JOSE LUIS MIRA-HERNANDEZ, MD SURGICAL PATHOLOGIST CSI LABORATORIES, ALPHARETTA, GA USA

1. CHALLENGING DIAGNOSIS IN SURGICAL PATHOLOGYANNUAL SYMPOSIUM 2014ACADEMY OF PATHOLOGY AND LABORATORY MEDICINE OF PUERTO RICO JOSE LUIS MIRA-HERNANDEZ, MD SURGICAL PATHOLOGIST CSI LABORATORIES, ALPHARETTA, GA USA

2. Case 1 72-year-old female underwent Whipple resection for a pancreatic head mass

17. D-PAS

18. D-PAS

22. CD10

23. CD56

24. B-CATENIN

25. B-CATENIN

26. PR

27. VIMENTIN

28. CD99

29. CD99

30. Additional pertinent markers • Few positive cells: • CAM 5.2 • CK 19 • Rare positive cells: • Chromogranin • Synaptophysin • Negative • CK 7 CK 20 • EMA S100 • CEA CA 19.9 • Trypsin Chymotrypsin • α1-AT α1-ACT • ER

31. DIAGNOSIS PANCREATIC SOLID PSEUDOPAPILLARY NEOPLASM

32. Solid neoplasms of the pancreas • Adenocarcinoma • Pancreatoblastoma • Acinar cell carcinoma • Pancreatic neuroendocrine neoplasm • Solid pseudopapillary neoplasm • Mixed tumors: each component should comprise at least 25% of the entire tumor: • Acinar-ductal • Acinar-endocrine • Acinar-endocrine-ductal

33. Solid pseudopapillary neoplasia • First described by Frantz in 1959 (AFIP Atlas of tumor pathology, fascicles 27 and 28); solid and cystic tumor of the pancreas, Frantz’s tumor. • Solid pseudopapillary neoplasm, WHO Classification of tumors, 2010 • Uncertain cell differentiation • Uncommon, 2-5% of pancreatic malignancies

34. Solid pseudopapillary neoplasia • Affects females predominantly (89%), 9.8:1 female to male ratio • Mean age 28 years, range 7-79 years • Males, mean age 5-10 years older than females • No hormonal, clinical syndrome or genetic disease association has been demonstrate • Frequently reported during pregnancy or postpartum, possibly explained by the high incidence during child-bearing age • Non specific symptoms, palpable abdominal mass • Asymptomatic, incidental radiographic finding

35. Solid pseudopapillary neoplasm • Gross • Anywhere within the pancreas • Large tumors, mean diameter 10 cm • Asymptomatic incidental tumors <5 cm • Well circumscribed, partially encapsulated • Red/tan, hemorrhagic, soft, friable solid areas • Cystic degeneration • Near complete cystic change may simulate a pseudocyst • True necrosis may occur but is rare • Firm consistency reflects abundant fibrous hyalinazed stroma

36. Solid pseudopapillary neoplasm • Microscopic • Solid sheets of uniform polygonal cells are separated into nests by abundant capillary sized blood vessels • No true acinar lumen formation

37. Solid pseudopapillary neoplasm • Microscopic • Solid sheets of uniform polygonal cells are separated into nests by abundant capillary sized blood vessels • No true acinar lumen formation

38. Solid pseudopapillary neoplasm • Microscopic • Ischemic degenerative changes with discohesive cell and cell drop leaving a ragged cuff of neoplastic cells clinging to blood vessels • pseudopapillary architecture • Microcystic and macrocystic architecture, pseudocysts

39. Solid pseudopapillary neoplasm • Microscopic • Ischemic degenerative changes with discohesive cell and cell drop leaving a ragged cuff of neoplastic cells clinging to blood vessels • pseudopapillary architecture • Microcystic and macrocystic architecture, pseudocysts

40. Solid pseudopapillary neoplasm • Microscopic • Tumor cells with foamy cytoplasm and aggregates of foamy macrophages

41. Solid pseudopapillary neoplasm • Microscopic • Intracytoplasmic and extracellular PAS and D-PAS positive hyaline globules

42. Solid pseudopapillary neoplasm • Microscopic • Intracytoplasmic and extracellular PAS and D-PAS positive hyaline globules D-PAS

43. Solid pseudopapillary neoplasm • Microscopic • Uniform round to oval nuclei, nuclear groves • Tumor cell nuclei oriented away from capillary wall resulting in a zone of cytoplasm separating the nuclei from the capillaries • Rare mitoses, 0-10 MF/50HPF • Nuclear pleomorphism is rare but may be present

44. Solid pseudopapillary neoplasm • Microscopic • Stromal fibrosis and hyalinization may be present • Mixoid change

45. Solid pseudopapillary neoplasm • Microscopic • Well circumscribed tumor but often there is tumor invasion within associated non neoplastic pancreatic parenchyma

46. Solid pseudopapillary neoplasm • Microscopic • Well circumscribed tumor but often there is tumor invasion within associated non neoplastic pancreatic parenchyma • Peripheral “blood lakes” suggesting blood vessel invasion

47. Solid pseudopapillary neoplasm • Microscopic • Well circumscribed tumor but often there is tumor invasion within associated non neoplastic pancreatic parenchyma • Peripheral “blood lakes” suggesting blood vessel invasion

48. Solid pseudopapillary neoplasm • Microscopic • Well circumscribed tumor but often there is tumor invasion within associated non neoplastic pancreatic parenchyma • Peripheral “blood lakes” suggesting blood vessel invasion

49. Solid pseudopapillary neoplasia • Genetics • Somatic point mutations in exon 3 of the β-catenin gene (same as in acinar cell carcinoma and pancreatoblastoma) • Β- catenin and Cyclin D1 overexpression • Chromosomal gains in 13q, 17q, 1q and 8q • Chromosomal losses in 11q • No ductal adenocarcinoma associated mutations: KRAS, p16, p53,DPC4 • No E-cadherin gene mutations • No KIT/PDGFRA mutations

50. Solid pseudopapillary neoplasm • Prognosis: • Low grade malignant neoplasm/low malignant potential • Indolent behavior • Potential for local invasion and metastatic disease • 95% cured by complete surgical excision when confined to the pancreas • 19.5% present with or develop local invasion and/or metastatic spread • Metastasis usually limited to liver and peritoneum • Lymph node metastasis are exceptional • Long-term survival even in patients with metastasis or unresectable disease • Rupture with potential life-threatening hemoperitoneum