Pediatric Residency Training Program

14

Oncology

Carole Hurvitz M.D.

Liliana Sloninsky M.D.

Margaret Sanford M.D.

Lloyd J. Brown M.D.

  1. General Considerations
  2. Incidence

Approximately 6, 000–7, 000 children between 1 and 15 years of age develop cancer each year.

  1. Cancer is the leading cause of death from diseasein 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.
  3. 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 14-1lists common genetic syndromes and their associated cancer(s).
  2. Immunodeficiency diseasesmay predispose to cancer.
  3. Wiskott-Aldrich syndrome, characterized by B- and T-cell dysfunction, atopic dermatitis, and thrombocytopenia, is associated with lymphoma and leukemia.
  4. X-linked lymphoproliferative disease, associated with Epstein-Barr virus (EBV) infection, may result in lymphoma.
  5. Infectious diseases, such as EBV and HIV, are associated with Burkitt's lymphoma and Kaposi's sarcoma, respectively.
  6. Environmental factors, such as prior chemotherapy and ionizing radiation, may result in malignancy.
  7. 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

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

Genetic Disorder

Type of 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's and non-Hodgkin's lymphoma, leukemia, sarcomas

Bloom syndrome

Leukemia, lymphomas, gastrointestinal malignancies, solid tumors

Beckwith-Wiedemann syndrome

Wilms' tumor, hepatoblastoma, rhabdomyosarcoma, adrenocortical carcinoma

Neurofibromatosis type I

Brain tumors, lymphoma, leukemia, malignant schwannoma

Neurofibromatosis type II

Acoustic neuroma

ALL = acute lymphocytic leukemia; AML = acute myelogenous leukemia

  1. P.424
  2. Abdominal massshould 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.
  3. Mass on the trunk or extremitiesmay be caused by rhabdomyosarcoma or bone tumor.
  4. Bone painmay reflect metastatic cancer, primary tumors of bone or connective tissue, or leukemic infiltration of bone marrow.
  5. Supraclavicular lymphadenopathy, nontender, firm lymph nodes, or enlarging lymph nodes may be caused by leukemia, lymphoma, or metastatic disease.
  6. Early morning headacheand vomiting, or change in gait, may be caused by a space-occupying tumor within the central nervous system (CNS).
  7. Bruising, petechiae, and pallormay be caused by tumor infiltration of bone marrow.
  8. Leukocoria(i.e., white reflex in the pupillary area) may be caused by retinoblastoma (see Chapter 18, section VIII.B).
  9. Hypertensionmay be caused by neuroblastoma, Wilms' tumor, or pheochromocytoma.
  10. Leukemias
  11. Acute Lymphocytic Leukemia (ALL)

[acute lymphoblastic leukemia]

  1. Epidemiology

P.425

 

  1. ALL is the most common childhood cancer.
  2. ALLrepresents 80–85% of childhood leukemias.
  3. Peak incidenceoccurs at 2–6 years of age. ALL is more common in males and in Caucasians.
  4. 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).
  5. Classificationis based on morphology and immunophenotype of the leukemic cells (i.e., lymphoblasts).
  6. Cell morphologyis classified as L1, L2, or L3, with L1 being the most common in childhood. L1 lymphoblasts are small with little cytoplasm and indistinct nucleoli, whereas L3 lymphoblasts are large with one or more nucleoli.
  7. Immunophenotype
  8. T-cell phenotype: 25%
  9. B-cell phenotype: <5%
  10. Pre–B-cell phenotype: 70%.Pre–B-cell ALL may be further subdivided on the basis of the presence of common acute lymphocytic leukemia antigen (CALLA).
  11. CALLA-positive (70%)
  12. CALLA-negative (30%)
  13. Clinical features
  14. Feverand bone or joint pain are the most common symptoms. Bone or joint pain often manifests as refusal to bear weight.
  15. Pallor, bruising, hepatosplenomegaly, and lymphadenopathyare the most common signs.
  16. Epistaxis, anorexia, fatigue, testicular pain and swelling, and abdominal pain may also be present.
  17. Diagnosis
  18. ALL is suggestedby a complete blood count (CBC) that demonstrates anemia and thrombocytopenia. The white blood cell (WBC) count is variable.
  19. WBCis 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).
  20. Leukemic blasts(i.e., lymphoblasts) are often seen.
  21. Note: A normal CBC does not rule out leukemia.
  22. Confirmationis 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.
  23. Prognostic factorsfor ALL at time of diagnosis are listed in Table 14-2. Most patients have disseminated disease at presentation, so there is no staging system for ALL.
  24. Management.The best treatment for ALL remains under investigation, and patients should be encouraged to participate in a national clinical trial. Management involves three stages: induction, consolidation, and maintenance.

P.426

 

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)

Organ involvement

None

Organomegaly, central nervous system involvement, mediastinal mass

Immunophenotype

CALLA (+)

CALLA (-)

Chromosomal translocation

None

t(9,22)

ALL = acute lymphocytic leukemia; CALLA = common acute lymphocytic leukemia antigen; WBC = white blood cell count.

  1. Inductionaims to destroy as many cancer cells as possible to induce remission.
  2. Drugs vary based on study protocol but typically include corticosteroids, vincristine, and L-asparaginase. Intrathecal methotrexateis given to all children during induction. Other agents are added on the basis of expected prognosis.
  3. Remission is induced in 95% of patients.
  4. Consolidationinvolves a continuation of systemic chemotherapeutic agents and prophylactic regimens to prevent CNS involvement because systemic chemotherapy poorly penetrates the blood-brain barrier.
  5. Intrathecal methotrexateis continued during consolidation.
  6. Cranial irradiationmay be given to high-risk children. Radiation should generally be avoided in children younger than 5 years of age, if possible, because of the risk of subsequent neuropsychological effects.
  7. Maintenancetherapy involves daily and periodic chemotherapy during remission for up to 3 years. Chemotherapy is usually discontinued after 2–3 years if the patient remains disease-free.
  8. Bone marrow transplantmay be performed for very high-risk children and for those who have relapsed. (The bone marrow is the most common site of relapse.)
  9. Complicationsduring 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:
  10. Infection associated with neutropenia is potentially life-threatening. Children with fever and severe neutropenia (absolute neutrophil count < 500 cells/mm13) 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.

P.427

 

  1. Opportunistic infectionswith organisms, such as herpes simplex virus, Pneumocystis carinii 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.
  2. Metabolic complicationsfrom spontaneous or therapy-induced cell lysis (tumor lysis syndrome)
  3. Hyperuricemiamay result in renal insufficiency.
  4. Hyperkalemiamay result in cardiac dysrhythmias.
  5. Hyperphosphatemiamay result in hypocalcemia with tetany.
  6. Other complications include medication-induced pancreatitis (L-asparaginase and corticosteroids), cardiomyopathy (doxorubicin), and cystitis (cyclophosphamide). Cranial irradiation may result in mental retardation, learning problems, stroke, hormonal 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.
  8. Acute Myelogenous Leukemia (AML)
  9. Epidemiology. AML represents 15–20% of childhood leukemias.
  10. 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.
  11. Classificationis based on cell morphology and histochemical characteristics. There are seven types of AML: M1, M2, M4, and M5 together account for 90% of childhood AML.
  12. M1: acute myeloblastic leukemia(no maturation)
  13. M2: acute myeloblastic leukemia(some maturation)
  14. M3: acute promyelocytic leukemia (Auer rods common)
  15. M4: acute myelomonocytic leukemia
  16. M5: acute monocytic leukemia
  17. M6: erythroleukemia
  18. M7: acute megakaryocytic leukemia(associated with Down syndrome)

P.428

 

  1. Clinical featuresare similar to those of ALL. However, CNS involvement occurs more commonly in AML than in ALL.
  2. Symptoms and signs include fever, hepatosplenomegaly, bruising and bleeding, gingival hypertrophy, and bone pain. Lymphadenopathy and testicular involvement are uncommon.
  3. Laboratory findingsmay include pancytopenia or leukocytosis, and disseminated intravascular coagulation (DIC).
  4. Diagnosisis suggested by clinical features and blood smear demonstrating leukemic myeloblasts. Blasts containing Auer rods are consistent with myeloid leukemia. Confirmationis by morphologic analysis and immunophenotyping of cells obtained by bone marrow biopsy.
  5. Management.AML, unlike ALL, requires very intensive myeloablative therapy to induce remission. Bone marrow transplant is recommended once patients are in remission, if they have an HLA-matched donor.
  6. Prognosis.Aggressive chemotherapy is effective in 50% of patients. Bone marrow transplant from a matched sibling is curative in 70% of patients. AML associated with Down syndrome is very responsive to therapy, for unknown reasons.
  7. Chronic Myelogenous Leukemia (CML)
  8. Epidemiology.CML is the least common type of leukemia, representing 3–5% of childhood leukemia. Males are more commonly affected.
  9. Classification.Two forms of CML occur in children.
  10. Adult-type CML
  11. Twice as common as the juvenile form
  12. Occurs predominantly in older children and adolescents
  13. Characterized by the presence of the Philadelphia chromosome(reciprocal translocation between the long arms of chromosomes 9 and 22, leading to the fusion geneBCR/ABL1 that produces the BCR-ABL fusion protein)
  14. Juvenile chronic myelogenous leukemia(juvenile myelomonocytic leukemia [JMML])
  15. Occurs predominantly in infants and childrenyounger than 2 years of age
  16. Sometimes characterized by abnormalities of chromosome 7 or 8. The Philadelphia chromosome is absent.
  17. Clinical features.Signs and symptoms vary based on the type of CML.
  18. Adult-type CML
  19. Nonspecific symptoms such as fatigue, weight loss, and pain
  20. Massive splenomegalyleading to abdominal distension. CML is typically discovered after an incidental finding of splenomegaly on examination.
  21. Extremely high WBC (often > 100, 000 cells/mm3)
  22. JMML
  23. Fever
  24. Chronic eczemalike facial rash

P.429

 

  1. Suppurative lymphadenopathy
  2. Petechiae and purpura
  3. Moderate leukocytosis(< 100, 000 cells/mm3), anemia, and thrombocytopenia
  4. Management.Treatment of both adult-type CML and JMML is bone marrow transplantation, either HLA-matched (ideally) or unmatched. Radiation therapy is not effective; however, the newer chemotherapeutic agent, imatinib mesylate has been shown to induce remission in adult-type CML.
  5. Prognosis
  6. Adult-type CMLmay have a biphasic course. During the initial chronic phase, chemotherapy controls the leukocytosis. During the subsequent acute phase resembling acute leukemia, the patient deteriorates and is unresponsive to therapy.
  7. JMMLis often fatal. Relapse occurs in 50% of cases, even with bone marrow transplantation.

III. Lymphomas

Lymphomas account for 10–15% of childhood cancers.

  1. Hodgkin's disease

is a cancer of the antigen-processing cells found within the lymph nodes or spleen.

  1. Epidemiology
  2. Hodgkin's disease isassociatedwith EBV infection. Patients with EBV-associated mononucleosis have a two to four times greater risk of developing Hodgkin's disease later in life.
  3. Hodgkin's disease is more common in older children and adolescents.
  4. Clinical features.Most children with Hodgkin's disease present with painless lymphadenopathy, most commonly in the supraclavicular or cervical regions. Signs and symptoms of Hodgkin's disease are listed in Table 14-3.
  5. 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.

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

Clinical Feature

Hodgkin's Disease

Non-Hodgkin's 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.

P.430

 

  1. 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.
  2. Stage I:involvement of a single lymph node or extralymphatic site
  3. 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
  4. Stage III:involvement of lymph nodes on both sides of the diaphragm (in this case, the spleen is considered a lymph node)
  5. Stage IV:diffuse or disseminated involvement of one or more extralymphatic organs or tissues
  6. Management.Treatment is based on the child's age, disease stage, and tumor burden. Treatment most commonly includes chemotherapy and radiation therapy. Late complications of therapy include the following:
  7. Growth retardationas a result of radiation therapy
  8. Secondary malignancies, including breast cancer, AML, and non-Hodgkin's lymphoma
  9. Hypothyroidism(10–20%)
  10. Male sterility (very common)
  11. Prognosis.Overall, prognosis of stages I and II disease is excellent, with ≥ 80% long-term survival. More advanced disease carries a long-term survival rate of 60–70%.
  12. Non-Hodgkin's lymphoma

is a very aggressive cancer and is 1.5 times more common than Hodgkin's disease.

  1. Epidemiology
  2. Male predominance
  3. Associated with immunodeficiency states, such as HIV, Wiskott-Aldrich syndrome, ataxia telangiectasia syndrome, and prior EBV infection.
  4. Increasing incidence after 5 years of age
  5. Classification.There are three major categories of non-Hodgkin's lymphoma. (The moreuncommon categories include anaplastic large cell and large cell, noncleaved immunoblastic lymphoma.)
  6. Lymphoblastic lymphomais histologically similar to the lymphoblast of ALL. It is generally T-cell in origin.
  7. Small, noncleaved cell lymphomaincludes Burkitt's lymphoma, the most common lymphoma in childhood. Burkitt's lymphoma is B-cell in origin.
  8. Large cell lymphomais generally B-cell in origin.
  9. Clinical features (see Table 14-3). Painless lymphadenopathy is the most common presenting feature.
  10. Lymphoblastic lymphomacommonly presents with an anterior mediastinal mass, and the patient may develop superior vena cava syndrome or airway obstruction as a result.

P.431

 

  1. Small, noncleaved cell lymphoma
  2. Intussusception, abdominal pain, or mass. Lymphoma must be considered as a possible cause (lead point) in any child older than 3 years of age presenting with intussusception.
  3. Burkitt's lymphomais endemic in Africa, where it presents as a jaw mass.
  4. Large cell lymphomacommonly presents as enlargement of lymphoid tissue in the tonsils, adenoids, or Peyer's patches.
  5. Diagnosis and staging.The basis of diagnosis is pathologic examination of tissue obtained by biopsy. 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, bone scan or gallium scan, measurement of hepatic transaminases, bone marrow biopsy, and cerebrospinal fluid analysis.
  6. Management. Treatment must be rapidbecause 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.
  7. Prognosis.Outlook is best for localized lymphoma, with a cure rate > 90%. Prognosis is poorest for patients with disseminated disease.
  8. Brain Tumors
  9. Epidemiology
  10. Brain tumors are the second most common childhood cancerafter leukemia and are the most common solid tumors.
  11. They account for 20% of all childhood cancers.
  12. Brain tumors may be associated with underlying diseases such as neurofibromatosis, tuberous sclerosis, and von Hippel-Lindau disease.
  13. Classification

is by histology, grade, and location.

  1. Histology
  2. 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.
  3. Primitive neuroectodermal tumors (PNETs)are the second most common tumor and include medulloblastomas arising from the cerebellum.
  4. Ependymomasare the third most common tumor.
  5. Craniopharyngiomasare the fourth most common tumor.
  6. Grade.The grade of the tumor refers to its aggressiveness.
  7. High grade:aggressive, proliferative cells
  8. Low grade:less aggressive, more-differentiated cells

P.432

 

  1. Location. Infratentorial tumors are more commonthan supratentorial tumors, except at age extremes of < 1 or > 12 years of age.
  2. Medulloblastomais the most common infratentorial tumor, followed by cerebellar astrocytoma and brainstem glioma.
  3. Astrocytomais the most common supratentorial tumor.
  4. 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 symptomsare 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.
  3. Headache:diffuse, occipital, or frontal
  4. Vomiting:often resolves the accompanying headache
  5. Drowsiness or irritability
  6. Abnormal behavior
  7. Ataxia:associated with cerebellar tumors
  8. Seizure:associated with supratentorial tumors
  9. Head tilt
  10. Physical examination findings
  11. Enlargedor bulging fontanelle in infants, or enlarged head circumference
  12. Nystagmus
  13. Papilledema
  14. Cranial nerve abnormalities, especially sixth nerve palsy
  15. Lethargy or irritability
  16. Features associated with specific tumors
  17. Optic gliomais associated with diminished vision, visual field deficits, and strabismus.
  18. Craniopharyngiomais associated with growth retardation, delayed puberty, visual changes, diabetes insipidus, and other hormonal problems because of involvement of the hypothalamic-pituitary axis.
  19. Diagnosis
  20. Neuroimagingby CT or magnetic resonance imaging (MRI) is critical for diagnosis and management. MRI is generally preferred because it is better able to visualize the temporal lobes, cranial base, and brainstem. MRI is also able to image the tumor in multiple planes, allowing for operative planning.
  21. Cerebrospinal fluidobtained 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).

P.433

 

  1. Management
  2. Surgery.Resection or debulking the tumor is the principal treatment.
  3. Radiation therapy.Almost all brain tumors are radiosensitive. However, radiation should be reserved, if possible, for children older than 5 years of age because of the risk of adverse effects (see Chapter 14, section II.A.6.e.(4)).
  4. Chemotherapy.This method is effective for many tumors and is often used together with radiation therapy and surgery.
  5. Prognosis

Outlook depends on tumor grade, size, and type.

  1. Astrocytomas.Low-grade, completely resectable astrocytomas have a good prognosis (> 75% survival). High-grade astrocytomas have a poor prognosis (35% survival at 3 years) because of their infiltrative nature.
  2. PNETs.Survival is > 75% 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 of age.
  3. Brainstem gliomas.The prognosis is poorest with brainstem gliomas. It is not possible to resect these tumors, and chemotherapy is ineffective.
  4. Renal and Suprarenal Tumors
  5. Neuroblastoma

This malignant tumor of neural crest cells may arise anywhere along the sympathetic ganglia chain and within the adrenal medulla.

  1. Epidemiology
  2. Neuroblastomas are the second most common solid tumors, after brain tumors.
  3. Neuroblastomas are responsible for 8–10% of all childhood cancers.
  4. Peak incidence is in the first 5 years of life.Median age at time of diagnosis is 2 years.
  5. Approximately 75% occur in the abdomen or pelvis, 20% occur in the posterior mediastinum, and 5% occur in the neck.
  6. Etiology.The cause is unknown; however, chromosomal abnormalities have been detected. Such abnormalities include a deletion on the short arm of chromosome 1, an unbalanced translocation between 1p and 17q, and anomalies on chromosomes 14q and 22q.
  7. Clinical features.Signs and symptoms are presented in Figure 14-1
  8. Diagnosis
  9. Urine excretion of excessive catecholamines, including VMA and HVA, is characteristic (found in 90% of patients).Definitive diagnosisis by positive bone marrow biopsy plus elevated urine catecholamines, or by results of tissue biopsy.
  10. CT or MRI is generally used to assess tumor spread.
  11. Skeletal survey or technetium 99m bone scan is used to assess for metastasis to bone.

P.434

 

 

Figure 14-1. Clinical features of neuroblastoma.

  1. Staging.Several systems may be used. The most commonly used system, the Evan's system, has five stages.
  2. Stage I:localized tumor confined to the structure of origin
  3. Stage II:tumor extends beyond structure of origin but does not cross midline

P.435

 

  1. Stage III:tumor extends past midline
  2. Stage IV:metastasis to bone, lymph nodes, bone marrow, or soft tissue
  3. Stage IVS:localized tumor at stage I or II but with distant metastasis to any organ but bone
  4. Management
  5. Surgery alone may be curative for stage I and II disease.
  6. Chemotherapyis used, especially for metastatic disease (stage IV and sometimes IVS) and for locally advanced disease.
  7. Radiation therapyis used for advanced disease.
  8. Prognosis
  9. Goodprognosis occurs in children younger than 1 year of age and in patients with stage I and II disease. Spontaneous regression without treatment may occur in young infants with stage IVS disease.
  10. Poorprognosis is associated with stage III and IV disease, amplification of the oncogene N -myc (found on chromosome 2), tumor cell diploidy, and high levels of the serum markers ferritin, lactic dehydrogenase, and neuron-specific enolase.
  11. Wilms' tumor

(nephroblastoma) is a tumor of the kidney.

  1. Epidemiology
  2. Wilms' tumor is themost common childhood renal tumor.It is responsible for 7% of childhood cancers.
  3. Seventy-five percent of cases occur in childrenyounger than 5 years of age(median age at diagnosis is 3 years).
  4. Associatedgenetic findings or syndromesinclude Beckwith-Wiedemann syndrome (hemihypertrophy, macroglossia, visceromegaly), deletion of the short arm of chromosome 11, and WAGR syndrome (Wilms' tumor, aniridia, genitourinary abnormalities, and mental retardation).
  5. Clinical features
  6. Abdominal mass, generally found on routine evaluation, is the most common presentation.The mass is smooth and firm, and rarely crosses the midline.
  7. Abdominal pain(50% of patients) with or without vomiting
  8. Hematuria(25% of patients)
  9. Hypertension(25% of patients) secondary to pressure on the renal artery or increased renin secretion by the tumor
  10. Nonspecificfindings including fever, anorexia, and weight loss.
  11. Associated congenital anomalies in 15% of cases
  12. Genitourinary malformations
  13. Hemihypertrophy
  14. Sporadic aniridia
  15. 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. Evaluation for distant metastasis to lung, liver, bone, and brain should also be completed.

P.436

 

  1. Staging.The National Wilms' Tumor Study Group classification is used to stage Wilms' tumor.
  2. Stage I:tumor limited to kidney and completely excised intact without rupture
  3. Stage II:tumor extends locally but can still be completely excised without residual disease
  4. Stage III:residual tumor remains in abdomen or spillage of tumor occurs during resection
  5. Stage IV:distant metastasis to lung (most common), liver, bone, and brain
  6. Stage V:bilateral renal involvement
  7. 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).
  8. 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 results in a 2-year survival > 95%. Unfavorable histology accounts for 12% of cases but 90% of deaths.
  9. 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.

  1. Epidemiology. Two thirds

of rhabdomyosarcomas occur in children younger than 10 years of age.

  1. Etiology

The cause is generally unknown. Patients with neurofibromatosis are at higher risk.

  1. 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 sitesof involvement (40% of cases).
  2. Orbital tumorstypically present with proptosis, chemosis (i.e., conjunctival edema), eyelid swelling and cranial nerve palsies.
  3. Nasopharyngeal tumorstypically present with epistaxis, airway obstruction and chronic sinusitis.
  4. Laryngeal tumorstypically present with hoarseness.
  5. Genitourinary tractis the 2nd 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.
  6. The extremitiesare the 3rd most common site of involvement (18% of cases). Tumors in this location present with a painless growing mass.

P.437

 

  1. Other sitesof involvement include the trunk, retroperitoneum, mediastinum, and paratesticular and perianal regions.
  2. 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. Histologic evaluation of tissue obtained by biopsy provides a definitive diagnosis.

  1. Management

Most importantly, treatment includes an attempt at complete surgical resection. Chemotherapy and radiation therapy are used (1) to treat local disease and distant metastases and (2) to prevent tumor recurrence.

  1. Prognosis

Tumors of the head and neck and the genitourinary tract have the best prognosis, with a cure rate > 90%. Poor prognosis is associated with metastases (20% have metastatic disease at time of diagnosis), tumor recurrence, and tumors at sites other than the head and neck or the genitourinary tract.

VII. Bone Tumors

  1. Osteogenic sarcoma

is a malignant tumor that forms osteoid, or new bone.

  1. Epidemiology
  2. Osteogenic sarcoma is the most common malignant bone tumor.
  3. The incidence of this tumor peaks during the rapid growth spurtof adolescence. Males are more commonly affected.
  4. Etiology.The cause is unknown; however, it is associated with previous retinoblastoma, Paget's disease of bone, radiation therapy for cancer, and fibrous dysplasia.
  5. Clinical features.About 50% of tumors occur near the knee. Other signs and symptoms are listed in Table 14-4, which compares osteogenic sarcoma with Ewing's sarcoma.

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

Feature

Osteogenic Sarcoma

Ewing's Sarcoma

Site

Metaphysis of tubular long bones
50% occur near the knee
Most common sites (in order): distal femur, proximal tibia, proximal humerus, proximal femur

Flat bones and diaphysis of tubular bones; occasionally extraosseous
Most common sites (in order): axial skeleton (especially pelvis), humerus, femur

Local and systemic findings

Pain, swelling, and soft tissue mass
Systemic symptoms uncommon

Pain, swelling, and soft tissue mass
Fever, malaise, and weight loss
Leukocytosis and ESR

Radiographic findings

Periosteal reaction with “sunburst” appearance
Lytic; or mixed lytic and destructive changes

Periosteal reaction with “onion skin” appearance
Destructive changes

Metastases

Occurs in 15% at presentation
Lungs (90%) and bone (10%)

Occurs in 25% at presentation
Lungs (50%), bone (25%), and bone marrow (25%)

ESR = erythrocyte sedimentation rate.

P.438

 

  1. 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.
  2. Management
  3. Surgeryto remove the primary tumor is performed by limb amputation or limb salvage procedures.
  4. Chemotherapyimproves survival. Drugs used include high-dose methotrexate, cisplatin, doxorubicin, ifosfamide, and cyclophosphamide.
  5. Pulmonary metastasesidentified at the time of diagnosis are usually removed surgically.
  6. Prognosis.Outcome has improved with the addition of chemotherapy, and survival is now > 60%.
  7. Ewing's sarcoma

is a sarcoma characterized as a small, round, blue cell tumor (undifferentiated, monomorphous cell appearance).

  1. Epidemiology
  2. Ewing's sarcoma is the second most common malignant bone tumor.
  3. It most commonly occurs during adolescence. Malesare more commonly affected.
  4. It israrein Asians and African Americans.
  5. 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).
  6. Clinical features.Signs and symptoms are listed in Table 14-4, which compares Ewing's sarcoma and osteogenic sarcoma. Ewing's sarcoma may occasionally develop in soft tissue instead of bone.
  7. Diagnosis
  8. Diagnosis is suggestedby radiographic findings; however, similar findings are found in osteomyelitis, lymphoma, osteogenic sarcoma, and Langerhans cell histiocytosis.
  9. MRIof affected bone can better delineate the tumor and its local extension.
  10. Definitive diagnosisis by histologic evaluation of tissue obtained by open biopsy.
  11. Bone scan, chest CT scan, chest radiograph, and bone marrow aspiration are generally performed to assess for metastases.
  12. Management.Treatment includes multiagent chemotherapy followed by surgical excision, when possible. Chemotherapy is important because of the high risk of metastasis. Radiation therapy is used when complete surgical excision is impossible. Late complications of radiation therapy include pathologic fractures at the tumor site, retarded bone growth, limb length discrepancy, functional impairment, and secondary malignancy.

P.439

 

  1. 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.

VIII. Liver Tumors

Liver tumors include hepatoblastoma and hepatocellular carcinoma.

  1. Epidemiology
  2. Hepatoblastomais 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.
  3. Hepatocellular carcinomamay 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.
  4. Clinical features

Signs and symptoms both are similar in liver tumors and include presentation with a right upper abdominal mass, loss of appetite, and weight loss. Jaundice is generally absent.

  1. Diagnosis

Diagnosis is made by abdominal imaging with CT or MRI scan and finding elevation of the serum tumor marker α-fetoprotein.

  1. Management

Treatment includes surgical resection, if possible, and chemotherapy. Chemotherapy may convert a previously unresectable tumor to one that is amenable to surgery.

  1. Prognosis

Outcome depends on surgical resectability. However, most tumors are unresectable and metastasize to the lungs, brain, and lymph nodes. Although the overall prognosis for both hepatoblastoma and hepatocellular carcinoma is very poor, hepatocellular carcinoma is generally less curable.

  1. Retinoblastoma

See Chapter 18, section VIII.B.

  1. Germ Cell Tumors (germinomas)

are malignancies derived from the cellular precursors of sperm and eggs.

  1. 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, retroperitoneum, neck). Types of germ cell tumors include seminoma (in males), dysgerminoma (in females), teratoma, yolk sac tumor, embryonal cell carcinoma, and choriocarcinoma.

  1. Specific Tumors
  2. Teratomasare 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.

P.440

 

  1. Sacrococcygeal teratomais 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 asoft tissue mass. Almost all (95%) arebenign. Treatment includes surgical excision of both the tumor and the coccyx to prevent recurrence.
  2. Anterior mediastinal teratomasare generally benign and may present with signs and symptoms of airway obstruction.
  3. Ovarian teratomasare the most common ovarian tumor and are generally benign. The teratoma is suggested by the presence of calcium within the tumor on abdominal radiograph.
  4. Testicular tumorsmay be derived from germ cells or stromal cells; 70% of childhood testicular tumors are germinomas.
  5. Epidemiology
  6. 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)
  7. Peak ages are younger than 5 years and during adolescence.
  8. There is an association with cryptorchid testes.
  9. One third of testicular tumors in childhood are benign, unlike in adults, in whom almost all testicular tumors are malignant.
  10. 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.
  11. 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.
  12. Ovarian tumorsmost commonly include yolk sac tumors, teratomas, and dysgerminomas.
  13. Epidemiology
  14. One third are malignant.The younger the child, the more likely it is that the tumor will be malignant.
  15. Tumorsincrease in frequency during puberty.
  16. Clinical features.Signs and symptoms include abdominal mass, abdominal pain caused by torsion of the tumor together with the ovary, and vaginal bleeding. Serum α-fetoprotein is elevated in yolk sac tumors.
  17. Management.Treatment is based on tumor type and typically includes surgical resection, chemotherapy, and, sometimes, radiation therapy.
  18. Langerhans Cell Histiocytosis (LCH)
  19. Definition
  20. LCH is a diverse group of disorders characterized by the uncontrolled growth of the Langerhans cell.

P.441

 

  1. LCHincludes the disorders eosinophilic granuloma, Hand-Schöller-Christian disease, and Letterer-Siwe disease, which range from more localized bony changes (eosinophilic granuloma) to more disseminated disease (Letterer-Siwe). LCH was also formerly known as histiocytosis X.
  2. Etiology

The cause is unknown. LCH is probably not a true malignancy but rather a severe immune dysregulation disease.

  1. Clinical features

are highly variable.

  1. Skeletal involvementoccurs in 80% of patients.
  2. The skull is most commonly involved.
  3. Single or multiple bony lesionsmay be present and may be painful, palpable, and associated with swelling.
  4. Pathologic fractures may occur.
  5. Chronic draining earsmay indicate LCH involving the mastoid.
  6. Skin involvementoccurs in 50% of patients. It typically manifests as seborrheic dermatitis of the diaper area and scalp (it mimics cradle cap).
  7. Pituitaryor hypothalamic involvement may lead to growth retardation, diabetes insipidus, hypogonadism, and panhypopituitarism.
  8. Other features include lymphadenopathy, hepatosplenomegaly, exophthalmos, anemia, and pulmonary infiltrates.
  9. Nonspecific systemic featuresinclude weight loss, fatigue, fever, and failure to thrive.
  10. Diagnosis

is by identifying the typical histologic features on biopsy of skin or bone lesions.

  1. Management
  2. If a single lesion or organ is involved, local curettage or low-dose radiation is used to stop disease progression. Corticosteroids or single-agent chemotherapy (e.g., vinblastine) may be used instead of radiation.
  3. If multiple lesions or organs are involved, multiagent chemotherapy is used.
  4. Prognosis

varies with the extent of disease. Single lesions may spontaneously resolve. Response rate to current treatments is high if the diagnosis is made rapidly. Long-term complications include growth impairment, learning problems, hearing loss, orthopedic deformities, and chronic lung disease.

P.442

 

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(-)

(B) WBC count at diagnosis < 50, 000 cells/mm3

(C) Female sex

(D) Leukemic cells that demonstrate hyperploidy

(E) Age of 3 years

  1. 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 of age.

(E) Tumor lysis syndrome may include hyperkalemia, hyperphosphatemia, and hyperuricemia.

  1. 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.

  1. 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's 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 sterility is rare.

(D) Prognosis is poor.

(E) The biopsy likely shows Reed-Sternberg cells.

P.443

 

  1. 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 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.

  1. 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.

  1. 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.

P.444

 

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

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.

(A) Acute myelogenous leukemia

(B) Retinoblastoma

(C) Burkitt's lymphoma

(D) Wilms' tumor

(E) Neuroblastoma

(F). Brain tumor

(G). Acoustic neuroma

  1. A 2-year-old girl with Down syndrome.

(A) Acute myelogenous leukemia

(B) Retinoblastoma

(C) Burkitt's lymphoma

(D) Wilms' tumor

(E) Neuroblastoma

(F). Brain tumor

(G). Acoustic neuroma

  1. A 6-year-old boy with Beckwith-Wiedemann syndrome.

(A) Acute myelogenous leukemia

(B) Retinoblastoma

(C) Burkitt's lymphoma

(D) Wilms' tumor

(E) Neuroblastoma

(F). Brain tumor

(G). Acoustic neuroma

  1. A 10-year-old boy with neurofibromatosis type II.

(A) Acute myelogenous leukemia

(B) Retinoblastoma

(C) Burkitt's lymphoma

(D) Wilms' tumor

(E) Neuroblastoma

(F). Brain tumor

(G). Acoustic neuroma

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

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.

(A) Osteogenic sarcoma

(B) Ewing's sarcoma

(C) Rhabdomyosarcoma

(D) Langerhans cell histiocytosis

(E) Yolk sac tumor

(F). Teratoma

(G). Non-Hodgkin's lymphoma

  1. A 14-year-old boy with a painful, growing, soft tissue mass at the distal femur. Radiography reveals periosteal elevation with a “sunburst” appearance.

(A) Osteogenic sarcoma

(B) Ewing's sarcoma

(C) Rhabdomyosarcoma

(D) Langerhans cell histiocytosis

(E) Yolk sac tumor

(F). Teratoma

(G). Non-Hodgkin's lymphoma

  1. A 5-month-old girl with a soft tissue mass in the lower portion of the back near the coccyx.

(A) Osteogenic sarcoma

(B) Ewing's sarcoma

(C) Rhabdomyosarcoma

(D) Langerhans cell histiocytosis

(E) Yolk sac tumor

(F). Teratoma

(G). Non-Hodgkin's lymphoma

  1. A 5-year-old boy with a painful, growing mass behind the right ear with chronic right ear discharge.

(A) Osteogenic sarcoma

(B) Ewing's sarcoma

(C) Rhabdomyosarcoma

(D) Langerhans cell histiocytosis

(E) Yolk sac tumor

(F). Teratoma

(G). Non-Hodgkin's lymphoma

  1. A 16-year-old girl with a painful, growing, soft tissue mass involving the right pelvis. Radiography reveals periosteal elevation with an “onion-skin” appearance.

(A) Osteogenic sarcoma

(B) Ewing's sarcoma

(C) Rhabdomyosarcoma

(D) Langerhans cell histiocytosis

(E) Yolk sac tumor

(F). Teratoma

(G). Non-Hodgkin's lymphoma

P.445

 

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 (+) is a favorable prognostic indicator.
  2. The answer is E[II.A.6.e]. 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 of age.
  3. The answer is B[II.B.5, 6, 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, 3, 4, Table 14-3]. Patients with Hodgkin's 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 stage IA, 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's lymphoma. Male sterility is very common in Hodgkin's 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.

P.446

 

  1. 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.
  2. 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. Although the prognosis is poor for all types of liver tumors, hepatocellular carcinoma has the worst prognosis. 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.

8–11. The answers are C, A, D, and G, respectively [Table 14-1, II.B.2, I.B.2.b, I.B.3]. Genetic syndromes and infections may predispose to childhood cancers. Epstein-Barr virus infection may predispose to both Hodgkin's disease and non-Hodgkin's lymphoma, including Burkitt's 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 II may predispose to acoustic neuroma, while neurofibromatosis type I may predispose to brain tumors and lymphoma.

12–16. The answers are C, A, F, D, and B, respectively [VI.C.1.a, Table 14-4, XI.C.1.d, 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's 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's 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's sarcoma reveal periosteal elevation; however, osteogenic sarcoma has a more typical “sunburst” appearance (question 13), whereas Ewing's sarcoma has a more typical “onion skin” 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.