1. hepatoblastoma
By: Brittni McClellan

2. Hepatoblastoma description
Most common form of liver cancer in children.
Tumor Marker: AFP
Can also secrete b-hCG
Pathophysiology:
Originate from Immature Liver Precursor Cells
Genetics:
Loss of Heterozygosity of the Chromosome Arm 11p.
Associated with Beckwith-Wiedemann Syndrome (BWS)

3. Hepatoblastoma – H&P Signs and Symptoms: Asymptomatic Abdominal Mass
Isosexual Precocity:
Penile/Testicular Enlargement without Pubic Hair
Anorexia
Talipes Equinovarus
Persistent Ductus Arteriosus
Tetralogy of Fallot
Extrahepatic Biliary Atresia
Renal Anomalies

4. Hepatoblastoma - Diagnosis
Imaging:
Radiography:
Mass in RUQ of Abdomen
U/S:
CT:
Reveals involvement of nearby structures
Reveals if Pulmonary Metastases are present
MRI:
Superior to CT if CT is inconclusive.
PET:
Follow-Up Evaluation
Radionuclide Bone Scanning:
Reveals Bone Metastases
Diagnosis:
CBC:
Normochromic Normocytic Anemia
Thrombocytosis
Other Labs
Liver Enzyme Levels
Elevated in 15-30%
AFP
As high as 100, ,000
Biopsy:
Open Biopsy or Complete Surgical Resection

5. Hepatoblastoma – treatment
Medication:
Cisplatin: Most active single agent
Cisplatin/5-FU/Vincristine Combo
Radiotherapy
Resection/Transplantation

6. Neuroblastoma description
Small Round Blue Cell Tumor
Homer Wright Rosettes
Bombesin +
Description:
Most Common Extracranial Solid Tumor of Childhood
Most Common Malignancy of Infancy
Pathophysiology:
Derived from Neural Crest Cells
Arises anywhere along the Sympathetic Chain of the Peripheral Nervous System
Most Common: Adrenal Medulla
Genetics:
Due to Inherited Mutations in the ALK Tyrosine Kinase
Associated with N-MYC Oncogene
Associated with Congenital Central Hypoventilation Syndrome and PHOX2B Mutations.

7. neuroblastoma – H&P History: Associated Conditions Signs and Symptoms:
General Appearance, Activity Level, and Appetite
Based on Tumor Location:
Thoracic:
Chest Pain, Cough, Respiratory Distress
Abdominal:
Pain, Swelling
Bone Marrow:
Fatigue (Anemia)
Associated Conditions
Neurofibromatosis Type I
Hirschsprung Disease
Central Congenital Hypoventilation Syndrome
Signs and Symptoms:
Based on Location:
Abdomen:
Firm, Fixed, Irregular Mass
Abdominal Distention
Signs of Bowel Obstruction
Hypertension (RAS)
Genital/Lower Extremity Edema (Lymphatic Obstruction)
Cervical/Thoracic Mass:
Respiratory Distress
Horner Syndrome
Superior Vena Cava Syndrome
Paraspinal Mass:
Nerve Root Compression
Metastatic Disease Symptoms
Bone Metastases (Pain)
Bony Orbit

8. neuroblastoma – H&P

9. neuroblastoma - Diagnosis
CBC:
Decreased Hemoglobin, Platelets, and/or WBC indicate Bone Marrow Involvement
Urine Catecholamine Metabolites are Elevated:
Homovanillic Acid (HVA)
Vanillylmandelic Acid (VMA)
Imaging
U/S or CT: Find Primary Tumor
Tumor is CALCIFIED
MIBG Scan:
Taken up by 90% of Neuroblastomas
Can detect bone/soft tissue involvement
Bone Scan: Find Bone Mets

10. neuroblastoma – treatment
Medication
Vincristine, Doxorubicin, Cyclophosphamide, Cisplatin, Carboplatin. Etoposide, Topotecan
13-cis-Retinoic Acid: Induces differentiation of Neuroblastoma Cells and Improves Survival
Immunotherapy: Antibodies against GD2
Possibility of Spontaneous Regression

11. retinoblastoma description
Most Common Primary Intraocular Tumor
Malignant Tumor of the Embryonic Neural Retina
Pathophysiology:
Loss of function of both copies of the RB1 gene
Located on Chromosome 13
Spreads via the Optic Nerve
Vitreous Seeding: Tumor Cells Break Off
Two Forms:
Hereditary Retinoblastoma
45% of all RB
1 RB Gene is Dysfunctional in all cells
Non-Hereditary Retinoblastoma
55% of all RB
2 acquired mutations must occur in a single retinal cell.

12. retinoblastoma – H&P Patient History: Physical Exam:
Family History
Leukocoria (White Pupil)
Physical Exam:
Strabismus
Only 3% discovered on routine fundoscopic examination
Rare: Pain, Inflammation, Vision Problems
Leukocoria/Strabismus
Metastatic Symptoms:
Check for Red Reflex in Darkened Room
Neurological Signs, Orbital Masses, Bone Pain, Anorexia, Cytopenia
Screen for RB in Office
Associated Conditions:
Evaluate Anisocoria
13q Deletion Syndrome
Unequal Pupils
RB, Dysmorphism, Mental Retardation, GU Anomalies
High Risk of Osteosarcoma in the Future

13. retinoblastoma - Diagnosis
Ophthalmologic Examination
By a specialist in pediatric ocular tumors
Biopsy:
Biopsy confirmation is RARE.
Risk of seeding
CBC:
Asses for Bone Marrow involvement
CSF Cytology
Evaluation of Leptomeningeal Spread
Chromosome Analysis
Only 5% are detectable, but should be done anyways.
Imaging:
CT/MRI:
Evaluation of Primary Tumor
Evaluation of any metastases.

14. retinoblastoma – treatment
Medication
Eradicate Tumor/Eye Salvage Therapy
Plaque Radiotherapy:
Radioactive seeds sewn into episcleral surface about RB lesion.
Provides local radiation to the tumor
External Beam Radiation Therapy
Photocoagulation:
Cryotherapy
Locally Delivered Chemotherapy
Systemic Chemotherapy
Tumor Resection with Enucleation

15. Wilms tumor (Nephroblastoma) description
Malignant Tumor of the Kidney
Also called Nephroblastoma
Pathophysiology:
10-20% Hereditary
Associated with WAGR, Beckwith- Wiedemann, and Denys-Drash Syndromes
Tumor Suppressor Gene:
WT1 on Chromosome 11p13
WT2 on Chromosome 11p15

16. Wilms tumor – H&P Patient History: Physical Exam: Family History
Asymptomatic Abdominal Mass
Abdominal Distention/Pain
Extends from Flank Towards Midline
Hematuria
Anemia
Fever, Anorexia, Vomiting
Fever
Rapid Increase in Abdominal Size
Hypertension
Varicocele
Aniridia, Hemihypertrophy, Cryptorchidism, Hypospadias
Proteinuria/Hematuria

17. Wilms tumor - Diagnosis
Labs:
CBC, Electrolytes, Urine Analysis, Liver and Kidney Function Tests, Coagulation Factors
Imaging:
U/S:
Diagnostic of Renal Mass
Evaluations extention into Inferior Vena Cava
CT Scan:
Evaluate for Metastases
Bone Scan:
Pathology:
CT/MRI:
Gross:
Cystic with hemorrhages and necrosis.
No calcification
May extend into Inferior Vena Cava
Histology:
Triphasic Pattern: Blastemal, Epithelial, and Stroma Cells
Blastemal Cells aggregate in nodules like primitive glomeruli
The presence of diffuse anaplasia indicates poor prognosis.

18. Wilms tumor – treatment
Medication
For stages I and II:
Vincristine and Actinomycin D every 3 weeks for 6 months
For stages III and IV:
Vincristine, Actinomycin D, and Doxorubicin for 6–15 months
Add cyclophosphamide and/or Etoposide for higher-stage anaplastic tumors (stage IV focal or II–IV diffuse).
Nephrectomy
Radiotherapy

19. Neuroblastoma vs wilms tumor
Neuroblastoma – Opsoclonus-Myoclonus Syndrome (uncontrolled eye movement and involuntary twitching)
Wilms: WAGR Syndrome (Wilms tumor (a tumor of the kidneys), Aniridia (absence of the colored part of the eye, the iris), Genitourinary anomalies, and mental Retardation), Beckwith Wiedemann Syndrome (macroglossia, macrosomia, hemihypertrophy).

20. Question 1
A 2-year-old girl is brought to the office by her parents after blood was noticed in her urine. The parents say the patient has had intermittent abdominal pain during the past two months but has been otherwise well. On physical examination, the abdomen is slightly distended and a mass is palpated in the right upper quadrant. Results of urinalysis are positive for blood and protein. Which of the following is the most likely diagnosis?
Cystic nephroma
Cystitis
Mesoblastic nephroma
Neuroblastoma
Wilms tumor
The correct answer is Option (E), Wilms tumor, because the clinical presentation of hematuria, abdominal pain of two months’ duration, and a palpable mass in the right upper quadrant of the abdomen is characteristic of this tumor.
Option (A), cystic nephroma, is incorrect because this tumor typically presents as an asymptomatic benign mass in the kidney that is found incidentally. Option (B), cystitis, is incorrect because this condition does not include a retroperitoneal mass. Option (C), mesoblastic nephroma, is incorrect because this condition is exceedingly rare; in more than 90% of cases, it presents before 1 year of age. Option (D), neuroblastoma, is incorrect because although it can present with intra-abdominal mass, proteinuria and hematuria are rarely associated with this condition. In addition, neuroblastomas also present more often in children younger than 1 year of age, making this diagnosis less likely in the patient described.
e) Wilms tumor

21. Question 2
A 3-year-old boy is found to have an abnormal red reflex in his left eye on routine examination. Funduscopic examination shows a proliferative retinal mass. After surgical removal of the specimen, pathologic examination reveals small, round cells with hyperchromatic nuclei, some rosette arrangement and isolated regions of necrosis. There is no involvement of the optic nerve or tumor extension into adjacent brain tissue. The patient undergoes eye enucleation without surgical complications. 
As the child ages, which of the following disorders is the patient also at risk for developing?
Acoustic neuroma.
Colon cancer.
Neurofibroma.
Osteosarcoma.
Wilms tumor.
This patient presents with a classic presentation of retinoblastoma, a rapidly progressive cancer arising from immature retinal cells. It occurs almost entirely in young children and symptoms include visual impairment and strabismus. However, many cases are discovered incidentally on family photographs or physical exam with an absent red reflex (leukocoria). Leukocoria can also be found in a number of other conditions including congenital cataracts, but should always prompt a work-up for retinoblastoma.
Retinoblastoma can either be inherited or sporadic. The disease is associated with a mutation in the Rb tumor suppressor gene located at chromosome 13q14. Rb protein regulates cell-cycle progression from G1 (growth phase) to S (synthesis) during replication. Loss of function causes unregulated cell division. Other diseases caused by germline mutations in the Rb gene include osteosarcoma. So, as part of patient management, the child should be monitored for the risk of osteosarcoma development in future years. Somatic mutations at this site are also seen in some cases of breast, lung, prostate and bladder cancer.
d) Osteosarcoma