Solid Pseudopapillary Neoplasm of the Pancreas Associated

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□ CASE REPORT □

Solid Pseudopapillary Neoplasm of the PancreasAssociated with Familial Adenomatous Polyposis

Tadahisa Inoue 1, Yuji Nishi 1, Fumihiro Okumura 1, Takashi Mizushima 1, Hirotada Nishie 1,

Hiroyasu Iwasaki 1, Kaiki Anbe 1, Takanori Ozeki 1, Kenta Kachi 1, Shigeki Fukusada 1,

Yuta Suzuki 1, Akira Mizuno 2, Masaki Kajikawa 2, Kazuko Watanabe 3 and Hitoshi Sano 1

Abstract

A man in his thirties visited our hospital for an evaluation of a 12×10-mm pancreatic solid tumor that was

accidentally detected on computed tomography performed for follow-up of familial adenomatous polyposis

(FAP). We diagnosed the patient with a solid pseudopapillary neoplasm (SPN) based on endoscopic

ultrasound-guided fine-needle aspiration, and he underwent pancreaticoduodenectomy. Small SPN tumors ap-

pear as solid tumors, without typical features of SPN, making the definitive diagnosis more difficult. The ge-

netic background of FAP patients can predispose them to SPN, and imaging of the pancreas should be per-

formed at prescribed intervals in FAP patients.

Key words: solid pseudopapillary neoplasm, familial adenomatous polyposis, β-catenin, endoscopic

ultrasound-guided fine-needle aspiration

(Intern Med 54: 1349-1355, 2015)(DOI: 10.2169/internalmedicine.54.4061)

Introduction

Solid pseudopapillary neoplasms (SPNs) of the pancreas

are rare, accounting for approximately 0.17-2.7% of all exo-

crine pancreatic tumors (1). Most SPN patients are women;

less than 10% of reported SPN patients in the literature are

men (2). SPN is usually detected as a heterogeneous mass

with a combination of solid and cystic areas, with larger tu-

mors containing areas of calcification in the tumor wall. In

contrast, small SPN tumors appear as solid tumors and lack

these typical features, making the definitive diagnosis more

difficult.

We herein present a case of SPN with a very small lesion

in an adult man. SPN was accidentally detected during

follow-up for familial adenomatous polyposis (FAP). The

clinicopathological features of SPN remain uncertain. How-

ever, it is possible that the genetic background of patients

with FAP predisposes them to developing SPN (3, 4). In

fact, patients with SPN associated with FAP have been re-

ported, although the number of cases is very few (5). We

believe that the present case is informative with respect to

the relationship between SPN and FAP. We thus present this

case along with a review of the literature.

Case Report

A Japanese man in his thirties visited our hospital for an

evaluation of a pancreatic tumor accidentally detected on

computed tomography (CT) performed for the follow-up of

FAP. The patient had a history of FAP and colon cancer,

while his father, paternal grandmother and all six paternal

uncles and aunts also had colon cancer and his sister had

colon polyposis. He currently had no symptoms, and the

laboratory findings were normal, including the levels of tu-

mor markers (Table). CT of the abdomen revealed a 12×10-

mm round solid mass in the pancreatic head (Fig. 1). The

tumor was increasingly enhanced, although the extent of en-

hancement was less than that observed in the non-tumor pa-

renchyma of the pancreas (Fig. 2). No cystic areas or sites

１Department of Gastroenterology, Gifu Prefectural Tajimi Hospital, Japan, ２Department of Surgery, Gifu Prefectural Tajimi Hospital, Japan and３Department of Pathology, Gifu Prefectural Tajimi Hospital, Japan

Received for publication September 7, 2014; Accepted for publication October 13, 2014

Correspondence to Dr. Tadahisa Inoue, [email protected]

Intern Med 54: 1349-1355, 2015 DOI: 10.2169/internalmedicine.54.4061

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Figure　1.　Abdominal computed tomography. (a) axial view; (b) coronal view. Computed tomogra-phy of the abdomen revealed a 12×10-mm round, solid mass (arrow) in the pancreatic head.

a b

Table.　Laboratory Findings.

WBC 4,700 / L Total protein 6.5 g/dL CEA 2.47 ng/mL

RBC 4.31×106 / L Albumin 4.0 g/dL CA19-9 11.98 U/mL

Hemoglobin 12.6 g/dL AST 21 IU/L

Platelets 34.3×104 / L ALT 21 IU/L

ALP 191 IU/L

Total bilirubin 1.17 mg/dL

BUN 10.2 mg/dL

Creatinine 0.79 mg/dL

Na 136 mEq/L

K 4.3 mEq/L

Cl 103 mEq/L

Amylase 111 IU/L

CRP 0.07 mg/dL*WBC: white blood cells, RBC: red blood cells, AST: aspartate aminotransferase, ALT: alanineaminotransferase, ALP: alkaline phosphatase, BUN: blood ureanitrogen, CRP: C-reactive protein,CEA: carcinoembryonic antigen, CA19-9: carbohydrate antigen 19-9

of calcification were detected in the tumor. T1-weighted

magnetic resonance imaging (MRI) of the lesion showed a

low signal intensity, whereas T2-weighted and diffusion-

weighted images showed hyperintense signals (Fig. 3). How-

ever, no signs of hemorrhage or low-intensity rims were de-

tected on T2-weighted MRI. Meanwhile, 18F-fluorodeoxy-

glucose-positron emission tomography (FDG-PET) showed

abnormal accumulation in the tumor (maximum standardized

uptake value, 3.6) (Fig. 4); no abnormal accumulation was

observed in any organs on FDG-PET. Furthermore, endo-

scopic ultrasonography (EUS) revealed a low echoic, round

tumor that was well demarcated from the surrounding pan-

creas (Fig. 5). The intratumoral echo density was slightly

heterogeneic; however, no cystic components were observed.

Although endoscopic retrograde cholangiopancreatography

(ERCP) showed no abnormalities of the pancreatic duct, the

duodenal papillae exhibited swelling, and adenoma was di-

agnosed based on the findings of the biopsy specimen

(Fig. 6).

According to these results, we set out to diagnose the

duodenal papillary adenoma and pancreatic head tumor. We

considered that the pancreatic tumor may be an adenocarci-

noma, acinar cell neoplasm, neuroendocrine neoplasm, SPN

or metastatic lesion. However, it was difficult to make a de-

finitive diagnosis based solely on the imaging results. We

therefore performed endoscopic ultrasound-guided fine-

needle aspiration (EUS-FNA) of the pancreatic head tumor.

Tissue samples were successfully obtained, and microscopy

revealed that the tumor cells contained eosinophilic cyto-

plasm and small, round nuclei. Immunohistochemically, the

tumor cells demonstrated positive staining for CD10,

vimentin and β-catenin (Fig. 7). Based on these findings, we

suspected a diagnosis of SPN, and pancreaticoduodenectomy

was performed.

The examination of the surgically resected specimen re-

vealed a 12×10-mm solid tumor in the pancreatic head. The


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Figure　2.　Dynamic contrast-enhanced computed tomography. (a) non-enhanced; (b) arterial phase; (c) portal venous phase; (d) equilibrium phase. The pancreatic head tumor was increasingly en-hanced, although the extent of enhancement was less than that observed in the non-tumor parenchy-ma of the pancreas.

a b c d

Figure　3.　Magnetic resonance imaging. (a) T1-weighted images (in phase); (b) T1-weighted images (out of phase); (c) T2-weighted images; (d) diffusion-weighted images. T1-weighted magnetic reso-nance imaging of the pancreatic head tumor (arrow) showed a low-intensity signal; T2- and diffusion-weighted images showed a hyperintense signal.

cut section contained a yellow, solid tumor that was well de-

marcated from the surrounding pancreas. The tumor did not

contain cystic components, and the histological findings

were similar to those of the EUS-FNA specimen. In particu-

lar, tumor cells with eosinophilic cytoplasm and small,

round nuclei were arranged around fibrovascular stalks and

displayed a pseudopapillary structure (Fig. 8). The final

pathological diagnosis of the pancreatic head tumor was

SPN. In contrast, the duodenal papillae was diagnosed as

low-grade adenoma without malignancy. No other lesions

were observed in the resected area, including the duodenum.

Discussion

SPN of the pancreas was first reported by Frantz in

1959 (6). According to the WHO classification, SPN is “a

low-grade malignant neoplasm composed of poorly cohe-

sive, monomorphic epithelial cells forming solid and pseu-

dopapillary structures. These neoplasms frequently undergo

hemorrhagic-cystic degeneration and occur predominantly in

young women (7).” The reported incidence of SPN is ex-

tremely low, accounting for only 0.17-2.7% of all exocrine

pancreatic tumors (1). In addition, only 10% of reported


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Figure　4.　18F-fluorodeoxyglucose-positron emission tomography showed abnormal accumulation in the pancreatic head tumor (arrow) (maximum standardized uptake value: 3.6).

Figure　5.　Endoscopic ultrasonography (EUS) revealed a low echoic, round tumor (arrow) that was well demarcated from the surrounding pancreas.

SPN patients are men (2). Most SPNs occur in the body or

tail of the pancreas and form large tumors (average size, 10

cm) (8). SPN lesions usually display calcification and signs

of degeneration, including hemorrhage and necrosis. There-

fore, diagnostic imaging, including CT, MRI and EUS, often

shows heterogeneous tumors with a combination of solid

and cystic areas. SPNs are initially solid tumors, although

they change over time into heterogeneous tumors with solid

and cystic areas exhibiting degeneration. Therefore, small-

sized tumors may not present with the typical features of

SPN. In fact, the tumor in the current case was very small

(12×10 mm) and appeared to be completely solid, with no

typical features of SPN, such as cystic areas, thick walls or

calcification. In addition, MRI showed the tumor to be al-

most homogeneous, and no signs of hemorrhage or necrosis

were observed. Furthermore, our patient was an adult man,

and the tumor occurred in the pancreatic head. We were un-

able to diagnose the tumor solely based on the imaging re-

sults. The relative risk of pancreatic adenocarcinoma in pa-

tients with FAP is reported to be 4.5 (9), and various tumor

complications, such as acinar cell carcinoma, may oc-

cur (10). Therefore, EUS-FNA was performed to obtain a

definitive diagnosis in this case.

EUS-FNA has been established to be a useful tool with

good diagnostic accuracy for detecting pancreatic tu-

mors (11), including SPNs (12). Romics et al. proposed an

algorithm for the diagnosis and treatment of SPN (13), ac-

cording to which, surgery should be performed if the tumor

shows typical features of SPN on US, CT and MRI. If the

radiological diagnosis is equivocal and further confirmation

is required, EUS-FNA is recommended. Even in cases in-

volving a tumor size of �10 mm, the diagnostic accuracy of

EUS-FNA is reported to be very good (14). The tumor in

the present case was 12×10 mm in size, and the tissue ob-


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Figure　6.　Endoscopic retrograde cholangiopancreatography (ERCP) showed no abnormalities of the pancreatic duct (a); however, the duodenal papillae were swollen (b), and adenoma was diagnosed based on the biopsy specimen.

a b

Figure　7.　Histopathology of the EUS-FNA specimen. Hematoxylin and Eosin staining (a) showed that the tumor cells contained eosinophilic cytoplasm and small, round nuclei. Immunohistochemi-cally, the tumor cells stained positively for CD10 (b), vimentin (c) and β-catenin (d).

tained via EUS-FNA was immunostained adequately, allow-

ing us to diagnose the tumor as SPN.

FAP is an autosomal dominant disease caused by a germ-

line mutation in the adenomatous polyposis coli (APC)

gene, resulting in the formation of hundreds to thousands of

large intestine adenomas. Colorectal cancer inevitably devel-

ops unless the tumors are removed (15, 16). FAP patients

may also develop a variety of extra-large intestinal and

extra-intestinal lesions, including duodenal papillary tumors,

desmoid tumors and thyroid tumors (10, 17). A point muta-

tion in exon 3 of CTNNB1, which encodes β-catenin, is de-

tected in most cases of SPN. Cytoplasmic β-catenin is ex-


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Figure　8.　Histopathology of the surgical specimen. A 12×10-mm solid tumor was detected in the pancreatic head (a). The cut section revealed a yellow, solid tumor (arrow) that was well demarcated from the surrounding pancreas (b). Tumor cells with eosinophilic cytoplasm and small, round nuclei were arranged around fibrovascular stalks and displayed a pseudopapillary structure (c, d).

pressed at low levels under normal conditions and increased

in most patients with SPN (18, 19). The FAP-related muta-

tion in APC activates the Wnt/β-catenin signaling pathway.

As a result, the cytoplasmic β-catenin expression increases,

as it does in cases involving the SPN-related CTNNB1 muta-

tion (20). Therefore, patients with FAP may develop tumors

commonly seen in those with CTNNB1. However, based on

our literature search, we were able to find only one case of

concurrent FAP and SPN (5). The fact that both FAP and

SPN are rare diseases and FAP can easily complicate cases

of pancreatic and duodenum papilla cancer may explain the

reduced rate of concurrent SPN cases. The current patient

was confirmed to have an APC mutation on a genetic ex-

amination, and the tumor specimen was shown to express

cytoplasmic β-catenin. These factors suggest that this case

of SPN occurred as a result of the FAP-related mechanism

described above. Furthermore, the present patient was male

with primary onset in the pancreatic head, which is atypical

for SPN. A case of FAP with primary onset in the pancre-

atic head has also been reported in a woman (5). Therefore,

a causal relationship with the site of onset is suspected, al-

though the details remain unclear due to the lack of avail-

able cases.

SPN is classified as a low-grade malignant neoplasm.

SPN patients treated with complete surgical resection have a

good prognosis (21). However, approximately 15-20% of

cases of SPN manifest with malignant behavior, including

perineural or vascular infiltration and metastasis (22, 23).

Fatal cases of recurrence have been reported (24). Therefore,

the diagnosis of SPN and subsequent surgical resection

should be performed without delay. In the present case, we

detected the tumor at a very early stage by chance because

CT was performed for the follow-up of FAP. As patients

with FAP may develop a variety of tumors, routine imaging

of the pancreas should be conducted at designated intervals

and practitioners should keep in mind the fact that FAP can

predispose patients to SPN.

The authors state that they have no Conflict of Interest (COI).

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Solid Pseudopapillary Neoplasm of the Pancreas Associated