Solid-pseudopapillary Neoplasm of the Pancreas

Definition

• Bland low grade malignant neoplasm characterized by solid and discohesive pseudopapillary areas

Alternate/Historical Names

• Papillary cystic neoplasm or tumor
• Solid-cystic tumor
• Solid and papillary epithelial neoplasm

Diagnostic Criteria

• Variably solid, pseudopapillary and cystic pattern
  • Occasionally completely solid
    • Usually smaller tumors
    • May be sclerotic
    • May have foamy macrophages and cholesterol clefts
  • Frequent pseudopapillary pattern
    • Formed by separation of vascular cores with adherent cells
      • Typically thin walled vessels in cores
    • Spaces may be acellular or contain RBCs (blood lakes)
  • Frequent cystic pattern
    • Degenerative changes may cause predominantly cystic structure
• Uniform polygonal cells
  • Cytoplasm clear to eosinophilic
    • Lack glycogen and mucin
    • May have intra or extracytoplasmic PASd+ globules
  • Bland round to oval nuclei
    • Mitotic figures rare
    • Frequent longitudinal nuclear grooves
  • Frequently radially oriented around vessels
    • May resemble rosettes
• Features proposed as predictive of malignant behavior
  • Perineural invasion
  • Vascular invasion
  • Deep invasion of pancreatic parenchyma
  • Invasion of surrounding organs
  • Nuclear atypia
  • Elevated mitotic rate
  • It is not clear if any of these are statistically significant predictors
  • Rare tumors lacking these features may still metastasize
• Rare anaplastic transformation has been reported
  • Very high mitotic rate, necrosis, atypia and high nuclear:cytoplasmic ratio

Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting / last update: 2/10/07, 7/14/11, 1/4/12

Supplemental studies

Histochemistry

• Mucin stain negative
• Glycogen negative
• PASd positive intra and extracellular globules may be present

Immunohistology

• One report describes paranuclear dot like staining seen in solid-pseudopapillary tumor but not in neuroendocrine tumors or adenocarcinoma (Guo 2012)
  • Other neoplasms have membrane or diffuse cytoplasmic staining
  • If confirmed, this may be a very useful marker
• Alpha 1 antitrypsin and antichymotrypsin may identify only scattered cells, but they should be intensely stained
• Keratin usually negative or at most focally positive
• One report on the use of claudins

Molecular Genetics

• EWS/FLI-1 translocation not present even though FLI-1 positive by immunohistochemistry

Differential Diagnosis

• Neuroendocrine carcinoma
• Acinar cell carcinoma
• Serous microcystic adenoma
• Serous oligocystic adenoma

Well Differentiated Pancreatic Neuroendocrine (Islet Cell) Tumor	Solid Pseudopapillary Neoplasm of the Pancreas
Lacks pseudopapillary architecture	Frequent pseudopapillary architecture
Chromogranin usually strongly positive	Chromogranin focal to negative
Keratin positive	Keratin variable
Galectin 3 negative	Galectin 3 positive (small numbers)
Vimentin, CD10 negative	Vimentin, CD10 positive
Nuclear beta catenin negative	Nuclear beta catenin positive
No PAS+ granules in cytoplasm	PAS+ granules may be present
CD99 variable but not paranuclear dots	CD99 paranuclear dots (one report)

Solid pseudopapillary neoplasm may be synaptophysin positive

Acinar Cell Carcinoma of the Pancreas	Solid Pseudopapillary Neoplasm of the Pancreas
Predominantly male	Overwhelmingly female
Granular PASd+ cytoplasm	PASd+ only scattered globules
Beta-catenin/CD56/CD10 negative	Beta-catenin/CD56/CD10 positive
BCL10, trypsin, chymotrypsin positive	BCL10, trypsin, chymotrypsin negative
Alpha 1 antitrypsin negative	Alpha 1 antitrypsin positive
Keratin positive	Keratin variable
Usually infiltrative	Usually circumscribed
Lacks pseudopapillary architecture	Frequent pseudopapillary architecture
May have true lumens	No true lumens
Frequently increased mitotic figures	Infrequent mitotic figures
CD99 negative	CD99 paranuclear dots (one report)

Serous Microcystic Adenoma	Solid Pseudopapillary Neoplasm of the Pancreas
True cysts lined by a single layer of cells	Variable thickness of lining of degenerate spaces
Occurs in males and females	Nearly all female
Median age 60's	Mean age 20's
Glycogen positive	Glycogen negative
Keratin positive	Keratin variable

Clear cell variant of solid pseudopapillary neoplasm is also reported to be glycogen negative

Serous Macrocystic / Oligocystic Adenoma	Solid Pseudopapillary Neoplasm of the Pancreas
True cysts lined by a single layer of cells	Variable thickness of lining of degenerate spaces
Occurs in males and females	Nearly all female
Glycogen positive	Glycogen negative
Keratin positive	Keratin variable

Clear cell variant of solid pseudopapillary neoplasm is also reported to be glycogen negative

Clinical

• Female predominance
• Mean age 30-35
  • Range 8-85
• Rare male cases at same mean age (4-7%)
• Not associated with abnormal endocrine states or endocrine therapy
• Best considered low grade malignant
  • >95% cured by resection
  • Most recurrences or metastases associated with atypical features
  • Rare non-atypical cases may metastasize
    • May occur years later
  • Most common metastatic sites
    • Liver
    • Peritoneum / omentum
    • Local lymph nodes involved rarely
  • Death rare even with metastases

Grading / Staging / Report

• Grading
  • Not applicable
• Staging
  • Not applicable
• Report
  • Comment on presence or absence of features predictive of malignant behavior
  • Comment that rare cases may behave aggressively even in the absence of atypical features

Lists

Cystic Pancreatic Lesions

• Acinar cell cystadenocarcinoma
• Acinar cell cystadenoma
• Enterogenous duplication cyst
• Epidermoid cyst in intrapancreatic accessory spleen
• Intraductal oncocytic papillary neoplasm
• Intraductal papillary mucinous neoplasm
• Islet cell / well differentiated neuroendocrine tumor (occasionally cystic)
• Lymphangioma
• Lymphoepithelial cyst
• Mucinous cystic neoplasm
• Paraduodenal wall cyst
• Pseudocyst
• Serous cystadenocarcinoma
• Serous oligocystic adenoma
• Serous microcystic adenoma
• Solid and cystic hamartoma
• Solid pseudopapillary neoplasm
• Squamoid cyst of pancreatic ducts
• von Hippel Lindau associated cystic lesions

Bibliography

• Solcia E, Capella C, Kloppel G . Tumors of the Pancreas, Atlas of Tumor Pathology, AFIP Third Series, Fascicle 20, 1997.
• Bosman FT, Carneiro F, Hruban RH, Thiese ND (Eds). WHO Classifiication of Tumors of the Digestive System, IARC, Lyon 2010.
• Nishihara K, Nagoshi M, Tsuneyoshi M, Yamaguchi K, Hayashi I. Papillary cystic tumors of the pancreas. Assessment of their malignant potential. Cancer. 1993 Jan 1;71(1):82-92.
• Tiemann K, Kosmahl M, Ohlendorf J, Krams M, Kloppel G. Solid pseudopapillary neoplasms of the pancreas are associated with FLI-1 expression, but not with EWS/FLI-1 translocation. Mod Pathol. 2006 Nov;19(11):1409-13.
• Geers C, Moulin P, Gigot JF, Weynand B, Deprez P, Rahier J, Sempoux C. Solid and pseudopapillary tumor of the pancreas--review and new insights into pathogenesis. Am J Surg Pathol. 2006 Oct;30(10):1243-9.
• Albores-Saavedra J, Simpson KW, Bilello SJ. The clear cell variant of solid pseudopapillary tumor of the pancreas: a previously unrecognized pancreatic neoplasm. Am J Surg Pathol. 2006 Oct;30(10):1237-42.
• Notohara K, Hamazaki S, Tsukayama C, Nakamoto S, Kawabata K, Mizobuchi K, Sakamoto K, Okada S, Solid-pseudopapillary tumor of the pancreas: immunohistochemical localization of neuroendocrine markers and CD10. Am J Surg Pathol. 2000 Oct;24(10):1361-71.
• Adams AL, Siegal GP, Jhala NC. Solid pseudopapillary tumor of the pancreas: a review of salient clinical and pathologic features. Adv Anat Pathol. 2008 Jan;15(1):39-45.
• Basturk O, Coban I, Adsay NV. Pancreatic cysts: pathologic classification, differential diagnosis, and clinical implications. Arch Pathol Lab Med. 2009 Mar;133(3):423-38.
• Tang LH, Aydin H, Brennan MF, Klimstra DS. Clinically aggressive solid pseudopapillary tumors of the pancreas: a report of two cases with components of undifferentiated carcinoma and a comparative clinicopathologic analysis of 34 conventional cases. Am J Surg Pathol. 2005 Apr;29(4):512-9.
• Comper F, Antonello D, Beghelli S, Gobbo S, Montagna L, Pederzoli P, Chilosi M, Scarpa A. Expression pattern of claudins 5 and 7 distinguishes solid-pseudopapillary from pancreatoblastoma, acinar cell and endocrine tumors of the pancreas. Am J Surg Pathol. 2009 May;33(5):768-74.
• Guo Y, Yuan F, Deng H, Wang HF, Jin XL, Xiao JC. Paranuclear dot-like immunostaining for CD99: a unique staining pattern for diagnosing solid-pseudopapillary neoplasm of the pancreas. Am J Surg Pathol. 2011 Jun;35(6):799-806.