Characteristics of Benign Neuroblastic Tumors: Is Surgery Always Necessary?

AbstractAdult Schwann cells (SCs) possess an inherent plastic potential. This plasticity allows SCs to acquire repair-specific functions essential for peripheral nerve regeneration. Here, we investigate whether stromal SCs in benign-behaving peripheral neuroblastic tumors adopt a similar cellular state. We profile ganglioneuromas and neuroblastomas, rich and poor in SC stroma, respectively, and peripheral nerves after injury, rich in repair SCs. Indeed, stromal SCs in ganglioneuromas and repair SCs share the expression of nerve repair-associated genes. Neuroblastoma cells, derived from aggressive tumors, respond to primary repair-related SCs and their secretome with increased neuronal differentiation and reduced proliferation. Within the pool of secreted stromal and repair SC factors, we identify EGFL8, a matricellular protein with so far undescribed function, to act as neuritogen and to rewire cellular signaling by activating kinases involved in neurogenesis. In summary, we report that human SCs undergo a similar adaptive response in two patho-physiologically distinct situations, peripheral nerve injury and tumor development.

Download Full-text

Diagnostic Immunohistochemistry of Neuroblastic Tumors

The American Journal of Surgical Pathology ◽

10.1097/00000478-199201000-00007 ◽

1992 ◽

Vol 16 (1) ◽

pp. 56-57 ◽

Cited By ~ 44

Author(s):

G. H. Wirnsberger ◽

H. Becker ◽

Karin Ziervogel ◽

H. Hofler

Keyword(s):

Neuroblastic Tumors

Download Full-text

Clinical and Pathological Evidence of Anti-GD2 Immunotherapy Induced Differentiation in Relapsed/Refractory High-Risk Neuroblastoma

Cancers ◽

10.3390/cancers13061264 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1264

Author(s):

Jaume Mora ◽

Alicia Castañeda ◽

Maria Cecilia Colombo ◽

Maite Gorostegui ◽

Fernando Gomez ◽

...

Keyword(s):

High Risk ◽

Fdg Pet ◽

Current Therapy ◽

Bone Lesions ◽

Functional Magnetic Resonance ◽

Positron Emission ◽

Apparent Diffusion ◽

Neuroblastic Tumors ◽

Direct Cell ◽

Magnetic Resonance Imaging Mri

Background: Neuroblastic tumors (NBTs) originate from a block in the process of differentiation. Histologically, NBTs are classified in neuroblastoma (NB), ganglioneuroblastoma (GNB), and ganglioneuroma (GN). Current therapy for high-risk (HR) NB includes chemotherapy, surgery, radiotherapy, and anti-GD2 monoclonal antibodies (mAbs). Anti-GD2 mAbs induce immunological cytoxicity but also direct cell death. Methods: We report on patients treated with naxitamab for chemorefractory NB showing lesions with long periods of stable disease. Target lesions with persisting 123I-Metaiodobenzylguanidine (MIBG) uptake after 4 cycles of immunotherapy were further evaluated by functional Magnetic Resonance Imaging (MRI) and/or Fluorodeoxyglucose (FDG)-positron emission tomography (PET). MIBG avid lesions that became non-restrictive on MRI (apparent diffusion coefficient (ADC) > 1) and/or FDG-PET negative (SUV < 2) were biopsied. Results: Twenty-seven relapse/refractory (R/R) HR-NB patients were enrolled on protocol Ymabs 201. Two (7.5%) of the 27 showed persistent bone lesions on MIBG, ADC high, and/or FDG-PET negative. Forty-four R/R HR-NB patients received chemo-immunotherapy. Twelve (27%) of the 44 developed persistent MIBG+ but FDG-PET- and/or high ADC lesions. Twelve (86%) of the 14 cases identified were successfully biopsied producing 16 evaluable samples. Histology showed ganglioneuroma maturing subtype in 6 (37.5%); ganglioneuroma mature subtype with no neuroblastic component in 4 (25%); differentiating NB with no Schwannian stroma in 5 (31%); and undifferentiated NB without Schwannian stroma in one (6%). Overall, 10 (62.5%) of the 16 specimens were histopathologically fully mature NBTs. Conclusions: Our results disclose an undescribed mechanism of action for naxitamab and highlight the limitations of conventional imaging in the evaluation of anti-GD2 immunotherapy clinical efficacy for HR-NB.

Download Full-text

Multiple Immunofluorescence Imaging Analysis Reveals Differential Expression of Disialogangliosides GD3 and GD2 in Neuroblastomas

Pediatric and Developmental Pathology ◽

10.1177/10935266211048733 ◽

2021 ◽

pp. 109352662110487

Author(s):

Haruna Nishimaki ◽

Yoko Nakanishi ◽

Hiroshi Yagasaki ◽

Shinobu Masuda

Keyword(s):

High Risk ◽

Risk Group ◽

Staging System ◽

Low Risk ◽

Overall Survival Rate ◽

Imaging Analysis ◽

Tissue Samples ◽

Risk Patients ◽

Neuroblastic Tumors ◽

Expression Status

Background Peripheral neuroblastic tumors (pNTs) are the most common childhood extracranial solid tumors. There are several therapeutic strategies targeting disialoganglioside GD2. Disialoganglioside GD3 has become a potential target. However, the mechanism by which pNTs express GD3 and GD2 remains unclear. We investigated the combined expression status of GD3 and GD2 in pNTs and delineated their clinicopathological values. Methods GD3 and GD2 expression was examined in pNT tissue samples (n = 35) using immunohistochemistry and multiple immunofluorescence imaging. Results GD3 and GD2 expression was positive in 32/35 and 25/35 samples, respectively. Combinatorial analysis of GD3 and GD2 expression in neuroblastoma showed that both were heterogeneously expressed from cell to cell. There were higher numbers of GD3-positive and GD2-negative cells in the low-risk group than in the intermediate-risk ( P = 0.014) and high-risk ( P = 0.009) groups. Cases with high proportions of GD3-positive and GD2-negative cells were associated with the International Neuroblastoma Staging System stage ( P = 0.004), Children’s Oncology Group risk group ( P = 0.001), and outcome ( P = 0.019) and tended to have a higher overall survival rate. Conclusion We demonstrated that neuroblastomas from low-risk patients included more GD3-positive and GD2-negative cells than those from high-risk patients. Clarifying the heterogeneity of neuroblastoma aids in better understanding the biological characteristics and clinical behavior.

Download Full-text

Role of CXCL13-CXCR5 Crosstalk Between Malignant Neuroblastoma Cells and Schwannian Stromal Cells in Neuroblastic Tumors

Molecular Cancer Research ◽

10.1158/1541-7786.mcr-10-0367 ◽

2011 ◽

Vol 9 (7) ◽

pp. 815-823 ◽

Cited By ~ 22

Author(s):

Federica Del Grosso ◽

Simona Coco ◽

Paola Scaruffi ◽

Sara Stigliani ◽

Francesca Valdora ◽

...

Keyword(s):

Stromal Cells ◽

Neuroblastoma Cells ◽

Neuroblastic Tumors

Download Full-text

Retrospective accuracy analysis of MRI based lesion size measurement in neuroblastic tumors: which sequence should we choose?

BMC Medical Imaging ◽

10.1186/s12880-020-00503-1 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Sebastian Gassenmaier ◽

Ilias Tsiflikas ◽

Simon Maennlin ◽

Cristian Urla ◽

Steven W. Warmann ◽

...

Keyword(s):

Mr Imaging ◽

Tumor Size ◽

Three Dimensional ◽

Lesion Size ◽

Three Dimensions ◽

Neuroblastic Tumor ◽

Significant Difference ◽

Dimensional Measurements ◽

Neuroblastic Tumors ◽

Mri Measurements

Abstract Background MR imaging of neuroblastic tumors is widely used for assessing the effect of chemotherapy on tumor size. However, there are some concerns that MRI might falsely estimate lesion diameters due to calcification and fibrosis. Therefore, the aim of our study was to compare neuroblastic tumor size based on MRI measurements to histopathology measurements of the resected specimens as standard of reference. Methods Inclusion criteria were diagnosis of a neuroblastic tumor, MR imaging within 100 days to surgery and gross total resection without fragmentation of the tumor between 2008 and 2019. Lesion diameters were measured by two radiologists according to RECIST 1.1 in axial plane in T2w turbo spin echo (TSE), diffusion-weighted imaging (DWI), and in T1w pre- and postcontrast sequences. Furthermore, the largest lesion size in three-dimensions was noted. The largest diameter of histopathology measurements of each specimen was used for comparison with MRI. Results Thirty-seven patients (mean age: 5 ± 4 years) with 38 lesions (neuroblastoma: n = 17; ganglioneuroblastoma: n = 11; ganglioneuroma: n = 10) were included in this retrospective study. There was excellent intra-class correlation coefficient between both readers for all sequences (> 0.9) Tumor dimensions of reader 1 based on axial MRI measurements were significantly smaller with the following median differences (cm): T1w precontrast − 1.4 (interquartile range (IQR): 1.8), T1w postcontrast − 1.0 (IQR: 1.9), T2w TSE: -1.0 (IQR: 1.6), and DWI -1.3 (IQR: 2.2) (p < 0.001 for all sequences). However, the evaluation revealed no significant differences between the three-dimensional measurements and histopathology measurements of the resected specimens regardless of the applied MRI sequence. Conclusions Axial MRI based lesion size measurements are significantly smaller than histopathological measurements. However, there was no significant difference between three-dimensional measurements and histopathology measurements of the resected specimens. T2w TSE and T1w postcontrast images provided the lowest deviation and might consequently be preferred for measurements.

Download Full-text

Adrenal Ganglioneuroma with Multifocal Retroperitoneal Extension: A Challenging Diagnosis

The Scientific World JOURNAL ◽

10.1100/tsw.2011.144 ◽

2011 ◽

Vol 11 ◽

pp. 1548-1553 ◽

Cited By ~ 9

Author(s):

Marco Oderda ◽

Elena Cattaneo ◽

Francesco Soria ◽

Antonella Barreca ◽

Luigi Chiusa ◽

...

Keyword(s):

Case Report ◽

Nervous Tissue ◽

Rare Case ◽

Histological Evaluation ◽

Adrenal Incidentalomas ◽

Complete Excision ◽

First Case ◽

Neuroblastic Tumors ◽

Sympathetic Nervous ◽

Adrenal Ganglioneuroma

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.

Download Full-text