1. Everything You Need to Know About Solid and Papillary Epithelial Neoplasms of the Pancreas RSNA 2004
O Qureshi MD
VJ Casillas MD
L Rivas MD
JU Levi MD +
M Jorda MD ++
C Solozarno MD +
Click Here to Begin
Department of Radiology/Surgery+/Pathology++
University of Miami School of Medicine/Jackson Memorial Hospital

2. History of Solid and Papillary Epithelial Neoplasms of the Pancreas (SPEN)
1959: Described by Frantz as “papillary tumor of pancreas, benign or malignant”
1970: Pathology first described by Hamoudi
1981: Became a well-known clinical entity after publication of cases by Klöppel
1996: Renamed by the World Health Organization as solid-pseudopapillary tumor (SPT)
Start from Beginning

3. Also Known As… Solid pseudopapillary tumor (SPT) Frantz’s tumor
Papillary cystic neoplasm of the pancreas
Solid cystic papillary tumor
Solid and cystic acinar cell tumor
Papillary tumor of the pancreas
Papillary epithelial neoplasm

4. Etiology Pluripotential pancreatic embryonic stem cells
Cells capable of endocrine or exocrine differentiation
Variety of markers from various pancreatic cell types

5. Etiology
Alternative hypothesis that SPEN originates from genital ridge-related cells incorporated into pancreas during organogenesis
Prevalence in women suggests hormonal influence
Case report of increased tumor growth during pregnancy

6. Genetics Alterations in APC/ß-catenin pathway
Also identified in pancreatoblastomas and acinar cell carcinomas
Nuclear and cytoplasmic accumulation of ß-catenin protein in 95% cases (study of 20 patients)
Activating ß-catenin oncogene mutations in 90%
Over expression of cyclin D1 protein in 74%
Predilection for young females not understood

7. Epidemiology Prevalence: 0.13 – 2.7% of all pancreatic tumors
82-93% cases in women
70% tumors occur under age of 30
Average age at presentation: 21-27
Men present with disease at an age 10 years older than women

8. Epidemiology Racial predilection
Blacks and East Asians
50% of reported cases in the United States amongst African-Americans
SPEN in children show less female preponderance than in adults

9. Gross Pathology Specimens range from 2 to 25 cm
May occur throughout pancreas, more common in head and tail; Exophytic growth pattern
Well-circumscribed with fibrous capsule
Solid, cystic, and papillary regions
Variable degrees of internal hemorrhage
Necrotic and thrombotic contents
Fluid-debris levels in cystic cavities

10. Cystic
Solid
Mixture of components
Hemorrhage and fluid levels
Peripheral calcifications

11. Cytology Aspirates are highly cellular
FNA: 72% diagnostic or suggestive of SPEN
Solid areas: Necrosis, foamy macrophages, cholesterol granulomas, and occasionally calcifications
Papillary configurations: Fibrovascular stalk surrounded by several layers of epithelial cells
Frequently arranged around tiny vessels as “pseudorosettes”
Poorly supported blood vessels that result in numerous and extensive hemorrhage

12. Tumor cells arranged around a hyalinized fibrovascular stalk

13. Cytology Absence of pleomorphism, hyperchromasia, or mitotic activity
Bland, oval to round nuclei that may contain small nucleoli and grooves or folds
Eosinophilic granular cytoplasm
Hyaline cytoplasmic globules, multinucleated giant cells
Infiltrative growth pattern into adjacent pancreas despite gross circumscription

14. Immunohistochemistry
Commonly seen immunoreactivity
CD 10 and CD 56
Found in all cases in a study of 19 patients
α-1 antitrypsin
Neuron-specific enolase
Vimentin
Progesterone receptors
Stains negative for:
chromogranin A

15. Immunohistochemistry
Neuron-specific enolase positive
Chromogranin A negative

16. Immunohistochemistry
Occasionally stains positive for:
Keratin
α-1 antichymotrypsin
Synapthophysin
S-100 protein
Neurosecretory granules occasionally seen

17. Clinical Presentation
Vague symptoms
Abdominal fullness or discomfort
Epigastric or LUQ abdominal pain
Early satiety
Asymptomatic: 9%
Duration of symptoms: acute to 5 years
Nontender, palpable mass in LUQ or RUQ

18. Clinical Presentation
Symptoms also seen: Jaundice, polyarthralgia, dyspepsia, weight loss, nausea, anorexia
Laboratory values are non-diagnostic
Rare cases exhibit mildly elevated CA 19-9 values, eosinophilia
Nonspecific symptomology often leads to a delay in diagnosis
Diagnosis is often incidental

19. University of Miami Case Series
Cases obtained from the institutional hospital of the University of Miami, Jackson Memorial Hospital
15 cases of surgically resected and pathology proven SPEN collected for retrospective review

20. University of Miami Case Series
Gender
# of Cases
Avg. Age
Range
Female 13
21.5
9-37
Male 2
58.5
56-61

21. University of Miami Case Series
87% of cases in females, consistent with expected prevalence
Average age at presentation of 21.5 within expected normal for SPEN
Male age of presentation > female, but also much higher than normally observed

22. Ultrasound Findings Well-encapsulated masses with variable echotexture
Combined cystic and solid portions
May demonstrate septations and internal echoes
Solid masses with good through-transmission correlate to friable neoplastic tissue with massive hemorrhagic necrosis
Masses of low echogenicity correspond to neoplastic tissue with focal cystic degeneration
Echogenic tumor capsules

23. 20 yr old white Latin female with RUQ pain, nausea,
fatty food intolerance and elevated liver function tests
US : Round complex mass predominantly solid with small cystic components in head of the pancreas

24. US: Ovoid cystic mass in the neck of the pancreas
Transverse scan
20 yr old female with RUQ abdominal pain
US: Ovoid cystic mass in the neck of the pancreas

25. 28 yr old female with abdominal pain
US: Complex mass in the pancreatic head mostly cystic with small solid components

26. m
Sagittal midline
17 yr old female with epigastric pain and early satiety
US : Well-circumscribed hypoechoic mass (m) in the body of the pancreas with minimal posterior enhancement (arrows)

27. US: Large hyperechoic solid mass, body and pancreatic tail
13 yr old Black female with abdominal fullness
US: Large hyperechoic solid mass, body and pancreatic tail

28. CT Findings Well-defined, round or lobulated masses
Heterogeneous with variable ratio of cystic and solid components
Regions of hyperdensity correspond to hemorrhage
Improved definition of mass with IV contrast administration, with slight peripheral enhancement
Peripheral calcifications in ~ 1/3rd patients
Mass effect on local structures

29. 21 yr old Hispanic female with vague abdominal symptoms
CT: Pancreatic mass mostly cystic with septations and small solid components

30. 55 yr old Hispanic male with known transitional cell carcinoma of the bladder
CT demonstrates large ovoid complex mass with cystic and solid components involving the body and tail of the pancreas. Biopsy showed that this was SPEN, and not metastasis.

31. CT: Well circumscribed solid mass in the pancreatic tail
26 yr old African-American female with abdominal discomfort
CT: Well circumscribed solid mass in the pancreatic tail

32. CT: Large complex mass involving the body and tail of the pancreas

33. CT : Pancreatic mass of low attenuation with thick walls
17 yr old female with epigastric pain and early satiety
CT : Pancreatic mass of low attenuation with thick walls

34. CT: Complex pancreatic masses with fluid levels
9 yr old Latin female
22 year old Latin female
CT: Complex pancreatic masses with fluid levels

35. CT: Large cystic pancreatic mass with mural nodule
19 yr old Black female with progressive LUQ abdominal fullness for three years
CT: Large cystic pancreatic mass with mural nodule

36. CT: Pancreatic mass with mostly cystic, thin walls
28 yr old female with left upper quadrant abdominal pain
CT: Pancreatic mass with mostly cystic, thin walls

37. CT: Pancreatic mass mostly cystic with peripheral calcifications
37 yr old female with early satiety and abdominal discomfort
CT: Pancreatic mass mostly cystic with peripheral calcifications

38. MRI Findings
Improved visualization of capsule and internal hemorrhage, hence more specific
Well-defined encapsulated lesion
T1: Heterogeneous hypointense or hyperintense signal relative to adjacent pancreatic parenchyma
T2: Heterogeneously hyperintense signal

39. MRI Findings Hematocrit effect: Fluid-fluid or fluid-debris levels
T1 and T2: Peripheral hypointense rim
T1 Post-Gadolinium
Arterial phase: Heterogeneous peripheral enhancement
Portal and delayed phase: Progressive heterogeneous fill-in (incomplete)

40. T1
T2 Fat Sat
20 yr old female with RUQ abdominal pain
MRI: Low signal intensity mass in the neck of the pancreas on T1WI and high signal intensity on T2WI with fat saturation

41. Classifying SPEN by MRI
Influences surgical strategy
Type 1: High signal on T1 and T2 – subacute
Type 2: Low signal on T1 and high signal on T2 – chronic phase after bleeding
Type 3: Low signal on T1 and homogeneous intermediate signal on T2 -- no bleeding
Type 1 and 2 lesions had peripheral rims corresponding to fibrous capsule
Type 3 had only partial capsules indicative of invasive disease, requiring extensive operations

42. Other Imaging Endoscopic ultrasonography Arteriography: Calcifications
Useful in diagnosis tumors that measure less than 2 cm; Limited utility as most SPEN > 4cm
Provides guidance for FNA
Arteriography:
Avascular or hypovascular mass
Useful in differentiating from islet cell tumors which are typically hypervascular
Calcifications
Case report of detection by bone scintigraphy
Rarely seen on abdominal plain film x-rays

43. 13 yr old Haitian female with abdominal fullness
Arteriography : Large hypovascular mass body and tail of the pancreas. Note the displacement of the SMA to the right

44. Differential Diagnosis
Cystic islet cell tumor
Serous microcystic adenoma
Mucinous cystic neoplasm
Intraductal papillary mucinous tumor
Acinar cell carcinoma
Papillary cystadenocarcinoma
Pancreatoblastoma
Vascular tumors: Hemangioma, lymphangioma, angiosarcoma
Calcified hemorrhagic pseudocyst
Inflammatory pseudocyst
Dysgenetic cyst, as seen in von Hippel-Lindau and polycystic kidney disease
Retention cyst, as seen in cystic fibrosis

45. Differential Diagnosis
Islet cell tumors
SPEN commonly misdiagnosed as non-functioning islet cell tumors
Islet cell tumors are hypervascular with different CT/MRI enhancement patterns
Cystic components have moderately elevated signal intensity on T1 and increased signal on T2
Pancreatoblastoma
Childhood malignant neoplasm with poor prognosis
Male predominance
No intratumoral hemorrhage

46. Differential Diagnosis
Acinar cell carcinoma
Always malignant
Affects both genders in 6th or 7th decades
Pancreatic pseudocyst
Thin walls
Totally cystic lesion without any solid component
History of pancreatitis
Intraductal papillary mucinous tumor
Dilatation of the main pancreatic duct
Soft villous tumor associate with Wirsung’s duct

47. Differential Diagnosis
Microcystic adenoma
Female predominance presenting in 6th decade
CT reveals low-attenuation with marked enhancement with “honeycomb pattern”
Echogenic central stellate scar
No peripheral or capsular enhancement on MRI
Mucinous cystic tumors
Female predominance presenting in 5th - 6th decades
Large mucin-secreting cysts
Multilocularity with thin septations

48. Treatment Definitive treatment is surgical
Partial pancreatectomy (48%)
Whipple procedure (29%)
Local excision (17%)
Pancreatectomy (6%)
No known role for chemotherapy or radiation therapy
Past cases have resulted in recurrence
Requires lengthy follow-up because of inability to determine aggressive behavior

49. Prognosis Surgical resection is often curable
Long-term survival is the rule despite local invasiveness
Not related to pathology
Microscopic positive margins not significant predictors of survival

50. Complications Metastatic disease (6-15%)
Predilection for males and older patients
Predominantly to the liver, less commonly to lymph nodes
Also described in spleen, colon, mesentery, skin, lung, generalized carcinomatosis
May be microscopic and undetectable by imaging
Long-term survival in 10-15% patients

51. Complications Pseudocyst formation Death (4%) Hemorrhagic coagulopathy
Cholangitis
Septic shock

52. Solid Pseudopapillary Carcinoma
SPEN/SPT with clear malignant criteria
Vascular and nerve sheath invasion
Metastasis to lymph node or liver
Morphologically identical to SPEN
Average age at presentation: 30
Slightly older than that of SPEN
Uncertain whether SPEN becomes malignant with tumor growth

53. Interesting Case
History: 24 year old black female presents to the ER with acute onset of abdominal pain. Pain is epigastric, sharp, and constant. Denies fever, nausea, vomiting, constipation, or diarrhea
Labs: Elevated LFT’s

54. CT: 2 x 2 cm mass located in the porta hepatis
CT: 2 x 2 cm mass located in the porta hepatis. CT-FNA was nondiagnostic

55. MRI: T1W images demonstrate hypointense mass in porta hepatis

56. MRI: Note the mass has relatively high signal on T2W image

57. MRCP: Obstruction of the biliary system at the biliary bifurcation and proximal CHD (mass effect)
Surgical pathology reveals solid mass engulfing bifurcation of CBD with extension to cystic and hepatic ducts
Cut section: Solid and cystic, filled with necrotic debris

58. Interesting Case
Histology: Fibrous capsule with lobules containing papillary pattern, consisting of epithelial cells around hyalinized fibrovascular stalks
RBC’s in spaces between papillary structures
Extensive perineural invasion and focal lymphovascular space involvement

59. Interesting Case
Diagnosis: Solid and papillary epithelial neoplasm of the extrahepatic bile ducts
Majority of extrapancreatic SPEN (a very rare entity) affiliated with heterotopic pancreatic tissue

60. Review Quiz Who is most likely to be affected by SPEN?
70 year old black male
6 year old white female
21 year old Asian female
45 year old white male

61. Review Quiz The answer is C, 21 year old Asian female.
SPEN has a racial predilection for young females, predominantly in the black and Asian population.

62. Review Quiz Which is uncharacteristic of SPEN? Internal hemorrhage
Cystic mucinous secretions
Fluid-debris levels
Fibrous capsule

63. Review Quiz The answer is B.
Cysts are seen in almost every case of SPEN. However, mucin secretion is NOT characteristic of this neoplasm. Such secretions are seen in mucinous cystic tumors of the pancreas, which is included in the differential diagnosis of SPEN.

64. Review Quiz MRI imaging offers which benefit?
Improved detection of intratumoral blood
Better visualization of the capsule
Specific enhancement pattern
All of the above

65. Review Quiz The answer is D, all of the above.
MRI offers all of the mentioned benefits, making it a more specific test than CT or ultrasound in the diagnosis of SPEN.

66. Review Quiz Which of the following statements about SPEN is false?
Clinical presentation is classic
Stains negative for chromogranin A
Fibrovascular stalks are seen in cytology
Pseudocyst is in the differential diagnosis

67. Review Quiz The answer is A.
SPEN presents with vague abdominal symptoms, including fullness, pain, and early satiety. However, presentation is anything but classic.

68. Review Quiz What percent of SPEN metastasize? Almost never 5-15% 50%
Greater than 80%

69. Review Quiz The answer is B, 5-15%.
SPEN has low malignant potential. Hence it is mandatory to establish early diagnosis, as surgical removal of tumor offers an excellent prognosis. Even in cases of local invasiveness or metastasis, the outcome can be promising if properly treated.

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