Pediatric Examination and Board Review (163 page)

Nephrogenic rests are sites of abnormal persistent embryonal nephroblastic tissue that are more commonly found in patients with syndromes that predispose to Wilms tumor, such as WAGR syndrome, Beckwith-Wiedemann syndrome, and Denys-Drash syndrome. Nephrogenic rests are renal parenchymal lesions that are precursors to Wilms tumor development. They occur in 1% of the general population, but in 35% of patients with unilateral Wilms tumors and in nearly 100% of patients with bilateral Wilms tumors. If present, particularly if multiple (called nephroblastomatosis), patients should undergo regular abdominal screening to monitor for progression of the lesions to Wilms tumor.

3.
(B)
Beckwith-Wiedemann syndrome occurs in approximately 1 in 15,000 infants and is associated with abnormal imprinting on chromosome 11p15. The normally imprinted (and thus inactive) maternal allele is lost, resulting in unipaternal disomy and Beckwith-Wiedemann syndrome. The syndrome is characterized by macrosomia, macroglossia, organomegaly, neonatal hypoglycemia, and abdominal wall defects such as omphalocele, diastasis recti, and umbilical hernia. Other common features include linear earlobe creases, macrocephaly, advanced bone age, and absent gonads. Beckwith-Wiedemann syndrome is also associated with an increased risk of hepatoblastoma, gonadoblastoma, Wilms tumor, and adrenal tumors, but not leukemias. Children with Beckwith-Wiedemann syndrome should be followed with abdominal ultrasounds and serum alpha-fetoprotein levels every 6 months until they are at least 6 years of age to monitor for these tumors.

4.
(C)
Neuroblastoma is the most common extracranial solid tumor in children and the third most common overall (after leukemias and brain tumors), with approximately 600 new cases in the United States each year. Wilms tumor is the fifth most common (with approximately 450 new cases in the United States each year); rhabdomyosarcoma and other soft tissue sarcomas are the sixth most common. Hepatoblastoma accounts for approximately 100 cases per year in the United States.

5.
(C)
Wilms tumor in children occurs most commonly at 2-4 years of age, and more than 80% of cases present before 5 years of age with 98% of cases by the age of 7 years. Bilateral and familial cases of Wilms tumor and those associated with tumor-predisposition syndromes tend to occur earlier than sporadic cases. Wilms tumor can occur both in infants and in adolescents, but infants have a higher incidence of other renal tumors such as congenital mesoblastic nephroma and rhabdoid kidney tumors, whereas adolescents have a higher incidence of renal cell carcinomas.

6.
(A)
Wilms tumor most commonly presents as an asymptomatic abdominal mass, with more than twothirds of children with Wilms tumor having masses detected incidentally by parents or physicians. Symptoms of Wilms tumor can include abdominal pain, which occurs in approximately 33% of cases, hypertension, which occurs in approximately 25% of cases and is rarely emergent, hematuria (gross or microscopic), which occurs in 20% of cases. and other symptoms of abdominal mass compression such as intestinal obstruction. Furthermore, anemia because of intratumoral hemorrhage can occur, although usually the onset of anemia is acute and associated with a rapid increase in apparent tumor size because of the hemorrhage. Constitutional symptoms such as fevers, fatigue, and weight loss are rare in cases of Wilms tumor; headaches are not generally associated with Wilms tumor.

7.
(B)
Approximately 5-10% of Wilms tumor cases are bilateral at diagnosis, although the frequency is much higher among those cases of Wilms tumor associated with genetic syndromes.

Approximately 10-15% of Wilms tumor cases are metastatic at diagnosis, most commonly to the lungs and lymph nodes. The tumor can also be identified in the contralateral kidney. Brain, bone, and liver metastases do occur, but they are rare. Local invasion into the renal vasculature, which can progress up the inferior vena cava to the right atrium, can also occur and can lead to hypertension and abdominal vein distention. Evaluation of any child for a suspected Wilms tumor should always include an abdominal ultrasound to evaluate the presence of a tumor thrombus in the renal vasculature and a chest CT scan to rule out pulmonary metastatic disease.

The survival of children with localized Wilms tumor is good, with a more than 90% long-term expected survival rate. Survival for children with stage 4 Wilms tumor is more than 85%.

8.
(D)
Neuroblastoma is a relatively common pediatric neoplasm and the most common extracranial solid tumor in children. Approximately 75% of cases occur in children younger than 2 years of age, and more than 90% occur in children younger than 5 years of age.

Neuroblastoma arises from primordial neural crest cells, and its primary sites are either abdominal or thoracic. Presenting symptoms of neuroblastoma can include bilateral periorbital ecchymoses (“raccoon eyes”), Horner syndrome (unilateral ptosis, miosis, and anhidrosis), or rapid eye movements (opsoclonus-myoclonus syndrome). Elevated alphafetoprotein levels are more commonly found in hepatoblastomas and some germ cell tumors but not in patients with neuroblastoma. Other presenting symptoms of neuroblastoma include fever, palpable abdominal mass, hypertension, respiratory distress, superior vena cava (SVC) syndrome, spinal cord compression, weight loss, bone pain, watery diarrhea as a result of vasoactive intestinal peptide secretion, and paraneoplastic ataxia.

9.
(C)
Elevation of urine catecholamines homovanillic acid (HVA) and vanillylmandelic acid (VMA) are found in almost all (approximately 95%) cases of neuroblastoma, and they are also elevated in most cases of pheochromocytoma. HVA and VMA are by-products of catecholamine metabolism and are increased in cases of neuroblastoma as a result of excessive production from adrenergic tissue. Although neuroblastoma can metastasize to the bone marrow in some cases, blood cell production is rarely impaired, although anemia and thrombocytopenia are more common than leukopenia. Furthermore, neuroblastoma that involves the liver can also cause elevated liver enzyme (AST and ALT) levels and prolonged coagulation tests, but these features are much less common than elevations in urine catecholamines.

10.
(C)
Stage 4S neuroblastoma is a form of neuroblastoma that occurs only in infants younger than 1 year of age, with metastatic disease limited exclusively to the liver, bone marrow (with <10% involvement), and skin. Bony disease is a feature of stage 4 neuroblastoma but not stage 4S. Outcomes for stage 4S neuroblastoma, as opposed to stage 4 disease, are extremely good, and can include complete disease resolution in the absence of any therapy.

11.
(C)
Neuroblastoma can metastasize to almost anywhere in the body but is most commonly found in the bone marrow, bones, and liver. Lung and CNS metastases can occur but are very rare and portend worse outcomes.

Treatment for neuroblastoma is stratified according to the patient’s age, stage, and the biology of the tumor. Age older than 18 months and widely disseminated disease are unfavorable clinical prognostic factors. Genetic aberrations including
MYCN
amplification, loss of chromosome 1p and 11q, and gain of chromosome 17q are associated with a worse prognosis. Patients classified as high risk are treated with intensive multimodality therapy. Infants with a specific pattern of metastatic disease (limited to the skin, liver, and bone marrow; stage 4S) who have tumors with favorable biology have a high incidence of spontaneous regression and favorable prognosis.

12.
(D)
Osteogenesis imperfecta is not associated with an increase in pediatric malignancies, whereas each of the other listed syndromes have an increased incidence of pediatric cancers. Ataxia-telangiectasia is a syndrome characterized by DNA repair defects and presents with cerebellar ataxia and oculocutaneous telangiectasias. Malignancies occur in approximately 15% of cases and include non-Hodgkin lymphomas and carcinomas. Li-Fraumeni syndrome is associated with mutations in the
p53
gene, which is important in cell cycle regulation. Patients with Li-Fraumeni syndrome are predisposed to a variety of malignancies, including soft tissue sarcomas, leukemias and lymphomas, adrenocortical carcinomas, and breast and bone cancers. Bloom syndrome is a rare syndrome most commonly found in patients of Ashkenazi Jewish heritage and is characterized by intrauterine growth retardation, abnormal facies, facial telangiectasias, and other skin lesions. Patients with Bloom syndrome are predisposed to all types of leukemias, and they occur in approximately a fourth of patients.

13.
(C)
Neurofibromatosis is an autosomal dominant syndrome with an incidence of approximately 1 in 2500 children in the United States. Mutations in the neurofibromin gene are responsible for neurofibromatosis. The features include café-au-lait spots, cutaneous neurofibromas, axillary and inguinal freckling, Lisch nodules, sphenoid dysplasia, tibial bowing, and other skeletal anomalies such as short stature and scoliosis. Other features can also include renovascular hypertension, seizures, and developmental delay. Type 1 neurofibromatosis is also associated with an increased incidence of malignancies, including plexiform neurofibromas and neurofibrosarcomas, pheochromocytomas, and brain tumors such as meningiomas, astrocytomas, acoustic neuromas, and optic gliomas. Patients with neurofibromatosis are not at increased risk for the development of medulloblastoma.

14.
(A)
Teratomas are the most common neonatal solid tumor, accounting for up to a third of all neonatal tumors. Teratomas are generally benign masses composed of tissues from at least 2 of the 3 embryonic germ layers: endoderm, mesoderm, and ectoderm. The tissues within a teratoma can be fully differentiated (resulting in a “mature” teratoma), partially differentiated (resulting in an “immature” teratoma), or malignant. Immature teratomas account for 30% of neonatal teratomas; malignant teratomas account for less than 10% (but up to 50% of teratomas in older children). The primary sites include the sacrococcygeal region, the anterior mediastinum, and the CNS. Treatment of teratomas is complete surgical excision, and metastases in mature and immature cases are extremely rare. Malignant teratomas require excision and chemotherapy to treat the type of malignant tissue present within the mass.

15.
(D)
The anterior mediastinum is a common site for pediatric tumors, with presenting symptoms ranging from cough or dysphagia to hoarseness, wheezing, dyspnea, or SVC syndrome. The most common anterior mediastinal tumors include lymphomas (particularly T-cell lymphomas), teratomas and other germ cell tumors, and thymic tumors. Neuroblastomas generally arise from sympathetic ganglia, and cases of thoracic neuroblastoma are more likely to be located in the posterior mediastinum. Cases of thoracic neuroblastoma are adjacent to the spinal cord and often are associated with spinal canal invasion and spinal cord compression, requiring urgent medical and/or surgical intervention. More than 50% of thymomas are asymptomatic, but approximately a third are associated with myasthenia gravis.

16.
(C)
Tumors that contain components of syncytiotrophoblastic tissue, such as choriocarcinomas, express high amounts of beta-hCG protein. Other germ cell tumors more commonly express high levels of alpha-fetoprotein (AFP) but not beta-hCG. Neuroblastomas express high levels of catecholamines but neither AFP nor beta-hCG. Mature teratomas also do not express AFP or beta-hCG, and so the presence of elevated AFP or beta-hCG levels indicates a malignant component to a teratoma.

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UGGESTED
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Chintagumpala MM, Steuber CP. Wilms tumor. In: McMillan JA, DeAngelis CD, Feigin RD, et al, eds.
Oski’s Pediatrics
:
Principles and Practice.
4th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2006.