BRAIN TUMOR/TESTICULAR CANCER
From 35th Annual Pediatric Trends, presented by Johns Hopkins Children’s Center, Baltimore, MD
| PEDIATRIC BRAIN TUMOR —Kenneth J. Cohen, MD, MBA, Associate Professor of Oncology and Pediatrics,
Johns Hopkins University School of Medicine, Baltimore
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| Background: brain tumors second most common pediatric cancer (most common group of solid neoplasms);
2500 to 3000 new diagnoses each year; 5-yr survival ≈70% (cure rate ≈60%); according to Surveillance, Epidemiology,
and End Results (SEER) database, prognosis much better for patients 0 to 20 yr of age than for
those >21 yr
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 | Reasons for better survival among children: low-grade tumors with good prognoses account for largest single
group of pediatric brain tumors; adults more likely to develop more lethal tumors, such as high-grade astrocytomas
(but more children die of brain tumors than any other cancer, due to frequency of occurrence)
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| Tumor classification: neuroglia, neurons, and microglia main cell types from which brain tumors arise; microglial
tumors rare in children
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| Gliomas: astrocytomas (pilocytic [most common brain tumors in children]); fibrillary (infiltrating or diffuse); diagnosis
often depends on pathologist’s judgment
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| Grading according to World Health Organization (WHO): WHO 1 (low grade)—pilocytic; WHO 2—low-grade
fibrillary; WHO 3—anaplastic astrocytoma; WHO 4—glioblastoma multiforme; assignment of nomenclature
challenging and often subjective
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| Topographic classification: primitive neuroectodermal tumor (PNET) of pineal region—pineoblastoma; PNET
of cerebellum—medulloblastoma; PNET of cerebrum—supratentorial PNET; similar histology, but prognosis
and natural history depend on tumor location (medulloblastoma has best prognosis; topography may be
more important than histology for predicting outcomes)
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| Signs and symptoms: depend on whether mass lesion above or below tentorium (supratentorial, infratentorial)
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| Infratentorium: includes posterior fossa (cerebellum), brain stem, region of 4th ventricle, and spinal cord; most pediatric
brain tumors infratentorial (incidence ≈50% in infants <1 yr of age)
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| Supratentorium: everything else; accounts for “vast majority” of adult brain tumors and ≈50% of those in infants
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| Presentation of pediatric infratentorial brain tumors: general nonlocalizing symptoms—headache, vomiting, behavioral
changes (listlessness), developmental delay, and weight changes; may be subtle; diagnosis often delayed,
especially with low-grade tumor; increased intracranial pressure—does not occur in all patients; usually
caused by obstructive hydrocephalus; symptoms include headache, irritability, vomiting, lethargy, bulging fontanelle,
or separation of sutures; papilledema; Parinaud’s syndrome (“setting sun” sign; child cannot look above
horizon; suggests pressure on midbrain); ataxia, unequal pupils, and head tilt (resolve when pressure relieved);
localizing signs—depend on tumor location; since most pediatric tumors infratentorial, cranial neuropathies
common due to proximity to cranial nerves; hemiparesis rare but localizing; ataxia; early handedness or change
in handedness (sign of hemiparesis); early rolling (also sign of hemiparesis); seizures (potentially localizing, but
rarely related to brain tumors in pediatric patients)
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| Headaches: most common brain tumor symptom (in children >1 yr of age); often associated with vomiting, due to
increased intracranial pressure or proximity to vomiting center of brain; location alone no clue to diagnosis;
headache upon awakening common but intermittent; in 80% to 85% of cases, abnormal physical findings occur
within 4 to 6 wk of headache onset; usually neurologic or ocular in nature; document neurologic and ocular examinations
(actual or attempted); papilledema—often difficult to discern, especially in dark-skinned children;
can rule out if vein crossing optic nerve pulsates; difficulty seeing vein on top of optic nerve suggests papilledema;
ocular examination essential if brain tumor suspected; referral to specialist reasonable
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| Indications for scan: headaches and neurologic and/or ocular findings; unexplained vomiting; change in character of
headaches; suspicious timing of headaches; other unexplained findings (diabetes insipidus, localized headaches
in very young child, genetic predisposition [neurofibromatosis type 1])
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| Type of scan: computed tomography good for initial screening; shows hydrocephalus, hemorrhage, and tumors
not isodense to brain; misses low-grade lesions
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| Seizures: rare as presenting symptom (<1% of new-onset pediatric seizures caused by mass lesion); usually associated
with supratentorial tumors; thus, more common in older children and adults
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| Treatment: surgery and radiation therapy most common; use of chemotherapy growing
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| Neurosurgeon’s role: diagnosis; tumor resection whenever possible; debulking; biopsy; placement of shunts, Ommaya
reservoirs, and other supportive measures
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| Radiation therapy: eliminates virtually every tumor type, but has serious neurodevelopmental effects, especially
when administered for craniospinal prophylaxis; whole-brain irradiation of child <5 yr of age has irrevocable
(“potentially devastating”) impact on intellect; child will need special attention, remedial classes, probably never
hold more than menial job, and may be unable to live independently
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| Chemotherapy: in children, currently used mostly as adjuvant therapy; germ cell tumors, medulloblastomas “exquisitely
sensitive” (outcomes dramatically improved due to chemotherapy); blood-brain barrier potential challenge;
considered more often in younger children, due to devastating effects of radiation therapy; hundreds of
new agents available; drawbacks include substantial long-term toxicity
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| Future directions: ongoing improvement of imaging techniques; minimizing adverse effects of irradiation; overcoming
blood-brain barrier; new types of chemotherapeutics, including immunotherapeutics; gene therapies; antiangiogenic
therapies
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| TESTICULAR CANCER SCREENING GUIDELINES FOR ADOLESCENTS —Arik V. Marcell, MD, MPH, Assistant
Professor of Pediatrics, Johns Hopkins University School of Medicine
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| Epidemiology: one of most common solid tumors in young men; most cases occur between 25 and 35 yr of age; accounts
for ≈1% of all malignant tumors in men; incidence increasing from 3.35 cases per 100,000 men (1973) to
4.84 cases per 100,000 men (1998); 7600 cases diagnosed annually, compared to 180,000 cases of lung cancer and
210,000 cases of prostate cancer diagnosed in men each year; responsible for ≈300 deaths per year; mortality declining
since 1970s, despite increasing incidence
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| Tumor types and prognosis: germ cell tumors comprise ≈95%
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| Types of germ cell tumors: seminoma—accounts for ≈50% of cases; peaks in fourth decade of life; presentation
usually localized; nonseminoma—accounts for remaining 50%; peaks in third decade of life; usually metastatic
in presentation
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| Prognosis: excellent; 5-yr survival has increased from 60% in 1970s to 90% within last decade
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| Screening guidelines: organizations that inform screening guidelines for pediatric and adolescent health care include
American Academy of Pediatrics/Maternal and Child Health Bureau (Bright Futures campaign), American
Medical Association Guidelines for Adolescent Preventive Services (GAPS), United States Preventive Services
Task Force (USPSTF), American Academy of Family Physicians (AAFP), and American Cancer Society; GAPS
recommends against screening, but Bright Futures and American Cancer Society recommend screening as part of
routine examination; USPSTF guidelines updated in 2004 from I (insufficient evidence on routine screening) to D
(recommendation against screening); AAFP defers its recommendations to those of USPSTF
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| Teaching of testicular self-examination: no specific comment from GAPS; recommended by Bright Futures; American
Cancer Society recommends for high-risk males; USPSTF and AAFP changed recommendation from I to D
(recommendation against teaching self-examination); overall trend to recommend against teaching self-examination
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| USPSTF 2004 statement: recommends against routine screening of asymptomatic men for testicular cancer; also
does not recommend screening of men at increased risk; notes that patients who present with symptoms of testicular
cancer frequently diagnosed with epididymitis, testicular trauma, hydrocele, or other benign conditions;
in speaker’s opinion, when young man presents with genital complaint, genital-testicular examination important;
consider testicular cancer as part of differential diagnosis
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| Rationale behind USPSTF statement: change in method of grading evidence; no new evidence, but also no studies
showing reduced mortality from screening with clinical examination and testicular self-examination; in absence
of screening, current treatments provide favorable health outcomes; harms of screening exceed potential
benefits, given low prevalence of testicular cancer and limited accuracy of screening tests; no evidence for incremental
benefits of screening; no studies address harms of screening
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| Determining strength of recommendation: quality of investigations; magnitude and consistency of findings; relative
value placed on outcomes; USPSTF utilizes 3 components to evaluate quality of evidence (individual
studies; body of evidence for each key question; collected evidence for entire issue)
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| Reasons for genital examination: screen for sexually transmitted disease if patient sexually active; evaluate and
document progress of development through Tanner staging; screen for genetic conditions such as Klinefelter’s syndrome;
identify structural anomalies, especially those that might affect future fertility (varicocele, spermatocele, hydrocele,
meatal abnormalities [hypospadias], and signs of testicular trauma); evaluate issues related to
uncircumcised penis (eg, phimosis, paraphimosis); opportunity to address hygiene; check for problems with hair
and skin (eg, folliculitis, tinea); identification of absent testes; identification of testicular atrophy due to central
cause, chronic abuse of steroids, or marijuana; reassurance from normal findings; give patient better understanding
of his body
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| Timing of examination: start in infancy; continue to examine and document findings as child develops; document
at least once during puberty if possible; with new, prepubertal patient, obtain baseline, then examine at least once
through puberty; if new patient peripubertal or postpubertal, obtain baseline examination to ascertain normal progression
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| Risk factors for testicular cancer: white ethnicity (risk 4-5 times higher than in other groups); cryptorchidism (increases
risk 2-4 times); testicular atrophy and dysgenesis; testicular trauma (may increase mitotic activity in already
malignant testicle, or raise patient’s awareness of previously unrecognized abnormality); genetic
predisposition; diet (high intake of fat, especially from dairy products, thought by some to increase risk for testicular
cancer); maternal factors; birth order (some suggestion that risk higher among firstborn sons); personal
factors (older age; birth month [diagnosis peaks in men born in August]); HIV infection (increases risk for
seminoma, possibly due to highly active antiretroviral therapy); Klinefelter’s syndrome (associated with increased
risk for mediastinal germ cell tumors)
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| Protective factors: later onset of puberty; high androgen levels
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Suggested Reading
Kanto S et al: Clinical features of testicular tumors in children. Int J Urol 11:890, 2004; Micklewright JL et al:
Attention and memory in children with brain tumors. Child Neuropsychol 13:522, 2007; Nasrallah P et al: Testicular
health awareness in pubertal males. J Urol 164:1115, 2000; Partap S, Fisher PG: Update on new treatments
and developments in childhood brain tumors. Curr Opin Pediatr 19:670, 2007; Pytel P: Spectrum of pediatric gliomas:
implications for the development of future therapies. Expert Rev Anticancer Ther 7(12 Suppl):S51, 2007; Reulecke
BC et al: Brain tumors in children: initial symptoms and their influence on the time span between symptom
onset and diagnosis. J Child Neurol 23:178, 2008; Schlatter M et al: Excellent outcome in patients with stage I
germ cell tumors of the testes: a study of the Children’s Cancer Group/Pediatric Oncology Group. J Pediatr Surg
38:319, 2003; Stargatt R et al: Multiple factors contribute to neuropsychological outcome in children with posterior
fossa tumors. Dev Neuropsychol 32:729, 2007; U.S. Preventive Services Task Force: Screening for testicular
cancer: update of the evidence for the U.S. Preventive Services Task Force. Agency for Healthcare Research and
Quality, 2004. Available at http://www.preventiveservices.ahrq.gov.
Educational Objectives
| The goal of this program is to improve management of pediatric brain tumors and testicular cancer. After hearing
and assimilating this program, the clinician will be better able to:
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| 1. Recognize the presenting symptoms of brain tumors in children.
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| 2. Explain the relationship between headaches, seizures, and brain tumors.
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| 3. Describe the epidemiology of pediatric brain and testicular tumors.
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| 4. Recognize the risk factors for testicular cancer in children and adolescents.
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| 5. Discuss the importance of a genital examination as part of the office visit for male adolescent.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and planning committee
members to disclose relevant financial relationships within the past 12 months that might create any personal conflicts
of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in
health care and not a proprietary business or commercial interest. For this program, the faculty and planning committee
reported nothing to disclose.
Acknowledgements
Drs. Cohen and Marcell were recorded at 35th Annual Pediatric Trends, held April 16-20, 2007, in Baltimore, MD,
and sponsored by the Johns Hopkins Children’s Center, Johns Hopkins University School of Medicine. The Audio-
Digest Foundation thanks the speakers and the sponsor for their cooperation in the production of this program.
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