Childhood Solid Tumors

Alexandra Walsh, MD Resident Lecture 1.26.12

Pediatric versus Adult Cancers

PEDIATRIC
Incidence Risk Factors
17.6 per 100,000 Uncommon

ADULT
538.8 per 100,000 Common

Outcomes
Biology

75-80% overall survival

Embryonic: derived from nonectodermal embryonal tissue

<60%
Carcinomas: derived from epithelial tissue

NCI, SEER data

Percentage Distribution of Childhood Cancers

Cancer Research UK, 2004

Cancer in Children
Cancer
Acute Leukemia CNS tumors Lymphomas

Children
28% 21% 11%

Adults
2.3% 1.6% 4.3%

Neuroblastoma
Wilms tumor Soft tissue sarcoma OS and Ewings sarcoma Retinoblastoma Others

7.5%
6% 6% 5% 3% 12.5%

0%
0% <0.5% <0.5% 0% >90%

Childhood Cancers
Cancer
Acute Leukemia CNS tumors Lymphomas Neuroblastoma Wilms tumor Soft tissue sarcoma

Children
28% 21% 11% 7.5% 6% 6%

61% of childhood cancers are solid tumors

Abdominal tumors Soft tissue tumors

OS and Ewings sarcoma 5% Retinoblastoma Others 3% 12.5%

Bone tumors
Eye tumors

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 or swelling anywhere else PMH unremarkable

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

Case #1 Labs

WBC 6000

40% segs, 60% lymphs (ANC 2400)

HVA, VMA Normal AFP, B-HCG Normal

Hgb 12

Hct 36
Plts 180,000 Normal CMP including BUN, creatinine Normal LDH, uric acid

Urinalysis 2+ blood

CT Scan of Abdomen

Wilms Tumor

5-6% of childhood cancers

5th most common cancer overall and 2nd most common abdominal malignancy
Occurs most commonly in children 2-5 yo

Arises from primitive metanephric blastema

Typically occurs sporadically but can occur in certain syndromes/ congential defects

Beckwith-Wiedemann Syndrome Denys-Drash syndrome WAGR syndrome

Beckwith-Wiedemann Syndrome

Congenital disorder of growth regulation

1/14,000 children
Macrosomia, macroglossia, neonatal hypoglycemia, abdominal wall defects, ear anomalies, 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

Wilms Tumor Associated Syndromes

Familial tumors- associated with 2 loci

WT1: primary gene implicated in development of Wilms

Located at 11p13 Deletions noted in WAGR (Wilms, Aniridia, GU anomalies, Retardation) Missense WT1 mutations in Denys Drash (gonadal dysgenesis, nephropathy)

Wilms Tumor

Presentation: Often asymptomatic increase in size of abdomen

Labs: Usually normal

May have anemia secondary to hemorrhage into the tumor Microscopic hematuria

Wilms Tumor

Imaging: CT scan or ultrasound

Must evaluate contralateral kidney Can metastasize to liver and lungs

Staging and histology of tumor important for prognosis

Overall survival rate of 90% (Stage IV, unfavorable histology has 17% overall survival rate)

Wilms Tumor Treatment/Outcome

Case #2 HPI/PMH

3 yo male presents to PMD secondary to lowgrade fever, fussiness, and decreased PO intake over the past 2-3 weeks
Several pound weight loss

Irritable and over the past few days wants to be held all the time and does not want to walk No URI symptoms, no N/V/D/C, no sick contacts
No significant PMH

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-sided abdominal mass that extends beyond the midline

WBC 4000

Case #2 Labs

40% segs, 60% lymphs (ANC 2400)

AFP, B-HCG Normal Urinalysis Normal

Hgb 9 Hct 27 Plts 95,000 Retic 0.4 Normal CMP including BUN, creatinine elevated LDH, normal uric acid

HVA, VMA Elevated

CT Scan of Abdomen

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

Neuroblastoma

Post-ganglionic sympathetic neuroblasts (primitive, pluripotent) Often constitutional symptoms: fever, irritability, weight loss

Other symptoms based on primary site

Cervical: neck mass, Horners syndrome Thoracic: Superior vena cava syndrome Paraspinous: cord compression Abdominal: fullness, pain, obstruction Metastatic disease: marrow, bone, liver, skin

Elevated VMA, HVA, elevated ferritin, LDH, Abnormal blood counts if marrow involvement

Neuroblastoma

< 18 mo tend to have low stage, curable disease (70-90% survival) > 18 months tend to have metastatic disease (< 15% survival)

Unique features: Stage 4S, opsoclonusmyoclonus, raccoon eyes

Neuroblastoma Origin

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

Case #3 HPI/PMH

3 yo male presents to PMD secondary to intermittent vomiting typically in the morning and irritability over the past couple of weeks Crying more, waking up at night, and his head seems to be hurting Over past few days, he seems to be weak and is falling more

No fever, URI symptoms

No significant PMH

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 on finger to nose CBC, CMP normal

CT Scan/MRI of Head

Brain Tumors

Most common solid tumor in childhood (25% of all childhood cancers)

Tumors tend to be infratentorial (posterior fossa) in young patients and supratentorial in older patients

Brain Tumors

Treatment consists of resection if possible, chemotherapy,+/- craniospinal radiation in tumors with high probability of neuroaxis dissemination ( 3 yo)
Prognosis variable depending on location, grade of tumor, resectability

Case #4 HPI/PMH

15 yo male presents with L knee pain of approximately 1 month duration

Originally began when he fell on his knee while being tackled playing touch-football with friends + swelling above the knee that seems to be getting worse No fever, no redness or warmth to the area PMH unremarkable

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

X-Ray, MRI of Knee

Bone Tumors

Signs of bone tumor include pain at site (often following minor trauma), mass, and fracture at area of bone destruction Osteosarcoma and Ewing sarcoma are most common types Outcomes variable depending on whether or not metastases present at diagnosis and location

Osteosarcoma
% of Bone Tumors 60%

Ewing Sarcoma
30%

Peak Occurrence
Sex Race

Adolescents
Males > Females African Americans > Caucasians Metaphysis of Distal Femur > Proximal Tibia > Humerus Sunburst Appearance Chemotherapy & Surgery

Adolescents
Males > Females Primarily Caucasians Pelvis > Diaphysis of Femur > Tibia > Humerus Onion-skin or Lamellated Chemo then Surgery +/Radiation & Chemo

Location Imaging Appearance Treatment

Case #5 HPI/PMH

6 month old WF presents to her pediatrician for evaluation of fussiness and vomiting.
She has been on zantac for GERD. PMH: term SVD, immunizations UTD FH: colon cancer and colon polyps in maternal family members SH: lives with family; only child

Case #5 PE/Labs

Vital signs stable; afebrile

PE notable for hepatomegaly Abdominal u/s reveals multilobular mass in right lobe 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)

CT Scan

Hepatoblastoma

Malignant liver tumors account for 1.1% of all childhood cancers (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 genetic syndromes.

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 tumor suppressor gene.

Associated also with colorectal cancer and hepatocellular carcinoma

Case 6: HPI/PMH

16 mo WM who has been tilting his head when trying to look at objects.
Appetite has been normal. Rest of ROS is negative. Pediatrician referred to ophthalmology who noted a lesion in the left eye on dilated exam. PMH/FH: unremarkable

Case continues
MRI of brain confirms lesion in left eye (1.1 x 0.7 x 1.4 cm). Exam under anesthesia confirms left eye lesion and revealed very small lesion in right eye.

Retinoblastoma

Malignant tumor of the embryonic neural retina Most common intraocular tumor of childhood Approx 3% of all childhood cancers 1/15,000 live births per year in US- estimated 200 new diagnosis per year (20-30% are bilateral)

Median age at diagnosis is 2 yrs (90% of cases are diagnosed before age 5)

Retinoblastoma presentation

Leukocoria

Strabismus
Lack of pain unless secondary glaucoma or inflammation. Diagnosis is made by ophthalmologic and radiographic evaluation with pathologic confirmation usually not needed. Labs are usually normal

Hereditary Retinoblastoma

Usually presents with bilateral disease/mutifocal tumors and at a younger age (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 and entry into S phase Vital for cell division/proliferation

RB1 mutations

Germline mutation- 90% risk of developing RB and 50% risk of passing mutation to offspring Genetic testing can identify mutations in 8090% of individuals Screening:

Fundoscopic exam 1-2 wks after birth and every 2 weeks until 3 months of age. Then space out and continue exams until 4-5 yrs. Yearly MRI from 6 mos to 5 yrs to screen for pineal tumors

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

Case #7

Presented to PMD with 3-day history of swelling in R neck

Dxd with sialthiothiasis and rxd augmentin bid, set him up see ENT if no improvement 11/24 saw ENT who agreed with diagnosis but obtained CT scan because it was not responding to antibiotics

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

PE: T 96.4, HR 76, BP 120/57, RR 20, GEN: pleasant, oriented HEENT: +proptosis of R eye, with subjunctival hemorrhage, EOMI, large mass over R max sinus, large palpable mass in R supraclavicular area, nonerythematous, somewhat tender, very firm CV, LUNG, LYMPH, ABD exams unremarkable LABS: CBC wnl, UA 10.3, LDH 1379

Soft tissue sarcoma

Sarcoma: malignant tumor of mesenchymal cell origin

Rhabdomyosarcoma: arises from immature mesenchymal cells that are committed to skeletal muscle lineage (55-60%) Non-RMS STS: Histology other than RMS (4055%)

Rhabdomyosarcoma

RMS Treatment

Childhood Cancers
Cancer
Acute Leukemia CNS tumors Lymphomas Neuroblastoma Wilms tumor Soft tissue sarcoma

Children
28% 21% 11% 7.5% 6% 6%

61% of childhood cancers are solid tumors

Abdominal tumors Soft tissue tumors

OS and Ewings sarcoma 5% Retinoblastoma Others 3% 12.5%

Bone tumors
Eye tumors

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. Rhabdomyosarcoma 5. Wilms tumor

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. Intussusception 4. Neuroblastoma 5. Wilms tumor