1. Pediatric Pancreatic Tumors Jonathan Sham, MD May 12, 2011

2. C.A. 15 months old Uneventful pregnancy Perinatal jaundice  hospitalized 4 days for r/o sepsis Continues to breastfeed, picky eater ~14 months  mother noticed scleral icterus pale stools

3. C.A. Tbili: 2.3 WBC: 15,000 VMA: 10, HMA: 18 AFP: 1.3 CA 19-9: 226 (nl <55)

6. Ultrasound pic

7. Standard pancreatic mass workup Appropriate labs (tumor markers, glucose) EUS – not often performed in children (significant false-negative bx rate ~12.5%) ERCP – often impossible in small children CT/MRI (pancreas protocol)

8. “Pancreatic Mass” in a Child Choledocholithiasis Pancreatitis Pancreatic Pseudocyst Choledochal cyst Hemangioma Neoplasm –Pseudopapillary tumors, pancreatoblastomas, adenomas, PNETs, sarcoma, lymphoma, (ductal adenocarcinoma exceedingly rare) Park, et al. J Pediatr Hematol Oncol 2011;33:295–300

9. 17 patients Pseudopapillary tumor – 7 Pancreatoblastoma -5 PNET – 3 Acinar cell carcinoma – 1 Malignant VIPoma - 1 J Ped Surg, Vol 37, No 6, 2002: pp887-892

10. Presenting Symptoms Chief Complaint Abdominal pain – 11 (65%) Mass – 4 (24%) Jaundice – 3 (18%) Other symptoms Wt. loss (29%) Nausea/Vomiting (24%) Anorexia (18%) Adults Wt. loss (92%) Pain (72%) Jaundice (82%) Sabiston, 18 th ed. J Ped Surg, Vol 37, No 6, 2002: pp887-892

11. J Pediatr Hematol Oncol 2011;33:295–300

12. Where’s the Jaundice? Jaundice occurs less frequently than in adults Tumors tend to distribute evenly throughout gland Tend to have expansive, rather than infiltrative growth patterns Rarely arise from ductal epithelium Shorter NA, et al. J Pediatr Surg. 2002;37:887–892.

13. Pseudopapillary Tumors (PST) vs. Pancreaticoblastoma (PB) Pseudopapillary Tumor Girls (85%) > Boys More common in non-whites (especially Asians) Normal AFP Pancreaticoblastoma Boys > Girls Most common pancreatic tumor in first decade Often elevated AFP Kissane JM. Semin Diag Pathol. 1994 May; 11(2):152-64

14. Pseudopapillary Tumors (PST) vs. Pancreaticoblastoma (PB) Both originate from pancreatic pluripotent progenitors - PST slightly earlier than PB International Publication Number WO 2007/047509 A3 PB PST

15. Adult vs. Pediatric Pancreatic Neoplasms Adults Adenocarcinoma (80-90%) Serous cystadenoma IPMN MCN Cholangiocarcinoma Neuroendocrine Pediatrics Pseudopapillary tumor (>50%) Pancreatoblastoma (~30-40%) PNET (think MEN) Acinar cell carcinoma Malignant VIPoma Lymphoma Rhabdomyosarcoma (rare) Neuroblastoma (rarer)

16. Patient C.A. Underwent pylorus preserving pancreaticoduodenectomy Pancreatic head mass/lymph nodes removed Initially tolerated procedure well Post-op course complicated by lymphatic leak, PO intolerance, anemia requiring transfusion

17. Neoplasm or not? 3 pts Obstructive jaundice & CT showing pancreatic head mass Intraoperative frozen sections negative for malignancy Managed with PPD, T-tube drainage, Roux-en-Y choledochojejunostomy J Ped Surg. 2006

19. After operation, all 3 patients diagnosed with pseudocyst Pseudocyst with mass effect: Abd/back pain, wt. loss, steatorrhea, obstructive jaundice Pancreatic cancer can cause chronic pancreatitis  pseudocyst J Ped Surg. 2006

20. Pseudocyst vs. Cancer Pancreatic cancer - 0.2% of all childhood malignancies (3% in adults) Different causes of pancreatitis Adults Alcohol Biliary Tract Disease Children Trauma Hereditary systemic disease Drug-induced choledocholithiasis Pancreaticobiliary nonunion Pancreas divisum Hypertensive Sphincter of Oddi Annular Pancreas Idiopathic Park et al. J Ped Surg. 2006

21. Pseudocyst vs. Cancer Recommendations for pancreatic head mass: Adults – PPPD or other resective procedure Children – Biopsy/biliary diversion unless histologic evidence of malignancy. Children - PPPD may be indicated in rare cases of both biliary and pancreatic obstruction resulting from benign disease Park et al. J Ped Surg. 2006

22. Patient C.A. - Pathology Poorly Differentiated Neuroblastoma 3.4cm Negative margins 12/21 positive lymph nodes (2 outside pancreas) Mitotic-Karyorrhectic Index: Low (<100/5000 cells) Stage 2B

23. Neuroblastoma Staging 1 - Localized tumor with complete gross excision, ipsilateral lymph nodes negative for tumor (attached nodes may be positive 2A - Localized tumor with incomplete gross excision, ipsilateral nonadherent lymph nodes negative for tumor 2B - Localized tumor with or without complete gross excision; with ipsilateral nonadherent lymph nodes positive for tumor. 3 – Unresectable tumor infiltrating across the midline, with or without regional lymph node involvement; or localized unilateral tumor with contralateral regional lymph node involvement; 4 - Any primary tumor with dissemination to distant lymph nodes, bone, bone marrow, liver, skin and/or other organs (except as defined for stage 4S) 4S - Localized primary tumor (as defined for stage 1, 2A or 2B), with dissemination limited to skin, liver, and/or bone marrow

24. Neuroblastoma Outcomes Stage 1 - Children of any age have a cure rate >90%. Stage 2 - Long-term survival: >18 months old 75 - 90% 90% Stage 2B or 3 – Long term survival: >18 months old 60 - 70% <18 months old ~80% Stage 4 or 4S – Long term survival: >18 months old 50% - 80%. <18 months 10% - 40%. National Cancer Institute. 2010

25. Neuroblastoma Outcomes Surgery most important intervention, but sometimes inadequate Chemotherapy/Radiation have shown potential, but not definitive benefit Stage, Age, MYCN status, Mytotic-Karryorhectic Index most important prognostic factors National Cancer Institute. 2010

26. Neuroblastoma in the Pancreas? NB is the most common solid tumor of infancy Adrenal NB >50% of cases Plurality arise along sympathetic chain

27. Neuroblastoma in the Pancreas? Current opinion suggest that pancreatic cells are from endodermal origin Neural crest cells may reside in pancreas to influence β-cell development Andrew A, Kramer B, Rawdon BB. The origin of gut and pancreatic neuroendocrine (APUD) cells—the last word? J Pathol 1998;186: 117-8.

28. 6 patients 1969-2009

29. 21y/o P1G0 woman at 35wks gestation w/ abd pain CT for r/o appendicitis

31. Summary Pediatric Pancreatic tumors are rare Pancreatic masses may present differently in children than in adults Given similar CT/lab findings, operative approach may be different in pediatric patients

32. Summary Pseudopapillary tumors/Pancreatoblastomas are the most common pediatric pancreatic tumors Pancreatic Neuroblastomas are RARE Neuroblastoma survival depends on stage, age at presentation, MYCN status, and MKI

33. Thank you