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8/13/2019 Solid Tumor Residents
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Childhood Solid Tumors
Alexandra Walsh, MD
Resident Lecture1.26.12
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Pediatric versus Adult Cancers
PEDIATRIC ADULTIncidence 17.6 per 100,000 538.8 per 100,000
Risk Factors Uncommon Common
Outcomes 75-80% overall survival <60%
Biology Embryonic: derived from non-ectodermal embryonal tissue
Carcinomas: derivedfrom epithelial tissue
NCI, SEER data
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Percentage Distribution of
Childhood Cancers
Cancer Research UK, 2004
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Cancer in Children
Cancer Children Adults
Acute Leukemia 28% 2.3%
CNS tumors 21% 1.6%
Lymphomas 11% 4.3%Neuroblastoma 7.5% 0%
Wilms’ tumor 6% 0%
Soft tissuesarcoma
6% <0.5%
OS and Ewing’ssarcoma
5% <0.5%
Retinoblastoma 3% 0%
Others 12.5% >90%
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Childhood Cancers
Cancer Children
Acute Leukemia 28%
CNS tumors 21%
Lymphomas 11%
Neuroblastoma 7.5%
Wilms’ tumor 6%
Soft tissue sarcoma 6%
OS and Ewing’s sarcoma 5%
Retinoblastoma 3%
Others 12.5%
Abdominal tumors
Soft tissue tumors
Bone tumors
Eye tumors
61% ofchildhoodcancers are “solid tumors”
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Case #1 HPI/PMH
3 yo female presents to PMD secondary to a “lump in the belly” that her mom felt while
bathing her the night before Child has been well
No fever, URI symptoms, N/V/D/C,
abdominal pain, urinary complaints orswelling anywhere else
PMH unremarkable
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Case #1 PE
Afebrile, stable vital signs
Alert, active, playful 3 yo
Shoddy cervical lymphadenopathy
Heart regular rate and rhythym
Lungs clear 6 x 5 cm firm, smooth, non-tender abdominal
mass in the right quadrant, not crossing midline,margins well defined
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Case #1 Labs WBC 6000
40% segs, 60% lymphs(ANC 2400)
Hgb 12 Hct 36
Plts 180,000
Normal CMPincluding BUN,creatinine
Normal LDH, uricacid
HVA, VMA Normal
AFP, B-HCG Normal
Urinalysis 2+ blood
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CT Scan of Abdomen
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Wilms Tumor 5-6% of childhood cancers
5th most common cancer overall and 2nd mostcommon abdominal malignancy
Occurs most commonly in children 2-5 yo
Arises from primitive metanephric blastema
Typically occurs sporadically but can occur incertain syndromes/ congential defects Beckwith-Wiedemann Syndrome Denys-Drash syndrome WAGR syndrome
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Beckwith-Wiedemann Syndrome
Congenital disorder of growth regulation
1/14,000 children
Macrosomia, macroglossia, neonatalhypoglycemia, abdominal wall defects, earanomalies, visceromegaly
May be associated with hemi-hypertrophy
4-21% of patients develop cancer
Wilms tumor (43%) and Hepatoblastoma (12%)
Q4 month abdominal u/s until age 8
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Wilms Tumor Associated
Syndromes Familial tumors- associated with 2 loci
WT1: primary gene implicated indevelopment of Wilms
Located at 11p13
Deletions noted in WAGR (Wilms, Aniridia, GUanomalies, Retardation)
Missense WT1 mutations in Denys Drash(gonadal dysgenesis, nephropathy)
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Wilms Tumor
Presentation: Often asymptomaticincrease in size of abdomen
Labs: Usually normal
May have anemia secondary to hemorrhageinto the tumor
Microscopic hematuria
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Wilms Tumor
Imaging: CT scan or ultrasound
Must evaluate contralateral kidney
Can metastasize to liver and lungs
Staging and histology of tumor importantfor prognosis
Overall survival rate of 90% (Stage IV,unfavorable histology has 17% overall survivalrate)
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Wilms’ Tumor Treatment/Outcome
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Case #2 HPI/PMH
3 yo male presents to PMD secondary to low-grade fever, fussiness, and decreased POintake over the past 2-3 weeks
Several pound weight loss
Irritable and over the past few days wants tobe held all the time and does not want towalk
No URI symptoms, no N/V/D/C, no sickcontacts
No significant PMH
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Case #2 PE
Temp 100.8, P 130, R 25
Irritable, difficult to console, pale, ill-appearing 3 yo
Shoddy cervical lymphadenopathy
Tachycardia with II/VI SEM
Lungs CTA bilaterally
6 x 5 cm firm, fixed, irregularly shaped, right-sidedabdominal mass that extends beyond the midline
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Case #2 Labs
WBC 4000 40% segs, 60%
lymphs (ANC2400)
Hgb 9
Hct 27
Plts 95,000
Retic 0.4
Normal CMP includingBUN, creatinine
elevated LDH, normaluric acid
AFP, B-HCG Normal
Urinalysis
Normal HVA, VMA Elevated
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CT Scan of Abdomen
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Neuroblastoma
7-10% of childhood cancers
50% diagnosed before 2 yo, 90% by 5 yo Arises from neural crest tissue of the
sympathetic ganglia or adrenal medulla
“Small round blue cell” malignancy
Must be differentiated from Ewings sarcoma(PNETs), rhabdomyosarcoma, lymphoma
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Neuroblastoma Post-ganglionic sympathetic neuroblasts
(primitive, pluripotent)
Often constitutional symptoms: fever, irritability,
weight loss
Other symptoms based on primary site
Cervical: neck mass, Horner’s syndrome
Thoracic: Superior vena cava syndrome Paraspinous: cord compression
Abdominal: fullness, pain, obstruction
Metastatic disease: marrow, bone, liver, skin
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Neuroblastoma
Elevated VMA, HVA,elevated ferritin, LDH, Abnormal blood counts ifmarrow involvement
< 18 mo tend to have low
stage, curable disease(70-90% survival)
> 18 months tend to havemetastatic disease (<15% survival)
Unique features: Stage4S, opsoclonus-myoclonus, raccoon eyes
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Neuroblastoma Origin
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Neuroblastoma IV-S
Infants with small primary tumors (stage I or II)
Distant metastases:
Liver Skin (blueberry muffin)
Bone marrow
NO BONE METS
Excellent prognosis with minimal or no therapy
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Case #3 HPI/PMH 3 yo male presents to PMD secondary to
intermittent vomiting typically in the morningand irritability over the past couple of weeks
Crying more, waking up at night, and hishead seems to be hurting
Over past few days, he seems to be weakand is falling more
No fever, URI symptoms
No significant PMH
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Case #3 PE/Labs
Afebrile, vitals stable
Fussy, somewhat lethargic 3 yo
Normal heart and lungs
Abdomen soft, NT/ND, active BS, no HSM or masses
Papilledema, CN II-XII normal, Normal motor
strength and sensation. Ataxic gait, dysmetria onfinger to nose
CBC, CMP normal
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CT Scan/MRI of Head
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Brain Tumors
Most common solidtumor in childhood(25% of all
childhood cancers) Tumors tend to be
infratentorial(posterior fossa) inyoung patients andsupratentorial inolder patients
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Brain Tumors
Treatment consists of resection if possible,chemotherapy,+/- craniospinal radiation in
tumors with high probability of neuroaxisdissemination (≥ 3 yo)
Prognosis variable depending on location,
grade of tumor, resectability
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Case #4 HPI/PMH
15 yo male presents with L knee pain ofapproximately 1 month duration
Originally began when he fell on his kneewhile being tackled playing touch-footballwith friends
+ swelling above the knee that seems to be
getting worse
No fever, no redness or warmth to the area
PMH unremarkable
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Case #4 PE/Labs
Afebrile, vitals signs stable
Healthy appearing 15 yo in NAD Mass palpated involving L distal femur, no
effusion, warmth, erythema noted
Normal CBC
Elevated alkaline phosphatase and LDH
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X-Ray, MRI of Knee
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Bone Tumors
Signs of bone tumor include pain at site(often following minor trauma), mass, andfracture at area of bone destruction
Osteosarcoma and Ewing sarcoma aremost common types
Outcomes variable depending on whetheror not metastases present at diagnosisand location
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Osteosarcoma Ewing Sarcoma
% of BoneTumors 60% 30%
PeakOccurrence
Adolescents Adolescents
Sex Males > Females Males > Females
Race African Americans > Caucasians Primarily Caucasians
Location
Metaphysis of Distal Femur >Proximal Tibia > Humerus
Pelvis > Diaphysis ofFemur > Tibia > Humerus
Imaging Appearance
Sunburst Appearance Onion-skin or Lamellated
Treatment Chemotherapy & Surgery Chemo then Surgery +/-Radiation & Chemo
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Case #5 HPI/PMH
6 month old WF presents to herpediatrician for evaluation of fussiness andvomiting.
She has been on zantac for GERD.
PMH: term SVD, immunizations UTD
FH: colon cancer and colon polyps inmaternal family members
SH: lives with family; only child
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Case #5 PE/Labs
Vital signs stable; afebrile
PE notable for hepatomegaly
Abdominal u/s reveals multilobular mass in rightlobe of liver measuring 7.6 x 10.9 cm.
CT scans without evidence of metastatic disease.
Labs: AST mildly elevated 96 T bili 1.1 (direct bilirubin 0.3) CBC notable for mild anemia AFP 2300 (<15)
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CT Scan
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Hepatoblastoma
Malignant liver tumors account for 1.1% of all childhoodcancers (1.5 cases/million children under age 15 yearly)
Hepatoblastoma accounts for 2/3rds
Usually occurs in first 4 yrs of life.
More common in males
Outcome is linked to stage of disease
Associated with prematurity
Occurs in association with several cancer geneticsyndromes.
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Genetic Syndromes leading to
Hepatoblastoma Beckwith-Wiedemann
Reports of Li-Fraumeni (TP53) and trisomy
18
Familial adenomatous polyposis (FAP):germline mutation of APC gene
(chromosome 5q21.22) which is a tumorsuppressor gene. Associated also with colorectal cancer and
hepatocellular carcinoma
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Case 6: HPI/PMH
16 mo WM who has been tilting his headwhen trying to look at objects.
Appetite has been normal. Rest of ROS isnegative.
Pediatrician referred to ophthalmology
who noted a lesion in the left eye ondilated exam.
PMH/FH: unremarkable
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Case continues
MRI of brain confirmslesion in left eye (1.1 x
0.7 x 1.4 cm).
Exam under anesthesiaconfirms left eye lesionand revealed very smalllesion in right eye.
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Retinoblastoma
Malignant tumor of the embryonic neuralretina
Most common intraocular tumor of childhood
Approx 3% of all childhood cancers
1/15,000 live births per year in US- estimated200 new diagnosis per year (20-30% are
bilateral) Median age at diagnosis is 2 yrs (90% of
cases are diagnosed before age 5)
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Retinoblastoma presentation
Leukocoria
Strabismus
Lack of pain unless secondary glaucoma orinflammation.
Diagnosis is made by ophthalmologic andradiographic evaluation with pathologicconfirmation usually not needed.
Labs are usually normal
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Hereditary Retinoblastoma
Usually presents with bilateraldisease/mutifocal tumors and at a youngerage (median age at dx is 11 mos).
RB1 gene Tumor suppressor gene on 13q14
RB protein- molecular switch controlling
passage thru G1 check point between G1 andentry into S phase
Vital for cell division/proliferation
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RB1 mutations
Germline mutation- 90% risk of developingRB and 50% risk of passing mutation tooffspring
Genetic testing can identify mutations in 80-90% of individuals
Screening: Fundoscopic exam 1-2 wks after birth and every 2
weeks until 3 months of age. Then space out andcontinue exams until 4-5 yrs.
Yearly MRI from 6 mos to 5 yrs to screen for pineal
tumors
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Treatment
90% overall 5 year survival Metastatic disease associated with a poor
prognosis
Trilateral retinoblastoma: Primary RB of pineal and parasellar sites Usually seen in familial disease Usually fatal
Mgmt: Local therapy- enucleation, cyrotherapy,
thermotherapy
Radiotherapy
Systemic chemotherapy
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Presented to PMD with 3-day history ofswelling in R neck
Dx’d with sialthiothiasis and rx’d augmentin bid, sethim up see ENT if no improvement
11/24 saw ENT who agreed with diagnosis butobtained CT scan because it was not responding toantibiotics
Increased dose of augmentin
11/26 CT scan Large mass in R maxillary, ethmoid and extrachonal orbit
12/4 CT instatrac and MRI done
Case #7
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PE: T 96.4, HR 76, BP 120/57,RR 20,
GEN: pleasant, oriented HEENT:+proptosis of R eye, withsubjunctival hemorrhage, EOMI,
large mass over R max sinus,large palpable mass in Rsupraclavicular area,nonerythematous, somewhat
tender, very firm CV, LUNG, LYMPH, ABD exams
unremarkable
LABS: CBC wnl, UA 10.3, LDH
1379
Case #7
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Soft tissue sarcoma
Sarcoma: malignant tumor ofmesenchymal cell origin
Rhabdomyosarcoma: arises from immaturemesenchymal cells that are committed toskeletal muscle lineage (55-60%)
Non-RMS STS: Histology other than RMS (40-55%)
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Rhabdomyosarcoma
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RMS Treatment
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Childhood Cancers
Cancer Children
Acute Leukemia 28%
CNS tumors 21%
Lymphomas 11%
Neuroblastoma 7.5%
Wilms’ tumor 6%
Soft tissue sarcoma 6%
OS and Ewing’s sarcoma 5%
Retinoblastoma 3%
Others 12.5%
Abdominal tumors
Soft tissue tumors
Bone tumors
Eye tumors
61% ofchildhoodcancers are “solid tumors”
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The parents of a child who was diagnosed at birth with Beckwith-Wiedemann
syndrome bring in the baby for his 2-month evaluation. They ask about future health
problems and his prognosis now that his omphalocele has been repaired.
Of the following, the child is MOST at risk for
1. acute lymphocytic leukemia
2. astrocytoma
3. Hodgkin disease
4. Rhabdomyosarcoma5. Wilms tumor
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A 2-year-old girl presents for evaluation of fussiness, low-grade fever, and what her
parents describe as "growing pains." On physical examination, you palpate a
nontender mass deep in the right periumbilical area and note mild purple
discoloration of the eyelids.
Of the following, the MOST likely diagnosis is
1. Hepatoblastoma
2. Hirschsprung disease
3. Intussusception4. Neuroblastoma
5. Wilms tumor