Revisiting Metastatic Adult Pancreatoblastoma

Kristofer M Charlton-Ouw
3
, Christy L Kaiser
4
,
Guo-Xia Tong
2
, John D Allendorf
1
, John A Chabot
1
Departments of
1
Surgery and
2
Pathology, New York-Presbyterian Hospital, Columbia University
Medical Center. New York, NY, USA.
3
Department of Cardiothoracic and Vascular Surgery,
University of Texas Health Science. Houston, TX, USA.
4
Department of Cardiovascular Surgery,
Methodist DeBakey Heart and Vascular Center, The Methodist Hospital. Houston, TX, USA
ABSTRACT
Context Most cases of pancreatoblastoma, a
rare tumor of neuroendocrine origin, are seen
in the pediatric population. To date, at least
sixteen case reports have been described of
pancreatoblastoma in patients 19-year old or
older. Surgical resection is the mainstay of
curative treatment. Even patients with liver
metastasis can have long-term disease-free
survival.
Case report One recent example is a 33-year-
old male who presented to us for a right
hepatic lobectomy for removal of the
presumed primary tumor - later discovered to
be a metastasis - followed by
pancreaticoduodenectomy for resection of the
true primary lesion. Five years after resection,
this patient is the longest disease-free survivor
of metastatic adult pancreatoblastoma.
Conclusion We review the literature and
propose that resection of pancreatoblastoma
can offer long-term disease-free survival even
with liver metastasis and microscopically-
positive surgical margins.
INTRODUCTION
Pancreatoblastoma is a rare tumor of the
pancreas and usually occurs in pediatric
patients. Since it was first described in 1957,
close to 200 cases have been described and
most were in the pediatric population [1]. In
1986, Palosaari et al. described the first case
of pancreatoblastoma in an adult [2]. Only 15
case reports of pancreatoblastoma in adults
have since been published. Most of these
cases describe patients with a short-term
survival of just several months after
diagnosis. The cases that do report patients
with disease-free survival had followed the
patients for at most three years at the time the
articles were published. Therefore, the long-
term prognosis and best treatment strategy for
these patients remains uncertain. We present a
case of an adult patient with
pancreatoblastoma who remains disease free
five years after his first resection, despite the
presence of liver metastasis and positive
microscopic tumor margins after surgery. To
our knowledge, this case represents the
longest reported period of disease-free
survival for an adult patient with metastatic
pancreatoblastoma and supports an aggressive
surgical and chemotherapeutic approach to
treatment.
CASE REPORT
The patient is a 33-year-old man who noted
right upper quadrant abdominal pain and a 9
kg weight loss over the preceding two
months. Past medical history included post-
pubertal gynecomastia with breast tissue
resection as a young adult and peptic ulcer
disease treated with oral antacids. Physical

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exam revealed a mildly tender right upper
quadrant abdominal mass. Computed
tomography (CT) of the abdomen
demonstrated a large mass in the right lobe of
the liver. No pancreatic lesions were
observed. A CT-guided fine needle aspiration
biopsy suggested a diagnosis of
neuroendocrine carcinoma. He had no
laboratory abnormalities, including normal
liver function tests, CA 19-9, and CEA levels.
At exploration, a firm 12 cm mass in the right
lobe of the liver was palpated. Intraoperative
ultrasound of the liver revealed no other
lesions and no lymphadenopathy was
appreciated. However, in the pancreas, two
distinct masses were felt. One mass was
located in the body of the pancreas and the
other was a hypoechoic mass in the head near
the portal vein. Multiple core-needle biopsies
of the pancreas were performed under
ultrasound guidance. The frozen section
showed only evidence of chronic pancreatitis
and the patient underwent a standard right
hepatic lobectomy (segments 5-8) and did
well post-operatively.
Grossly, the resected liver mass, measuring
12x11x7 cm, was well circumscribed and
solid with areas of necrosis and hemorrhage.
Microscopically, the tumor was highly
cellular and composed of variably-sized
nodules or lobules of tumor cells separated by
fibrous tissue. The tumor cells were
predominantly arranged in sheets of rosette-
like structures with lumens resembling the
pancreatic acini (Figure 1). Less commonly,
there were tubular, trabecular, or solid
patterns. The tumor cells were uniform and
had a moderate amount of fine eosinophilic
granular cytoplasm. The nuclei were
uniformly round or oval with stippled
chromatin and small nucleoli. Mitotic activity
was easily identified with one mitotic figure
per high power field. Necrosis was evident. In
addition, there were small whorled areas
composed of large tumor cells with abundant
eosinophilic cytoplasm, consistent with
squamous morules (Figure 2).
Immunohistochemistry showed the tumor
cells to be positive for pancytokeratin, CK7,
low molecular weight cytokeratins, trypsin,
alpha-1 antitrypsin, alpha antichymotrypsin,
and variably positive for synatophsin,
chromogranin, and neuron specific enolase.
The tumor cells were negative for insulin,
glucagons, gastrin, and VIP. There was focal
weak staining for somatostatin, CD99, and
progesterone receptors. The findings of
squamous morules and tumor cells resembling
pancreatic acini on histology, together with
the presence of epithelial, endocrine, and
exocrine cells on immunohistochemistry
confirmed a diagnosis of metastatic
pancreatoblastoma.
The final pathology reports of the biopsies of
the pancreatic mass - in contrast to the
previous frozen sections - showed similar
histologic features characteristic of
pancreatoblastoma, making it the presumed
primary lesion. Two and one-half months
after his initial operation, the patient was
therefore admitted for resection of the
presumed primary lesion in the head of the
Figure 1. On histologic section, the tumor was mainly
composed of neoplastic cells in acini-like structures
(H&E, x100).
Figure 2. A squamous morule (H&E, x200).

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pancreas. A CT scan prior to the second
operation showed ascites and postoperative
inflammatory changes in the pancreatic bed,
as well as a small pseudocyst, but still no
evidence of a pancreatic tumor (Figure 3).
Repeat exploration revealed a palpable mass,
measuring approximately 5x5x5 cm, in the
head of the pancreas. A pancreatico-
duodenectomy with distal gastrectomy was
performed. A frozen section of the pancreatic
margin was negative for malignant cells. No
lymph node involvement was noted. In the
final pathology report following surgery, the
tumor histology and immunohistochemistry
was consistent with the findings of the first
resection. Tumor was seen infiltrating the
main pancreatic duct. Of note, despite the
negative margins on frozen sections,
microscopic tumor cells were evident at the
margin of resection on one slide.
Following surgery, the patient was treated
with adjuvant radiation and cisplatin and
doxorubicin (PLADO) chemotherapy. During
the next few years, the patient developed
complications of his medical treatment,
including bleeding at his gastrojejunostomy
anastomosis that was within the radiation
field and bilateral osteonecrosis of the
femoral heads, both of which were treated
surgically. The patient today remains free of
recurrent disease 60 months after his initial
operation and 57 months after his
pancreaticoduodenectomy. Repeat CT scans
have also shown no signs of recurrent disease.
He has had normal liver function tests and
normal levels of CA 125, CA 19-9 and CEA
to date.
DISCUSSION
Adult pancreatoblastoma is an extremely rare
neoplasm with optimal treatment regimens
still uncertain. Although slightly over 200
cases have been described in the world
literature, most involve patients less than 10
years old [1]. Adult cases present with
slightly different clinical characteristics and
outcomes than those in children. We defined
adult cases as those occurring in patients 19
years of age or older, according to the criteria
described by Klimstra et al. in 1995 [3]. Since
1986, when Palosaari et al. presented the first
case of adult pancreatoblastoma in a 37-year-
old [2], 15 additional case reports have been
published, which are reviewed in Table 1
along with our patient and Palosaari’s. There
are also nine other cases reported in the
literature (mostly in reviews or described in
the pathology and radiology literature) for
which details of the cases and patient
outcomes were not available [4, 5, 6, 7].
Adults with pancreatoblastoma seem to have
a generally poorer prognosis than children [3].
Six of 17 cases died within one year of
diagnosis (Table 1). The survival difference
between pediatric and adult cases may reflect
different tumor biology. One clue is that
pediatric cases frequently have elevated
serum tumor markers. Alpha-fetoprotein is
often high in children with pancreatoblastoma
but has not been consistently elevated in
adults [8]. Whereas children can sometimes
have prolonged survival with chemotherapy
and radiation without surgical resection,
surgery seems to offer the only chance of
long-term survival in adults. Details of the
etiology, presentation, and management of
adult pancreatoblastoma are described below.
Genetics
Unlike pancreatic ductal adenocarcinoma,
pancreatoblastoma does not seem to exhibit k-
ras oncogene or p53 tumor suppressor
mutations. Abraham’s group found frequent
mutations of APC/B-catenin pathway
chromosome 11p leading them to postulate a
genetic kinship to hepatoblastoma [9]. Due to
the small number of adult cases, it is unclear
Figure 3. A computed tomography scan after the first
operation showed a small pseudocyst but did not reveal
evidence of a pancreatic tumor.

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whether there is a genetic difference between
pediatric and adult pancreatoblastoma.
Several pediatric cases of pancreatoblastoma
occurred in patients with Beckwith-
Wiedemann syndrome and one case occurred
in a patient with familial adenomatosis
polyposis [9].
Tumor Location
The pancreatic head was the most common
site of tumor origin, found in 8 of 17 adults
(47%), followed by the tail in 6 (35%), the
body in 2 (12%), and the ampulla in 1 (6%)
(Table 1). This is comparable to the review of
Dhebri et al. of both pediatric and adult
patients [10]. The liver is the most common
site of metastasis.
Histopathology
The distinctive pathologic features of
pancreatoblastoma are the combined features
of ductal, acinar, and endocrine cells both
histologically and immunohistochemically,
and the presence of squamoid corpuscles.
Grossly, the tumors tend to be large at the
time of diagnosis, often with metastases.
Symptoms
Most adult patients present with abdominal
pain or a mass (Table 1). Weight loss,
Table 1. Adult cases of pancreatoblastoma in world literature.
Case
Age,
sex
Clinical
presentation
Tumor size,
pancreatic location
Treatment
Outcome
Palosarri [2] 37 M Abdominal pain,
weight loss, diarrhea
8 cm, head; +LN;
vascular involvement
Ex-lap, unresectable,
chemo/XRT
With liver metastases
at 15 months
Hoorens [13] 39 F Abdominal mass
13 cm, tail
Resection
NED at 30 months
Dunn [14]
61 M
Splenomegaly
9 cm, tail
Resection, chemo
Died at 11 months
Klimstra [3] 19 M Abdominal mass
15 cm, head;
+LN; wide metastasis
Resection
Died at 10 months
Klimstra [3] 36 M Obstructive jaundice
"Large", head;
+LN; liver metastasis
None
Died at 5 months
Klimstra [3] 37 M Abdominal mass,
weight loss
12 cm, head;
liver metastasis
Chemo, XRT
Died at 38 months
Klimstra [3]
54 F Abdominal pain
20 cm, tail
Resection
NED at 15 months
Klimstra [3] 56 M Abdominal mass
20 cm, tail
Resection
NED at 5 months
Levey [15]
68 F Diarrhea, weight loss
9 cm, head
Resection
Died at 4 months
Robin [16]
20 M Abdominal mass
9cm head
Resection, chemo
Died at 7 months
Mumme [17] 22 F Abdominal pain,
mass, weight loss
9 cm, tail
Resection, intraoperative
XRT, chemo
Died at 9 months
Benoist [12]
48 F Abdominal pain,
melena
10 cm, body;
liver metastasis
Resection,
metastectomy, chemo
NED at 36 months
Gruppioni [18] 30 M Abdominal pain
8 cm, head
Resection
NED at 10mo
Du [1]
78 F Obstructive jaundice 2.7 cm, ampulla of Vater
Resection
NED at 6 months, alive
at 4 yrs, unknown if
disease free
Rajpal [8]
50 M Abdominal pain,
weight loss
13 cm, tail; colon
invasion; liver metastasis
Resection, chemo
Died at 17 months
Zhu [19]
24 F Obstructive jaundice
4 cm, body;
liver metastases
Chemo, unresectable With liver metastases
at 9 months
Our patient
33 M Abdominal pain,
mass, weight loss
5cm, head;
liver metastasis
Metastectomy, resection,
chemo, XRT
NED at 60 months
+LN: positive lymph node involvement
NED: no evidence of disease
XRT: radiation therapy

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anorexia, change in bowel habits, and
jaundice are other common symptoms on
initial presentation. Patients may also
manifest
symptoms
of
endocrine
abnormalities. One pediatric patient presented
with Cushing’s syndrome as the result of an
ACTH-secreting tumor [11]. Our patient
presented with a tender right upper quadrant
mass due to a large liver metastasis.
Laboratory
In pediatric cases, serum CEA and AFP are
often elevated whereas adult pancreato-
blastomas seem not to secrete AFP, CA 19-9,
chromogranin A, or CEA. Frequently, as in
our patient, tumor markers and liver function
tests are unremarkable. Anemia is sometimes
reported [8]. In only one case, Du et al.
reported an elevated preoperative CA19-9 in
an adult with pancreatoblastoma [1]. Rajpal et
al. reported a case with an elevated lipase and
proinsulin level [8]. Occasionally, adult
pancreatoblastoma causes liver function test
abnormalities due to biliary obstruction or
hepatic metastasis.
Imaging
Most tumors are well-defined on cross-
sectional imaging. However, in the report by
Montemarano et al. [4], only five of ten
patients (9 children, 1 adult) had their tumors
identified as pancreatic in origin on
preoperative radiologic studies [4]. Although
pancreatoblastomas often arise in the
pancreatic head, biliary obstruction is
uncommon. With magnetic resonance
imaging (MRI), the tumors are most often
described as heterogeneous with low-
intermediate T1 signal intensity and high T2
intensity. Enhancement on CT is common [4].
Treatment
In the adult population, surgical resection
remains the mainstay of treatment and
appears to offer the only chance of cure. The
three of 16 patients who did not undergo
resection all died of their disease.
Interestingly, Klimstra et al. reported a
relatively long survival with radiation and
chemotherapy alone in one patient [3].
Although the patient eventually died of his
disease at 38 months, it demonstrates that
radiation and chemotherapy can have a role in
management.
Metastatic lesions should also be resected if
possible. Benoist et al. first reported a patient
with successful resection of two hepatic
lesions along with the primary tumor in the
pancreatic body [12]. Our patient is the
second reported case of resection of both the
primary mass and metastasis. Both Benoist’s
patient and ours achieved long-term disease-
free survival of 36 and 60 months,
respectively.
SUMMARY
The long-term survival observed in our
patient is remarkable considering the finding
of microscopic malignant cells at the margin
of resection on pathology. Despite this, after
receiving radiation and chemotherapy, our
patient remains disease-free five years after
resection, even by subsequent exploratory
laparotomy. To our knowledge, he has the
longest disease-free survival in an adult
reported in the world literature. Aggressive
surgical resection of the primary tumor and
metastatic liver lesions should be the
mainstay of therapy for pancreatoblastoma.
The goal of surgical resection should be
disease-free margins. The role of adjuvant
radiation and chemotherapy when
microscopic disease is found at the surgical
margin is uncertain but certainly warrants
further study.
Received August 4
th
, 2008 - Accepted
September 8
th
, 2008
Keywords Neoplasms; Pancreas; Pulmonary
Blastoma
Acknowledgement The authors would like to
acknowledge the assistance of Michael
Kluger, MD. This case was presented at the
2006 AHPBA Meeting, Miami Beach, FL,
USA
Conflict of interest and funding None
Correspondence
John D Allendorf
Department of Surgery
New York-Presbyterian Hospital
Columbia University Medical Center

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