Methylated catecholamine metabolites for diagnosis of neuroblastoma

Assays of urinary catecholamines and their metabolites (HVA, VMA, dopamine) permit biochemical diagnosis of neuroblastoma in approximately 80% of patients. The urinary methylated catecholamine metabolites normetanephrine (NMN), metanephrine (MN), and 3-methoxytyramine (3-MT) were analyzed in 18 patients with neuroblastoma and compared with reference values established for 69 healthy pediatric controls. All 18 neuroblastoma patients had raised urinary excretion of at least one of the three commonly assayed metabolites (HVA, VMA, dopamine). Similarly, raised urinary excretion of a methylated metabolite was noted in all but one of the neuroblastoma patients. The 3-MT level was pathologic in 16 of the 18 patients (89%). In this series, 3-MT assay sensitivity was sufficient to warrant trials on a larger population including comparison with patients considered nonsecretors by routine assay procedures. © 1992 Wiley-Liss, Inc.     

Methylated catecholamine metabolites for diagnosis of neuroblastoma.

Assays of urinary catecholamines and their metabolites (HVA, VMA, dopamine) permit biochemical diagnosis of neuroblastoma in approximately 80% of patients. The urinary methylated catecholamine metabolites normetanephrine (NMN), metanephrine (MN), and 3-methoxytyramine (3-MT) were analyzed in 18 patients with neuroblastoma and compared with reference values established for 69 healthy pediatric controls. All 18 neuroblastoma patients had raised urinary excretion of at least one of the three commonly assayed metabolites (HVA, VMA, dopamine). Similarly, raised urinary excretion of a methylated metabolite was noted in all but one of the neuroblastoma patients. The 3-MT level was pathologic in 16 of the 18 patients (89%). In this series, 3-MT assay sensitivity was sufficient to warrant trials on a larger population including comparison with patients considered nonsecretors by routine assay procedures.     

Prenatal diagnosis of neuroblastoma]

One of the prognostic factors for neuroblastoma is age at the time of diagnosis: neuroblastoma detected prenatally or in the first year of live have a more favorable outcome. Antenatal diagnosis is essential early management. Knowledge of local tumor extent is invaluable in determining the appropriate treatment, and MR imaging has proved to be the most useful procedure in this regard.     

Ultrasound diagnosis of abdomino-pelvic neuroblastoma

Ultrasound scans of 16 children with abdomino-pelvic neuroblastoma (11 adrenal, 5 extraadrenal) were reviewed to determine their specific features. With large suprarenal masses, renal displacement and distortion are such that differentiation between renal and extrarenal origin relies on other parameters. The typical ultrasound appearance of an adrenal neuroblastoma is a mass greater than 8 cm in diameter, displacing adjacent great vessels anteriorly and to the opposite side. One hundred percent show echogenicity greater than liver, either focally or diffusely. Ultrasound parameters of great vessel displacement and echo texture have been found reliable in distinguishing between neuroblastoma and other loin masses.     

Prenatal diagnosis of adrenal neuroblastoma

A right retroperitoneal mass with mixed solid and cystic pattern was detected sonographically in a fetus in the 36th week of pregnancy. After term delivery radiologic, sonographic, and CT studies confirmed the presence of a spherical, 5 × 4-cm mass above the right kidney with mixed echogenicity. At operation an enlarged adrenal gland containing hemorrhagic spaces was removed. Histological studies revealed adrenal neuroblastoma. This prenatal sonographic pattern was suggestive of neuroblastoma because it was identical to that of the only similar case reported so far. Prenatal detection is therefore possible and should be regarded as desirable since early diagnosis and treatment provide the best chances for cure. Offprint requests to: J. A. Tovar     

Scintigraphic diagnosis of neuroblastoma using meta-iodobenzylguanidine

In 1979/80 meta-iodobenzylguanidine (MIBG) was introduced as a radiopharmaceutical agent with high affinity to the adrenal medulla. It could be shown, that scintigraphic imaging with 131J labeled MIBG is a sensitive and highly specific method for localization of pheochromocytoma. In this connection we could demonstrate in 1983 that neuroblastoma can be visualized scintigraphically with MIBG as well. Until now 13 patients were examined with 131J-MIBG by our group: In 10 children with histologically proven neuroblastoma we found a specific enrichment in the tumor area. Besides the primary tumor local recurrence and metastases to bones, bone marrow and brain were detected. There was no neuroblastoma manifestation without MIBG uptake. In 3 patients with tumors other than neuroblastoma no uptake of MIBG was noticed. The results agree with those of other studies: If the physiological pattern of distribution is taken into consideration and if the proper imaging technique is adapted, 131J-MIBG scintigraphy is a highly sensitive and specific method for staging, monitoring of disease and follow-up of neuroblastoma.     

MIBG in neuroblastoma diagnosis and treatment

Neuroblastoma is a heterogenous disease, with solid tumors arising in the adrenal gland or paraspinal regions in young children. Neuroblastoma is unique, with varied presentation and prognosis based on primary location and tumor stage. Tumor behavior and response to treatment ranges from spontaneous regression to disseminated, lethal disease depending on the individual biology of a patient’s tumor. Stratification of the disease has changed, with patients now placed in low, intermediate, and high-risk categories depending on age, stage, and tumor biology. Long-term survival for the high-risk subset of patients with metastatic disease is <40% despite aggressive multimodal therapy. Derived from sympathoadrenal cells of the adrenal medulla and sympathetic nervous system, both malignant neuroblastoma and differentiated tumors have specialized norepinephrine transporter (NET) receptors which are naturally occurring in the sympathetic nervous system throughout the body. Metaiodobenzylguanidine (MIBG) is a norepinephrine analog that undergoes active uptake by NET receptors resulting in accumulation in neuroblastoma as well as tissues normally expressing the NET receptor. When radioiodine labeled, MIBG can be used for both diagnosis and treatment. This article describes the history of MIBG use in neuroblastoma, including its utility as an imaging modality for diagnosis as well as the varied ways in which is it included in the multimodal treatment algorithm.     

Comparative values of catecholamines and metabolites for the diagnosis of neuroblastoma

In order to diagnose neuroblastomas, we assayed the three adrenal hormones and five of their metabolites by high-performance liquid chromatography followed by electrochemical detection in urine samples of 395 children with tumours of unknown nature (including 29 neuroblastomas). The analytes (expressed as analyte/creatinine ratios) performances were determined by calculating the related sensitivity and specificity and receiver operating characteristics curves within the different age groups. Normetanephrine (NME), vanillylmandelic and homovanillic acids (VMA, HVA) were the best analytes. Calculated optimal thresholds (best specificity/sensitivity couples) of these analytes minimised the number of false-positive diagnosis. Conclusion: combined determination of normetanephrine with vanillylmandelic acid (0-1 year) or homovanillic acid (1-5 years and 5-10 years) further enhanced the diagnostic power up to 100% sensitivity and specificity of the testing depending on the age group. Plotting individual levels (normetanephrine versus vanillylmandelic acid or homovanillic acid) allowed a rapid visual analysis that would have missed only one small low grade non-secreting tumour.     

Hyperexcitable blink reflex preceding the diagnosis of neuroblastoma

The diagnosis of neuroblastoma is sometimes preceded by development of a paraneoplastic syndrome, most commonly opsoclonus-myoclonus-ataxia (OMA). The authors describe a patient who developed a hyperexcitable blink reflex, without symptoms of OMA, prior to his oncologic diagnosis. The authors believe this may represent a distinct paraneoplastic process caused by increased dopaminergic stimulation of the blink reflex and suggest that children manifesting an unexplained hyperexcitable blink reflex should be screened for occult neuroblastoma.     

生物学及病理学检查在神经母细胞瘤诊断治疗中的应用

神经母细胞瘤是最常见的外周神经系统恶性肿瘤,起源于交感神经节和肾上腺髓质细胞,占儿童肿瘤的8%~10%[1]。好发于5岁以内,临床表现差异很大,从自行消退到病情迅速进展,提示其疾病的异质性。因此,合理的分类对判断预后及决定治疗强度十分重要。现就近几年来临床工作中常用的生物学检查及病理检查作一简要介绍。一、MYCN MYCN为MYC癌基因家族成员之一,于1983年首先在神经母细胞瘤细胞系中克隆成功,它位于染色体2p24,主要功能是促进细胞增殖、抑制分化和凋亡[2]。每个正常人体细胞含1个拷贝,并只在胚胎发育期表达。目前发现多种肿瘤存在M…     

Primary paratesticular neuroblastoma: An important differential diagnosis

Primary neuroblastoma as a paratesticular tumor is extremely rare with only 8 described cases worldwide. In this article, we present the case of a 5-month-old boy with this rare tumor location and give an update on the current literature. As in our case, typically these tumors present as Stage 1 disease and simple tumorectomy alone leads to excellent outcome and long-term survival. However, unawareness of this differential diagnosis and misinterpretation of intraoperative frozen sections have shown to result in delay of diagnosis and worse, overtreatment including orchiectomy and unnecessary chemotherapy. Therefore, primary paratesticular neuroblastoma must be considered as a differential diagnosis when evaluating and operating children with paratesticular tumors.