Case Presentation

1. Case Presentation 9 mo M presents to clinic with a chief compliant of vomiting

2. Case Presentation • Mother reports the child has had a long history of constipation and she gives him extra water and a high fiber diet to no avail • He has been fussy for the last three days • Yesterday he began vomiting nonbilious nonbloody emesis x 2 • His last BM was two days ago • He is otherwise well

3. Case Presentation • PMH: FT, uncomplicated pregnancy and delivery • Mother is 20yo G2P2 • Medication: polyethylene glycol (for constipation) • FH: 4yo sister is healthy

4. Case Presentation • O/E: • VS T 36.8 HR 110 RR 38 BP 111/65 Wt: 9.3 kg • Gen: well-appearing and playful, well hydrated • Skin: no rash, no lesions • HEENT: Normocephalic; EOMI, PERRL, sclera nonicteric, TMs pearly and translucent; oropharynx benign

5. Case Presentation • Nodes: no cervical, axillary, inguinal adenopathy • CV: RRR, nl S1/S2, no m/r/g • Lungs: clear breath sounds bilaterally • Abdomen: soft, tenderness diffusely along left side, no rebound, no guarding, palpable mass in LLQ, normal bowel sounds • Extr: warm and well perfused

6. Case Presentation • Differential Dx: • Constipation • Wilm’s tumor • Neuroblastoma • Splenomegaly • Multicystic kidney disease • Renal tumor • Clear cell sarcoma • Rhabdoid tumor • Mesoblastic nephroma • Renal cell carcinoma • Renal medullary cancer

7. Case Presentation Studies: • KUB: bowel gas is distributed primarily along the right side of the abdomen; no obstruction; minimal stool seen in the colon • US: large mass eminating from the left kidney, fully encapsulated

8. Case Presentation

9. Case Presentation • Diagnosis: Wilm’s Tumor

10. Wilm’s Tumor and Neuroblastoma Venée Tubman, MD Children’s Hospital Boston HEARTT

11. Wilm’s Tumor (WT) • Wilm’s tumor is the most common renal malignancy in pediatrics • Amongst Americans, more common in African Americans • Slightly more common in females, bilateral disease more common in females

12. WT: Associated Syndromes • Syndrome are associated with mutations or deletions in WT1/FWT1/FWT2/p53 genes • Beckwith-Wiedeman syndrome: macrosomia, macroglossia, omphalocele, large kidneys, hemihypertrophy • 5-10% of children will develop WT • WAGR: WT, aniridia, GU anomalies, mental retardation • Denys-Drash: male pseudohermaphrodite and renal disease

13. WT: Pathology • Approximately 7% of cases have bilateral disease • Most tumors are enclosed by renal capsule or intrarenal pseudocapsule • Tumor can contain a mixture of cells: • blastemal cells • stromal cells • epithelial cells • High degree of anaplasia associated with poor outcomes

14. WT: CLINICAL PRESENTATION • Many cases present with an abdominal mass discovered by the parents during bath or changing time • Associated findings: abdominal pain (30%), hematuria (12-25%), hypertension (25%) • Firm, nontender mass which does not cross the midline • Examine carefully given risk of capsular rupture • Examine for associated anomlaies

15. WT: EVALUATION • KUB/US • If available, CT (chest/abdomen) • Labs: chemistries, LFTs, urinalysis

16. WT: STAGING National Wilm’s Tumor Study (US): staging is determined before chemotherapy is initiated

17. WT: STAGING International Society of Pediatric Oncologists (SIOP) (Europe): staging is determined after chemotherapy is initiated for 4-6 weeks • Stage 1: fully resected and encapsulated • Stage 2: beyond renal capsule but fully resected • Stage 3: extends into abdomen • Stage 4: hematogenous spread • Stage 5: bilateral renal disease

18. WT: TREATMENT • Resection is the mainstay of treatment, but without chemotherapy there is a high rate of recurrence • Stage 1 or 2: 18 weeks of vincristine and dactinomycin • Stage 3: 24 weeks of vincristine, doxorubicin, and dactinomycin; and radiation to the flank • Stage 4: 24 weeks of chemotherapy with radiation to flank and lungs

19. WT: OUTCOMES • Response rate of 90% with chemotherapy and resection • Best prognosis is under 2 years and stage 1 disease • 15% recurrence rate if histology is favorable; 50% recurrence if anaplasia is present • Complications are largely related to chemotherapy

20. NEUROBLASTOMA

21. NEUROBLASTOMA (NB) • Represents a variety of tumors including neuroblastoma, ganglioneuroma, ganglioneuroblastoma • Tumors arise from primitive sympathetic ganglion cells • Characterized by variable location, histology and behavior • Most common extracranial solid tumor in children,accounting for 8% to 10% of all childhood cancers • Prevalence is about 1 case per 7,000 live births

22. NB: PATHOLOGY • Small blue round cell tumor • MYCN oncogene is activated in neoplastic cell lines • Associated with advanced disease and poor outcome

23. NB: CLINICAL • Can occur anywhere along the sympathetic nervous system: adrenal (40%), abdomen (25%), thoracic (15%), cervical (5%) • Majority of tumors are diagnosed prior to age 5 • Hepatomegaly • Single, large left supraclavicular LN is highly suggestive • Presentation depends on location of tumor: • Fixed, firm abdominal mass: LE edema, abdominal pain, obstruction • Thoracic: incidental, Horner’s syndrome • Paravertebral: oncologic emergency

24. NB: CLINICAL • Cathecolamine secretion causes hypertenison • Opsoclonus-myoclonus: dancing eyes, jerking movements, ataxia • Metastasizes to lymph nodes, bone marrow, bone, dura, orbits, liver, skin

25. NB: Diagnosis • An unequivocal pathologic diagnosis is made from: • tumor tissue • increased urine (or serum) catecholamines or metabolites • bone marrow aspirate contains unequivocal tumor cells AND increased urine or serum catecholamines

26. NB: EVALUATION • Excess cathecolamines cause urinary secretion of homovanillic acid (HVA), vanillylmandelic acid (VMA) and dopamine • CT scan brain, chest, abdomen • Bone marrow aspirate

27. NB: STAGING International Neuroblastoma Staging System • Stage 1: Localized tumor • Stage 2A: Unilateral tumor with incomplete resection; identifiable lymph node negative for tumor. • Stage 2B: Unilateral tumor with complete or incomplete resection; with ipsilateral lymph node positive for tumor; identifiable contralateral lymph node negative for tumor. • Stage 3: Tumor infiltrating across midline involvement; or unilateral tumor with contralateral lymph node involvement; or midline tumor with bilateral lymph node involvement. • Stage 4: Dissemination of tumor to distant lymph nodes, bone marrow, bone, liver, or other organs except as defined by Stage 4S. • Stage 4S: Age <1 year old with localized primary tumor as defined in Stage 1 or 2, with dissemination limited to liver, skin, or bone marrow (less than 10 percent of nucleated bone marrow cells are tumors).

28. NB: Treatment • Surgery, chemotherapy, radiation • Low risk disease may warrant surgery alone • Multiple chemotherapy regimens can be used for intermediate arisk • Radiation, chemotherapy, bone marrow transplant regimens have 15% survival for high risk disease

29. NB: Outcomes • Prognosis depends on age, stage, histology, DNA content, presence of MYCN mutation • Good outcomes are suggested by: • Age less than 18 months without MYCN amplification • Stage 4S