondrial energy metabolism in ganglioneuroma (GN) individual OXPHOS enzymes were analyzed by activity assays and by immunohistochemical staining methods. GN (n=7) showed a significant reduction in the activity and content of OXPHOS enzymes. Citrate synthase activity was also severely diminished in GN compared to normal cortical kidney (p=0.0002) and adrenal (p=0.0024) tissues. Furthermore, the mitochondrial membrane protein porin was undetectable or significantly reduced. Accordingly, a reduction of the copy number of mitochondrial DNA was observed in GN compared to cortical kidney tissue. The striking decline of mitochondrial mass is specific for GN but not for neuroblastoma, in which a reduction of the OXPHOS complexes without reduction of mitochondrial mass was reported. Knowledge of the mechanism by which tumor cells achieve the Warburg effect will provide a starting point for functional studies aimed at restoring aerobic energy metabolism as a potential new therapeutic strategy to treat malignancies.

Morbidity After Ganglioneuroma Excision: Is Surgery Necessary?

Ganglioneuroma (GN), the benign form of peripheral neuroblastic tumour, is often asymptomatic and the diagnosis can be incidental. Our aim was to evaluate the incidence of complications after surgical treatment following diagnosis of this tumour. 24 consecutive children were diagnosed with GN in our centre between January 1989 and December 2009. All patients had negative urinary catecholamines and/or biopsy confirming the diagnosis of GN. Data are reported as mean ± SD. Age at diagnosis was 73 ± 43 months. The most common presentation was respiratory symptoms and/or abdominal pain; 9 (38%) patients were asymptomatic. Tumour location was in the chest (n=14), abdomen (n=7), or pelvis (n=3). 23 children (9 asymptomatic) were operated on; 1 child with a thoracic mass did not undergo surgery because of severe neurological impairments from birth unrelated to GN. 13 children (4 asymptomatic) had a thoracotomy, 8 children (4 asymptomatic) had laparotomy, and 2 (1 asymptomatic) underwent perineal resection. A macroscopically complete surgical excision was performed in 17 cases (74%) and a macroscopically near-complete excision in 6 (26%). At histological examination, resection margins contained tumour in 10 patients (43%) and were free of tumour in the remaining 13 (57%). 7 children (30%) had complications after surgery including 3 patients with Horner's syndrome (which persisted in 2), 1 with chylothorax, 1 with pneumothorax, 1 with pain in the arm, and 1 who developed adhesive intestinal obstruction. 2 children received adjuvant chemotherapy. We re-evaluated the histology specimens according to the International Neuroblastoma Pathology Classification and found that the diagnosis of GN was confirmed in 20 cases (83%), while intermixed ganglioneuroblastoma (iGNB) was diagnosed in 4 patients (17%). At 33.5 ± 40 months (range 1-137) follow-up, all 24 patients, including the child not operated on and the children with incomplete resection or iGNB, are alive with no tumour progression or recurrence. GN excision is associated with postoperative complications which can be persistent and may affect the quality of life of survivors. In our series we did not observe tumour progression in spite of incomplete excision. The rationale for GN excision should be revisited.

Isolated Ganglioneuroma of the Colon

Purpose: Ganglioneuromas (GN) are neuroectodermal tumors consisting of ganglion cells, nerve fibers and Schwann sheath elements. When found in the gastrointestinal tract, they are of uncommon occurrence. We report a case of an isolated ganglioneuroma of the colon. Case: A 43 year old Ecuadorian female who was otherwise healthy, underwent surveillance colonoscopy that revealed a 6mm polyp at the hepatic flexure and a 4mm polyp at the sigmoid colon. Histology of the resected polyps from the hepatic flexure and sigmoid colon showed tubular adenoma and ganglioneuroma respectively. Discussion: GI ganglioneuromas are rare, benign, and well differentiated reported as 3 subtypes: (1) solitary polypoid GN, (2) ganglioneuromatous polyposis and (3) diffuse ganglioneuromatosis. Polypoid GNs are small, sessile polyps that resemble juvenile polyps, adenomas, or hyperplastic polyps. Gangioneuromatous polyposis is characterized by small multiple polyps (20-40 lesions) with mature ganglion cells in the mucosa and submucosa. Diffuse ganglioneuromatosis (GNM) have band-like enlargement of the submucosal plexus and myenteric nerve plexus caused by hyperplasia of nerve fibers and ganglion cells. There are no specific symptoms eluding toward the clinical diagnosis of ganglioneuromas of the GI tract. Isolated ganglioneuromas are usually asymptomatic. Ganglion cells are not normally found within the GI mucosa. Diagnosis can be facilitated through immunostaining; S-100 protein, neuronase specific enolase (NSE) and neurofilament protein (NFP). In our patient, stains were not performed in order to make the final diagnosis. Mature ganglion cells infiltrating the submucosa as seen in the clusters of large cells with vesicular eccentrically placed nuclei and abundant eosinophilic cytoplasm are seen in high power field (See Figure 1). In the background stroma, spindle and Schwann cells are present. There is no indication for resection in asymptomatic patients. Isolated colonic ganglioneuromas have no reported predilection toward malignancy and there is no indication for long term follow-up in this patient population.Figure

Concomitant Carcinoid, Gastrointestinal Stromal Tumor and Ganglioneuroma in a Male with Abdominal Pain

Purpose: Concomitant presentation of Carcinoid, Gastrointestinal Stromal Tumor (GIST) and Ganglioneuroma (GN) has not yet been reported. Due to its novelty, screening, management, and prognosis of tri-concomitant malignancies involving carcinoid tumor is unknown. We describe a 51-year-old male with no significant medical history who initially presented to the PCP for diffuse intermittent abdominal pain. He was subsequently referred to Gastroenterology and underwent a screening colonoscopy which showed superficial lobular changes at the proximal colon. Immunostain analysis on biopsy specimen was positive for chromogranin and synaptophysin confirming Carcinoid tumor. Imaging studies for staging revealed two hepatic lesions that were positive on Octreotide scan. He subsequently underwent exploratory laparotomy, right hemicolectomy, resection of the small bowel and jejunal tumors and liver wedge resection. Pathologic findings on resected small bowel identified a Gastrointestinal stromal tumor (GIST), while the right colon and distal ileum showed Carcinoid tumor with liver metastasis. Furthermore, a solitary Ganglioneuroma was identified within the colon. To our knowledge, synchronous presentation of Carcinoid, GIST and Ganglioneuroma has not yet been reported, and a thorough literature search failed to yield any such cases. Pathogenesis of concomitant presentation within this patient remains unclear. One could speculate that the occurrence of these neoplasms may involve common oncogenic pathways that are yet to be discovered, or alternatively carcinoid tumor render other cell types susceptible for malignancies. The reported increased incidence of other malignancies in carcinoid patients begs the question whether a thorough screening protocol should be instituted at time of carcinoid diagnosis. Furthermore, does synchronous presentation affect prognosis that may perhaps influence management?

Ganglioneuroma of Posterior Mediastinum in a 6-year-old Girl: Imaging for Pediatric Intrathoracic Incidentaloma

Intrathoracic tumor is a rare entity in the pediatric population and neurogenic tumors account for 40-50% of childhood intrathoracic tumors. They can cause severe symptoms, such as respiratory distress, neurological dysfunction and metabolic disturbances. Posterior mediastinal ganglioneuroma (GN) usually occurs in children and can be found accidentally. Precise preoperative diagnosis is very difficult and has a great influence on surgical intervention. Here, we report a 6-year-old girl with a posterior mediastinal GN that was found incidentally on chest radiography. Computed tomography and magnetic resonance imaging demonstrated a right paraspinal tumor with punctuate calcification and intraspinal extension. (18)F-fluorodeoxyglucose positron emission tomography revealed low-grade fluorodeoxyglucose avidity of this tumor. Computed tomography and magnetic resonance imaging can characterize GN and positron emission tomography is helpful for differentiating benign or malignant lesions.

Balance of pro‐ versus anti‐angiogenic splice isoforms of vascular endothelial growth factor as a regulator of neuroblastoma growth

Neuroblastoma (NB) is the second most common extracranial tumour of childhood. Angiogenesis plays a crucial role in the growth and development of NB and vascular endothelial growth factor (VEGF), one of the most potent stimuli of angiogenesis, has been studied extensively in vitro. VEGF(165) has been shown to be the predominant angiogenic isoform expressed in NB cell lines and tumours. In this study, we investigated the anti-angiogenic isoform of VEGF-A, generated from distal splice site selection in the terminal exon of VEGF (VEGF(165)b) and shown to be down-regulated in epithelial malignancies. The expression of both the pro- (VEGF(xxx)) and the anti-angiogenic (VEGF(xxx)b) isoforms was compared in a range of NB and ganglioneuroma (GN) tumours. Whereas VEGF(xxx)b and VEGF(xxx) were both expressed in GN, specific up-regulation of the VEGF(xxx) isoforms was seen in NB at RNA and protein levels. Highly tumourigenic NB cell lines also showed up-regulation of the angiogenic isoforms relative to VEGF(xxx)b compared to less tumourigenic cell lines, and the isoforms were differentially secreted. These results indicate that VEGF(165) is up-regulated in NB and that there is a difference in the balance of isoform expression from anti-angiogenic VEGF(165)b to angiogenic VEGF(165). Treatment with recombinant human VEGF(165)b significantly reduced the growth rate of established xenografts of SK-N-BE(2)-C cells (4.24 +/- 1.01 fold increase in volume) compared with those treated with saline (9.76 +/- 3.58, p < 0.01). Microvascular density (MVD) was significantly decreased in rhVEGF(165)b-treated tumours (19.4 +/- 1.9 vessels/mm(3)) in contrast to the saline-treated tumours (45.5 +/- 8.6 vessels/mm(3)). VEGF(165)b had no significant effect on the proliferative or apoptotic activity, viability or cytotoxicity of SK-N-BE(2)-C cells after 48 h. In conclusion, VEGF(165)b is an effective inhibitor of NB growth. These findings provide the rationale for further investigation of VEGF(165)b in NB and other paediatric malignancies.

A clinicopathological analysis of 172 cases with intractable epilepsy

Objective To discuss the clinicopathologic characteristics of surgically removed tissues in patients with intractable epilepsy. Methods From 2008 to 2009, the histological sections of 172 specimens of cerebral epileptogenic foci, which were acquired by surgery, were performed respectively by HE staining and immunohisto - chemical staining,the characteristics of clinical pathology were also analyzed. Results Of all the 172 cases, according to the pathological features of the epilepto -genic foci, there were 138 focal cortical dysp lasia (FCD) ,including 115 FCD ⅠB, 15 FCD ⅡA and 8 FCD ⅡB, 2 micro cortical dysplasia, 4 dysembryoplastic neuropithelial tumors,7 Rasmussen's encephalitis, 16 ulegyrias; 1 ganglioneuroma; 1 microgyria malformation, 1 vascular malformation, 1 hypothalamic hamartoma, 1 tuberous sclerosis. ConclusionFCD is the most commonly present in intractable epilepsy, and FCDⅠB is most common among the FCD. Key words: Epilepsy; Malformations of cortical development; Tuberous sclerosis

Clinical and Biochemical Features of Seven Adult Adrenal Ganglioneuromas

Adrenal ganglioneuroma (GN) is seldom considered in the differential diagnosis of adrenal lesions, and its clinical presentation is not well known. Our aim was to describe the clinical, biochemical, and radiological features of adrenal GNs in adults. Seven adults underwent endocrine investigation for adrenal lesions that were confirmed to be adrenal GNs. Mean age of the seven patients was 49 yr (range, 23 to 71 yr). Average tumor diameter was 5.0 cm (range, 1.5 to 10.4 cm). In five patients, the adrenal lesions were found incidentally. A 49-yr-old female carried a germline mutation in MSH2 gene. A 57-yr-old female presented with mild virilization and increased testosterone levels. Bilateral adrenal venous sampling revealed testosterone production from her right adrenal lesion. All tumors showed nonenhanced attenuation between 25 and 40 Hounsfield units on computed tomography scan. Magnetic resonance imaging revealed low- to iso-signal intensity on T1-weighted imaging and high-signal intensity on T2-weighted imaging. [(18)F]-2-Fluoro-deoxy-d-glucose-positron emission tomography scan (n = 5) disclosed a mean standard uptake value of 2.4. Three tumors were composite pheochromocytoma-GN. Microsatellite instability study and immunohistochemical analysis of MSH2 protein in a patient carrying a MSH2 mutation showed normal MSH2 protein expression and low microsatellite instability, indicating that the adrenal GN was not related to the patient's MSH2 germline defect. We describe one of the largest series of adult adrenal GNs. Adrenal GNs may secrete testosterone or be part of a composite tumor with pheochromocytoma. The association of adrenal GN with MSH2 mutation seems to be a coincidental finding.

Abstract 4842: Lysosomal-associated protein multispanning transmembrane 5 gene (LAPTM5) is associated with spontaneous regression of neuroblastomas

Abstract Background; Neuroblastoma (NB) is the most frequently occurring solid tumor in children, and shows heterogeneous clinical behavior. Favorable tumors, which are usually detected by mass screening based on increased levels of catecholamines in urine, regress spontaneously via programmed cell death (PCD) or mature through differentiation into benign ganglioneuroma (GN). In contrast, advanced-type NB tumors often grow aggressively, despite intensive chemotherapy. Understanding the molecular mechanisms of PCD during spontaneous regression in favorable NB tumors, as well as identifying genes with a pro-death role, is a matter of urgency for developing novel approaches to the treatment of advanced-type NB tumors. Key findings; We found that the expression of lysosomal associated protein multispanning transmembrane 5 (LAPTM5) was usually down-regulated due to DNA methylation in an NB cell-specific manner, but up-regulated in degenerating NB cells within locally regressing areas of favorable tumors detected by mass-screening. Experiments in vitro showed that not only a restoration of its expression but also the accumulation of LAPTM5 protein, was required to induce non-apoptotic cell death with autophagic vacuoles and lysosomal destabilization with lysosomal-membrane permeabilization (LMP) in a caspase-independent manner. While autophagy is a membrane-trafficking pathway to degrade the proteins in lysosomes, the LAPTM5-mediated lysosomal destabilization with LMP leads to an interruption of autophagic flux, resulting in the accumulation of immature autophagic vacuoles, p62/SQSTM1, and ubiqitinated proteins as substrates of autophagic degradation. In addition, ubiquitin-positive inclusion bodies appeared in degenerating NB cells. Conclusions; We propose a novel molecular mechanism for PCD with the accumulation of autophagic vacuoles due to LAPTM5-mediated lysosomal destabilization. LAPTM5-induced cell death is lysosomal cell death with impaired autophagy, not cell death by autophagy, so-called autophagic cell death. Thus LAPTM5-mediated PCD is closely associated with the spontaneous regression of NBs and opens new avenues for exploring innovative clinical interventions for this tumor. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4842.

CT diagnosis of retoperitoneal ganglioneuroma and review of the literature

Objective To describe CT appearance of retoperitoneal ganglioneuroma. Methods CT findings of retroperitoneal tumor in 8 cases patients with ganglioneroma proved histopathologically were retrospectively analyzed. Results In 8 patients with retoperitoneal ganglioneuroma,these lesions appeared as homogeneous hypodense oval or round masses with well delineated margins. On arterial phase enhanced scans, 8 lesions showed no enhancement. On venous phase enhanced scans,3 lesions were mild-or moderate homogeneous enhancement. No delayed enhancement in 5 cases were showed. Conclusion The feature of retoperitoneal ganglioneuroma would help to diagnosis and differential diagnosis of retoperitoneal tumor. Key words: Ganglioneuroma; Retroperitoneum; Tomography; X-ray computed