Annals oj Surgical Oncology, 9(1):3540

Published by LippincottWilliams& Wilkins © 2002 The Societyof Surgical Oncology,Inc.

Solid-Pseudopapillary Tumor of the Pancreas:

A Surgical Enigma?

Robert C. G. Martin, MD, David S. Klimstra, MD, Murray F. Brennan, MD, and
Kevin C. Conlon, MD

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. Clinicopatholog-
ical, operative, and survival data were obtained. The Kaplan-Meier method and X2 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.
Key Words: Solid-pseudopapillary tumor--Peripancreatic malignancy--Liver metastasis Tumor
resection.

Solid-pseudopapillary tumors (SPTs) of the pancreas
were first described by Frantz in 1959.1 They are con-
sidered a rare pathologic entity with low malignant po-
tential, 2 affecting primarily young w o m e n ?
Recently there has been a steady increase in the num-
ber of SPTs of the pancreas, with more than two thirds of
the total cases described in the last 10 years. Despite the
increase in recognition, the pathogenesis and apparent
Received February 27, 2001; accepted August 29, 2001.
From the Gastric and Mixed Tumor Service, Department of Surgery
(RCGM, MFB, KCC), and the Department of Pathology (DSK), Me-
morial Sloan-Ket~ering Cancer Center, New York, New York.
Presented at lhe 54th Annual Cancer Symposium of the Society of
Surgical Oncology, Washington, DC, March 15-18, 2001.
Address correspondence and reprint requests to: Kevin C. Conlon,
MD, Memorial Sloan-Kettering Cancer Center, Department of Surgery,
1275 York Ave., New York, NY 10021; Fax: 212-717-3097; E-mail:
conlonk@mskcc.org.
therapeutic algorithm remain unclear. This study was
designed to e x a m i n e the clinicopathological character-
istics of the disease and to define the effect of surgical
i n t e r v e n t i o n by e x a m i n i n g a s i n g l e i n s t i t u t i o n ' s
experience.
METHODS
A review of the Memorial Sloan-Kettering Cancer
Center Department of Surgery's prospective pancreatic
database from January 1, 1985, to July 31, 2000, was
performed. Patients admitted to our institution with a
diagnosis of SPT of the pancreas were identified. Clini-
copathological, operative, and survival data were ob-
tained. The Kaplan-Meier method and X2 analysis were
performed. All cases were re-reviewed by a senior pa-
thologist (D.S.K.).

35
36 R. C. G. MARTIN ET AL.
RESULTS
During the time this study reviewed, 2486 patients
with peripancreatic malignancy were admitted to our
institution, with 24 diagnosed as having SPTs (.9%).
There were 20 females and 4 males with a median age of
39 years (range, 12-79). The median size of the lesions
was 8.0 cm (range, 1-20). Eight patients had their pri-
mary tumors within the head, 6 in the body, and 10 in the
tail of the gland. The predominant presenting symptom
was abdominal pain (58%); seven patients (29%) were
asymptomatic
A total of 18 patients presented with local disease and
underwent resection. Eleven patients underwent a distal
pancreatectomy; seven patients underwent pancreati-
coduodenectomy for treatment of their primary disease.
One of these patients was found to have a single focus of
metastatic disease in a single lymph node after complete
resection. This patient's disease recurred 1 year after
resection, and the patient died of systemic recurrence.
At a median follow-up of 8 years, no patient who
underwent an R0 resection and was node negative (n =
17) had evidence of recurrence. Microscopic margin
positive (P = .26), invasion of surrounding structures (P
= .51), and size > 5 cm (P = .20) were not significant
predictors of survival in this group, although the numbers
are very small.
Four patients presented with synchronous liver metas-
tasis, and all four underwent resection of both the pri-
Am~ Sur~, Omol, VoL 9. No. 1. 2002
mary lesion and the liver metastasis. Of these four pa-
tients with liver involvement, one patient died of
progression of metastatic disease at 8 months, another
was alive with recurrence in the liver at 6 years, and two
were alive without evidence of disease at 6 months and
I 1 years. Two patients were found to have unresectable
disease at initial presentation because of vascular inva-
sion, and both patients have remained alive with disease:
one for 13 years and the other for 1 year.
Tumors were generally large, varied from tan to yel-
low, and showed irregular cystic cavities lined by soft,
friable tissue. Foci of hemorrhage were common. Some
examples also demonstrated firm, fibrotic regions within
the tumor. Most cases appeared to be grossly well cir-
cumscribed or even partially encapsulated.
The microscopic appearance of all the cases demon-
strated the characteristic microscopic features of SPT.
The solid areas were composed of monotonous polygo-
nal epithelioid cells, often with minimal intervening
stroma, accompanied by innumerable capillary-sized
vessels (Fig. 1A). Some areas showed more extensive
stromal fibrosis, with round aggregates of perivascular
hyalinized stroma imparting a cylindromatous appear-
ance. In the pseudopapillary regions, the cells located
away from the small vessels appeared to have dropped
away, leaving an irregular cuff of cells surrounding each
vascular core (Fig. 1B). There was evidence of cellular
degeneration, including aggregates of foamy histiocytes,
FIG. 1. Histologically (A), solid-
pseudopapillary tumors exhibit solid,
cellular areas that lack gland forma-
tion or other specific architectural
features (lo~rer left). Characteristi-
cally pseudopapillary formations are
formed when the cells located distant
from the rich capillary network de-
generate. The resulting pseudopapil-
lae ( a r r o w s ) consist of" irregular cuffs
of cells clinging to the central fibro-
vascular cores. At high power (B),
the polygonal tumor cells are rela-
tively unifl~rm and exhibit round to
oval nuclei with nuclear grooves.
Clusters of cells contain large eosin-
ophilic globules (arro~rs).
 SOL1D-PSEUDOPAPILL4RY TUMORS OF THE PANCREAS
cholesterol clefts, and cytoplasmic vacuolization. Clus-
ters of cells demonstrated large eosinophilic cytoplasmic
globules. The nuclei were generally uniform and round
to oval, with longitudinal grooves. Despite the apparent
gross circumscription, the microscopic interface between
the tumors and the adjacent pancreas commonly showed
an infiltrative growth pattern, with islands of nonneo-
plastic pancreatic parenchyma entrapped within the tu-
mor and nests of tumor cells extending into the adjacent
pancreas.
Two of the cases showed unusual histological features
in some regions, in addition to exhibiting the typical
morphology described previously. In these cases, there
were large regions demonstrating a diffuse, sheetlike
growth pattern (Fig. 2A). The tumor cells in these re-
gions showed increased nuclear pleomorphism (a higher
nucleus to cytoplasm ratio) when the miotic rate was
increased (up to 20 mitoses per 10 high-power micro-
scopic fields). In addition, both cases exhibited some
spindling of the tumor cells (Fig. 2B). In fact, in one of
these cases a discrete 1.0-cm focus in the center of the
tumor was composed of a highly pleomorphic spindle
cell population that showed anaplastic tumor giant cells
and atypical mitotic figures; this focus had the appear-
ance of sarcomatoid carcinoma. One of these two cases
also exhibited a lymph node metastasis, a finding not
encountered in any of the other cases under study.
Although the diagnosis was based largely on the pres-
ence of typical histological features, the immunohisto-
37
chemical staining performed on these cases displayed a
consistent pattern of reactivity for vimentin and %-
antitrypsin, with inconsistent, generally focal positivity
for keratin. Stains for the pancreatic enzymes trypsin and
chymotrypsin were consistently negative, as was the
specific endocrine marker chromogranin. Some cases did
display focal positivity for synaptophysin and for the less
specific marker neuron-specific enolase.
DISCUSSION
SPT has been described by many other terms, such as
papillary epithelial neoplasm, solid and cystic acinar cell
tumor, papillary cystic neoplasm, papillary cystic carci-
noma, solid and cystic tumor, low-grade papillary tumor,
and Frantz's tumor. SPT has also been misdiagnosed as
adenocarcinoma, islet cell tumors, cystadenomas, papil-
lary cystadenocarcinoma, or cystadenocarcinoma.
A total of 450 cases of SPT of the pancreas have been
reported in the literature since it was first described in
1959.1.4 ~5 SPT of the pancreas is a rare tumor and
represents < 1.0% of all pancreatic admissions at Memo-
rial Sloan-Kettering Cancer Center. There has been an
increasing incidence of this entity in recent years, both in
reported cases and in our institution (Fig. 3). A possible
explanation is a greater awareness of this disease, as well
as a better understanding of pancreatic pathology with
the 1996 new classifications of pancreatic neoplasms
FIG. 2. Two cases exhibited a
more diffuse, sheetlike arrange-
ment of tumor cells (A), with rela-
tively few pseudopapillae. At high
power (B) the tumor cells have in-
creased nuclear atypia, a high nu-
cleus to cytoplasm ratio, and
readily identifiable mitotic figures
(arrows'). Some of the ceils are
spindle shaped.
Am~ ,Surf¢ O~(d, I/.L ~), No. /, 2002
38 R. C. G. M A R T I N ET AL.

when they occur, are often vague and nonspecific, lead-

350-
ing to a delay in diagnosis. As a result of these subtle
300 . . . . . . . . : : { {
:==,=,= L symptoms, tumor presentation can be quite large, as
demonstrated in our experience. Size of the lesion is not
250-
a predictor of unresectability, as seen in this series and in
200 others, with lesions 20 to 30 cm in size still being
15o! [] Number of
patients resectable.~-t~-~9 These lesions rarely invade contiguous

lOOi~ structures or occlude the bile ducts. Vascular invasion,

s0i ~
1980-1990 1991-2000
A resection and reconstruction.
20-
18-
16-
14-
12-
10- [] Number of
Patients
8-
6-
4-
2-
0 tein markers of ductal differentiation. Some cases do
1980-1991 1991-2000
B though the most specific marker of neuroendocrine
FIG. 3. Incidence of pseudopapillary tumors of the pancreas, (A)
Total reported cases of solid-pseudopapillary tumors of the pancreas;
(B) Memorial Sloan-Kettering Cancer Center experience with solid-
pseudopapillary tumors of the pancreas.
from the World Health Organization.l(' Our own experi-
ence has led to a greater awareness of the pathologic
characteristics and the radiographical and clinical pre-
sentation and has led to an increase in diagnosis, as well
as an improved understanding of the natural history of
these lesions.
The majority of SPTs of the pancreas have been diag-
nosed in young women. However, this series has dem-
onstrated the incidence of male patients diagnosed with
this disease. A majority of reports have found the great-
est incidence of SPT of the pancreas in the third decade
of life; however, our patients presented with a median
age of 39 years, which is significantly older than in the
two large single institutional series and in the total num-
ber of cases reported (median age of 26 years). 6.1°,17 Our
series found only seven patients who were under the age
of 25 years, of whom five were female.
Almost all of the patients in this series presented with
vague mild abdominal pain or early satiety. Symptoms,
although uncommon, does occur, as evidenced by our
two patients who presented with superior mesenteric
encasement. Reports have demonstrated resectability and
long-term survival with isolated portal vein and arterial
The pathologic diagnosis of SPT is based on the
presence of characteristic light microscopic features.
Solid areas alternating with pseudopapillary forma-
tions; evidence of cellular degeneration, including
cholesterol clefts and aggregates of foamy histiocytes;
nuclear grooves; and aggregates of hyaline cytoplas-
mic globules are found, at least focally, in every case.
The line of cellular differentiation reflected in SPTs
remains unclear, so immunohistochemical staining for
specific cell lineage markers is of marginal utility in
proving the diagnosis of SPT. Markers of acinar dif-
ferentiation (the pancreatic enzymes trypsin and chy-
motrypsin) are consistently negative, as are glycopro-
express the neuroendocrine marker synaptophysin, al-
differentiation, chromogranin, is always negative. De-
spite the lack of specific lines of differentiation, SPT
does display a characteristic immunophenotype. Vi-
mentin is consistently expressed, and the hyaline cy-
toplasmic globules contain a l-antitrypsin. In many
examples, keratins are not expressed or are found only
focally. Thus, the staining pattern of most examples of
SPT is distinctive and differs from that of other pri-
mary pancreatic tumors that could be considered the
differential diagnosis, such as pancreatic endocrine
neoplasms and acinar cell carcinomas. 2°
In most studies of the clinical outcome of SPTs, no
pathologic factors predictive of prognosis have been
identified, in part because of the favorable prognosis. In
fact, the occmTence of long-term survival in the presence
of stable metastatic disease 4 and the rarity of death from
this tumor make it difficult to identify any clinicopath-
ological features predictive of survival. In the largest
clinicopathological study to date (published only in ab-
stract form), pathologic factors including mitotic rate,
nuclear pleomorphism, and vascular invasion were not
found to correlate with prognosis. 2~ It is of interest that
two patients in this study died of tumor, both within 1

Amt Sur~, O m ol, Vol. 9, No. I, 2002

 SOLtD-PSEUDOPAPILLARY TUMORS OF THE PANCREAS
year of diagnosis. In both of these tumors, the histolog-
ical appearance was somewhat unusual, with large areas
exhibiting a more diffuse, sheetlike growth pattern, in-
creased nuclear pleomorphism, and a markedly increased
mitotic rate. One of these tumors contained a focus of
sarcomatoid carcinoma, and the other exhibited lymph
node metastasis, both exceptional (if not singular) find-
ings in this neoplasm. The fact that both of these patients
died of progressive disease raises the possibility that
these histological findings may allow identification of a
variant of SPT associated with aggressive behavior, al-
though definitive conclusions cannot be drawn on the
basis of these small numbers. Attention to these histo-
logical features in the future may allow a more specific
statement to be made regarding their prospective prog-
nostic significance.
Metastatic disease does occur with SPTs, with 20
previously reported cases. 4,: 19,22 33 The most com-
mon site of distant disease is the liver; very rare cases
of lymph node (n = 5) and peritoneal spread (n = 4)
have been reported. Disseminated disease is also not a
negative predictor of survival. Long-term survival, 7
to 10 years, has been reported in patients undergoing
complete resection, but it is more important to note
that it has also been reported in patients with residual
disease.~,.~7 In tb.is series, two patients with liver me-
tastasis had significant overall survival, with one alive
at 11 years and the other alive with liver recurrence at
4 years.
Experience with adjuvant therapy has been used
only in a small number of patients because the reseet-
ability rate for SPT of the pancreas is so high. Many
different regimens of chemotherapy have been used
without any demonstration of response. One patient in
this series was treated with complete cycles of 5-flu-
orouracil, doxorubicin, and streptozocin and inter-
feron, cisplatin, and topotecan without any response to
the primary lesion. Radiotherapy has been used infre-
quently. Only one case report indicates significant
success in a locally advanced lesion involving the
porta hepatis; it responded to 4000 cGy over 6 weeks
with a 3-year follow-up, l~ Other reports have also
looked at estrogen receptor status and have found no
indication that overexpression exists in these lesions. ~o
Recurrence of SPT of the pancreas has not been re-
ported with complete resection of local disease. Neither
local, nor vascular, nor perineural invasion has been a
factor to predict recurrence or overall survival. This
series did not demonstrate any factors significant for
overall survival.
39
CONCLUSION
We believe that SPT of the pancreas should be treated
aggressively, with attempts made for complete resection,
even if this requires metastasectomy. Long-term survival
can be achieved with an aggressive approach to both the
primary lesion and to the synchronous or metachronous
metastatic lesion, predominantly found in the liver.
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