Case 5 -

Solid pseudopapillary (SPN) of the Tail of the Pancreas Gladwyn Leiman Fletcher Allen Health Care University of Vermont, Burlington, VT

Click on slide thumbnail images for an enlarged view.

If you have any difficulties viewing these slides, email the webmaster.

Clinical History: 57 year old man with 4cm heterogeneous mass in the tail of the pancreas; FNA performed under endoscopic ultrasound guidance. Case 5 - Figure 1 Low power view of dispersed cells with rare tumor giant cells (Papanicolaou stain). Case 5 - Figure 2 Medium power emphasizing small cell size and multinucleated giant cells (Papanicolaou stain) Case 5 - Figure 3 At high magnification, note bland chromatin in mononuclear cells (Papanicolaou stain) Case 5 - Figure 4 Low power view emphasizing areas with good cellular cohesion (Giemsa stain) Case 5 - Figure 5 High power of airdried slide demonstrating small nuclear size compared iewth rbc's (Giemsa stain) Case 5 - Figure 6 Medium magnification displaying vascular association of monotonous tumor cells (Papanicolaou stain) Case 5 - Figure 7 Area of neplastic cells surrounding hint of amorphous material (Papanicolaou stain) Case 5 - Figure 8 High power view of central core of tumor cell mass (Papanicolaou stain) Case 5 - Figure 9 Air-dried slide showing complex vascular core (Giemsa stain) Case 5 - Figure 10 Beta-catenin immunostaining of FNA slide Case 5 - Figure 11 Surgical resection specimen shoeing classic features of solid pseudopapillary neoplasm of pancreas (H&E stain) Introduction: Fifty years after its first recognition by Frantz as a distinct and unique entity in 1959, Solid-Pseudopapillary Neoplasm (SPN) of the pancreas remains a Still Puzzling Neoplasm in some respects! Although it accounts for less than 2% of epithelial neoplasms of the exocrine pancreas, its generally excellent prognosis and resectability in most cases, makes it an important entity for cytopathologic recognition. The neoplasm predominantly occurs in very young persons, mostly female, in their teens and twenties. What is less well known about this neoplasm is that in the Far East, particularly in Japan, and to a lesser extent in Africa and in African Americans, it appears that SPN occurs in men as well as women, and in older age groups, at a higher incidence than in the West. The current case is of a 57-year-old Vermont man, preoperatively diagnosed as having an SPN on endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in; subsequent histopathological correlation was confirmatory. The patient was a Vietnamese male who had lived in the north-eastern US for approximately twelve years. Pathological/Microscopic Findings and any Immunohistochemical or Other Studies: The cytopathology of SPN is relatively well known, despite the rarity of the tumors encountered in the West. Tumor may occur throughout the pancreas and frequently reaches large sizes. Mean sizes are quoted as 8-10 cm. The tumors may be found as incidental lesions in patients undergoing upper GI and ultrasound or endoscopy for vague abdominal pain. Aspirates are usually highly cellular and consist of small cells lying singly in the background, or in loose clusters, and most characteristically attached to intact fibrovascular cores giving the "pseudopapillary" appearance. If the vascular core is branching and complex, the vessel-associated cell aggregates have been compared with Chinese lettering. In the background, myxoid material may be identified, together with many degenerating tumor cells. Within the fibrovascular core of the pseudopapillae, metachromatic staining is characteristically seen on air-dried slides. Further, hyaline globules have been reported either extracellularly or within glands in these cases. Nuclei of SPN have very fine granular chromatin and small nucleoli. Longitudinal grooving is fairly characteristic. These features assist in the distinction of SPN from pancreatic endocrine neoplasms (PENs). Differential Diagnoses: The most common misdiagnosis in large series of SPN is found to be pancreatic endocrine neoplasms (PEN), as these may be found in a younger age group, may be both cystic or solid, and may also result in FNAs displaying a small celled population. PENs, however, lack papillary architecture, hyaline grooves, and particularly the fine grooved chromatin of SPN. Nevertheless, immunochemistry is strongly advisable. Nuclear catenin expression is absent, and chromogranin positive in PENs; these are therefore the two most helpful stains in the distinction of SPN and PEN. Pancreatoblastoma usually affects children younger than 10, although cases in adults have been described. The nested cells are small, separated by quite cellular stroma. The cytology also reveals two cell populations, epithelial and immature mesenchymal cells. Heterologous elements may be found and squamoid corpuscles are a diagnostic hallmark. This is a tumor which, like SPN and acinar cell carcinoma, may exhibit β-catenin nuclear immunoreactivity. It will not, however, have the characteristic pseudopapillary architecture. Final Diagnosis: Solid pseudopapillary (SPN) of the tail of the pancreas in a 57 year old man living in Vermont. Case Discussion: Characteristics of SPN The exact cell of origin of SPN has yet to be finally determined. Hypotheses over the decades have varied with consideration of islet cells cells, ductal cells and acinar cells as likely progenitors. At this point, it is best regarded as a tumor of the exocrine pancreas derived from the "ductal-acinar unit". Innumerable cases, totaling about 750, have been reported in the English literature, reflecting not only increased awareness of the entity, but also increasingly early diagnosis after the advent of EUS-FNA. The average age has been quoted to be 22 and 28 years in different literature sources. The range, however, is very extensive, quoted from 2 to 85 years. Whereas pancreatoblastoma is the most common tumor in the first decade of life, SPN is the predominant tumor in the second and early third decades of life. SPN has not been linked to any known clinical or genetic syndrome, but because of its peculiar predilection for young women, it has been investigated and certainly does show both estrogen and progesterone receptors in many cases. Recent evidence has identified β-catenin mutation in most SPNs. This results in activation of the Wnt pathway, which is usually down regulated in adults. This finding not only permits very definitive diagnosis by β-catenin staining, but may also bring into focus the mysteries of tumorigenesis of this neoplasm. Axon 3 of the β-catenin gene is the target of point mutation in most cases. Solid-pseudopapillary neoplasms in men It is now established that some Asian and some black populations have a higher incidence of this neoplasm in male patients than in Western countries. Furthermore, in males, the disease is not exclusive to teenagers and young adults, but rather may be found in an older, and male population. Thus, in one study from Japan, the male to female ratio in patients under 50 was 1:10, whereas that in patients 50 years or older was 1:3. Men in their eighth decade have been diagnosed with this entity in the East. In one review, the tumors were of larger size in those over 50 (9.8 vs 7.5 cm), and furthermore demonstrated malignant change more frequently in the older males than in those under 50 (66.7% vs 16.6%) (2009 Takahashi, H). In a separate and later study (2010, Takahashi, Y), also emanating from Japan, SPNs were investigated as to possible differences between men and women in terms of their histopathology and their diagnostic features. This study was performed on resection specimens accumulated over 14 years. The findings suggested that SPNs in men tend to be more solid, with slower progression of degenerative changes during their growth compared to that of women. All SPNs, whether from male or female patients, demonstrated nuclear and cytoplasmic accumulation of β-catenin protein by immunochemistry, thus permitting definitive diagnosis despite the unexpected gender and age of some of these patients. Neither ductal adenocarcinomas nor pancreatic endocrine tumors are associated with mutations in the β- catenin gene. Immunochemistry Until the most recent work on β-catenin was conducted, which now allows very characteristic staining of SPN, many other markers were used in an attempt to separate SPN from other tumors in which small cell size is comparable. Hence, SPN has also been shown to express vimentin, CD10, CD56 and, in 30% of cases, keratin. As one of the main differential diagnoses is NET, it is interesting to note that SPN will stain for synaptophysin in a fair number of cases, but chromogranin is always negative. As mentioned previously, SPN will also stain positively for the presence of progesterone, as well as for estrogen receptor B (but not A). Alpha-1 antitrypsin may be positive, highlighting the PAS-positive hyaline granules if present. Reflective of the indolent nature of this tumor, expression of Ki-67 is usually low. Review of the Literature/Treatment Options: This particular required a distal pancreatectomy only, and is currently well, undergoing long term surveillance. Conclusion(s): A case of SPN in a 57-year-old adult male has been presented. It was unusual in that it occurred in an Asian male, but the diagnosis was made in the low incidence area of New England. Preoperative positive beta-catenin staining of an EUS-FNA supported the morphologic diagnosis, which was based on the presence of pseudopapillary architecture and monotonous nuclei without characteristics of endocrine neoplasia. The tumor was amenable to resection, which is hoped will be curative in this patient. References: Basturk O, Coban I, Adsay NV. Pancreatic cysts: pathologic classification, differential diagnosis, and clinical implications. Arch Pathol Lab Med 2009; 133:423- 438. Chakhachiro ZI, Zaatari G. Solid-pseudopapillary neoplasm: a pancreatic enigma. Arch Pathol Lab Med 2009; 133:1989-1993. Kim M-J, Jang S-J, Yu E. Loss of E-Cadherin and cytoplasmic-nuclear expression of β-catenin are the most useful immunoprofiles in the diagnosis of solid- pseudopapillary neoplasm of the pancreas. Human Path 2008; 39:251-258. Klimstra DS, Pitman MB, Hruban RH. An algorithmic approach to the diagnosis of pancreatic neoplasms. Arch Pathol Lab Med 2009; 454-464. Takahashi H, Hashimoto K, Hayakawa H, Kusakawa M, Okamura K, Kosaka A, Mizumoto R, Katsuta K. Solid cystic tumor of the pancreas in elderly men: report of a case. Surg Today 1999; 29:1264-1267. Takahashi Y, Hiraoka N, Onozato K, Shibata T, Kosuge T, Nimura Y, Kanai Y, Hirohasi S. Solid- pseudopapillary neoplasms of the pancreas in men and women: do they differ? Virchows Arch 2006; 448:561-569.