and Daniela Cristina Stefan2
(1)
Université Mohammed VI des Sciences de la Santé Cheikh Khalifa Hospital, Casablanca, Morocco
(2)
South African Medical Research Council, Cape Town, South Africa
Keywords
Cancer of adrenal glandUrinary catecholamine (VMA and HVA)MIBGOpsomyoclonus syndrome“Raccoon eyes”INSS stagingLiverBone marrow metastasisSurgeryChemotherapyCase Presentation
A 4-year-old girl (Figs. 11.1 and 11.2) presented with abdominal mass . Ultrasound showed retroperitoneal mass without other specifications. During her stay at the hospital, a faint eyelid bruising was noticed which was more evident after 5 days.
Fig. 11.1
Fig. 11.2
- 1.
What diagnostic tests would you propose?
- 2.
How would you confirm the diagnosis?
- 3.
How would you estimate the prognosis in this case?
- 4.
What would your treatment approach be?
Neuroblastoma originates from the neural crest giving rise to the adrenal medulla and the sympathetic ganglia. This tumor occurs mainly in infants and young children, and the abdomen is the most frequent location. The tumor has great heterogeneity features ranging from spontaneous regression to resistance to intensive therapies. Furthermore, it is also characterized by the secretion of catecholamine (vanillylmandelic acid VMA or homovanillic acid HVA). Biological characterization of these tumors have made a tremendous progress towards a more accurate diagnosis and prognosis evaluation and opening the era of targeted therapy. This tumor seems very rare in Africa and usually diagnosed at an advanced stage.
Epidemiological Features
Neuroblastoma represents 8–10 % of cancers in children. Annual incidence is 10 new cases per million children younger than 15 years old. This disease seems less frequent in the African population presenting at late stages in most cases. Diagnostic difficulties contribute in these factors.
In Western industrialized countries, this tumor is the most common extracranial solid type. More than 50 % of neuroblastomas are diagnosed before the age of 2 years and more than 90 % before the age of 5 years. Screening determination of urinary catecholamine found a higher incidence of biologically favourable neuroblastoma with good clinical outcomes. However, cases found have been associated with benign clinical features and therefore with spontaneous regression.
Some neural crest derived diseases particularly Hirschprung disease are associated with increased incidence of neuroblastoma. Familial forms are reported occuring at an early age and generally with favourable outcome.
Pathology and Genetic Characteristics
Neuroblastoma or peripheral neuroblastic tumors are derived from sympathetic, progenitor cells of the sympathetic nervous system. Depending on the level of maturation, these tumors can be described as the immature and malignant neuroblastoma, ganglioneuroblastoma, a mixed form, and the ganglioneuroma, a completely differentiated tumor. These tumors can originate anywhere along the path where neural crest cells migrate, including the adrenal medulla, paraspinal sympathetic ganglia, and sympathetic paraganglia.
Neuroblastoma is a homogeneous small round cellular tumor, with a hyperchromatic nucleus and reduced cytoplasm. Pseudo-rosette figures are observed in nearly 50 % of cases.
In immunohistochemistry, the tumor expresses neural cell markers including Neuron Specific Enolase (NSE), synaptophysin, chromogranin A, and ganglioside GD2.
The international neuroblastoma pathology classification (INPC) based on the Shimada classification takes into account age, the level of neuroblastic differentiation, richness in Schwannian stroma, and mitosis-karyorrhexis index (MKI) (Table 11.1).
Table 11.1
International neuroblastoma staging system (modified Shimada) pathology classification of neuroblastic tumors (MKI: Mitosis-Karyorrhexis Index)
Stroma features | Age | Favorable histology | Unfavorable histology |
|---|---|---|---|
Stroma-rich appearance | All | Well-differentiated (ganglioneuroma) Ganglioneuroblastoma Intermixed | Ganglioneuroblastoma, nodular |
Stroma-poor appearance (i.e., neuroblastoma) | <18 months | MKI <4 % | MKI >4 % or undifferentiated |
18–60 months | MKI >2 % and differentiated | MKI >2 % or undifferentiated or poorly differentiated | |
>60 months | None | All |
Besides pathological features, molecular biology contributed significantly in improving characterization of these tumors and prognostic evaluation. MYCN amplification has been found as an important prognostic marker and is associated with advanced stages, rapid tumor progression, and poor outcome. The 1p deletion also carries a bad prognosis, and is however associated with MYCN deletion.
Clinical Features
Clinical manifestation includes symptoms related to the primary tumor, or to metastasis, and rarely to a paraneoplastic syndrome. The most common site of the tumor is the abdomen, especially the adrenal gland. Mediastinal locations and in the neck are associated with better outcomes. The localized forms are usually asymptomatic, and sometimes fortuitously discovered.
General signs include fever, anorexia, lethargy, pallor, weight loss, or irritability. They may also be the main manifestation of the disease and are usually associated with aggressive characteristics.
In the abdomen , the tumor is usually present as an abdominal mass associated with pain, anorexia, and more rarely vomiting.
In the pelvis , signs of compression including constipation or urinary retention is present. On rectal examination, the mass is found in the presacral area.
In the thorax , the appearance varies according to the main location. In the thorax, the tumor appears in the posterior mediastinum, in the paraspinal region. At the upper mediastinum, the tumor can induce dyspnea, dysphagia, or pulmonary infectious complications or lymphatic compression. Lower chest locations are usually not symptomatic.
In the neck , the tumor is usually present as a palpable mass, sometimes associated with the Claude Bernard Horner syndrome (ptosis, myosis, enophthalmia), iris heterochromia or anisocoria.
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