Pancreatoblastoma, a Rare Childhood Tumor: A Case Report
Asuman ARGON1, Ahmet ÇELİK2, Haldun ÖNİZ3, Geylani ÖZOK2, Funda YILMAZ BARBET4
1Department of Pathology, İzmir Bozyaka Training and Research Hospital, İZMİR, TURKEY
2Department of Pediatric Surgery, Ege University, Faculty of Medicine, İZMİR, TURKEY
3Clinic of Pediatric Oncology and Bone Marrow Transplantation, İzmir Tepecik Training and Research Hospital, İZMİR, TURKEY
4Department of Pathology, Ege University, Faculty of Medicine, İZMİR, TURKEY
Keywords: Child, Pancreatic neoplasms, Pancreatoblastoma
Pancreatoblastoma, rarely encountered in the literature, is a malignant
exocrine tumor seen in the pancreas. A 5-year-old boy suffering from
abdominal pain was sent to our institute for further examination
and treatment. Clinical examination was normal but for a palpable
abdominal tumor mass. Abdominal Doppler ultrasonography showed
a mass with well-defined margins within the body of the pancreas.
Laboratory tests, including lactic dehydrogenase, alpha-fetoprotein
and cancer antigen 125 were abnormal. The tumor invading the
splenic vein and transverse colon was removed totally. We observed
a hypercellular tumor in histopathological examination. The tumor
had epithelial acinar cells and squamoid morules (corpuscles)
separated by stromal bands. Adjuvant chemotherapy was used after
surgery. However, the patient died 14 months later. All data about
pancreatoblastoma have to be collected in order to choose the
treatment to elucidate the molecular pathogenesis of the tumor, to
diagnose it early and to develop target-specific treatments.
In childhood, exocrine pancreatic tumors are unusual
diseases (1). Recently, there is a growing interest in these
unusual tumors along with the advances in the therapeutic
concepts. Pancreatoblastoma (PB) arises in pancreas and
is reported with an annual incidence of around 0.004
new case per 100,000 population (2). PB is a rare tumor;
nevertheless, it is among the most common malignant
neoplasms in pancreas (3). PB is frequently seen in
childhood, but it may occur at any stage of life; nevertheless,
adults and fetus appear to be free from this disease (4,5). PB
is seen more often in females than males (3). Although this
tumor was formerly known as infantile carcinoma of the
pancreas, Horie et al. (6) named the tumor PB in 1977. PB
is composed of squamoid corpuscles and acinar cells with
zymogen granules and these cells form an organoid pattern
containing lobular structures (1). The above-mentioned
appearance resembles fetal pancreatic tissue. Alphafetoprotein
(AFP) is the tumor marker used most often
in PB (7). The biological behavior of PB in children is less
aggressive but local invasion, recurrence, and metastasis are
frequently seen (8). Although the surgical approach for PB
is not standardized, total resection is so far the only choice
for treating these patients (9).
A 5-year-old boy suffering from abdominal pain was referred
to our institute for further examination and treatment.
Three days earlier, he had been examined for abdominal
pain elsewhere and abdominal ultrasonography (US) had
identified a solid heterogeneous mass measuring 11 cm in
diameter close to the left kidney, together with three solid
hypoechoic metastatic masses measuring 28 mm, 25 mm
and 15 mm in the liver left lobe, respectively. The initial
diagnosis was germ cell tumor. Clinical examination was
normal in our hospital except for a palpable abdominal
tumor mass. He had no co-morbidities and his medical
history revealed nothing of significance. Laboratory tests
showed that hemoglobin was 9.4 ng/ml, hematocrit 28%, and
lactic dehydrogenase 833 ng/ml. Abnormal tumor markers
levels including alpha feto protein (AFP) of 55117 ng/ml,
and carcino embryonic antigen 125 835 ng/ml were present
while human chorionic gonadotropin-beta was normal.
Abdominal Doppler US showed a mass in the body of the
pancreas which had well-defined margins and measured
11x8 cm. The tumor was solid but it also contained a hyper
echoic component. Computed tomography identified
a solid heterogeneous mass measuring 11x10x8 cm in
diameter (Figure 1).
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|Figure 1: Computed tomography identified a solid heterogeneous mass measuring 11x10x8 cm in diameter close to the left kidney
The tumor invading the splenic vein and transverse colon
was removed totally (Figure 2). On gross examination,
the perforated capsule surrounding the tumor was seen.
The tumor measured 12.5x12x6 cm. On cut section
there was hemorrhage and also necrosis. We observed a
hypercellular tumor in the histopathological examination.
The tumor had cell clusters separated by stromal bands
and composed of squamoid morules (corpuscles) and
epithelial acinar cells. An increase in the nucleus/cytoplasm
ratio and nucleomegaly were seen in the epithelial cells
that had a pancreatic acini-like pattern. Although the
nuclear membranes of the neoplastic cells were regular,
coarse chromatin and multiple conspicuous nucleoli were
observed and the cells had a pale eosinophilic cytoplasm.
Squamoid corpuscles were seen in many clusters of tumor
cells. In the squamoid corpuscles, the epithelioid cells were
plump and contained dense eosinophilic cytoplasm (Figure
3). Immunohistochemically, the neoplastic cells were
positive with alpha-1-antitrypsin but showed no staining
with WT-1, monoclonal carcinoembryogenic antigen
or Tag72. CD10 and fascin were positive in squamoid
corpuscle cells. Nuclear and strong cytoplasmic staining for
ß-catenin (Figure 4) was seen in squamoid corpuscle cells
but non-neoplastic pancreatic acini showed the expected
membranous and faint cytoplasmic staining. In addition,
chromogranin A and synaptophysin showed positivity
in a few endocrine cells. Typical histological features and
immunohistochemistry were suggestive of the diagnosis
of PB. After surgery, AFP levels decreased to 72.6 IU/
ml gradually. Adjuvant chemotherapy was used as of the
14th day after surgery. The chemotherapy regimen was as
follows: every fifteen days; cisplatin 80 mg/m2, 24 hours
constant infusion; carboplatin 500 mg/m2, 1-hour infusion
and doxorubicin 60 mg/m2, 48 hours constant infusion. On
the postoperative 43rd day, metastatic lesions in the liver
were stable and there was a recurrent mass in the pancreas
region. With these findings, we concluded that the disease
had progressed. The chemotherapy regimen was changed
to carboplatin 400 mg/m2/day, intravenous, 1-day infusion
for 2 days; ifosfamide 1800 mg/m2/day, intravenous, 1-day
infusion for 5 days; etoposide 100 mg/m2/day, intravenous,
1-day infusion for 5 days. The radiological evaluation after
6th chemotherapy regimen revealed that the recurrent mass
in the pancreatic region had disappeared and metastatic
lesions in the liver had regressed. However, an operation was
not considered in the case of this patient as the metastatic
lesions in the liver were multiple and unresectable. The
chemotherapy was therefore continued. Severe neutropenia
and progression in the metastatic lesions in the liver
were detected during the evaluation following the 9th
chemotherapy regimen, The treatment was discontinued
upon the request of the parents. The patient died on the
14th month following the operation.
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|Figure 2: The tumor invading the splenic vein and transverse colon was totally removed. Gross pathologic examination showed an encapsulated tumor and measuring 12.5x12x6 cm in diameter.
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|Figure 3: Squamoid corpuscles were seen in many clusters of tumor cells. In the squamoid corpuscles, epithelioid cells were plump and also had a dense eosinophilic cytoplasm (H&E; x20).
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|Figure 4: Immunohistochemically, nuclear and cytoplasmic staining were seen in the neoplastic cells for ß-catenin (ß-catenin; x20).
Pancreatoblastoma (PB) is an unusual malignant exocrine
tumor arising in pancreas (1). There have been approximately
200 cases in literature since Becker described PB in 1957 (3).
PB is frequently seen in Asians, females and childhood as in
our case (10). It may stem from any part of the pancreas. This
tumor was divided into two categories by Horie et al. (6) as
right-side tumors and left-side tumors. According to Horie
et al. (6), the right-side tumors arise from the primordial
ventral pancreas, do not contain calcification and islet cells,
are usually well-encapsulated and have a better prognosis.
However, the left-side tumors arise from the primordial
dorsal pancreas, contain calcification and islet cells, have
no encapsulation, and indicate a poorer prognosis than
right-side tumors (6,11). The tumor in our patient has the
features of a left-side tumor because it arose from the body
of pancreas, contained islet cells and had a poor prognosis.
However it also had the features of a right side tumor as
it was well-encapsulated and did not show calcification.
Larger series are needed in order to understand the clinical
and prognostic significance of the tumors that have mixed
features as in our case.
As already known, both the pancreas and the liver stem
from the same primitive cells (12). Therefore, the fact that
serum AFP levels are increased in PB cases is not surprising,
as in hepatoblastoma (7). Some authors reported a loss of
heterozygosity (LOH) on chromosome 11 in PBs (13,14).
According to Kerr et al. (14), although extensive LOH of the
chromosome 11 encompassed the WT-1 gene, mutations
were not detected in WT1 gene exons. Abraham et al. (13)
observed somatic mutations in the APC/ß-catenin pathway
but they did not detect any changes in the p53 and K-ras
genes. Also, they postulated that a significant correlation
was detected between immunohistochemical ß-catenin
positivity and the APC/ß-catenin gene alterations (13).
The molecular and immunohistochemical studies suggest
that most PBs exhibit typical genetic alterations and they
are similar to other embryonal tumors such as acinar
cell carcinoma and hepatoblastoma (12-15). In our case,
immunohistochemically, ßcatenin positivity and WT-1
negativity resemble the data in the literature. Molecular
studies in large series may help elucidate the pathogenesis
The radiological differential diagnosis includes pancreatic
cystic neoplasm, ductal adenocarcinoma, acinar cell
carcinoma, nonfunctioning endocrine pancreatic tumors,
solid pseudo papillary tumors, peripancreatic and
pancreatic lesions, especially tuberculosis and autoimmune
pancreatitis (4,16). In early childhood, the spectrum of
differential diagnosis is wide when it cannot be clearly
seen that the tumor arises from the pancreas (11). The
tumors that must be considered first are Wilms tumor,
neuroblastoma, hepatoblastoma, and other primary liver
tumors (12,13). Acinar cell carcinoma and PB have similar
histopathological and radiologic appearances (1,11).
However, PB usually occurs in the first decade of childhood,
whereas acinar carcinoma is encountered in older patients.
Moreover, squamoid corpuscles are typical in PB but they
do not exist in acinar cell carcinoma (1,12).
Clinicopathologic features, treatment and prognosis of
PB were evaluated in the paper by Dhebri et al. (17).
They reported that 78% of the 153 patients were under 10
years. The symptoms and signs were like those described
in other articles (10,18). Moreover, 17% of their patients
had metastatic disease at the time of diagnosis. The study
of Dhebri et al. (17) showed that the 5-year survival rate
of patients after total resection was 65% whereas median
survival of their patients with non resectable disease at
the time of diagnosis was 36 months. Furthermore, all of
these patients died before 40 months. According to their
study, the best choice of treatment is complete resection. If
the tumor is unresectable, PB is treated with chemotherapy
(17,19). Although vincristine, doxorubicin, etoposide,
cyclophosphamide, cisplatin and adriamycin have turned
out to be effective chemotherapeutic agents, there are no
established or proven chemotherapy regimens (19). The
efficiency of neoadjuvant chemotherapy was not clearly
proven in any studies (17). New studies with larger series
are still needed. Our patient underwent chemotherapy that
contained two different groups of medicine for 12 cycles.
The first group contained carboplatin, doxorubicin and
cisplatin and early relapse and progression were detected
during this treatment. The second group contained
ifosfamide, carboplatin and etoposide. Regression was
found during the 6 courses of chemotherapy but the
disease then progressed. Data on the basis of similar cases
are needed in order to determine the alternative treatment
options and the efficiency of the chemotherapy treatments.
According to SEER data (1973-2004), median survival in
PB is 193 months and the 15-year survival rate is 75% but
the initial tumor stage was not reported in this study (2).
Our patient had metastatic disease at the time of diagnosis.
Although the primary tumor was completely resected in our
patient, metastatic lesions in the liver could not be resected.
While the first chemotherapy regime was inefficient,
response to the second chemotherapy regimen was limited.
When these findings were assessed together with literature,
early diagnosis and complete resection of the tumors seem
to be important in order to decrease the tumor load and to
increase the response to treatment.
All data about PB have to be collected in order to choose
the treatment to elucidate the molecular pathogenesis of
the tumor, to enable early diagnosis, and to develop targetspecific
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