BRS – Pediatrics: Oncology

I. General Considerations

A. Incidence. Approximately 6000–7000 children between 1 and 15 years of age develop cancer each year.

1. Cancer is the leading cause of death from disease in childhood.
2. Unlike adult cancers, most childhood cancers are not carcinomas. The most common childhood cancers, in order of declining incidence, are leukemia, brain tumors, lymphoma, neuroblastoma, soft tissue sarcomas, Wilms tumor, and bone tumors.

B. Etiology. The cause of childhood cancers is often unknown. However, genetic disorders, immunodeficiency diseases, infections, and environmental factors may predispose to certain cancers.

1. Ten to fifteen percent of cancers have a familial association or are associated with a genetic disorder. Table 14-1 lists common genetic syndromes and their associated cancer(s).
2. Immunodeficiency diseases may predispose to cancer, including the following examples:

a. Wiskott–Aldrich syndrome, characterized by B- and T-cell dysfunction, atopic dermatitis, and thrombocytopenia, is associated with lymphoma and leukemia.
b. X-linked lymphoproliferative disease, associated with Epstein–Barr virus (EBV) infection, may result in lymphoma.

3. Infectious diseases, such as EBV infection, which can be associated with Burkitt lymphoma and Hodgkin disease, human papillomavirus (HPV) which can cause cervical, orophayngeal and penile cancer, and human immunodeficiency virus (HIV) infection, which can predispose to Kaposi sarcoma
4. Environmental factors, such as prior chemotherapy and ionizing radiation, may result in malignancy.

C. Typical presenting features of childhood cancer

1. Persistent fever, especially if associated with weight loss or night sweats, may be associated with leukemia, lymphoma, and other cancers.
2. Palpable or visible mass

a. Abdominal mass should be considered malignant until proven otherwise. Wilms tumor and neuroblastoma are the two most common malignant abdominal tumors that may present with an abdominal mass.
b. Mass on the trunk or extremities may be caused by rhabdomyosarcoma or bone tumor.

3. Bone pain may reflect metastatic cancer, primary tumors of bone or connective tissue, or leukemic infiltration of bone marrow.
4. Supraclavicular lymphadenopathy, nontender, firm lymph nodes, or enlarging lymph nodes may be caused by leukemia, lymphoma, or metastatic disease.
5. Early morning headache with vomiting, or change in gait, may be caused by a space- occupying tumor within the central nervous system (CNS).
6. Bruising, petechiae, and pallor may be caused by tumor infiltration of the bone marrow.
7. Leukocoria (i.e., white reflex in the pupillary area) may be caused by retinoblastoma (see Chapter 18, section VIII.B).
8. Hypertension may be caused by neuroblastoma, Wilms tumor, or pheochromocytoma.

Table 14-1. Genetic Disorders and Their Association with Childhood Cancer

Down syndrome Leukemia (ALL or AML)
Turner syndrome Gonadoblastoma
Trisomy 13 Leukemia, teratoma
Trisomy 18 Wilms tumor, neurogenic tumors
Klinefelter syndrome Leukemia, germ cell tumors, breast cancer
Fanconi anemia Leukemia
Xeroderma pigmentosa Basal and squamous cell carcinoma, melanoma
Ataxia telangiectasia Hodgkin and non-Hodgkin lymphoma, leukemia, sarcomas
Bloom syndrome Leukemia, lymphomas, gastrointestinal malignancies, solid tumors
Beckwith–Wiedemann syndrome Wilms tumor, hepatoblastoma, rhabdomyosarcoma, adrenocortical carcinoma
Neurofibromatosis type 1 Brain tumors, lymphoma, leukemia, malignant schwannoma
Neurofibromatosis type 2 Acoustic neuroma
ALL = acute lymphocytic leukemia; AML = acute myelogenous leukemia.

II. Leukemias

A. Acute lymphocytic leukemia (ALL) [acute lymphoblastic leukemia] 1. Epidemiology
a. ALL accounts for 30% of all pediatric cancers.
b. ALL represents 80–85% of childhood leukemias.
c. Peak incidence occurs at 2–6 years of age. ALL is more common in males and in Caucasians.
2. Etiology. The cause is generally unknown; however, ALL may be associated with ionizing radiation, chemotherapy, genetic syndromes (e.g., Down syndrome, Bloom syndrome), chemical agents, and immunodeficiency diseases (e.g., ataxia telangiectasia).
3. Classification is based on the cell of origin, immunophenotype, and cytogenetic characteristics of the leukemic cells (i.e., lymphoblasts). The immunophenotype classification is as follows:
a. T-cell phenotype: 20%
b. Mature B-cell phenotype: <5%
c. Precursor B-cell phenotype: 70–80%. Pre–B-cell ALL may be further subdivided on the basis of the presence of common acute lymphocytic leukemia antigen (CALLA).
1. CALLA-positive (70%)
2. CALLA-negative (30%)
4. Clinical features
a. Fever and bone or joint pain are the most common symptoms. Bone or joint pain often manifests as refusal to bear weight.
b. Pallor, bruising, hepatosplenomegaly, and lymphadenopathy are the most common signs.
c. Epistaxis, anorexia, fatigue, testicular pain and swelling, and abdominal pain may also be present.
5. Diagnosis
a. ALL is suggested by a complete blood count (CBC) that demonstrates anemia and
thrombocytopenia. The white blood cell (WBC) count is variable.
1. WBC is high in one-third of cases (>50,000 cells/mm3), normal in one-third of cases, and low in one-third of cases (<10,000 cells/mm3).
2. Leukemic blasts (i.e., lymphoblasts) are often seen.
3. Note: A normal CBC does not rule out leukemia.
b. Confirmation is by bone marrow evaluation demonstrating marrow replacement by lymphoblasts. Other normal marrow elements are decreased or absent. Cytogenetics to evaluate for translocations and immunophenotyping must be performed. Spinal fluid must also be obtained to determine the presence of CNS involvement.
c. Prognostic factors for ALL at the time of diagnosis are listed in Table 14-2. Most patients have disseminated disease at presentation, so there is no staging system for ALL.
6. Management. The best treatment for ALL remains under investigation, and patients should be encouraged to participate in a national clinical trial. Treatment is stratified by risk and initial response to therapy. Management involves four stages: induction, consolidation, delayed intensification, and maintenance.
a. Induction aims to destroy as many cancer cells as possible to induce remission.
1. Drugs vary based on study protocol but typically include corticosteroids, vincristine, and l-asparaginase. Intrathecal methotrexate is given to all

children during induction. Other agents are added on the basis of expected prognosis.
2. Remission is induced in 95% of patients.
3. Minimal residual disease (MRD), refers to the small number of leukemic cells that remain in the patient during or after treatment. It is assessed in peripheral blood and marrow by immunophenotyping at the end of induction, is a very powerful indicator of prognosis and guides further therapy.
b. Consolidation involves a continuation of systemic chemotherapeutic agents and prophylactic regimens to prevent CNS involvement, because systemic chemotherapy poorly penetrates the blood–brain barrier.
1. Intrathecal methotrexate is continued during consolidation.
2. Cranial irradiation may be given to high-risk children. Radiation should generally be avoided in children younger than 5 years, if possible, because of the risk of subsequent neuropsychological effects.
c. Delayed intensification is commonly used during the first few months of maintenance. It is comprised of regimens similar to those used during induction. Children with higher risk disease may receive longer periods of intensification.
d. Maintenance therapy involves daily and periodic chemotherapy during remission for up to 3 years. Chemotherapy is discontinued after 2–3 years if the patient remains disease-free.
e. Bone marrow transplant may be performed for very high–risk children and for those who have relapsed or were slow to enter remission after the first several months of therapy. (The bone marrow is the most common site of relapse.)
f. Complications during treatment often occur. Supportive care is important and includes management of anemia and thrombocytopenia with appropriate blood products and therapy for the following common complications:
1. Infection associated with neutropenia is potentially life-threatening.
Children with fever and severe neutropenia (absolute neutrophil
count < 500 cells/mm3) must be assumed to have a serious bacterial infection, such as sepsis, until proven otherwise. Common infectious agents include Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Escherichia coli. It is necessary to give empiric treatment with intravenous broad-spectrum antibiotics after appropriate cultures of blood and urine and any other noticeable sources of infection are obtained.
2. Opportunistic infections with organisms, such as herpes simplex virus, Pneumocystis jiroveci (i.e., P. jiroveci pneumonia [PCP]), and fungi (Candida albicans, Aspergillus), may occur as a result of immunosuppression associated with chemotherapy. Fungal infection should be considered in patients with fever lasting longer than 1 week while on intravenous antibiotics. Prophylaxis with trimethoprim–sulfamethoxazole is generally effective in preventing PCP infection.
3. Metabolic complications from spontaneous or therapy-induced cell lysis (tumor lysis syndrome)
a. Hyperuricemia may result in renal insufficiency.
b. Hyperkalemia may result in cardiac dysrhythmias.
c. Hyperphosphatemia may result in hypocalcemia with tetany.
4. Other complications include medication-induced pancreatitis (l-asparaginase and corticosteroids), cardiomyopathy (doxorubicin), and cystitis (cyclophosphamide). Cranial irradiation may result in cognitive impairment, stroke, endocrine problems (e.g., growth delay, hypothyroidism,

hypopituitarism), and secondary malignancy.
7. Prognosis. The outlook for patients with ALL is generally good. Overall long-term survival occurs in 85% of patients.
B. Acute myelogenous leukemia (AML)
1. Epidemiology. AML represents 15–20% of childhood leukemias.
2. Etiology. The cause of AML is unknown. AML is associated with Down syndrome, Fanconi anemia, Kostmann syndrome, and neurofibromatosis. It may also be associated with ionizing radiation and occur as a secondary malignancy resulting from chemotherapy.
3. Classification is based on cell of origin, immunophenotype, and cytogenetic characteristics.
4. Clinical features are similar to those of ALL.
a. Symptoms and signs include fever, hepatosplenomegaly, bruising and bleeding, gingival hypertrophy, and bone pain. Lymphadenopathy and testicular involvement are uncommon.
b. Laboratory findings may include pancytopenia or leukocytosis and disseminated intravascular coagulation (DIC).
5. Diagnosis is suggested by clinical features and blood smear demonstrating leukemic myeloblasts. Blasts containing Auer rods are consistent with myeloid leukemia. Confirmation is by immunophenotyping and cytogenetics of cells obtained by bone marrow evaluation.
6. Management. AML, unlike ALL, requires very intensive myeloablative therapy to induce remission. Bone marrow transplant is recommended for most patients in remission, if they have a human leukocyte antigen (HLA)–matched donor.
7. Prognosis. Aggressive chemotherapy is effective in 60% of patients. Bone marrow transplant from a matched sibling is curative in 70% of patients. Megakaryoblastic AML associated with Down syndrome is unusually responsive to chemotherapy and carries an excellent prognosis.
C. Chronic myelogenous leukemia (CML)
1. Epidemiology. CML is the least common type of leukemia in children, representing 3– 5% of childhood leukemia. Males are more commonly affected.
2. Classification. Two forms of CML occur in children.
a. Adult-type CML
1. Twice as common as the juvenile form
2. Occurs predominantly in older children and adolescents
3. Characterized by the presence of the Philadelphia chromosome (reciprocal translocation between the long arms of chromosomes 9 and 22, leading to the fusion gene BCR/ABL1 that produces the BCR-ABL fusion protein)
b. Juvenile chronic myelogenous leukemia (juvenile myelomonocytic leukemia [JMML])
1. Occurs predominantly in infants and children younger than 2 years
2. Sometimes characterized by abnormalities of chromosome 7 or 8. The Philadelphia chromosome is absent.
3. Clinical features. Signs and symptoms vary based on the type of CML.
a. Adult-type CML
1. Nonspecific symptoms such as fatigue, weight loss, and abdominal discomfort
2. Massive splenomegaly leading to abdominal distension. CML is typically discovered after an incidental finding of splenomegaly on examination.
3. Extremely high WBC (often >100,000 cells/mm3)
b. JMML

1. Fever and malaise
2. Chronic eczema-like facial rash
3. Suppurative lymphadenopathy
4. Petechiae and purpura
5. Moderate leukocytosis (<100,000 cells/mm3), anemia, and thrombocytopenia
4. Management. The first line of therapy for CML is a tyrosine kinase inhibitor (imatinib mesylate), which induces sustained remission in most patients. Bone marrow transplantation (BMT), with either HLA-matched (ideally) or unmatched donor, is reserved for those who do not have a rapid response, fall out of remission, or progress to acute leukemia. Radiation therapy is not effective.
5. Prognosis
a. Adult-type CML. With a tyrosine kinase inhibitor, the majority of patients can achieve and maintain a sustained remission, but BMT is still considered curative.
b. JMML is often fatal. Relapse occurs in 60% of cases, even with BMT.

Table 14-2
Prognostic Factors for ALL at Time of Diagnosis

Prognostic Factor Favorable Unfavorable
Age 1–9 years of age <1 or >9 years of age
Sex Female Male
Race White Black
WBC <50,000 cells/mm3 >50,000 cells/mm3
Ploidy Hyperploidy (more than 53 chromosomes
within leukemic cells) Low ploidy (fewer than 53 chromosomes within leukemic
cells) or extreme hyperploidy
Organ
involvement None Organomegaly, central nervous system involvement,
mediastinal mass
Immunophenotype CALLA-positive CALLA-negative
ALL = acute lymphocytic leukemia; CALLA = common acute lymphocytic leukemia antigen; WBC = white blood cell count.

III. Lymphomas
Lymphomas account for 10–15% of childhood cancers.

A. Hodgkin disease is a cancer of the B-cell lineage.
1. Epidemiology
a. Hodgkin disease can be associated with EBV infection. Patients with EBV- associated mononucleosis have a two to four times greater risk of developing Hodgkin disease later in life.
b. Hodgkin disease is more common in older children and adolescents.
2. Clinical features. Most children with Hodgkin disease present with painless lymphadenopathy, most commonly in the supraclavicular or cervical regions. Signs and symptoms of Hodgkin disease are listed in Table 14-3.
3. Diagnosis. The basis of diagnosis is histologic review of tissue obtained by lymph node biopsy. The hallmark histologic feature is the Reed–Sternberg cell, a large multinucleated cell with abundant cytoplasm.
4. Staging. Classification by the Ann Arbor system is the basis for treatment and provides prognostic information. There are four basic stages, and each stage is subclassified into “A” or “B,” reflecting clinical symptoms. A refers to lack of systemic symptoms. B refers to the presence of systemic symptoms, such as fever, night sweats, or >10% weight loss.
a. Stage I: involvement of a single lymph node or extralymphatic site
b. Stage II: involvement of two or more lymph node regions on the same side of the diaphragm, or extension to an extralymphatic site and one or more lymph node regions on the same side of the diaphragm
c. Stage III: involvement of lymph nodes on both sides of the diaphragm (in this case, the spleen is considered a lymph node)
d. Stage IV: diffuse or disseminated involvement of one or more extralymphatic organs or tissues
5. Management. Treatment is based on the child’s age, disease stage, and in some protocols, initial treatment response. Treatment most commonly includes chemotherapy and radiation therapy. Late complications of therapy include the following:
a. Growth retardation as a result of radiation therapy
b. Secondary malignancies, including breast cancer, AML, non-Hodgkin lymphoma, and thyroid and skin cancers.
c. Hypothyroidism
d. Impaired fertility
6. Prognosis. Overall, prognosis of stages I and II disease is excellent, with ≥90% long-term survival. More advanced disease carries a long-term survival rate of about 80%.
B. Non-Hodgkin lymphoma is an aggressive cancer and is 1.5 times more common than Hodgkin disease.
1. Epidemiology
a. Male predominance
b. Associated with immunodeficiency states, such as HIV infection, Wiskott–Aldrich syndrome, ataxia telangiectasia syndrome, and prior EBV infection.
c. Increasing incidence after 5 years of age
2. Classification. There are three major categories of non-Hodgkin lymphoma. (The more uncommon categories include anaplastic large cell and large cell, noncleaved immunoblastic lymphoma.)
a. Lymphoblastic lymphoma is histologically similar to the lymphoblast of ALL. It is generally T cell in origin. This accounts for about 30% of non-Hodgkin lymphoma.

b. Small, noncleaved cell lymphoma includes Burkitt lymphoma, the most common lymphoma in childhood. Burkitt lymphoma is B cell in origin. This accounts for about 40% of all non-Hodgkin lymphoma.
c. Large cell lymphoma is generally B cell in origin.
3. Clinical features (see Table 14-3). Painless lymphadenopathy is the most common presenting feature.
a. Lymphoblastic lymphoma commonly presents with an anterior mediastinal mass, and the patient may develop superior vena cava syndrome or airway obstruction as a result.
b. Small, noncleaved cell lymphoma
1. Intussusception, abdominal pain, or mass can be the presenting signs or symptoms. Lymphoma must be considered as a possible cause (lead point) in any child older than 3 years presenting with intussusception.
2. Burkitt lymphoma is endemic in Africa, where it presents as a jaw mass and is most often associated with EBV.
c. Large cell lymphoma commonly presents as enlargement of lymphoid tissue in the tonsils, adenoids, or Peyer patches.
4. Diagnosis and staging. The basis of diagnosis is on immunophenotyping, cytogenetics, and morphologic appearance of tissue. Evaluation for dissemination is the basis of staging. This evaluation often includes chest radiograph or chest computed tomography (CT) scan, abdominal and pelvis CT scan, positron emission tomography (PET) scan, bone marrow aspirate and biopsy, and cerebrospinal fluid analysis.
5. Management. Treatment must be rapid because of the aggressiveness of this cancer. Management includes surgery to remove or debulk the tumor, chemotherapy specific for the tumor type, prophylaxis for CNS disease, and treatment of tumor lysis syndrome, should it occur. Lymphoblastic lymphoma is treated in a similar way to ALL with at least 2 years of therapy, whereas the other non-Hodgkin lymphomas are treated with a shorter duration of therapy.
6. Prognosis. Outlook is best for localized lymphoma, with a cure rate >90%. Prognosis is poorest for patients with disseminated disease and for those who do not respond to therapy well initially, but overall greater than 70% of patients are cured with the current regimens used.

Table 14-3
Clinical Features of Hodgkin Disease and Non-Hodgkin Lymphoma

Clinical Feature Hodgkin Disease Non-Hodgkin Lymphoma
Symptom onset Slow, indolent Rapid
Common location Cervical and supraclavicular nodes Abdominal, mediastinal, and supraclavicular nodes
Systemic symptoms*
Relatively common (30%) Uncommon
Abdominal findings†
Rare Common
Painless adenopathy Common Common
SVC syndrome Rare Common
Airway compression Rare Common
*Systemic symptoms include fever, drenching night sweats, and weight loss.
†Abdominal findings include abdominal pain, intussusception, abdominal mass, and obstruction.
SVC = superior vena cava.

IV. Brain Tumors
A. Epidemiology
1. Brain tumors are the second most common childhood cancer after leukemia and are the
most common solid tumors.
2. They account for 20% of all childhood cancers.
3. Brain tumors may be associated with underlying diseases such as neurofibromatosis, tuberous sclerosis, and von Hippel–Lindau disease.
B. Classification is by histology, grade, location, and molecular signature.
1. Histology
a. Glial cell tumors are most common (40–60% of brain tumors) and include astrocytomas. High-grade (i.e., aggressive) tumors often arise in the supratentorial region, and low-grade (i.e., less aggressive) tumors arise in the infratentorial region.
b. Primitive neuroectodermal tumors (PNETs) are the second most common tumor and include medulloblastomas arising from the cerebellum.
c. Ependymomas are the third most common tumor.
d. Craniopharyngiomas are the fourth most common tumor.
2. Grade. The grade of the tumor refers to its aggressiveness.
a. High grade: aggressive, proliferative cells
b. Low grade: less aggressive, more-differentiated cells
3. Location. Infratentorial tumors are more common than supratentorial tumors, except at age extremes of <1 or >12 years.
a. Medulloblastoma is the most common infratentorial tumor, followed by cerebellar astrocytoma and brainstem glioma.
b. Astrocytoma is the most common supratentorial tumor.
C. Clinical features. Signs and symptoms are typically based on the location of the tumor and the child’s age.
1. Key point: Even benign tumors can be lethal if their location interferes with brain function.
2. Initial nonspecific symptoms are caused by increased intracranial pressure (and are often worse during sleep or on awakening). Symptoms commonly subside during the day as venous return from the head improves with upright posture.
a. Headache: diffuse, occipital, or frontal
b. Vomiting: often resolves the accompanying headache
c. Drowsiness or irritability
d. Abnormal behavior
e. Ataxia: associated with cerebellar tumors
f. Seizure: associated with supratentorial tumors
g. Head tilt (torticollis)
3. Physical examination findings
a. Enlarged or bulging fontanelle in infants, or enlarged head circumference
b. Nystagmus
c. Papilledema
d. Cranial nerve abnormalities, especially sixth nerve palsy
e. Lethargy or irritability
4. Features associated with specific tumors
a. Optic glioma is associated with diminished vision, visual field deficits, and strabismus.
b. Craniopharyngioma is associated with growth retardation, delayed puberty, visual

D. Diagnosis

changes, diabetes insipidus, and other hormonal problems because of involvement of the hypothalamic–pituitary axis.

1. Neuroimaging by magnetic resonance imaging (MRI) is critical for diagnosis and management.
2. Cerebrospinal fluid obtained at surgery is useful for staging and assessment of tumor markers (i.e., α-fetoprotein or β-human chorionic gonadotropin for germ cell tumors; homovanillic acid [HVA], vanillylmandelic acid [VMA], and polyamines for medulloblastoma).
E. Management
1. Surgery. Resection or debulking of the tumor is the principal treatment.
2. Radiation therapy. Almost all brain tumors are radiosensitive. However, radiation should be reserved, if possible, for children older than 5 years because of the risk of adverse effects [see section II.A.6.f.(4)].
3. Chemotherapy. This method is effective for many tumors and is often used together with radiation therapy and surgery. Stem cell transplant is used, particularly for the younger child, to avoid radiation and thus avoid the late adverse effects of radiation.
F. Prognosis. Outlook depends on tumor grade, size, type, and resectability.
1. Astrocytomas. Low-grade, completely resectable astrocytomas have a good prognosis (>80% survival). High-grade astrocytomas have a poor prognosis (35% survival at
3 years) because of their infiltrative nature.
2. PNETs. Survival is >80% if the majority of the tumor can be resected and there are no metastases or extension. Prognosis is worse in children younger than 4 years.
3. Brainstem gliomas. The prognosis is poorest for intrinsic brainstem gliomas, which can respond temporarily to radiation, but are typically fatal.

V. Renal and Suprarenal Tumors
A. Neuroblastoma. This malignant tumor of neural crest cells may arise anywhere along the sympathetic ganglia chain and within the adrenal medulla.
1. Epidemiology
a. Neuroblastomas are the second most common solid tumors, after brain tumors.
b. Neuroblastomas are responsible for 8–10% of all childhood cancers.
c. Peak incidence is in the first 5 years of life. Median age at time of diagnosis is 2 years.
d. Approximately 75% occur in the abdomen or pelvis, 20% occur in the posterior mediastinum, and 5% occur in the neck.
2. Etiology. The cause is unknown; however, chromosomal abnormalities have been detected.
3. Clinical features. Signs and symptoms are presented in Figure 14-1.
4. Diagnosis
a. Urine excretion of excessive catecholamines, including VMA and HVA, is characteristic (found in 90% of patients). Definitive diagnosis is by tissue biopsy.
b. Staging is achieved with bone marrow biopsy, MRI or CT, and MIBG (metaiodobenzylguanidine) or PET scanning.
5. Staging. The most commonly used staging system is the International Neuroblastoma Staging System.
a. Stage 1: localized tumor with complete gross excision, with or without microscopic residual disease; representative ipsilateral lymph nodes are microscopically negative for tumor
b. Stage 2A: localized tumor with incomplete gross excision; representative ipsilateral nonadherent lymph nodes are microscopically negative for tumor
c. Stage 2B: localized tumor with or without complete gross resection, with ipsilateral nonadherent lymph nodes microscopically positive for tumor. Enlarged contralateral nodes must be negative for tumor.
d. Stage 3: unresectable unilateral tumor infiltrating across the midline, with or without regional lymph node involvement, or localized unilateral tumor with contralateral regional lymph node involvement, or midline tumor with bilateral extension by infiltration or by lymph node involvement
e. Stage 4: any primary tumor with dissemination to distant lymph nodes, bone, bone marrow, liver, or skin
f. Stage 4S: localized primary tumor with dissemination limited to the skin, liver, and marrow. Stage 4S is limited to infants.
6. Management. In addition to staging, the biologic features of the tumor, which include ploidy, morphology, and n-myc amplification, and the patient’s age determine treatment. Except for stage 4S, more aggressive biologic features generally correlate with the disease extent at diagnosis.
a. Surgery alone may be curative for stage 1 and 2 disease.
b. Chemotherapy and surgery are used for intermediate-risk disease (stage 3).
c. Advanced disease (stage 4) requires chemotherapy, surgery, stem cell transplant, radiation, and immunotherapy.
7. Prognosis
a. Excellent prognosis occurs in children younger than 1 year and in patients with stage 1 and 2 disease. Spontaneous regression without treatment may occur in young infants with stage 4S disease.

b. Prognosis is good with stage 3 disease, but for stage 4 disease, despite very aggressive treatment, including immunotherapy, only about 65% have long-term survival.
B. Wilms tumor (nephroblastoma) is a tumor of the kidney.
1. Epidemiology
a. Wilms tumor is the most common childhood renal tumor. It is responsible for 7% of childhood cancers.
b. Seventy-five percent of cases occur in children younger than 5 years (median age at diagnosis is 3 years).
c. Associated genetic findings or syndromes include Beckwith–Wiedemann syndrome (hemihypertrophy, macroglossia, and visceromegaly), deletion of the short arm of chromosome 11, and WAGR syndrome (Wilms tumor, aniridia, genitourinary abnormalities, and mental retardation).
2. Clinical features
a. Abdominal mass, generally found on routine evaluation, is the most common presentation. The mass is smooth and firm and sometimes crosses the midline.
b. Abdominal pain (50% of patients) with or without vomiting
c. Hematuria (25% of patients)
d. Hypertension (25% of patients) secondary to pressure on the renal artery or increased renin secretion by the tumor
e. Nonspecific findings include fever (rare), anorexia, weight loss, and constipation.
f. Associated congenital anomalies in 15% of cases
1. Genitourinary malformations
2. Hemihypertrophy
3. Sporadic aniridia
3. Diagnosis. Wilms tumor should be considered in any child who presents with hematuria or abdominal mass. Wilms tumor is bilateral in 5% of cases. Confirmation is by imaging with abdominal CT or MRI scan and by histologic evaluation of tissue.
4. Staging. The National Wilms Tumor Study Group classification is used to stage Wilms tumor.
a. Stage I: tumor limited to the kidney and completely excised intact without rupture
b. Stage II: tumor extends locally but can still be completely excised without residual disease
c. Stage III: residual tumor remains in the abdomen or spillage of tumor occurs during resection
d. Stage IV: distant metastasis to the lung (most common), liver, bone, and brain
e. Stage V: bilateral renal involvement
5. Management. Treatment includes prompt surgery for staging and to remove as much tumor as possible. Chemotherapy is used for all stages. Radiation therapy is also used for advanced disease (stages III and IV).
6. Prognosis. Outcome is usually excellent, with an overall cure rate >90%. Prognosis is dependent on staging and histology. Favorable histology and stage I, II, or III disease result in a 2-year survival rate >95%. Unfavorable histology accounts for 12% of cases but 90% of deaths.

FIGURE 14.1 Clinical features of neuroblastoma.

VI. Soft Tissue Tumors
Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood, and is a malignant tumor of the same embryonic mesenchyme that gives rise to skeletal muscle.

A. Epidemiology. Two-thirds of rhabdomyosarcomas occur in children younger than 10 years.
B. Etiology. The cause is generally unknown. Patients with neurofibromatosis are at higher risk.
C. Clinical features. Signs and symptoms depend on the site of involvement. Any part of the body may be affected. The initial presentation is usually a painless soft tissue mass.
1. Head and neck, including the orbit, are the most common sites of involvement (40% of cases).
a. Orbital tumors typically present with proptosis, chemosis (i.e., conjunctival edema), eyelid swelling, and cranial nerve palsies.
b. Nasopharyngeal tumors typically present with epistaxis, airway obstruction, and chronic sinusitis.
c. Laryngeal tumors typically present with hoarseness.
2. Genitourinary tract is the second most common site of involvement (20% of cases). Tumors in this location typically present with hematuria, urinary tract obstruction, vaginal bleeding, and/or an abdominal mass.
3. The extremities are the third most common site of involvement (18% of cases). Tumors in this location present with a painless growing mass.
4. Other sites of involvement include the trunk, retroperitoneum, mediastinum, and paratesticular and perianal regions.
D. Diagnosis. Rhabdomyosarcoma should be considered in any patient presenting with a painless enlarging mass. Imaging studies (CT or MRI) are performed to determine the extent of local extension and to prepare for surgical excision. Immunohistochemistry and cytogenetic evaluation of tissue obtained by biopsy provides a definitive diagnosis.
E. Management. Treatment requires chemotherapy and either surgery or surgery and radiation for local control.
F. Prognosis. Tumors of the head and neck and the genitourinary tract have the best prognosis, with a cure rate >90% if localized. Poor prognosis is associated with metastases (20% have metastatic disease at time of diagnosis) and with recurrence. Tumors at sites other than the head and neck or the genitourinary tract carry an intermediate prognosis with survival about 70%.

VII. Bone Tumors
A. Osteogenic sarcoma is a malignant tumor that forms osteoid or new bone.
1. Epidemiology
a. Osteogenic sarcoma is the most common malignant bone tumor in children.
b. The incidence of this tumor peaks during the rapid growth spurt of adolescence.
Males are more commonly affected.
2. Etiology. The cause is unknown; however, it is associated with previous retinoblastoma, Paget disease of bone, radiation therapy for cancer, and fibrous dysplasia.
3. Clinical features. About 50% of tumors occur in the distal femur or proximal tibia. Other signs and symptoms are listed in Table 14-4, which compares osteogenic sarcoma with Ewing sarcoma, the second most common malignancy of bone in children.
4. Diagnosis. Diagnosis is suggested by findings on radiographs and MRI. Definitive diagnosis is by tissue biopsy. Bone scan and chest CT scan are performed to evaluate for metastatic disease.
5. Management
a. Surgery to remove the primary tumor is performed by limb amputation or limb salvage procedures after initial chemotherapy.
b. Chemotherapy includes high-dose methotrexate, cisplatin, and doxorubicin.
c. Pulmonary metastases identified at the time of diagnosis are resected if still evident after initial chemotherapy.
6. Prognosis. For nonmetastatic disease, about 70% of patients are cured, and if metastatic at diagnosis, about 50% are cured. Prognosis for those who do not respond to chemotherapy or relapse is very poor.
B. Ewing sarcoma is a sarcoma characterized as a small, round, blue cell tumor (undifferentiated, monomorphous cell appearance).
1. Epidemiology
a. Ewing sarcoma is the second most common malignant bone tumor.
b. It most commonly occurs during adolescence. Males are more commonly affected.
c. It is rare in Asians and African Americans.
2. Etiology. The cause is unknown. However, 95% have a chromosomal translocation between chromosomes 11 and 21 (a similar translocation to that noted in PNET brain tumors).
3. Clinical features. Signs and symptoms are listed in Table 14-4, which compares Ewing sarcoma and osteogenic sarcoma. Ewing sarcoma may occasionally develop in soft tissue instead of bone.
4. Diagnosis
a. Diagnosis is suggested by radiographic findings; however, similar findings are found in osteomyelitis, lymphoma, osteogenic sarcoma, and Langerhans cell histiocytosis (LCH).
b. MRI of affected bone can better delineate the tumor and its local extension.
c. Definitive diagnosis is by histologic evaluation of tissue obtained by open biopsy.
d. Bone scan, chest CT scan, and bone marrow aspiration and biopsy are performed to assess for metastatic disease.
5. Management. Treatment includes multiagent chemotherapy followed by surgical excision, when possible. If the lesion is not surgically resectable, radiation therapy is used for local control. Late complications of radiation therapy include pathologic fractures at the tumor site, retarded bone growth, limb length discrepancy, functional impairment, and secondary malignancy.

6. Prognosis. Outcome is good for local disease, with a 3- to 5-year survival rate of 80%. Prognosis is especially poor if metastases are present at diagnosis.

Table 14-4
Clinical and Radiographic Features of Osteogenic Sarcoma and Ewing Sarcoma

Feature Osteogenic Sarcoma Ewing Sarcoma
Site Metaphysis of tubular long bones Flat bones and diaphysis of tubular bones;
occasionally extraosseous
50% occur near the knee
Most common sites (in order): distal femur, proximal
tibia, proximal humerus, proximal femur Most common sites (in order): axial skeleton
(especially pelvis), humerus, femur
Local and Pain, swelling, and soft tissue massSystemic symptoms
systemic uncommon
findings Pain, swelling, and soft tissue mass
Fever, malaise, and weight loss
Leukocytosis and elevated ESR
Radiographic findings Periosteal reaction with “sunburst” appearance Periosteal reaction with “onion skin”
appearance
Lytic; or mixed lytic and destructive changes Destructive changes
Metastases Occurs in 15% at presentation Occurs in 25% at presentation
Lungs (90%) and bone (10%) Lungs (50%), bone (25%), and bone marrow
(25%)
ESR = erythrocyte sedimentation rate.

VIII. Liver Tumors
Liver tumors include hepatoblastoma and hepatocellular carcinoma.

A. Epidemiology
1. Hepatoblastoma is the most common type of liver tumor in childhood. It almost always occurs in children younger than 3 years of age. It is also associated with Beckwith– Wiedemann syndrome and familial polyposis, and is more common in children born prematurely.
2. Hepatocellular carcinoma may occur in both young children and in adolescents. It is associated with chronic active hepatitis B infection, biliary atresia, glycogen storage disease type I, α1-antitrypsin deficiency, and hereditary tyrosinemia.
B. Clinical features. Signs and symptoms are similar in liver tumors and include presentation with a right upper abdominal mass, loss of appetite, and weight loss. Jaundice is generally absent, and quite often patients are asymptomatic.
C. Diagnosis. Diagnosis is made by abdominal imaging with CT or MRI scan and finding elevation of the serum tumor marker α-fetoprotein.
D. Management. Treatment includes surgical resection, if possible, and chemotherapy. Chemotherapy may convert a previously unresectable tumor to one that is amenable to surgery.
E. Prognosis. Outcome depends on surgical resectability and chemosensitivity. Nonmetastatic hepatoblastoma carries a cure rate of about 75%, whereas hepatocellular carcinoma carries a cure rate of about 40%.

IX. Retinoblastoma
See Chapter 18, section VIII.B.

X. Germ Cell Tumors (Germinomas)
Germ cell tumors are rare malignancies derived from the cellular precursors of sperm and eggs.

A. Classification is by location and degree of cell differentiation. Germ cell tumors may be located in the gonadal region (i.e., testis, ovary) or in extragonadal regions (i.e., anterior mediastinum, sacrococcygeal area, pineal gland or suprasellar region of the brain, retroperitoneum, neck). Types of germ cell tumors include seminoma (in males), dysgerminoma (in females), teratoma, yolk sac tumor, embryonal cell carcinoma, and choriocarcinoma.
B. Specific tumors
1. Teratomas are tumors containing more than one of the three primary germ cell layers (i.e., ectoderm, mesoderm, and endoderm). Mature teratomas often contain skin, hair, or teeth, whereas immature teratomas contain fetal- or embryonal-type structures. Teratomas may be benign or malignant. Malignant potential is based on the amount of immature tissue and the presence or absence of other germ cell tumor cells within the teratoma.
a. Sacrococcygeal teratoma is the most common teratoma during the first year of life. The majority (75%) occur in females. The tumor arises from the coccyx and presents as a soft tissue mass. Almost all (95%) are benign. Treatment includes surgical excision of both the tumor and the coccyx to prevent recurrence.
b. Anterior mediastinal teratomas are generally benign and may present with signs and symptoms of airway obstruction.
c. Ovarian teratomas are the most common ovarian tumor and are generally benign. The teratoma is suggested by the presence of calcium within the tumor on an abdominal radiograph.
2. Testicular tumors may be derived from germ cells or stromal cells; 70% of childhood testicular tumors are germinomas.
a. Epidemiology
1. The most common of these germinomas are yolk sac tumors (60%), followed by teratomas (15%) and, rarely, seminomas and embryonal carcinoma. (See also Chapter 3, section IX.C.1.)
2. Peak ages are younger than 5 years and during adolescence.
3. There is an association with cryptorchid testes.
4. One-third of testicular tumors in childhood are benign, unlike in adults, in whom almost all testicular tumors are malignant.
5. Germ cell tumors are more common in patients with sex chromosome abnormalities.
b. Clinical features. Signs and symptoms include a solid, firm, painless testicular mass or generalized testicular swelling. Serum α-fetoprotein is elevated in yolk sac tumors. Malignant tumors may extend locally or may metastasize to retroperitoneal lymph nodes, lung, or liver.
c. Management. Treatment is based on the tumor type and size. Treatment of yolk sac tumors involves radical orchiectomy and, if necessary, retroperitoneal lymph node dissection.
3. Ovarian tumors most commonly include yolk sac tumors, teratomas, and dysgerminomas.
a. Epidemiology
1. One-third are malignant. The younger the child, the more likely it is that the tumor will be malignant.

2. Tumors increase in frequency during puberty.
b. Clinical features. Signs and symptoms include abdominal mass, abdominal pain caused by torsion of the tumor together with the ovary, and vaginal bleeding. As with males, serum α-fetoprotein is elevated in yolk sac tumors in females.
c. Management. Treatment is based on tumor type and typically includes surgical resection, chemotherapy, and, sometimes, radiation therapy.

XI. Langerhans Cell Histiocytosis (LCH)
A. Definition. LCH is characterized by infiltration of organs with Langerhans cells.
B. Etiology. The cause is unknown. It appears that some cases represent clonal cellular proliferation, whereas others represent immunologic dysregulation.
C. Clinical features are highly variable.
1. Skeletal involvement occurs in 80% of patients.
a. The skull is most commonly involved.
b. Single or multiple bony lesions may be present and may be painful, palpable, and associated with swelling.
c. Pathologic fractures may occur.
d. Chronic draining ears may indicate LCH involving the mastoid.
2. Skin involvement occurs in 50% of patients. It typically manifests as seborrheic dermatitis of the diaper area and scalp (it mimics cradle cap) and is most common in intertriginous areas.
3. Pituitary or hypothalamic involvement may lead to growth retardation, diabetes insipidus, hypogonadism, and panhypopituitarism.
4. Other features include lymphadenopathy, hepatosplenomegaly, exophthalmos, anemia, and pulmonary infiltrates.
5. Nonspecific systemic features are very uncommon and include weight loss, fatigue, fever, and failure to thrive.
D. Diagnosis is by identifying the typical histologic features on biopsy of skin or bone lesions. There are characteristic morphologic features and immunohistochemical markings.
E. Management
1. Therapy is geared to abort organ destruction or dissemination.
2. Corticosteroids and chemotherapeutics are considered standard of care. If a single lesion or organ is involved, local curettage may be used.
F. Prognosis varies with the extent and location of disease. Single lesions may spontaneously resolve after curettage. Response rate to current treatments is high. Long-term complications include growth impairment, learning problems, hearing loss, orthopedic deformities, and chronic lung disease.

Review Test
1. A 3-year-old Caucasian girl is brought to your office with a 3-week history of bruising, left elbow pain, and fever. Her white blood cell (WBC) count is 25,000 cells/mm3. You refer her to a pediatric oncologist who performs a bone marrow aspirate, which confirms your suspicion that she has acute lymphocytic leukemia (ALL). Immunophenotyping reveals that the leukemic cells have pre–B-cell phenotype and are common acute lymphocytic leukemia antigen (CALLA) negative. In addition, the leukemic cells demonstrate hyperploidy (>53 chromosomes). Which of the following characteristics predict an unfavorable prognosis in this patient?
A. Leukemic cells that are CALLA-negative
B. WBC count at diagnosis <50,000 cells/mm3
C. Female sex
D. Leukemic cells that demonstrate hyperploidy
E. Age of 3 years
2. A 10-year-old girl has started induction chemotherapy for acute lymphocytic leukemia (ALL). Which of the following statements regarding the treatment of childhood ALL and its complications is correct?
A. Remission is induced in 25% of patients.
B. Fever associated with neutropenia is an anticipated complication of treatment and may be managed with acetaminophen alone.
C. Intrathecal methotrexate is used only for children with an unfavorable prognosis at the time of diagnosis.
D. Intracranial radiation is generally safe and free from side effects in children older than 1 year.
E. Tumor lysis syndrome may include hyperkalemia, hyperphosphatemia, and hyperuricemia.
3. A 4-year-old boy has fever of unknown origin, enlargement of the spleen and liver, and gingival hypertrophy. A complete blood count shows leukemic myeloblasts. Which of the following statements regarding this patient’s diagnosis is correct?
A. Further examination would likely reveal generalized lymphadenopathy and testicular swelling.
B. A blood smear may demonstrate Auer rods within his leukemic blasts.
C. Evaluation of the chromosomes would reveal the Philadelphia chromosome.
D. Bone marrow transplant is usually not necessary for treatment, given the high cure rate with standard chemotherapy.
E. If this boy had Down syndrome, his leukemia would be very difficult to treat and would likely be fatal.
4. A 15-year-old boy has a 3-month history of fever and weight loss. Physical examination reveals posterior cervical and supraclavicular lymphadenopathy. You refer the patient to a pediatric general surgeon, who performs a lymph node biopsy. The diagnosis is Hodgkin disease. Which of the following statements regarding this diagnosis is correct?
A. The cancer would be classified as stage IA.
B. Airway obstruction is a common complication of this type of cancer.
C. Associated infertility is rare.
D. Prognosis is poor.
E. The biopsy likely shows Reed–Sternberg cells.
5. A 6-year-old girl has a 1-month history of vomiting in the early morning on awakening, occipital headache, and an unsteady gait. Physical examination is normal with the exception of

a noticeable wide-based gait with ataxia. Although you were unable to view her optic discs to determine whether papilledema is present, you suspect that she may have a brain tumor.
Which of the following statements regarding her probable diagnosis and her evaluation is correct?
A. She most likely has a high-grade astrocytoma.
B. She likely has a medulloblastoma in the infratentorial region.
C. A head computed tomography (CT) is the best imaging modality for diagnosis.
D. Combination chemotherapy and radiation therapy are the principal treatments for suspected brain tumor.
E. The cerebrospinal fluid tumor markers homovanillic acid and vanillylmandelic acid will be absent on evaluation.
6. A 15-year-old boy has a routine health maintenance examination. A firm, painless right testicular mass is found. Which of the following statements regarding a testicular tumor in this boy is correct?
A. The tumor is most likely benign.
B. Teratoma is the most common type of testicular tumor.
C. Metastasis most commonly occurs to bone.
D. A history of unilateral cryptorchid testes has put this patient at higher than usual risk for a testicular tumor.
E. Chemotherapy and radiation therapy are the most appropriate initial treatments.
7. A 7-year-old boy with a history of biliary atresia managed with a Kasai portojejunostomy performed at 5 weeks of age now presents with a 10-pound weight loss during a 4-month period. His parents state that his appetite has been very poor. Physical examination shows a mass in the right upper quadrant of the abdomen. You suspect hepatocellular carcinoma given his prior history of biliary atresia. Which of the following statements regarding this type of cancer in childhood is correct?
A. The malignancy is also associated with chronic active hepatitis B infection.
B. Careful examination of the conjunctiva would likely reveal evidence of jaundice.
C. A liver transplant is recommended because of the poor prognosis associated with this malignancy.
D. Urine catecholamines are elevated.
E. Human chorionic gonadotropin is elevated and diagnostic.

The response items for statements 8–11 are the same. You will be required to select one answer for each statement in the following set.

A. Acute myelogenous leukemia
B. Retinoblastoma
C. Burkitt lymphoma
D. Wilms tumor
E. Neuroblastoma
F. Brain tumor
G. Acoustic neuroma

For each patient with a genetic syndrome or infection, select the associated malignancy.

1. A 7-year-old African boy with a history of Epstein–Barr virus infection.
2. A 2-year-old girl with Down syndrome.
3. A 6-year-old boy with Beckwith–Wiedemann syndrome.
4. A 10-year-old boy with neurofibromatosis type 2.

The response items for statements 12–16 are the same. You will be required to select one answer for each statement in the following set.

A. Osteogenic sarcoma
B. Ewing sarcoma
C. Rhabdomyosarcoma
D. Langerhans cell histiocytosis
E. Yolk sac tumor
F. Teratoma
G. Non-Hodgkin lymphoma

For each patient, select the most likely diagnosis.

1. A 4-year-old boy with a painless, growing, soft tissue mass within the orbit, with accompanying proptosis and eyelid swelling.
2. A 14-year-old boy with a painful, growing, soft tissue mass at the distal femur. Radiography reveals periosteal elevation with a “sunburst” appearance.
3. A 5-month-old girl with a soft tissue mass in the lower portion of the back near the coccyx.
4. A 5-year-old boy with a painful, growing mass behind the right ear with chronic right ear discharge.
5. A 16-year-old girl with a painful, growing, soft tissue mass involving the right pelvis. Radiography reveals periosteal elevation with an “onionskin” appearance.

Answers and Explanations
1. The answer is A [Table 14-2]. Factors at the time of diagnosis that predict a favorable prognosis include female sex, age between 1 and 9 years, Caucasian race, white blood cell (WBC) count <50,000 cells/mm3, hyperploidy of leukemic cells, absence of chromosomal translocation, and lack of involvement of the central nervous system, liver, spleen, and other organs. However, a common acute lymphocytic leukemia antigen (CALLA) negative immunophenotype is an unfavorable prognostic indicator, whereas CALLA-positive is a favorable prognostic indicator.
2. The answer is E [II.A.6.f]. Many complications may result from therapy for leukemia. Tumor lysis syndrome occurs when cells break apart spontaneously or after chemotherapy and release uric acid, potassium, and phosphate into the circulation. Therefore, hyperuricemia, hyperkalemia, and hyperphosphatemia may be seen. Induction chemotherapy induces remission in approximately 95% of patients. Fever associated with neutropenia is a feared complication that mandates immediate therapy with intravenous antibiotics because of the higher than usual risk of serious bacterial infection in immunosuppressed patients. Intrathecal methotrexate is administered to all patients, regardless of prognosis, during induction as prophylaxis against central nervous system involvement, and to all patients during the consolidation phase of chemotherapy. Intracranial radiation is associated with many long- term complications and should generally be avoided, if possible, in children younger than
5 years.
3. The answer is B [II.B.5–7]. This patient’s clinical presentation and the finding of leukemic myeloblasts are consistent with the diagnosis of acute myelogenous leukemia (AML). Auer rods found within the leukemic blast cells are consistent with the diagnosis of AML. AML is generally more difficult to treat than acute lymphocytic leukemia (ALL), and remission occurs with aggressive chemotherapy in only approximately 50% of patients. Bone marrow transplant is one of the mainstays of therapy in AML. Patients with AML may present with fever, hepatosplenomegaly, bruising, bone pain, and gingival hypertrophy, but testicular involvement and lymphadenopathy are not common clinical features. The Philadelphia chromosome is found in adult-type chronic myelogenous leukemia, rather than in AML. AML associated with Down syndrome is highly treatable.
4. The answer is E [III.A.2–4 and Table 14-3]. Patients with Hodgkin disease most commonly present with painless lymphadenopathy, generally in the cervical or supraclavicular regions. Systemic features, such as weight loss, night sweats, and fever, may also be present. Diagnosis is proven on the basis of the finding of Reed–Sternberg cells on lymph node biopsy. From the involvement of two lymph node regions on the same side of the diaphragm and systemic features in this patient, his cancer would be classified as stage IIB, rather than stage IA (in which only one lymph node region is involved and there would be no systemic manifestations such as fever and weight loss). Airway obstruction caused by involvement of anterior mediastinal nodes is more common in non-Hodgkin lymphoma. Impaired fertility is common in Hodgkin disease. Prognosis for stage II disease is excellent.
5. The answer is B [IV.B–D]. The clinical presentation is consistent with a brain tumor. Between 1 and 12 years of age, infratentorial brain tumors are most common. In addition, the ataxia suggests an infratentorial tumor. Medulloblastoma, a primitive neuroectodermal tumor, is the most common infratentorial tumor and would therefore be the most likely tumor in this patient. Astrocytoma is the second most common infratentorial tumor, and brainstem glioma is the third most common infratentorial tumor. Although astrocytomas are possible tumors in the infratentorial region, they tend to be low-grade, rather than high-grade, tumors. Magnetic resonance imaging is the preferred diagnostic imaging study because of the likely cerebellar

location of the medulloblastoma. The principal treatment is surgical resection, if it is possible. The tumor markers, homovanillic acid and vanillylmandelic acid, which are secreted by medulloblastomas, are detectable in the cerebrospinal fluid.
6. The answer is D [X.B.2]. Cryptorchid testes (testes that fail to descend into the scrotum) are at much higher than usual risk for malignancy. Two-thirds of testicular tumors in childhood are malignant and one-third are benign. Teratomas account for approximately 15% of testicular tumors. In contrast, yolk sac tumors account for 60% of testicular tumors and are the most common testicular tumor. Management of testicular tumors is based on the tumor type, size, and presence of metastases that may involve the retroperitoneal lymph nodes, liver, or lung. Metastasis to bone is more unusual. Treatment of yolk sac tumors involves radical orchiectomy and retroperitoneal lymph node dissection, if necessary.
7. The answer is A [VIII.A.2]. Hepatocellular carcinoma is associated with chronic active hepatitis B infection, biliary atresia, α1-antitrypsin deficiency, and glycogen storage disease type I. Typical presentation includes a right upper quadrant abdominal mass, weight loss, and anorexia; however, jaundice is generally absent. Liver transplant is not curative because of the high rate of metastatic disease. Diagnosis is based on findings on abdominal imaging and elevation of the serum marker α-fetoprotein. Urine catecholamines are not present, and human chorionic gonadotropin is not elevated.
8. The answers are C, A, D, and G, respectively [Table 14-1, II.B.2, I.B.2.b, and I.B.3]. Genetic syndromes and infections may predispose to childhood cancers. Epstein–Barr virus infection may predispose to both Hodgkin disease and non-Hodgkin lymphoma, including Burkitt lymphoma, which is endemic in Africa. Down syndrome may predispose to both acute myelogenous leukemia and acute lymphocytic leukemia. Beckwith–Wiedemann syndrome may predispose to Wilms tumor, rhabdomyosarcoma, and hepatoblastoma. Neurofibromatosis type 2 may predispose to acoustic neuroma, whereas neurofibromatosis type 1 may predispose to brain tumors and lymphoma.
9. The answers are C, A, F, D, and B, respectively [VI.C.1.a, Table 14-4, XI.C.1.d, and X.B.1.a]. Rhabdomyosarcoma is the most common soft tissue sarcoma and typically presents as a painless soft tissue mass. The head and neck are involved 40% of the time, and if the orbit is involved, the patient may present with proptosis, eyelid swelling, or cranial nerve palsies. Both osteogenic sarcoma and Ewing sarcoma present as painful soft tissue masses. Osteogenic sarcoma generally involves the metaphysis of tubular long bones, especially the distal femur and proximal tibia. Ewing sarcoma more commonly involves flat bones and the diaphysis of tubular bones. The axial skeleton, including the pelvis, is most commonly involved. Radiographic appearances of both osteogenic sarcoma and Ewing sarcoma reveal periosteal elevation; however, osteogenic sarcoma has a more typical “sunburst” appearance (question 13), whereas Ewing sarcoma has a more typical “onionskin” appearance (question 16). Langerhans cell histiocytosis often presents as bony lesions. If the mastoid bone is involved, a child may present with a mass behind the ear and chronic ear drainage. Sacrococcygeal teratoma, the most common teratoma in infancy, occurs as a soft tissue mass in the area of the coccyx. The majority (75%) of these teratomas occur in females.