2022 5.4b.

Childhood Malignancy (Part 2)

DR. MELANIE VICTORIA G. DAR | 05/07/2021
PEDIATRICS II

OUTLINE Treatment
E. Rhabdomyosarcoma H. Brain Tumors in Childhood • Local control management: SURGERY
F. Ewing Sarcoma I. Retinoblastoma − Fastest way to remove the disease
G. Osteosarcoma J. Gonadal and Germ Cell − Best prognosis: completely resected tumors
Neoplasms ○ Even with complete excision of the mass, we would still need to
have your other treatment modalities (radiotherapy &
chemotherapy)
• Local control management: Radiation therapy
LEGEND − Effective in achieving local control for patients with microscopic or
Remember Lecturer Book Previous Trans Presentation gross residual disease
HELLO − Given over 5-6 weeks, after 1-3 months of chemotherapy
• Chemotherapy
E. RHABDOMYOSARCOMA − Low risk: Vincristine, Actinomycin
• Most common soft tissue sarcoma − Intermediate risk (Embryonal type): Vincristine, Actinomycin,
• 75% occur in children below 10 years old Cyclophosphamide
• Peak incidence: between 3-5 years old − High risk: Vincristine, Actinomycin, Cyclophosphamide (VAC)
• 2nd peak: adolescence
• Tumor site F. EWING SARCOMA
− Head and neck (40%): most common in younger than 8 years • 2nd most common primary bone malignancy
○ Orbital tumors: almost always of the embryonal subtype • More common in males
− Genitourinary tract (20%) • Usually occurs in the second decade of life
− Extremities (20%): more common in adolescents, usually alveolar • Manifests as a continuum of neurogenic differentiation
subtype
Clinical manifestation
Histology • Pain: most common symptom
• 4 general subtypes − Intermittent with different intensities
1.Botryoid and spindle cell RMS − Often does not completely disappear during the night
 Variants of embryonal RMS ○ To differentiate this with growing pains, if this occurs in younger
 Occur infrequently children
 Best prognosis − Usually followed by a mass
 LOH at chromosome 11p15 locus • Red flags
2. Embryonal RMS (ERMS) 1.Pain without defined trauma lasting more than a month that
 Intermediate prognosis continues at night
3. Alveolar RMS (ARMS) 2. A visible swelling that follows soon afterward
 Poorest prognosis • Mostly occur in the bone (flat bones of the axial skeleton)
 Associated with chromosome 13 translocation − Long bones: arise from the diaphyseal part
4. Undifferentiated sarcoma − 3 most common sites
 prognosis is in between embryonal and alveolar RMS ○ Pelvis (26%)
○ Femur (10%)
Clinical Manifestation ○ Chest wall (16%)
− Presenting symptoms depend on the area of the tumor • Metastasis
○ Head and neck − Lungs, bone, bone marrow
 Nasal congestion, nasal discharge, CN palsies, headache,
vomiting, systemic hypertension Diagnosis
○ Bladder tumors • Serum studies
 Hematuria, urinary obstruction, extrusion of
− Elevated ESR, moderate anemia, elevate WBC count, elevated
mucosanguineous tissue
LDH
○ Prostate tumors
• Imaging
 Large pelvic masses, occasional constipation
− Radiograph of the bone
○ Uterine RMS
○ Malignant bone tumor
 Common in older girls
1.Tumor-related osteolysis
 Present with uterine mass
 Initial presenting symptom: mucosanguineous discharge 2.Detachment of the periosteum from the bone (Codman
triangle)
○ Paratesticular tumors
3. Spiculae of calcification in the soft tissue tumor masses
 Painless, unilateral scrotal or inguinal enlargement
○ Diaphyseal location
○ Extremities
 Soft tissue mass, regional LN are affected in half of the cases − MRI
• Histology and immunopathology
− Definitive diagnosis: BIOPSY
Diagnosis
− Plain film of affected area Treatment
− CT scan: allow to assess the volume at risk for tumor spread
− Ultrasound: useful for serial assessment of pelvic tumors − Chemotherapy followed by surgery and/or radiation therapy
− MRI: ideal imaging for head and neck, extremity, and pelvis − Prognosis
− Biopsy: establish the diagnosis ○ Overall 5-year EFS rate: 60-70%
○ Patient with metastasis: 5-year EFS 20-30%
− Pulmonary and metastases to the marrow
○ Chest CT
○ BM biopsy
− Bone scan
○ In some cases, we would require it as a part of staging

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 2022 5.4b. Childhood Malignancy (Part 2)
DR. MELANIE VICTORIA G. DAR | 05/07/2021
PEDIATRICS II

G. OSTEOSARCOMA Clinical Presentation

• Bimodal age distribution • Nonspecific symptoms
• Peak age coincides with a period of rapid bone growth • High index of suspicion
• Taller individuals and those with earlier pubertal growth spurts are • Pain: most common and first symptom (90%)
at higher risk − If at osseous site other that primary tumor may represent metastatic
− Related to polymorphisms in growth related genes with an involvement
association with a Vitamin D receptor polymorphism • Tumor-related swelling (50%) and loss of function of adjacent
• Metaphyses of the most rapidly growing bone joints (45%)
− To differentiate with Ewing Sarcoma, ES affects the diaphyseal • Pathologic fracture (8%)
part of the bone • Most common metastatic site: lungs
− Distal femur, proximal humerus, proximal tibia − Systemic symptoms: fever, weight loss, and malaise
− Lag time: 2-4 months
Pathology − 2nd most frequent site of metastasis: distant bone
• Histologic diagnosis − Skip metastases (MRI): isolated tumor foci within the same bone
− malignant tumor characterized as the primary tumor
by production of osteoid by
the neoplastic cells in
association with a malignant
spindle cell
• Hallmark: production of osteoid

WHO classification of Osteosarcoma

• Conventional
− Osteoblastic
− Chondroblastic
− Fibroblastic
• Telangiectic • Massive swelling caused by a large osteosarcoma of the left distal
femur in a 15-year old male
• Small Cell
− Some of them would be painful
• Low grade central
− Showing asymmetry of the other leg
• Secondary
• Parasteal
• Periosteal Evaluation: Clinical
• High-grade • History and PE
− Determining the extent and duration of physical symptoms,
associated physical limitations
− Pain and swelling (lasting 2-6 months)
− Soft tissue mass at the site of primary tumor
− Redness and warmth
− Regional or distant LN spread
− Most important prognostic factor: presence of metastatic disease
(lungs)

Evaluation: Laboratory
• Alkaline Phosphatase (ALP): elevated correlate with an increase
likelihood for recurrence
• Lactate Dehydrogenase (LDH): elevated
− Before chemotherapy labs: CBC, Serum electrolytes, Magnesium,
Phosphate, renal function test, Creatinine, Creatinine clearance,
liver function tests, coagulation profile, test for hepatitis and
HIV infection

Evaluation: Radiologic
• Use to determine extent of local disease, metastasis and response to
treatment
• Conventional radiograph, MRI, CT scan FDG PET/CT, Dynamic
contrast enhanced MRI
− MRI better than CT

• The most common affected area is the humerus. Other parts that
would be affected are the clavicle, scapula, rib, spine, ulna, radius,
pelvis, hand, femur, tibia, fibular and foot
• I have seen 1 case where the orbital or occipital bones are affected,
however, it is very rare

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DR. MELANIE VICTORIA G. DAR | 05/07/2021
PEDIATRICS II

Conventional radiograph Classification and Staging

FIGURE 34.3. Conventional
radiograph shows mixed lytic and MUSCULOSKELETEL TUMOR SOCIETY(MSTS) CLASSIFICATION AND
sclerotic lesion with osteoid STAGING
matrix and Codman triangle Stage T N M Grade
involving the proximal tibia Stage 1A T1 N0 M0 Low grade
• Mixed sclerotic and lucent Stage 1B T2 N0 M0 low grade
metaphyseal lesion with fluffy, Stage 11A T1 N0 M0 High grade
cloud-like calcific opacities
Stage 11B T2 N0 M0 High grade
(osteoid matrix production)
• Codman triangle: soft tissue Stage 111 T3 N0 M0 Any grade
mass breaking through the Stage 1VA Any T N0 M1a Any grade
overlying ossified periosteal Stage 1VB Any T N1 any M Any grade
new bone Any T ANY N Any M Any grade
• Tumors in the diaphysis: onion- • Recognizes tumor extent and malignant potential
skin periosteal reaction • Intra (T1) or extracompartmental (T2), low grade (A) or high grade (B),
metastatic (T3)
CT scan or MRI
• Determine the extent of the tumor within the bone SIXTH EDITION OF UICC TNN CLASSIFICATION OF MALIGNANT
• Assess the relationship of the tumor to the nearby neurovascular TUMORS
bundle, muscles and joints T.N.M Definition
• Equally accurate for local staging Tx Primary tumor cannot be assessed
• MRI: imaging study of choice for evaluation of the primary tumor
• CT: imaging study of choice to detect lung metastasis T0 No evidence of primary tumor
T1 Tumor < 8cm
T2 Tumor > 8cm
T3 Discontinuous tumors in the primary bone
Nx Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
Mx Distant metastases cannot be assessed
M0 No distant metastases
M1 Distant metastases

• Lung metastases are typically round or ovoid, sharply marginated M1a Lung
• Lung periphery M1b Other distant sites
• > 5 mm, multiple nodules are likely metastases
• More advanced (grade of malignancy and local tumor extent)
• Distinguishes between smaller and larger primary tumors and allows
Bone Scintigraphy (Technetium-99mmethlenediphosphonate (MDP))
description of skip metastases
• Assess bone metastases and skip lesions
• Distinguish between pulmonary (M1a) and extrapulmonary (M1b)
distant metastases
Thallium-201
• Evaluates tumor response to chemotherapy
Treatment: Surgical Management
DCE-MRI • Goal: perform a complete, en bloc removal of the lesion with
• Provides information on tissue vascularization and perfusion, adequate margins
capillary permeability, interstitial space • Limb-sparing surgery in combination with improved neoadjuvant
• Assess tumor response and disease prognosis therapy: standard approach to obtain local control rates

FDG-PET and PET/CT
• Detection of bone metastases, lung metastases, assessment of
tumor response and detection of recurrent disease
Evaluation: Biopsy
• Incisional (needle and open) and excisional biopsy
• If a malignant bone tumor is suspected, an excisional biopsy is rarely
utilized.
− Tumor is often large at presentation and neoadjuvant therapy is
usually appropriate prior to definitive resection
• At the time of biopsy, the surgeon must be familiar with orthopedic
oncologic principles of flap development, coverage and even
amputation when definitive limb salvage is the proposed plan
Indications for Limb Salvage versus Amputation Surgery
• Limb-sparing surgery results in a local recurrence rate of 5-10%
• Noncontiguous disease (skip lesions) proximal to the main tumor can
result in recurrence within the stump in up to 20% of cases
• The decision to amputate is a complex one and must involve the
entire team of health care providers
− Age of the patient, location of the tumor, presence or absence of
pathologic fracture, and the desires of the patient and family must
be considered carefully
○ Most of the patients are in their childhood years so complete
amputation will have a psychological effect
 One patient was referred to the psychology department
because of the thought of amputating her leg caused her
depression
○ Location is to know the extent of the amputation
○ Before doing complete amputation, you have to have a family
conference so that everybody would understand well the
consequences of the procedure

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 2022 5.4b. Childhood Malignancy (Part 2)
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PEDIATRICS II

Adjuvant Treatment • Adolescents (15-19 years old)

− Most common: Pituitary tumors, Pilocytic Astrocytomas (PAs)
• The administration of chemotherapy allowed extra time for
• Location:
construction of prosthetic devices and theoretical advantage of
− Infratentorial: 43.2%
treating presumed micrometastatic disease
○ 1 – 10 yrs old: Juvenile Pilocytic Astrocytoma and
• Most active agents: Cisplatin, Doxorubicin, High-dose Methotrexate
Medulloblastoma
• Others: Ifosfamide and Etoposide
− Supratentorial: 40.9%
• Most published protocols are based upon Doxorubicin and/or HD-
○ 1st yr of life: Choroid Plexus Tumors and Teratomas
MTX, combined with Cisplatin and/or Ifosfamide and other drugs
○ >10 yrs old: Diffuse Astrocytoma
• Most protocols from Europe and elsewhere have included preoperative
− Spinal cord: 4.9%
(neoadjuvant) chemotherapy, followed by surgery of the primary
− Multiple sites: 11%
tumor and post-operative (adjuvant) chemotherapy

Treatment of Metastatic Osteosarcoma at Presentation Clinical Manifestation

• Depends on tumor location, tumor type, and age of the child
• 15-20%
• S/Sxs are related to obstruction of CSF drainage paths leading to
• Worse prognosis
increased ICP or focal brain dysfunction
• Methotrexate, Doxorubicin, and Cisplatin (MAP) plus IFO and
• Classic triad: associated with midline or infratentorial tumors
Etoposide
− Headache
• Surgery
○ Characterized as occurring most upon waking up and relieved
• Radiation (for local control)
by vomiting
• Open thoracotomy for lung metastases
− Nausea / Vomiting
− Papilledema
Treatment of Relapse • Infratentorial tumors:
• Most common site of disease recurrence remains the lungs (20-30%) − Disorders of equilibrium, gait and coordination
• Most important factor predicting outcome was complete surgical − Blurred vision, diplopia, nystagmus
resection • Torticollis: in cerebellar tonsil herniation
• Brainstem tumors:
Long-Term Outcome − Gaze palsy, multiple cranial nerve palsy, upper motor neuron
deficits (hemiparesis, hyperreflexia, clonus)
• Patients with localized, resectable osteosarcoma has 3-year disease-
• Supratentorial tumors:
free survival rate of 60-70%
− Motor weakness, sensory changes, speech disorders, seizures,
• This would also depend on the presentation of necrosis when you do
reflex abnormalities
your biopsy especially for patients who underwent neoadjuvant
chemotherapy and local control (surgery) in the middle and then − Infants: hand preference
continuation of chemotherapy • Optic pathway tumors
• It really matters most how many percent of cases are included to − Visual disturbance
predict the good prognosis of the patient ○ Decreased visual acuity
• Therapy-related complications ○ Marcus Gunn pupil (afferent pupillary defect)
− Anthracycline-induced cardiomyopathy ○ Nystagmus
○ Request baseline 2D-Echo ○ Visual field defects
− Hearing loss • Suprasellar and third ventricular region tumors
○ Caused by cisplatin − Neuroendocrine deficits:
− Kidney dysfunction ○ Diabetes Insipidus (DI), galactorrhea, precocious puberty,
○ Caused by methotrexate and cisplatin delayed puberty, hypothyroidism
− Second malignancies − Infants and young children: Diencephalic Syndrome
○ Because of the high doses of the medication ○ Failure to thrive, emaciation, increased appetite, euphoric affect
− Sterility • Pineal region tumors
− Parinaud syndrome
○ Paresis of upward gaze, pupillary dilatation reactive to dilatation
Follow-up Studies but not to light, nystagmus to convergence or retraction, eyelid
1.CT scan of the chest q 3 months x 2 years after completion of retraction
chemotherapy; then q 6 months x 1 year, then q year x 2 years − Spinal cord tumors and spinal cord dissemination
2. Chest radiography yearly for 5 years starting after the last CT of the ○ Long nerve tract motor and/or sensory deficits
chest ○ Bowel and bladder deficits
3. Evaluation of the primary site q 3 months x 2 years after completion ○ Back or radicular pain
of therapy; then q 6 months x 3 years, then q year x 5 years
Diagnosis
H. BRAIN TUMORS IN CHILDHOOD
• Complete history and PE
• 2nd most common malignancy in childhood and adolescence
• MRI: neuroimaging standard
• Overall mortality: 4.5%
• Neuroendocrine dysfunction evaluation
• Ophthalmologic evaluation
Etiology • Serum and CSF bHCG and AFP (in ruling out germ cell tumors that is
• Not well defined extragonadal)
• Familial and hereditary syndromes: 5% of cases • Lumbar puncture (LP) with cytologic evaluation of CSF
• Cranial exposure to ionizing radiation
1. ASTROCYTOMA
Pathogenesis • Most common CNS tumor
• 0 – 14 years old • 40% of CNS tumors
− Most common: Pilocytic Astrocytoma (PAs), Medulloblastoma/ • Occur throughout the CNS
PNETs

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PEDIATRICS II

• Low Grade Astrocytoma (LGA) Histologic characteristics:

− Predominant group in childhood
• Perivascular pseudorosettes
− Indolent course
• Ependymal rosettes
− Examples:
• Monomorphic nuclear morphology
○ Pilocytic Astrocytoma
○ Fibrillary infiltrating Astocytoma • Nonpalisading foci of necrosis
○ Pilomyxoid Astrocytoma
Other histologic subtypes
PILOCYTIC ASTROCYTOMA (WHO GRADE 1 TUMOR) • Anaplastic Ependymoma (WHO grade III)
• Most common (20%) − Less common in childhood
• Occur anywhere in the CNS − Characterized by a high mitotic index, microvascular proliferation
− Classic site: cerebellum and pseudopalisading necrosis
• Classic but not exclusive neuroradiologic finding: • Myxopapillary Ependymoma (WHO grade I)
− Presence of a contrast medium-enhancing nodule within the wall − Slow-growing tumor arising from the filum terminale and conus
of a cystic mass medullaris
• Rosenthal fibers
− Microscopic findings help establish the diagnosis Treatment
• Low metastatic potential, rarely invasive • Surgery is the primary treatment modality
− Extent of surgical resection a major prognostic factor
FIBRILLARY INFILTRATING ASTROCYTOMA • Other major prognostic factors:
• 2nd most common − Age: younger children having poorer outcomes
• Characterized by a pattern of diffuse infiltration of tumor cells − Tumor location: posterior fossa having poorer outcomes
among normal neural tissue and potential for anaplastic progression • Radiation therapy
• Grouped as: • Chemotherapy
− Low-grade astrocytoma (WHO grade II)
− Malignant Astrocytomas (anaplastic astrocytoma, WHO grade III)
4. CHOROID PLEXUS TUMORS
− Glioblastoma multiforme (GBM; WHO grade IV)
• 2-4% of childhood CNS tumor
• Most common CNS tumor in children <1 yr of age and 10-20% of CNS
PILOMYXOID ASTROCYTOMA (WHO GRADE II TUMOR) tumors in infants
• Most common in the hypothalamic/ Optic chiasm region • Intraventricular epithelial neoplasms arising from the choroid
• High risk of local as well as cerebrospinal spread plexus
• Children presents with signs and symptoms of increased ICP
Clinical management of LGA • Infants may present with macrocephaly and focal neurologic deficits
• Multimodal approach • Predominantly occur supratentorially in the lateral ventricles
− Surgery as primary treatment • Choroid Plexus Papilloma (WHO grade I): Most common
− Radiation therapy and chemotherapy • Choroid Plexus Carcinoma (WHO grade III):
• Outcome of PA is better than with Fibrillary LGAs − Malignant tumor with metastatic potential to seed into the CSF
• Radiation therapy: 50-55 Gy given on daily schedule over 6 weeks pathways
• Chemotherapy approach have permitted delay and potentially • Associated with Li-Fraumeni syndrome
avoidance of radiation therapy • Simian virus 40 (SV40): play an etiologic role in choroid plexus tumors
− Carboplatin, Vinblastine, Lomustine, and procarbazine • Treatment: Surgery, radiotherapy, chemotherapy
• Observation: primary approach in biologically indolent LGAs
5. EMBRYONAL TUMORS OR PRIMITIVE NEUROECTODERMAL
MALIGNANT ASTROCYTOMA TUMORS (PNETS)
• Less common in children and adolescents • Most common group of malignant CNS tumors of childhood
• Anaplastic Astrocytoma (WHO Grade III) • Have potential to metastasize to the neuroaxis and beyond
• Glioblastoma multiforme (GBM) (WHO Grade IV)
• Overexpression of p53 is an adverse prognostic factor MEDULLOBLASTOMA (90%)
• Standard therapy: surgical resection followed by involved-field • Cerebellar tumor occurring predominantly in males
radiation therapy • Median age of 5-7 years
• Most occur in the midline cerebellar vermis, older patients in the
2. OLIGODENDROGLIOMAS cerebellar hemisphere
• Rare in children • CT and MRI: solid, homogenous, contrast medium-enhancing
• Calcified cortical mass on CT in a patient presenting with seizure mass in the posterior fossa causing 4th ventricular obstruction and
hydrocephalus
3. EPENDYMAL TUMORS • Neuronal differentiation is more common among these tumors
− Homer Wright rosettes
EPENDYMOMA (WHO GRADE II)
− Immunopositivity for Synaptophysins
• Most common
• Anaplastic variant: more aggressive, worse prognosis
• 70% occur in the posterior fossa
• Signs and symptoms of increased ICP and cerebellar dysfunction
• Mean age: 6 years old
• Prognostic factors:
− 40%: <4 years old
− Age at diagnosis: <4 years old: poorer outcome
− Extent of disease
Clinical presentation ○ Disseminated disease at diagnosis (M>0), including positive
• insidious, depends on the anatomic location of the tumor CSF cytologic result alone (M1): worse outcome
• Noninvasive, extending into the ventricular lumen and/ or displacing − Extent of surgical resection
normal structures, leading to significant hydrocephalus ○ Gross residual disease after surgery: worse outcome

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 2022 5.4b. Childhood Malignancy (Part 2)
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PEDIATRICS II

• Multimodal treatment approach 12. METASTATIC TUMORS

• Sensitive to both radiotherapy and chemotherapy
• RT dose: 50-55 Gy
• <4 years of age: high-dose chemotherapy with peripheral stem cell
re-infusion, exclude radiation
• Risk stratification of treatment approach
1. Patient <3 years of age (cannot do radiation in this age group)
2. Standard risk patients >3 years of age with surgical total
resection and no disease dissemination (M0)
3. High-risk patients >3 years of age with disease dissemination
(M>0) and/ or bulky residual disease after surgery
6. SUPRATENTORIAL PRIMITIVE NEUROECTODERMAL
TUMORS (SPNETS)
• 2-3% of childhood brain tumors
• Composed of undifferentiated or poorly differentiated
neuroepithelial cells
• Poorer outcome
7. ATYPICAL TERATOID/ RHABDOID TUMOR
• Very aggressive embryonal malignancy
• Occurs predominantly in children <5 years of age
• Occur at any location in the neuroaxis
• Very poor outcome
8. 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 (Surgery, Radiotherapy, Chemotherapy)
9. 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
10. 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 years of age
• Male preponderance, female preponderance for suprasellar tumors
• Occur multifocally in 5-10% of cases
• Insidious course, subtle initial presenting symptoms: poor school
performance and behavior problems
• Protein markers: AFP and bHCG
• Multimodal treatment (Surgery, Radiotherapy, Chemotherapy)
11. 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
• Four types
1. Focal (5-10%) - Surgery as primary treatment approach
2. Dorsally exophytic (5-10%) - Surgery as primary treatment
approach
3. Cervicomedullary (5-10%): RT sensitive
4. Diffuse intrinsic (75-85%): associated with poor outcome
• Treatment: Radiotherapy (RT)
• Acute lymphoblastic leukemia (ALL) and Non-Hodgkin’s Lymphoma
(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
I. 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 years
− 90% diagnosed in children under 5 years of age
• Bilateral involvement is more common under the age of 1 year
• 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
• 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
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
− Parents would usually describe it as “cat’s eye” in appearance
• Strabismus
• Orbital inflammation, hyphema, pupil irregularity
• Pain if with secondary glaucoma
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

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PEDIATRICS II

Treatment 2. TERATOMAS
• Determined by the size and location of the tumors • Occur in many locations
• Primary goal of treatment: CURE • Not associated with elevated markers unless malignancy is present
• Secondary goal of treatment: PRESERVING VISION AND THE EYE • Sacrococcygeal site is the most common site
ITSELF • Occur most commonly in infants
• Enucleation • May be diagnosed in utero or at birth, most found in girls
• Bilateral disease: chemoreduction in combination with focal therapy
(laser photocoagulation or cryotherapy) 3. GERMINOMAS
− Goal is to save the best eye • Occur intracranially, in the mediastinum, in the gonads
• Multiagent chemotherapy: Vinblastine, Carboplatin, Etoposide • Ovary: dysgerminomas
• External Beam Irradiation • Testis: seminomas
• Brachytherapy or episcleral plaque radiotherapy • Tumor marker negative despite being malignant
• 1st-degree relatives of hereditary RB patient • Endodermal Sinus Tumor, yolk sac tumor, choriocarcinoma:
− Retinal examination to identify retinomas or retinal scars are highly malignant
indicated or advised
4. NON-GERM CELL GONADAL TUMORS
J. GONADAL AND GERM CELL NEOPLASMS • Uncommon
Epidemiology • Occur predominantly in the ovary
• Epithelial carcinoma, Sertoli-Leydig cell tumors, granulosa cell
• Rare tumors may occur in children
• Most malignant tumors of the gonads in children are Germ Cell
Tumors (GCTs)
Treatment
• Sacrococcygeal tumors: occur predominantly in infant girls
• Testicular GCTs: occur predominantly before age 4 year and after • Complete surgical excision
puberty • Intracranial tumors: RT and chemotherapy
• Klinefelter syndrome: increased risk of Mediastinal GCT • Testicular tumor: inguinal approach, preoperative chemotherapy
• Down SY, undescended testes, infertility, testicular atrophy and • Overall cure rate: >80%
inguinal hernias: increased risk of testicular CA • Age is the most important predictive factor of survival

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
• 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

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

1. 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

Trans Group 5: Agbuya, Crisologo, Garcia, Guilang, Landingin, Pacio, Zamudio EDITORS: Garcia & Guilang 7 of 7