Solid-Pseudopapillary Tumor of the Pancreas

Background

This rare pancreatic tumor has a predilection for occurring in young women and has an indolent growth pattern. These tumors tend to be evenly distributed throughout the pancreas ranging in size from 1.4-13 cm.

OUTLINE

Epidemiology

Disease Associations

Pathogenesis

Laboratory/Radiologic/Other Diagnostic Testing

Gross Appearance and Clinical Variants

Histopathological Features and Variants

Special Stains/
Immunohistochemistry/
Electron Microscopy

Differential Diagnosis

Prognosis

Treatment

Commonly Used Terms

Internet Links

EPIDEMIOLOGY CHARACTERIZATION

SYNONYMS Frantz's tumor
Solid and cystic acinar tumor
Papillary epithelial neoplasm
Solid and Papillary Epithelial tumor/neoplasm

INCIDENCE Rare

AGE RANGE-MEDIAN 12-71 years

SEX (M:F)
Female predominance

PATHOGENESIS CHARACTERIZATION

GENERAL Speculated to be ductal, acinar, ductaloacinar

Solid and Pseudopapillary Tumor of the Pancreas-Review and New Insights Into Pathogenesis.

Geers C,
Pierre M,
Jean-Francois G,
Birgit W,
Pierre D,
Jacques R,
Christine S.

Departments of *Pathology daggerSurgery double daggerGastro-enterology, Cliniques Universitaires Saint Luc, UCL, Brussels, Belgium.

Am J Surg Pathol. 2006 Oct;30(10):1243-1249 Abstract quote

Solid pseudopapillary tumors (SPT) of the pancreas are rare neoplasms that occur mostly in young women. Despite of a low malignant potential, 10% to 15% of the cases have aggressive behavior with metastatic dissemination possibly leading to death. To date, no pathological factor can reliably predict the outcome of these tumours.

Galectin-3, a major actor in the carcinogenesis of pancreatic ductal adenocarcinoma, has not been investigated in SPT. The presence of progesterone receptors is frequently reported in SPT, whereas that of estrogen receptor (ER) is unclear.

We studied 5 cases of SPT consisting of 4 pancreatic tumors and 1 metastatic case. The morphological distinctive feature of metastatic nodules was the presence of polygonal or spindle cells with pleiomorphic nuclei and high mitotic count exhibiting a diffuse, infiltrative growth pattern.

We found a strong expression of galectin-3 in all SPTs, whereas, interestingly, it was lower in metastatic nodules. Conversely, no galectin-3 expression was found in normal pancreatic endocrine cells or in neuroendocrine tumors. We suggest therefore that galectin-3 is a useful marker to distinguish SPT from neuroendocrine tumor, and also indicator of behavior because its low expression is associated with metastatic spreading. Moreover, the presence of galectin-3 in both SPT and pancreatic ducts rises the hypothesis of a posible ductal origin of these tumors. Specific antibodies for anti-ERalpha and anti-ERbeta demonstrated a strong expression of ERbeta whereas ERalpha was not detected.

In conclusion, the present study brings the first evidence of the involvement of galectin-3 in SPT but also brought up clues which allowed to reconcile previously conflicting results on the presence of ER.

E-CADHERIN

E-cadherin/Catenin Complex Status in Solid Pseudopapillary Tumor of the Pancreas.

El-Bahrawy MA, Rowan A, Horncastle D, Tomlinson I, Theis BA, Russell RC, Stamp G.

*Department of Histopathology, Imperial College, Hammersmith Campus †Molecular and Population Genetics Laboratory, London Research Institute, Cancer Research UK ‡Department of Histopathology, Hammersmith Hospital, London §Department of Surgery, University College London, UK.

Am J Surg Pathol. 2008 Jan;32(1):1-7. Abstract quote

Solid pseudopapillary tumor (SPT) of the pancreas is an uncommon neoplasm of uncertain lineage. They have been shown to express nuclear beta-catenin believed to be due to mutations of the beta-catenin gene. The aim of this study was to investigate the status of the E-cadherin/catenin complex in SPTs.

We studied the expression of 4 principal members of the E-cadherin/catenin complex using immunohistochemistry and the E-cadherin gene status by screening all exons of the gene for mutations, in 6 cases of SPT. In addition to the nuclear localization of beta-catenin, we found nuclear localization of E-cadherin in all tumors with complete absence of membranous and cytoplasmic localization. Nuclear localization of E-cadherin was independent of beta-catenin. No mutations were identified in the E-cadherin gene in any of the tumors.

Ten cases of pancreatic adenocarcinomas and 15 neuroendocrine tumors were studied as well for comparison. The reported changes in the expression of the principal members of the E-cadherin/catenin complex were unique to SPTs.

Our study shows abnormalities in the expression of 4 principal members of the E-cadherin/catenin complex in SPTs, which may help to explain the discohesive nature of the cells and the cystic changes in these tumors, and provide additional diagnostic features.

Wnt PATHWAY

Solid pseudopapillary neoplasms of the pancreas show an interruption of the Wnt-signaling pathway and express gene products of 11q.

Tiemann K, Heitling U, Kosmahl M, Klöppel G.

1Department of Pathology, University of Kiel, Kiel, Germany.

Mod Pathol. 2007 Sep;20(9):955-60 Abstract quote

Solid pseudopapillary neoplasms of the pancreas almost consistently show a beta-catenin mutation activating the Wnt-signaling pathway, resulting in overexpression of cyclin D1, but not in overt malignancy of this tumor. Besides cyclin D1, a set of markers (ie FLI-1, CD56 and progesterone receptor), whose genes map to chromosome 11q, are frequently expressed in solid pseudopapillary neoplasms. Chromosome 11q is a region that is also often affected in pancreatic neuroendocrine tumors.

This immunohistochemical study was undertaken to gain insights into the downstream regulation of the Wnt-signaling pathway and the significance of overexpressed gene products belonging to chromosome 11q for the tumorigenesis in solid pseudopapillary neoplasms. Fourteen solid pseudopapillary neoplasms were analyzed for the expression of cyclin-dependent kinase inhibitors p21, p27, p16 and hyperphosphorylated retinoblastoma (pRb) proteins. In an extended series of 93 solid pseudopapillary neoplasms, beta-catenin, cyclin D1, FLI-1 and CD56 expression was examined and compared with that in 22 pancreatic neuroendocrine tumors. Solid pseudopapillary neoplasms (98%) showed aberrant expression of beta-catenin with a concomitant cyclin D1 expression in 69% of the cases, but no expression of pRb (0%) was found. p27 and p21 were expressed in 100% (14/14) and 86% (12/14) of the cases, but only 2/14 (14%) were positive for p16. FLI-1 was expressed in 63% of solid pseudopapillary neoplasms, but only in 1/22 pancreatic neuroendocrine tumors (5%), cyclin D1 expression was present in 14% of the latter.

We conclude that in solid pseudopapillary neoplasms the activated Wnt-signaling pathway is disrupted, and that p21 and p27 are contributing to this fact by blocking of the hyperphosphorylation of the Rb protein, thus causing the very low proliferation rate characterizing the solid pseudopapillary neoplasms. The accumulation of high expression of proteins whose genes are located on chromosome 11q is characteristic of solid pseudopapillary neoplasms, but not of pancreatic neuroendocrine tumors.

CLINICAL VARIANTS CHARACTERIZATION

PEDIATRIC

Solid and papillary epithelial neoplasm of the pancreas in children.

Jung SE, Kim DY, Park KW, Lee SC, Jang JJ, Kim WK.

Department of Surgery, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-ku, Seoul 110-744, Korea.
World J Surg 1999 Mar;23(3):233-6 Abstract quote
Solid and papillary epithelial neoplasm of the pancreas is an uncommon low-grade malignant tumor found predominantly in young females.

In this paper, the authors report the tumor's clinical characteristics and the results of surgery in six children. Six cases of solid and papillary epithelial neoplasm of the pancreas pathologically verified at Seoul National University Children's Hospital between 1985 and 1997 were retrospectively analyzed. Four were girls and two were boys, and their mean age at surgery was 11.2 years (range 8-13 years). All patients presented with an abdominal mass and tumor ranging in size from 6.5 x 6.0 cm to 10.5 x 8.0 cm. Five were located in the head and one in the tail of the pancreas; exploration showed that no case involved local invasion or metastasis. All patients underwent complete resection, which involved five pancreaticoduodenectomies and one distal pancreatectomy. No patient died during surgery, and after a mean follow-up period of 5.5 years (range 1.5-12.5 years) all were alive with no recurrences.

We believe that the malignancy of this tumor is low grade and that the prognosis is good. For a neoplasm arising anywhere in the pancreas, complete resection is the treatment of choice. Solid and papillary epithelial neoplasm of the pancreas of children shows less female preponderance in children than in adults.

Solid-pseudopapillary tumor of the pancreas (Frantz tumor) in children: report of four cases and review of the literature.

Rebhandl W, Felberbauer FX, Puig S, Paya K, Hochschorner S, Barlan M, Horcher E.

Division of Pediatric Surgery, Department of Surgery, General Hospital of Vienna, University of Vienna Medical School, Vienna, Austria
J Surg Oncol 2001 Apr;76(4):289-96 Abstract quote
BACKGROUND: Solid-pseudopapillary tumor of the pancreas (SPT) is an exceptionally rare neoplasm in children. Its origin remains enigmatic. It is of low malignant potential and occurs most frequently in young females.

PATIENTS AND METHODS: A cumulative review of the tumor's clinicopathological characteristics from the world's literature is presented. The clinical course, pathohistologic data and outcome of surgery of four Austrian children treated at the general hospital of Vienna are analyzed.

RESULTS: Between 1987 and 1999, four girls (age: 12--16 years) with SPT were diagnosed at our institution. All patients presented with an abdominal mass and uncharacteristic abdominal pain. Two tumors were located in the tail, one in the body and tail and one in the head of the pancreas (diameter: 7--15 cm). Surgical procedures included three distal pancreatectomies and one partial duodenopancreatectomy (Whipple procedure). One patient had two recurrences with metastases that could only be partially resected. Chemotherapy was initiated for this patient. In the follow-up period (range: 6 months to 12 years) all patients are alive with no evidence of recurrence.

CONCLUSIONS: SPT is a rare differential diagnosis of a pancreatic mass in children. It is mandatory to establish this diagnosis since complete surgical removal of the tumor even in case of metastases or local invasion offers an excellent prognosis.

HISTOPATHOLOGY CHARACTERIZATION

CYTOLOGY

Endoscopic Ultrasound–Guided Fine-Needle Aspiration Cytology Diagnosis of Solid-Pseudopapillary Tumor of the Pancreas

A Rare Neoplasm of Elusive Origin but Characteristic Cytomorphologic Features

Ricardo H. Bardales, MD, Barbara Centeno, MD, J. Shawn Mallery, MD, Rebecca Lai, MD, Mark Pochapin, MD, Gerardo Guiter, MD, and Michael W. Stanley, MD

Am J Clin Pathol 2004;121:654-662 Abstract quote

Clinical histories, endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) material, and immunohistochemical stains performed on cell block samples of 6 solid-pseudopapillary tumors of the pancreas (SPTPs) were reviewed in the cases of 5 females (13-58 years) and 1 man (57 years); all had abdominal pain. Preliminary cytologic diagnoses at endoscopy included 1 SPTP, 2 low-grade neoplasms, and 3 pancreatic endocrine tumors.

Variable numbers of branching fragments with central capillaries and myxoid stroma were seen in the smears of 5 of 6 cases but were more apparent in the cell block material of all cases. The cells had bland nuclear features and rare grooves. Extensive necrosis was noted in 1 case and rare mitotic figures in 1. SPTPs showed strong cellular immunoreactivity for vimentin and focal weak keratin reactivity. Neuron-specific enolase, a₁-antitrypsin, and a₁-antichymotrypsin stains performed in 2 cases were strongly positive. Subsequent surgical resection confirmed all diagnoses.

EUS-guided FNA diagnosis of SPTP is accurate. The characteristic branching papillae with myxoid stroma are best seen in cell block slides.

Clinical setting, cytomorphologic features, and immunostains of the cell block help distinguish SPTP from pancreatic endocrine tumors, acinar cell carcinoma, and papillary mucinous carcinoma.

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.

Tang LH, Aydin H, Brennan MF, Klimstra DS.

From the Departments of *Pathology and daggerSurgery, Memorial Sloan-Kettering Cancer Center, New York, NY.

Am J Surg Pathol. 2005 Apr;29(4):512-519. Abstract quote

Solid pseudopapillary tumors (SPTs) are unusual neoplasms of the pancreas of uncertain histogenesis that occur mostly, but not exclusively, in young women. The pathologic features and immunophenotype of SPT are unique and well characterized. Despite its low malignant potential, proximately 15% of patients with SPT develop metastatic disease, mostly involving the liver or peritoneum. Even in the presence of disseminated disease, the clinical course is usually protracted, and the overall 5-year survival is reportedly 97%.

We have encountered 2 cases of SPT possessing unusual pathologic features and exhibiting an aggressive clinical course. At the time of presentation, 1 patient had liver metastasis, and the other had a lymph node metastasis and developed liver metastases within 3 months. Both died of disease at 6 and 16 months, respectively, following the initial diagnosis. Review of other cases of SPT treated at Memorial Sloan-Kettering Cancer Center (New York, NY) revealed that 5 of 34 cases (15%) with conventional histologic features developed liver metastases.

In contrast to the 2 cases reported here, all 5 patients survived for a mean of 106 months (39-193 months), and only 2 died of disease 5 and 10 years, respectively, following the initial resection. The pathologic features of the two rapidly fatal cases, which might have been indicative of their aggressive behavior, included a diffuse growth pattern, extensive tumor necrosis, significant nuclear atypia, an unusually high mitotic rate (35-70/50 high power fields), and in one a component of sarcomatoid carcinoma. However, regions displaying the typical histologic features of SPT were also evident. Abnormal beta-catenin distribution and markedly increased MIB1 expression were detected by immunohistochemistry in both cases. The immunohistochemical staining patterns were otherwise similar to those of conventional SPTs.

Although precise pathologic criteria suggesting a high risk for aggressive behavior are uncertain, recognition of some of the unusual pathologic features displayed in these 2 cases may be useful in the prediction of potentially more aggressive SPTs. The possibility that these tumors represent high-grade malignant transformation of a conventional low-grade SPT is proposed.

CLEAR CELL

The clear cell variant of solid pseudopapillary tumor of the pancreas: a previously unrecognized pancreatic neoplasm.

Albores-Saavedra J,
Simpson KW,
Bilello SJ.

Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA.

Am J Surg Pathol. 2006 Oct;30(10):1237-42. Abstract quote

Solid pseudopapillary tumor is a rare but distinctive pancreatic neoplasm whose cell phenotype remains a mystery.

We report 3 cases of a previously undescribed variant of solid pseudopapillary tumor of the pancreas composed almost entirely of multivacuolated clear cells (>90%). The cytoplasmic vacuoles did not contain glycogen, mucin, or lipid but seemed to be formed by dilatation of the endoplasmic reticulum and mitochondria. The tumors displayed prominent trabeculae and a solid growth pattern but lacked the characteristic pseudopapillary pattern of the classical solid pseudopapillary tumor. In contrast, the clinical features, gross characteristics, and immunoprofile were similar to those of classical solid pseudopapillary tumor.

Two of the patients were young adult females with well-demarcated tumors involving the body and tail of the pancreas. Tumor cells showed immunoreactivity for vimentin, CD10, CD56, synaptophysin, and nuclear accumulation of beta catenin. In 2 patients, 1 male and 1 female, the tumors were discovered incidentally. Despite vascular invasion in one of the tumors all 3 patients are disease free after distal pancreatectomy.

Clues to distinguish the clear cell variant of solid pseudopapillary tumor from endocrine pancreatic tumor composed of clear cells, clear and foamy cell variants of ductal carcinoma, metastatic renal cell carcinoma, serous cystadenoma and ectopic adrenocortical nodules are provided.

SPECIAL STAINS/
IMMUNOPEROXIDASE CHARACTERIZATION

Special stains

Immunoperoxidase

Positive
CD56
CD10 (Usually focal)
Synaptophysin

Negative
Chromgranin A

Solid-Pseudopapillary Tumor of the Pancreas Immunohistochemical Localization of Neuroendocrine Markers and CD10

Kenji Notohara, M.D.; Shuji Hamazaki, M.D.; Choutatsu Tsukayama, M.D.; Shu Nakamoto, M.D.; Kenji Kawabata, M.D.; Kohichi Mizobuchi, M.D.; Kazuhiro Sakamoto, M.D.; Shigeru Okada, M.D.

From the Department of Pathology I (K.N., S.O.), Okayama University Medical School, Okayama; Department of Pathology (S.H.), Okayama University Hospital, Okayama; Department of Pathology (C.T.), Kurashiki Central Hospital, Kurashiki; Department of Laboratory Medicine (S.N.), Tottori Prefectural Central Hospital, Tottori; Department of Pathology (K.K.), Akashi Municipal Hospital, Akashi; Department of Anatomical Pathology (K.M.), Kagawa Rosai Hospital, Marugame; and Department of Pathology (K.S.), Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan.

Am J Surg Pathol 2000;24:1361-1371 Abstract quote

To clarify the neuroendocrine differentiation and CD10 expression in solid-pseudopapillary tumors (SPTs) of the pancreas, we performed immunohistochemical analysis in 19 such tumors, including one solid-pseudopapillary carcinoma (SPC), along with 20 pancreatic neuroendocrine tumors (PNTs), six acinar cell carcinomas (ACCs), and one pancreatoblastoma (PB).

We used antisera directed against CD56, synaptophysin, protein gene product 9.5, the alpha-subunit of Go protein, chromogranin A, CD10, trypsin, chymotrypsin, various cytokeratins (CKs), CA19-9, vimentin, and alpha-1-antitrypsin (AAT). All SPTs exhibited immunoreactivity for CD56 and CD10, and 15 expressed other neuroendocrine markers focally with the exception of chromogranin A. Frequent clustering of synaptophysin-positive cells was noted. Two cases contained a peculiar nodule that cytomorphologically and immunohistochemically resembled PNT. CD10-positive cells were scarce in one SPC. PNTs were CD56-positive, but often with faint intensity, and staining for other neuroendocrine markers, including chromogranin A, was diffusely positive. CD10 was detected, mostly in a focal pattern, in five PNTs. Pan-CK, CK8, CK18, and CK19 were more frequently demonstrated in PNT than SPT. Vimentin and AAT were often identified in PNT as well and were not specific for SPT. ACCs were CD56-negative, with the exception of one case designated as a mixed acinar-endocrine carcinoma. PB was focally positive for CD56 at the periphery of the tumor nests. Four ACCs and one PB exhibited focal CD10 reactivity.

This study demonstrated the unique immunohistochemical features of SPT. Our results also suggest that SPT exhibits, at least focally, neuroendocrine differentiation, and that these neuroendocrine markers and CD10 are diagnostically useful.

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES

Cystic neoplasms of the pancreas.

Kerlin DL, Frey CF, Bodai BI, Twomey PL, Ruebner B.

Department of Surgery, University of California, Davis Medical Center, Sacramento 95817.
Surg Gynecol Obstet 1987 Dec;165(6):475-8 Abstract quote
Eight patients with cystic neoplasms of the pancreas were seen at four Northern California hospitals between the years 1978 and 1986. Three of the tumors were benign and five were malignant. Three females, whose average age was 61 years, had cystadenomas. Three females and two males, whose average age was 48 years, had mucinous cystadenocarcinomas.

Clinical presentations were similar among all patients. Abdominal pain was a prominent feature. Anorexia, weight loss, nausea and vomiting with a palpable abdominal mass were seen in five of eight patients. Obstructive jaundice was seen in two of eight patients. Among patients with benign lesions, one lesion was in the head and two lesions were in the tail of the pancreas. The malignant lesions were in the head of the pancreas in three patients and in the tail or body in two. A presumptive diagnosis was made preoperatively on the basis of the clinical, laboratory and roentgenographic findings in seven of eight patients. Of the patients with benign tumors, two are alive and well at seven years and four months and one patient was lost to follow-up study at four years. Among the patients with a malignant condition who underwent operation, resection for cure was performed upon four patients. One patient died postoperatively and the other three patients are alive and well without evidence of a recurrence at three and one-half, four and four years after resection. Pancreaticoduodenectomy was performed upon two patients and distal pancreatectomy in another. Palliation was attempted in one critically ill patient with an unresectable tumor by longitudinal pancreaticojejunostomy. This procedure was not effective in providing pain relief because of obstruction of the pancreatic duct by the viscous mucoid secretion of the tumor. The preoperative diagnosis of these very rare tumors is usually possible roentgenographically, especially with the use of the computed tomography scan.

The presence of a thick mucoid secretion of high viscosity is diagnostic of mucinous cystadenocarcinoma. Cystic neoplasms of the pancreas should always be resected, if possible, with the expectation of long term survival.

PROGNOSIS AND TREATMENT CHARACTERIZATION

PROGNOSIS Vascular invasion may be a poor prognostic factor

GENERAL

Solid and papillary epithelial neoplasms of the pancreas.

Zinner MJ, Shurbaji MS, Cameron JL.

Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Md.
Surgery 1990 Sep;108(3):475-80 Abstract quote
Seven patients with solid and papillary epithelial neoplasms of the pancreas are reported. All were young women with a mean age of 22 years (range, 16 to 33 years old). Each patient had a large asymptomatic abdominal mass.

The tumors ranged in size from 7 to 20 cm (average size, 13 cm) and were evenly distributed throughout the head, body, and tail of the pancreas. One patient had a metastatic tumor to her liver, which was unresectable. All other patients underwent resection, which included two distal pancreatectomies, two total pancreatectomies, one pancreaticoduodenectomy, and one local excision. Four of the seven patients had evidence of local invasions alone, and one had a liver metastasis and local invasion. All patients had the characteristic histologic pattern of a solid and papillary epithelial pancreatic neoplasm. All patients are alive with a mean follow-up of 10 years (range, 4 to 20 years).

This is an unusual malignant neoplasm of the pancreas occurring predominantly in young women. Even though they are locally invasive, long-term survival is the rule. Surgical therapy should be aggressive, since liver metastasis may occur.

Recurrence Duodenal invasion with ulceration

Metastasis Rare liver metastasis

TREATMENT Surgical removal

SURGERY

Solid and papillary epithelial neoplasms of the pancreas: aggressive resection for cure.

Yoon DY, Hines OJ, Bilchik AJ, Lewin K, Cortina G, Reber HA.

Department of Surgery, UCLA School of Medicine and Olive View-UCLA Medical Center, Los Angeles, California 90024, USA.

Am Surg 2001 Dec;67(12):1195-9 Abstract quote

Solid and papillary epithelial neoplasms of the pancreas (SPENP) are extremely rare and usually affect young women. We retrospectively reviewed our experience with pancreatic neoplasms from 1986 to the present and identified nine patients with SPENP.

All nine patients were female with a mean age of 32 years (range 16-66). All patients presented with gastrointestinal complaints including pain, mass, dyspepsia, or bloating and were subsequently diagnosed with a tumor of the pancreas by CT scan. All patients underwent surgical resection. Two patients had tumors located in the head of the pancreas and underwent a pancreaticoduodenectomy. The remainder had tumors located in the tail of the pancreas and underwent distal pancreatectomy. Pathology demonstrated solid and papillary or solid and cystic pseudopapillary neoplasm of the pancreas. Three tumors were positive for both vimentin and alpha-1 antitrypsin on immunohistochemical studies, and three were positive for neuron-specific enolase. All nine patients underwent curative resection and are alive without any evidence of recurrence with a mean follow-up of 5.4 years.

SPENP is considered to be a low-grade malignancy with an excellent prognosis. Prompt diagnosis and surgical resection can result in cure.

Solid-pseudopapillary tumor of the pancreas: a surgical enigma?

Martin RC, Klimstra DS, Brennan MF, Conlon KC.

Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Ann Surg Oncol 2002 Jan-Feb;9(1):35-40 Abstract quote
BACKGROUND: Solid-pseudopapillary tumors (SPTs) of the pancreas have been reported as rare lesions with "low malignant potential" occurring mainly in young women. This study was designed to define the clinicopathological characteristics and the effect of surgical intervention.

METHODS: A retrospective review from January 1985 to July 2000 was performed. Clinicopathological, operative, and survival data were obtained. The Kaplan-Meier method and chi2 analysis were performed. All cases were re-reviewed by a senior pathologist.

RESULTS: During this time, 24 patients were diagnosed as having SPTs (0.9%). Twenty females and four males were identified, with a median age of 39 years (range, 12-79). The median size of the lesions was 8.0 cm (range, 1-20). Two patients' tumors were found to be unresectable at initial presentation because of vascular invasion; both patients have remained alive with disease, one for 13 years and the other 1 year. At a median follow-up of 8 years, one recurrence occurred in 17 patients who underwent complete resection. Microscopic margin positive (P = .26), invasion of surrounding structures (P = .51), and size >5 cm (P = .20) were not significant predictors of survival. Four patients presented with synchronous liver metastasis and underwent resection of the primary tumor and the liver metastasis, with one patient dying of progression of metastatic disease at 8 months, another alive with recurrence in the liver at 6 years, and the last two alive without evidence of disease at 1 month and 11 years.

CONCLUSIONS: SPT occurs predominantly in women (82%), although it can occur in men; all age groups are affected. Complete resection is associated with long-term survival even in the presence of metastatic disease.

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CLINICAL VARIANTS	CHARACTERIZATION
PEDIATRIC
Solid and papillary epithelial neoplasm of the pancreas in children. Jung SE, Kim DY, Park KW, Lee SC, Jang JJ, Kim WK. Department of Surgery, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-ku, Seoul 110-744, Korea.	World J Surg 1999 Mar;23(3):233-6 Abstract quote Solid and papillary epithelial neoplasm of the pancreas is an uncommon low-grade malignant tumor found predominantly in young females. In this paper, the authors report the tumor's clinical characteristics and the results of surgery in six children. Six cases of solid and papillary epithelial neoplasm of the pancreas pathologically verified at Seoul National University Children's Hospital between 1985 and 1997 were retrospectively analyzed. Four were girls and two were boys, and their mean age at surgery was 11.2 years (range 8-13 years). All patients presented with an abdominal mass and tumor ranging in size from 6.5 x 6.0 cm to 10.5 x 8.0 cm. Five were located in the head and one in the tail of the pancreas; exploration showed that no case involved local invasion or metastasis. All patients underwent complete resection, which involved five pancreaticoduodenectomies and one distal pancreatectomy. No patient died during surgery, and after a mean follow-up period of 5.5 years (range 1.5-12.5 years) all were alive with no recurrences. We believe that the malignancy of this tumor is low grade and that the prognosis is good. For a neoplasm arising anywhere in the pancreas, complete resection is the treatment of choice. Solid and papillary epithelial neoplasm of the pancreas of children shows less female preponderance in children than in adults.
Solid-pseudopapillary tumor of the pancreas (Frantz tumor) in children: report of four cases and review of the literature. Rebhandl W, Felberbauer FX, Puig S, Paya K, Hochschorner S, Barlan M, Horcher E. Division of Pediatric Surgery, Department of Surgery, General Hospital of Vienna, University of Vienna Medical School, Vienna, Austria	J Surg Oncol 2001 Apr;76(4):289-96 Abstract quote BACKGROUND: Solid-pseudopapillary tumor of the pancreas (SPT) is an exceptionally rare neoplasm in children. Its origin remains enigmatic. It is of low malignant potential and occurs most frequently in young females. PATIENTS AND METHODS: A cumulative review of the tumor's clinicopathological characteristics from the world's literature is presented. The clinical course, pathohistologic data and outcome of surgery of four Austrian children treated at the general hospital of Vienna are analyzed. RESULTS: Between 1987 and 1999, four girls (age: 12--16 years) with SPT were diagnosed at our institution. All patients presented with an abdominal mass and uncharacteristic abdominal pain. Two tumors were located in the tail, one in the body and tail and one in the head of the pancreas (diameter: 7--15 cm). Surgical procedures included three distal pancreatectomies and one partial duodenopancreatectomy (Whipple procedure). One patient had two recurrences with metastases that could only be partially resected. Chemotherapy was initiated for this patient. In the follow-up period (range: 6 months to 12 years) all patients are alive with no evidence of recurrence. CONCLUSIONS: SPT is a rare differential diagnosis of a pancreatic mass in children. It is mandatory to establish this diagnosis since complete surgical removal of the tumor even in case of metastases or local invasion offers an excellent prognosis.

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

EPIDEMIOLOGY	CHARACTERIZATION
SYNONYMS	Frantz's tumor Solid and cystic acinar tumor Papillary epithelial neoplasm Solid and Papillary Epithelial tumor/neoplasm
INCIDENCE	Rare
AGE RANGE-MEDIAN	12-71 years
SEX (M:F)	Female predominance

PATHOGENESIS	CHARACTERIZATION
GENERAL	Speculated to be ductal, acinar, ductaloacinar
Solid and Pseudopapillary Tumor of the Pancreas-Review and New Insights Into Pathogenesis. Geers C, Pierre M, Jean-Francois G, Birgit W, Pierre D, Jacques R, Christine S. *Departments of Pathology daggerSurgery double daggerGastro-enterology, Cliniques Universitaires Saint Luc, UCL, Brussels, Belgium.**	Am J Surg Pathol. 2006 Oct;30(10):1243-1249 Abstract quote Solid pseudopapillary tumors (SPT) of the pancreas are rare neoplasms that occur mostly in young women. Despite of a low malignant potential, 10% to 15% of the cases have aggressive behavior with metastatic dissemination possibly leading to death. To date, no pathological factor can reliably predict the outcome of these tumours. Galectin-3, a major actor in the carcinogenesis of pancreatic ductal adenocarcinoma, has not been investigated in SPT. The presence of progesterone receptors is frequently reported in SPT, whereas that of estrogen receptor (ER) is unclear. We studied 5 cases of SPT consisting of 4 pancreatic tumors and 1 metastatic case. The morphological distinctive feature of metastatic nodules was the presence of polygonal or spindle cells with pleiomorphic nuclei and high mitotic count exhibiting a diffuse, infiltrative growth pattern. We found a strong expression of galectin-3 in all SPTs, whereas, interestingly, it was lower in metastatic nodules. Conversely, no galectin-3 expression was found in normal pancreatic endocrine cells or in neuroendocrine tumors. We suggest therefore that galectin-3 is a useful marker to distinguish SPT from neuroendocrine tumor, and also indicator of behavior because its low expression is associated with metastatic spreading. Moreover, the presence of galectin-3 in both SPT and pancreatic ducts rises the hypothesis of a posible ductal origin of these tumors. Specific antibodies for anti-ERalpha and anti-ERbeta demonstrated a strong expression of ERbeta whereas ERalpha was not detected. In conclusion, the present study brings the first evidence of the involvement of galectin-3 in SPT but also brought up clues which allowed to reconcile previously conflicting results on the presence of ER.
E-CADHERIN
E-cadherin/Catenin Complex Status in Solid Pseudopapillary Tumor of the Pancreas. El-Bahrawy MA, Rowan A, Horncastle D, Tomlinson I, Theis BA, Russell RC, Stamp G. *Department of Histopathology, Imperial College, Hammersmith Campus †Molecular and Population Genetics Laboratory, London Research Institute, Cancer Research UK ‡Department of Histopathology, Hammersmith Hospital, London §Department of Surgery, University College London, UK.	Am J Surg Pathol. 2008 Jan;32(1):1-7. Abstract quote Solid pseudopapillary tumor (SPT) of the pancreas is an uncommon neoplasm of uncertain lineage. They have been shown to express nuclear beta-catenin believed to be due to mutations of the beta-catenin gene. The aim of this study was to investigate the status of the E-cadherin/catenin complex in SPTs. We studied the expression of 4 principal members of the E-cadherin/catenin complex using immunohistochemistry and the E-cadherin gene status by screening all exons of the gene for mutations, in 6 cases of SPT. In addition to the nuclear localization of beta-catenin, we found nuclear localization of E-cadherin in all tumors with complete absence of membranous and cytoplasmic localization. Nuclear localization of E-cadherin was independent of beta-catenin. No mutations were identified in the E-cadherin gene in any of the tumors. Ten cases of pancreatic adenocarcinomas and 15 neuroendocrine tumors were studied as well for comparison. The reported changes in the expression of the principal members of the E-cadherin/catenin complex were unique to SPTs. Our study shows abnormalities in the expression of 4 principal members of the E-cadherin/catenin complex in SPTs, which may help to explain the discohesive nature of the cells and the cystic changes in these tumors, and provide additional diagnostic features.
Wnt PATHWAY
Solid pseudopapillary neoplasms of the pancreas show an interruption of the Wnt-signaling pathway and express gene products of 11q. Tiemann K, Heitling U, Kosmahl M, Klöppel G. 1Department of Pathology, University of Kiel, Kiel, Germany.	Mod Pathol. 2007 Sep;20(9):955-60 Abstract quote Solid pseudopapillary neoplasms of the pancreas almost consistently show a beta-catenin mutation activating the Wnt-signaling pathway, resulting in overexpression of cyclin D1, but not in overt malignancy of this tumor. Besides cyclin D1, a set of markers (ie FLI-1, CD56 and progesterone receptor), whose genes map to chromosome 11q, are frequently expressed in solid pseudopapillary neoplasms. Chromosome 11q is a region that is also often affected in pancreatic neuroendocrine tumors. This immunohistochemical study was undertaken to gain insights into the downstream regulation of the Wnt-signaling pathway and the significance of overexpressed gene products belonging to chromosome 11q for the tumorigenesis in solid pseudopapillary neoplasms. Fourteen solid pseudopapillary neoplasms were analyzed for the expression of cyclin-dependent kinase inhibitors p21, p27, p16 and hyperphosphorylated retinoblastoma (pRb) proteins. In an extended series of 93 solid pseudopapillary neoplasms, beta-catenin, cyclin D1, FLI-1 and CD56 expression was examined and compared with that in 22 pancreatic neuroendocrine tumors. Solid pseudopapillary neoplasms (98%) showed aberrant expression of beta-catenin with a concomitant cyclin D1 expression in 69% of the cases, but no expression of pRb (0%) was found. p27 and p21 were expressed in 100% (14/14) and 86% (12/14) of the cases, but only 2/14 (14%) were positive for p16. FLI-1 was expressed in 63% of solid pseudopapillary neoplasms, but only in 1/22 pancreatic neuroendocrine tumors (5%), cyclin D1 expression was present in 14% of the latter. We conclude that in solid pseudopapillary neoplasms the activated Wnt-signaling pathway is disrupted, and that p21 and p27 are contributing to this fact by blocking of the hyperphosphorylation of the Rb protein, thus causing the very low proliferation rate characterizing the solid pseudopapillary neoplasms. The accumulation of high expression of proteins whose genes are located on chromosome 11q is characteristic of solid pseudopapillary neoplasms, but not of pancreatic neuroendocrine tumors.

SPECIAL STAINS/ IMMUNOPEROXIDASE	CHARACTERIZATION
Special stains
Immunoperoxidase
Positive	CD56 CD10 (Usually focal) Synaptophysin
Negative	Chromgranin A
Solid-Pseudopapillary Tumor of the Pancreas Immunohistochemical Localization of Neuroendocrine Markers and CD10 Kenji Notohara, M.D.; Shuji Hamazaki, M.D.; Choutatsu Tsukayama, M.D.; Shu Nakamoto, M.D.; Kenji Kawabata, M.D.; Kohichi Mizobuchi, M.D.; Kazuhiro Sakamoto, M.D.; Shigeru Okada, M.D. From the Department of Pathology I (K.N., S.O.), Okayama University Medical School, Okayama; Department of Pathology (S.H.), Okayama University Hospital, Okayama; Department of Pathology (C.T.), Kurashiki Central Hospital, Kurashiki; Department of Laboratory Medicine (S.N.), Tottori Prefectural Central Hospital, Tottori; Department of Pathology (K.K.), Akashi Municipal Hospital, Akashi; Department of Anatomical Pathology (K.M.), Kagawa Rosai Hospital, Marugame; and Department of Pathology (K.S.), Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan.	Am J Surg Pathol 2000;24:1361-1371 Abstract quote To clarify the neuroendocrine differentiation and CD10 expression in solid-pseudopapillary tumors (SPTs) of the pancreas, we performed immunohistochemical analysis in 19 such tumors, including one solid-pseudopapillary carcinoma (SPC), along with 20 pancreatic neuroendocrine tumors (PNTs), six acinar cell carcinomas (ACCs), and one pancreatoblastoma (PB). We used antisera directed against CD56, synaptophysin, protein gene product 9.5, the alpha-subunit of Go protein, chromogranin A, CD10, trypsin, chymotrypsin, various cytokeratins (CKs), CA19-9, vimentin, and alpha-1-antitrypsin (AAT). All SPTs exhibited immunoreactivity for CD56 and CD10, and 15 expressed other neuroendocrine markers focally with the exception of chromogranin A. Frequent clustering of synaptophysin-positive cells was noted. Two cases contained a peculiar nodule that cytomorphologically and immunohistochemically resembled PNT. CD10-positive cells were scarce in one SPC. PNTs were CD56-positive, but often with faint intensity, and staining for other neuroendocrine markers, including chromogranin A, was diffusely positive. CD10 was detected, mostly in a focal pattern, in five PNTs. Pan-CK, CK8, CK18, and CK19 were more frequently demonstrated in PNT than SPT. Vimentin and AAT were often identified in PNT as well and were not specific for SPT. ACCs were CD56-negative, with the exception of one case designated as a mixed acinar-endocrine carcinoma. PB was focally positive for CD56 at the periphery of the tumor nests. Four ACCs and one PB exhibited focal CD10 reactivity. This study demonstrated the unique immunohistochemical features of SPT. Our results also suggest that SPT exhibits, at least focally, neuroendocrine differentiation, and that these neuroendocrine markers and CD10 are diagnostically useful.

PROGNOSIS AND TREATMENT	CHARACTERIZATION
PROGNOSIS	Vascular invasion may be a poor prognostic factor
GENERAL
Solid and papillary epithelial neoplasms of the pancreas. Zinner MJ, Shurbaji MS, Cameron JL. Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Md.	Surgery 1990 Sep;108(3):475-80 Abstract quote Seven patients with solid and papillary epithelial neoplasms of the pancreas are reported. All were young women with a mean age of 22 years (range, 16 to 33 years old). Each patient had a large asymptomatic abdominal mass. The tumors ranged in size from 7 to 20 cm (average size, 13 cm) and were evenly distributed throughout the head, body, and tail of the pancreas. One patient had a metastatic tumor to her liver, which was unresectable. All other patients underwent resection, which included two distal pancreatectomies, two total pancreatectomies, one pancreaticoduodenectomy, and one local excision. Four of the seven patients had evidence of local invasions alone, and one had a liver metastasis and local invasion. All patients had the characteristic histologic pattern of a solid and papillary epithelial pancreatic neoplasm. All patients are alive with a mean follow-up of 10 years (range, 4 to 20 years). This is an unusual malignant neoplasm of the pancreas occurring predominantly in young women. Even though they are locally invasive, long-term survival is the rule. Surgical therapy should be aggressive, since liver metastasis may occur.
Recurrence	Duodenal invasion with ulceration
Metastasis	Rare liver metastasis
TREATMENT	Surgical removal
SURGERY
Solid and papillary epithelial neoplasms of the pancreas: aggressive resection for cure. Yoon DY, Hines OJ, Bilchik AJ, Lewin K, Cortina G, Reber HA. Department of Surgery, UCLA School of Medicine and Olive View-UCLA Medical Center, Los Angeles, California 90024, USA.	Am Surg 2001 Dec;67(12):1195-9 Abstract quote Solid and papillary epithelial neoplasms of the pancreas (SPENP) are extremely rare and usually affect young women. We retrospectively reviewed our experience with pancreatic neoplasms from 1986 to the present and identified nine patients with SPENP. All nine patients were female with a mean age of 32 years (range 16-66). All patients presented with gastrointestinal complaints including pain, mass, dyspepsia, or bloating and were subsequently diagnosed with a tumor of the pancreas by CT scan. All patients underwent surgical resection. Two patients had tumors located in the head of the pancreas and underwent a pancreaticoduodenectomy. The remainder had tumors located in the tail of the pancreas and underwent distal pancreatectomy. Pathology demonstrated solid and papillary or solid and cystic pseudopapillary neoplasm of the pancreas. Three tumors were positive for both vimentin and alpha-1 antitrypsin on immunohistochemical studies, and three were positive for neuron-specific enolase. All nine patients underwent curative resection and are alive without any evidence of recurrence with a mean follow-up of 5.4 years. SPENP is considered to be a low-grade malignancy with an excellent prognosis. Prompt diagnosis and surgical resection can result in cure.
Solid-pseudopapillary tumor of the pancreas: a surgical enigma? Martin RC, Klimstra DS, Brennan MF, Conlon KC. Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.	Ann Surg Oncol 2002 Jan-Feb;9(1):35-40 Abstract quote BACKGROUND: Solid-pseudopapillary tumors (SPTs) of the pancreas have been reported as rare lesions with "low malignant potential" occurring mainly in young women. This study was designed to define the clinicopathological characteristics and the effect of surgical intervention. METHODS: A retrospective review from January 1985 to July 2000 was performed. Clinicopathological, operative, and survival data were obtained. The Kaplan-Meier method and chi2 analysis were performed. All cases were re-reviewed by a senior pathologist. RESULTS: During this time, 24 patients were diagnosed as having SPTs (0.9%). Twenty females and four males were identified, with a median age of 39 years (range, 12-79). The median size of the lesions was 8.0 cm (range, 1-20). Two patients' tumors were found to be unresectable at initial presentation because of vascular invasion; both patients have remained alive with disease, one for 13 years and the other 1 year. At a median follow-up of 8 years, one recurrence occurred in 17 patients who underwent complete resection. Microscopic margin positive (P = .26), invasion of surrounding structures (P = .51), and size >5 cm (P = .20) were not significant predictors of survival. Four patients presented with synchronous liver metastasis and underwent resection of the primary tumor and the liver metastasis, with one patient dying of progression of metastatic disease at 8 months, another alive with recurrence in the liver at 6 years, and the last two alive without evidence of disease at 1 month and 11 years. CONCLUSIONS: SPT occurs predominantly in women (82%), although it can occur in men; all age groups are affected. Complete resection is associated with long-term survival even in the presence of metastatic disease.