Common Childhood Solid Tumors

(Part 2)
 Brain Tumors in Childhood
• 2nd most common malignancy in childhood
and adolescence
• Overall mortality: 4.5%
• Etiology:
• Not well defined
• Familial and hereditary syndromes: 5% of cases
• Cranial exposure too ionizing radiation
 Brain Tumors in Childhood
• Pathogenesis
– 0 – 14 yrs old
• Most common: Pilocytic Astrocytoma (PAs), Medulloblastoma/
PNETs
– Adolescents (15-19 yrs old)
• Most common: Pituitary tumors, PAs
– Location:
• Infratentorial: 43.2%
– 1 – 10 yrs old: Juvenile Pilocytic Astrocytoma and Medulloblastoma
• Supratentorial: 40.9%
– 1st yr of life: Choroid Plexus Tumors and Teratomas
– >10 yrs old: Diffuse Astrocytoma
• Spinal cord: 4.9%
• Multiple sites: 11%
 Brain Tumors in Childhood
• Clinical Manifestation
– Depends on tumor location, tumor type, and age of
the child
– S/Sxs are related to obstruction of CSF drainage paths
leading to increased ICP or focal brain dysfunction
– Classic triad: associated with midline or infratentorial
tumors
• Headache
• Nausea / Vomiting
• Papilledema
 Brain Tumors in Childhood
• Clinical Manifestations
– Infratentorial tumors:
• Disorders of equilibrium, gait and coordination
• Blurred vision, diplopia, nystagmus
– Torticollis: in cerebellar tonsil herniation
– Brainstem tumors:
• Gaze palsy, multiple cranial nerve palsy, upper motor
neuron deficits (hemiparesis, hyperreflexia, clonus)
 Brain Tumors in Childhood
• Clinical Manifestation:
– Supratentorial tumors:
• Motor weakness, sensory changes, speech disorders,
seizures, reflex abnormalities
• Infants: hand preference
– Optic pathway tumors
• Visual disturbance
– Decreased visual acuity
– Marcus Gunn pupil (afferent pupillary defect)
– Nystagmus
– Visual field defects
 Brain Tumors in Childhood
• Clinical Manifestation:
– Suprasellar and third ventricular region tumors
• Neuroendocrine deficits:
– DI, galactorrhea, precocious puberty, delayed puberty,
hypothyroidism
• Infants and young children: Diencephalic Syndrome
– Failure to thrive, emaciation, increased appetite, euphoric
affect
 Brain Tumors in Childhood
• Clinical Manifestation:
– Pineal region tumors
• Parinaud syndrome
– Paresis of upward gaze, pupillary dilatation reactive to
dilatation but not to light, nystagmus to convergence or
retraction, eyelid retraction
– Spinal cord tumors and spinal cord dissemination
• Long nerve tract motor and/or sensory deficits
• Bowel and bladder deficits
• Back or radicular pain
 Brain Tumors in Childhood
• Diagnosis:
– Complete history and PE
– MRI: neuroimaging standard
– Neuroendocrine dysfunction evaluation
– Ophthalmologic evaluation
– Serum and CSF bHCG and AFP
– LP with cytologic evaluation of CSF
 Astrocytoma
• 40% of CNS tumors
• Occur throughout the CNS
• Low Grade Astrocytoma (LGA)
– Predominant group in childhood
– Indolent course
– Pilocytic Astrocytoma
– Fibrillary infiltrating Astocytoma
– Pilomyxoid Astrocytoma
 Astrocytoma
• Pilocytic Astocytoma (WHO grade 1 tumor)
– Most common (20%)
– Occur anywhere in the CNS
• Classic site: cerebellum
– Classic but not exclusive neuroradiologic finding:
• Presence of a contrast medium-enhancing nodule
within the wall of a cystic mass
– Rosenthal fibers
• Microscopic findings help establish the diagnosis
– Low metastatic potential, rarely invasive
 Astrocytoma
• Fibrillary Infiltrating Astocytoma
– 2nd most common
– Characterized by a pattern of diffuse infiltration of
tumor cells among normal neural tissue and
potential for anaplastic progression
– Grouped as:
• Low-grade astrocytoma (WHO grade II
• Malignant Astrocytomas (anaplastic atrocytoma, WHO
grade III)
• Glioblastma multiforme (GBM; WHO grade IV)
 Astrocytoma
• Pilomyxoid Astrocytoma (WHO grade II tumor)
– Most common in the hypothalamic/ Optic chiasm
region
– High risk of local as well as cerebrospinal spread
 Astrocytoma
• Clinical management of LGA
– Multimodal approach
• Surgery as primary treatment
• Radiation therapy and chemotherapy
– Outcome of PA is better than with Fibrillary LGAs
– Radiation therapy: 50-5 Gy given on daily schedule
over 6 weeks
– Chemotherapy approach have permitted delay and
potentially avoidance of radiation therapy
• Carboplatin, Vinblastine, Lomustine, and procarbazine
– Observation: primary approach in biologically indolent
LGAs
 Astrocytoma
• Malignant Astocytoma
– Less common in children and adolescents
– Anaplastic Astocytoma (WHO Grade III)
– GBM (WHO Grade IV)
– Overexpression of p53 is an adverse prognostic factor
– Standard therapy: surgical resection followed by
involved-field radiation therapy
• Oligodendrogliomas
– Rare in children
– Calcified cortical mass on CT in a patient presenting
with seizure
 Ependymal Tumors
• Ependymoma (WHO gradeII)
– Most common
– 70% occur in the posterior fossa
– Mean age: 6 years old
• 40%: <4 years old
– Clinical presentation is insidious, depends on the
anatomic location of the tumor
– Noninvasive, extending into the ventricular lumen
and/ or displacing normal structures, leading to
significant hydrocephalus
 Ependymal Tumors
• Ependymoma
– Histologic characteristics:
• Perivascular pseudorosettes
• Ependymal rosettes
• Monomorphic nuclear morphology
• Nonpalisading foci of necrosis
 Ependymal Tumors
• Other histologic subtypes
– Anaplastic Ependymoma (WHO grade III)
• Less common in childhood
• Characterized by a high mitotic index, microvascular
proliferarion and pseudopalisading necrosis
– Myxopapillary Ependymoma (WHO grade I)
• Slow-growing tumor arising from the filum terminale
and conus medullaris
 Ependymal Tumors
• Surgery is the primary treatment modality
– Extent of surgical resection a major prognostic
factor
• Other major prognostic factors:
– Age: younger children having poorer outcomes
– Tumor location: posterior fossa having poorer
outcomes
• Radiation therapy
• Chemotherapy
 Choroid Plexus Tumors
• 2-4% of childhood CNS tumor
• Most common CNS tumor in children <1 yr of
age and 10-20% of CNS tumors in infants
• Intraventricular epithelial neoplasms arising
from the choroid plexus
• Children presents with signs and symptoms of
increased ICP
• Infants may present with macrocephaly and
focal neurologic deficits
 Choroid Plexus Tumors
• Predominantly occur supratentorially in the
lateral ventricles
• Choroid Plexus Papilloma (WHO grade I): MC
• Choroid Plexus Carcinoma (WHO grade III):
– Malignant tumor with metastatic potential to seed
into the CSF pathways
• Associated with Li-Fraumeni syndrome
• Simian virus 40 (SV40): play an etiologic role in
choroid plexus tumors
• Treatment: Surgery, radiotherapy, chemotherapy
 Embryonal Tumors or Primitive
Neuroectodermal Tumors (PNETs)
• Most common group of malignant CNS tumors
of childhood
• Have potential to metastasize to the neuroaxis
and beyond
 Embryonal Tumors or Primitive
Neuroectodermal Tumors (PNETs)
• Medulloblastoma (90%)
– Cerebellar tumor occurring predominantly in
males
– Median age of 5-7 yr
– Most occur in the midline cerebellar vermis, older
patients in the cerebellar hemisphere
– CT and MRI: solid, homogenous, contrast
medium-enhancing mass in the posterior fossa
causing 4th ventricular obstruction and
hydrocephalus
 Embryonal Tumors or Primitive
Neuroectodermal Tumors (PNETs)
• Medulloblastoma
– Neuronal differentiation is more common among
these tumors
• Homer Wright rosettes
• Immunopositivity for Synaptophysins
– Anaplastic variant: more aggressive, worse
prognosis
– Signs and symptoms of increased ICP and
cerebellar dysfunction
 Embryonal Tumors or Primitive
Neuroectodermal Tumors (PNETs)
• Medulloblastoma
– Prognostic factors:
• Age at diagnosis: <4yr old: poorer outcome
• Extent of disease
– Disseminated disease at diagnosis (M>0), including positive
CSF cytologic result alone (M1): worse outcome
• Extent of surgical resection
– Gross residual disease after surgery: worse outcome
 Embryonal Tumors or Primitive
Neuroectodermal Tumors (PNETs)
• Medulloblastoma
– Multimodal treatment approach
• Sensitive to both radiotherapy and chemotherapy
• RT dose: 50-55 Gy
• <4 yr of age: high-dose chemotherapy with peripheral stem
cell re-infusion, exclude ratiation
– Risk stratification of treatment approach
1. Patient <3 yr of age
2. Standard risk patients >3 yr of age with surgical total
resection and no disease dissemination (M0)
3. High-risk patients >3 yr of age with disease dissemination
(M>0) and/ or bulky residual disease after surgery
 Embryonal Tumors or Primitive
Neuroectodermal Tumors (PNETs)
• Supratentorial primitive neuroectodermal
tumors (SPNETs)
– 2-3% of childhood brain tumors
– Composed of undifferentiated or poorly
differentiated neuroepithelial cells
– Poorer outcome
 Embryonal Tumors or Primitive
Neuroectodermal Tumors (PNETs)
• Atypical Teratoid/ Rhabdoid Tumor
– Very aggressive embryonal malignancy
– Occurs predominantly in children <5yr of age
– Occur at any location in the neuroaxis
– Very poor outcome
 Pineal Parenchymal Tumors
• Most common malignancies after germ cell
tumors that occur in pineal region
• Include Pineoblastoma, Pineocytoma, and
Mixed Pineal Parenchymal Tumors
• Multimodal treatment
Craniopharyngioma (WHO grade I)
• 7-10% of childhood tumors
• Children present with endocrinologic
abnormalities such as growth failure and
delayed sexual maturation
• Visual changes: decrease acuity or visual field
deficits
• Surgery: primary treatment modality
• No role for chemotherapy
 Germ Cell Tumors
• Heterogenous group of tumors that are primarily
tumors of childhood
• Arising predominantly in midline structures of the
pineal and suprasellar regions
• 3-5% of pediatric brain tumors
• Peak incidence: 10-12 yr of age
• Male preponderance, female preponderance for
suprasellar tumors
• Occur multifocally in 5-10% of cases
 Germ Cell Tumors
• Insidious course, subtle initial presenting
symptoms: poor school performance and
behavior problems
• Protein markers: AFP and bHCG
• Multimodal treatment
 Tumors of the Brainstem
• 10-15% of childhood primary CNS tumors
• Outcome depends on
– Tumor location
– Imaging characteristics
– Patient’s clinical status
• Patient presents with motor weakness, cranial
nerve deficits, cerebellar deficits, and/ or signs
of increased ICP
 Tumors of the Brainstem
• Four types
1. Focal (5-10%) Surgery as primary
treatment approach
2. Dorsally exophytic (5-10%)
3. Cervicomedullary (5-10%): RT sensitive
4. Diffuse intrinsic (75-85%) : associated with poor
outcome
• Treatment: RT
 Metastatic Tumors
• ALL and NHL: spread to leptomeninges
causing symptoms of communicating
hydrocephalus
• Chloromas: collection of myeloid leukemia
cells can occur in the neuroaxis
• TXT: RT, intrathecal administration of
chemotherapy, and /or systemic
administration of chemotherapy
 Complications and Long-Term
Management
• 50% will experience chronic problems as a
direct result of their tumors and treatment
– Chronic neurologic deficits
• Focal motor and sensory abnormalities, seizure
disorders, neurocognitive deficits, and neuroendocrine
deficiencies
– Significant risk of secondary malignancies
• Supportive multidisciplinary interventions
RETINOBLASTOMA
 Retinoblastoma
• Embryonal malignancy of the retina
• Most common intraocular tumor in children
• Progresses to metastatic disease and death in
50%
• Account for 4% of all pediatric malignancy
• Median age at diagnosis: 2 yr
– 90% diagnosed in children under 5yr of age
 Retinoblastomma
• Bilateral involvement is more common under
the age of 1 yr
• Either hereditary or sporadic
– Hereditary: diagnosed at a younger age,
multifocal, bilateral
• Associated with loss of function of the retinoblastoma
gene (RB1) via gene mutation or deletion
– RB1 gene in chromosome 13q14
– Encodes Rb protein: tumor suppressor protein, role in
apoptosis and cell differentiation
– Sporadic: diagnosed in older children, unilateral,
unifocal involvement
 Retinoblastoma
• Appears as a small round blue cell tumor with
rosette formation (Flexner-Wintersteiner
Rosettes)
• Endophytic tumors
– Arise from the inner surface of the retina and
grow into the vitreous
– Can grow as tumors suspended within the
vitreous itself: Vitreous seeding
• Exophytic tumors
– Grow from the outer retinal layer
– Can cause retinal detachment
 Retinoblastoma
• Clinical Manifestations:
– Leukocoria: white pupillary reflex
• First noticed when a red reflex is not present at a
routine newborn or well child examination or in a flash
photography of the child
– Strabismus
– Orbital inflammation, hyphema, pupil irregularity
– Pain if with secondary glaucoma
 Retinoblastoma
• Diagnosis
– Established by the characteristic ophthalmologic
findings
– Imaging studies are not diagnostic
– Biopsies are contraindicated
– Indirect ophthalmoscopy with slit-lamp evaluation
– Orbital ultrasonography, CT, or MRI: evaluate
extent of intraocular disease and extraocular
spread
– Trilateral Retinoblastoma: pineal area tumor in a
child with hereditary Rb
 Retinoblastoma
• Treatment
– Determined by the size and location of the tumors
– Primary goal of treatment: CURE
– Secondary goal of treatment: PRESERVING VISION
AND THE EYE ITSELF
– Enucleation
– Bilateral disease: chemoreduction in combination
with focal therapy (laser photocoagulation or
cryotherapy)
 Retinoblastoma
• Treatment
– Multiagent chemotherapy: Vinblastine,
Carboplatin, Etoposide
– External Beam Irradiation
– Brachytherapy or episcleral plaque radiotherapy
– 1st-degree relatives of hereditary RB patient
• Retinal examination to identify retinomas or retinal
scars
GONADAL AND GERM CELL
NEOPLASMS
 Epidemiology
• Rare
• Most malignant tumors of the gonads in children are
GCTs
• Saccrococygeal tumors: occur predominantly in infant
girls
• Testicular GCTs: occur predominantly before age 4 yr
and after puberty
• Klienfelter SY: increased risk of Mediastinal GCT
• Down SY, undescended testes, infertility, testicular
atrophy and inguinal hernias: increased risk of
tescticular CA
 Pathogenesis
• GCTs and non-GCTs arise from primordial
germ cells and coelomic epithelium,
respectively
 Clinical Manifestation and Diagnosis
• Depends on location of tumor
• Extragonadal GCTs occur in the midline
– Suprasellar region, pineal region, neck,
mediastinum, retroperitoneal and sacrococcygeal
areas
• Intracranial GCTs often present with anterior
and posterior pituitary defects
 Clinical Manifestation and Diagnosis
• Serum α-fetoprotein (AFP)
– Elevated with endodermal sinus tumors, minimally
elevated with teratomas
• Human chorionic gonadotropin (β-hCG)
– Secreted by syncytiotrophoblasts
– Seen in choriocarcinoma and germinomas
• Lactate Dehydrogenase (LDH)
– If elevated, provide important confirmation of the
diagnosis
– Provide means to monitor the patient for tumor
response and recurrence
 Clinical Manifestation and Diagnosis
• Other diagnostics
– Plain radiographs of the chest
– Ultrasound of the abdomen
– CT or MRI
– Preoperative staging with CT of the chest and
bone scan
– Pelvic washings
– Intracranial lesions: Serum and CSF AFP and bHCG
 Clinical Manifestation and Diagnosis
• Gonadoblastomas
– Occur in patients with gonadal dysgenesis and all
parts of a Y chromosome
• Gonadal dysgenesis: failure to fully masculinize the
external genitalia
• Imaging of the gonad with ultrasonography or CT
• Surgical resection is usually curative
• Prophylactic resection of dysgenetic gonads is
recommended
– Produce abnormal amount of estrogen
 Clinical Manifestation and Diagnosis
• Teratomas
– Occur in many locations
– Not associated with elevated markers unless
malignancy is present
– Sacrococcygeal site is the most common site
– Occur most commonly in infants
– May be diagnosed in utero or at birth, most found
in girls
 Clinical Manifestation and Diagnosis
• Germinomas
– Occur intracranially, in the mediastinum, in the
gonads
– Ovary: dysgerminomas
– Testis: seminomas
– Tumor marker negative despite being malignant
– Endodermal Sinus Tumor, yolk sac tumor,
choriocarcinoma: highly malignant
 Clinical Manifestation and Diagnosis
• Non-germ cell gonadal tumors
– Uncommon
– Occur predominantly in the ovary
– Epithelial carcinoma, Sertoli-Leydig cell tumors,
granulosa cell tumors may occur in children
 Treatment
• Complete surgical excision
• Intracranial tumors: RT and chemotherapy
• Testicular tumor: inguinal approach,
preoperative chemotherapy
• Overall cure rate: >80%
• Age is the most important predictive factor of
survival
THANK YOU!