hepatoblastoma

1. hepatoblastoma By: Brittni McClellan

2. Hepatoblastoma description • 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 • TalipesEquinovarus • 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 100,000-300,000 • 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 • 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 • History: • 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

8. neuroblastoma – H&P

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

13. retinoblastoma - Diagnosis 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 • 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: • Family History • Abdominal Distention/Pain • Hematuria • Fever, Anorexia, Vomiting • Rapid Increase in Abdominal Size • Physical Exam: • Asymptomatic Abdominal Mass • Extends from Flank Towards Midline • Anemia • Fever • Hypertension • Varicocele • Aniridia, Hemihypertrophy, Cryptorchidism, Hypospadias • Proteinuria/Hematuria

17. Wilms tumor - Diagnosis 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: • Evaluate for Metastases 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

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 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. d) Osteosarcoma