Discrimination of histopathologic types of childhood peripheral neuroblastic tumors based on clinical and biological factors.

The aim of this study was to discriminate the children malignant peripheral neuroblastic tumors (PNTs) from those with benign histotype ganglioneuroma (GN) based on clinical and biological characteristics in all PNTs. Four hundred and seventy-six patients were included in this study, containing 345 patients for model development and 131 patients for external validation. Multivariate logistic regression analysis was conducted to select potentially useful characteristics for discrimination of histopathology. External validation was performed for model evaluation. Compared with the main characteristics of GN (85/345, 24.6%), those of malignant PNTs (260/345, 75.4%) showed significant differences. Multivariate analysis was performed to further find the characteristics linked to histopathology. The results indicated that for the patients younger than 49 months, the primary site of adrenal and thoracic, the level of serum neuron-specific enolase (NSE) > 33 ng/mL, and tumor encasing blood vessels were the extremely important discrimination factors of malignant PNTs. The area under the receiver-operating-characteristic of the discrimination model was 0.96. The accuracy rate, sensitivity and specificity were 93.4%, 96.3% and 83.8%, respectively. Meanwhile, the accuracy rate of the external validation from the 131 patients was 97.0%. Overall, histopathologic type of childhood malignant PNTs can be discriminated based on age, primary site, NSE level and the relationship between primary tumor and blood vessels.

Angiogenin up-regulation correlates with adverse clinicopathological and biological factors, increased microvascular density and poor patient outcome in neuroblastomas.

AIMS: As new biomarkers are urgently needed to identify children with high-risk neuroblastoma (NB), we studied the contribution of angiogenin (ANG) to angiogenesis and its association with clinicopathological and biological features and patient outcome in NB. METHODS AND RESULTS: Ninety NBs and 12 ganglioneuromas (GNs) were immunostained for ANG and CD31. ANG expression in NB tumoral cells (ANG scores) and vessels [ANG microvascular density (MVD)] and total MVD (CD31 MVD) were determined. The ANG score was significantly greater in NBs than in GNs (P = 0.015) and in NBs from children with stage 4 tumours, high-risk disease, unfavourable pathology (P < 0.001 for each), MYCN amplification (P = 0.003), and 1p deletion (P = 0.002). ANG scores correlated with ANG MVD and CD31 MVD (P < 0.001 for each). Total ANG and CD31 protein levels, measured with a sensitive enzyme-linked immunosorbent assay, were highly correlated (P = 0.003). High ANG scores were associated with decreased overall and event-free survival (log-rank test, P = 0.025 and P = 0.018, respectively). High ANG MVD was associated with decreased overall and event-free survival (log-rank test, P = 0.009 and P = 0.026, respectively). High CD31 MVD was associated with decreased event-free survival (P = 0.045). CONCLUSIONS: The strong correlation of ANG up-regulation with total MVD and adverse clinicopathological and biological factors indicates that ANG supports growth and progression in NB.

Postoperative paraplegia after resection of a giant posterior mediastinal tumour. Importance of the blood supply in the upper spinal cord.

A 10-cm diameter tumour was revealed in the left upper posterior mediastinum in a 15-year-old female. After exclusion of the possibility of a dumbbell tumour and confirmation of a ganglioneurinoma, an encapsulated, but vascularised tumour was removed via a left posterolateral thoracotomy from the level of the first-third costo-vertebral angle, without intraoperative complications. Following surgery, acute paraplegia was diagnosed, with a spinal cord lesion at the high thoracic level. Magnetic resonance imaging did not reveal any disorder in the spinal cord. In response to medical treatment, the patient's locomotor and sensation functions normalised within six months. On revising the preoperative computed tomography, we found dilated vessels passing through the tumour and the hypoplastic vertebral artery on the left side. This finding led us to suspect that the spinal cord circulation was partially supplied by the arteries passing through the tumour, which were clipped during surgery. Verification of the blood supply of the spinal cord is therefore highly recommended before resection of a giant tumour from the posterior mediastinum.

Spinal ganglioneuroma presenting as a highly vascular lesion with hypertrophic venous drainage.

We present the case of a 33-year-old man with a highly vascular spinal ganglioneuroma associated with hypertrophic draining veins mimicking arteriovenous malformation. Ganglioneuromas are classically known as avascular and association with hypertrohic venous drainage has not been previously reported. The magnetic resonance imaging and digital subtraction angiography features of this benign tumor were strongly suspicious for malignancy because of the high vascularity caused by intratumoral arteriovenous shunts. This case emphasizes the importance of including ganglioneuroma in the differential diagnosis of vascular spinal tumors and recalls that hypertrophic draining veins may be associated with spinal tumors.

Schwann cell-conditioned medium inhibits angiogenesis.

Neuroblastomas are biologically heterogeneous tumors that consist of two main cell populations: neuroblastic/ganglionic cells and Schwann cells. The amount of Schwannian stroma strongly impacts prognosis, and favorable outcome is associated with tumors that are Schwannian stroma rich/stroma dominant. At the present time, there is controversy regarding the origin of Schwann cells in neuroblastoma tumors. However, recent studies have suggested that the Schwann cells in mature neuroblastoma tumors may be normal cells that produce soluble substances that enhance the survival and differentiation of neuroblastoma cell lines. Previously, we reported that in neuroblastoma, high vascular index correlated with clinically aggressive disease. In contrast, tumors with favorable histology and abundant Schwannian stroma had low tumor vascularity. As a first step toward investigating whether Schwann cells also play a role in inhibiting angiogenesis in neuroblastoma tumors, we examined the ability of conditioned medium collected from normal human Schwann cells to affect basic fibroblast growth factor- and vascular endothelial growth factor-induced endothelial cell proliferation and migration and in vivo angiogenesis. In vitro angiogenesis assays were also performed with conditioned medium collected from Schwann cells derived from a Schwannian stroma-dominant neuroblastoma tumor. Our results indicate that Schwann cells derived from either adult nerve or tumor tissue produce a potent inhibitor(s) of angiogenesis. Expression studies revealed tissue inhibitor of metalloproteinase (TIMP)-2 in conditioned medium collected from both normal and tumor-derived Schwann cells. In addition, TIMP-2 was detected in the cytoplasm of Schwann cells and ganglion cells in stroma-rich/stroma-dominant neuroblastoma tumors by immunohistochemistry studies. We postulate that the low level of vascularity and more benign clinical behavior of Schwannian stroma-rich/stroma-dominant neuroblastoma tumors result from the Schwann cell production of TIMP-2 and/or other inhibitors of angiogenesis.

Hypervascularity in Lhermitte-Duclos disease--case report.

A 61-year-old male presented with a hypervascular variant of dysplastic gangliocytoma (Lhermitte-Duclos disease) manifesting as gait disorder. Computed tomography and magnetic resonance imaging both showed enhancement of the tumor after injection of contrast medium. Angiography demonstrated a tumor stain. Histological examination showed a double-layered structure comprising an outer layer of myelinated axons and an inner layer of dysplastic granular cells, and numerous dilated thin-walled blood vessels. Partial resection of the tumor resulted in resolution of the neurological deficit.

Vascular contrast enhancement in Lhermitte-Duclos disease: case report.

We report a patient with surgically proven Lhermitte-Duclos disease. The radiologic and pathologic features of this cerebellar lesion are reviewed, including the newly reported presence of vascular contrast enhancement within the mass.

Paraganglioneuroma of the duodenum. Report of a case with radiographic findings, angiographic findings and a review of the literature.

A 59-year old Cuban male had seven episodes of gastrointestinal bleeding. Angiographic and radiographic studies revealed a polypoid mass in the second portion of the duodenum. The mass proved to be paraganglioneuroma. A review of the literature reveals only 25 previously recorded such cases. Eighty-eight per cent of the lesions were located in the second part of the duodenum: 84% of the patients were symptomatic. The two main symptoms noted were abdominal discomfort (45.5%) and bleeding (47.6%). None of the lesions was a malignant or functional tumor.

[Significance of parasitic blood supply in malignant retroperitoneal tumours (author's transl)]. / Die Bedeutung der parasitären Gefässversorgung bei malignen retroperitonealen Tumoren.

Twenty-one neoplastic retroperitoneal tumours- in particular Wilm's tumours and neuroblastomas of the suprarenal glands in children - are analyzed angiographically and the significance of the parasitic blood supply evaluated. More than half of the tumours had penetrating or perforating vessels, but in only 50% there were operative and histologic signs of tumour spread into neighbouring structures. The remaining tumours had vascular adhesions. A hint may be the demarcation and the slight vascularity of the tumours. The value of the presence of penetrating or perforating vessels must not be overestimated regarding the spread of the tumour and inoperability.