Case 4 -
Richard M. Demay, University Of Chicago, Chicago, IL
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- FNA biopsy
- 16 y/o male
- Pancreatic mass
Pancreatoblastoma was first reported in the surgical literature by Walter F Becker in 1957, although
the case was thought to be an islet cell tumor at the time [Becker 1957]. In 1971, William J Frable et
al published the first histopathologic study of this neoplasm, then known as the infantile type of
pancreatic carcinoma [Frable 1971]. A Horie et al proposed the term "pancreatoblastoma" in 1977, because
of its resemblance to fetal pancreatic tissue at ~7 weeks gestation [Horie 1977].
Although very rare, pancreatoblastoma is the most common pediatric pancreatic malignancy and accounts
for ~25% of all pancreatic neoplasms in childhood [Brennan 2004, Taxy 1976]. Pancreatoblastoma has
a bimodal age incidence, with a mean age of 2.5 years, and a smaller, broader peak in adults, with a mean
age of 35 years [Dunn 1995, Hoorens 1994, Klimstra 1995, Levey 1996, Palosaari 1986, Savastano 2009]. It
is somewhat more common in males [Kissane 1994, Klimstra 1995]. Pancreatoblastoma is sometimes
associated with Beckwith-Wiedemann syndrome (congenital overgrowth syndrome, classic triad: macrosomia,
macroglossia, and omphalocele [due to abdominal weakness]) [Klimstra 1995] or familial adenomatous
polyposis of the colon [Abraham 2001, Drut 1988, Koh 1996, Saif 2007 ]. Pancreatoblastoma is thought to
arise from multipotential stem cells (blastema) that recapitulate pancreatic embryogenesis, with acinar
and endocrine cells developing from primitive ducts.
Clinically, patients usually present with weight loss, abdominal pain, and abdominal mass. Diarrhea
is common, but jaundice is not. Serum a-fetoprotein (a-FP) is elevated in up to 80% of cases and
provides a useful clinical tumor marker [Cingolani 2000, Defachelles 2001]. Other possible serum tumor
markers include carcinoembryonic antigen (CEA), amylase, and lipase.
Pancreatoblastoma can occur in any part of the pancreas. Diagnostic imaging studies help to delineate
the extent of the disease, including presence of metastases [Montemarano 2000]. The most common sites of
metastasis are the liver, lymph nodes, and lung. Although the long-term prognosis is poor, it is better
for children than adults and also better than that of ordinary pancreatic carcinoma [Henke 2001, Klimstra
Grossly, the tumor can be solid or cystic. Histologically, the tumor is very cellular, composed of
sheets and nests of uniform epithelial cells admixed with well-formed glandular or acinar structures and
occasional dilated ducts. Squamoid corpuscles (pearls) are a constant and characteristic feature [Horie
1997]. Acinar differentiation occurs in >90% of cases. A stromal component is also usually present
and can be helpful in diagnosis of this tumor [Henke 2001].
The fine needle aspiration biopsy characteristically demonstrates a biphasic population of epithelial
cells (including anaplastic "small blue cells," acinar cells, and squamous cells) plus spindle
mesenchymal cells [Bellizzi 2009, Henke 2001, Sahu 2009, Silverman 1990b].
Anaplastic small blue cells are cytologically similar to those occurring in other pediatric small blue
cell tumors. They are small to intermediate in size, with dark molded nuclei, scant cytoplasm, and high
nuclear/cytoplasmic ratios [Henke 2001].
Squamous pearls, or corpuscles, are highly characteristic of this tumor; they probably arise from
squamous metaplasia within primitive ducts. The squamous cells may have optically clear nuclei owing to
biotin content [Hasegawa 2003, Tanaka 1998].
Acinar cells may form acinar structures or syncytial sheets. The cells are oval to cuboidal, with
eccentric round nuclei, fine chromatin, small nucleoli, and a moderate amount of granular cytoplasm.
Cytologically similar endocrine cells may also be present; however, special studies may be needed to
identify them specifically.
A mesenchymal component is frequently present. It is composed of primitive spindle cells in a
fibromyxoid stroma [Zhu 2005]. Heterologous elements, such as neoplastic bone or cartilage, occur rarely
[Pitman 2004]. Stromal fragments and capillaries may also be present.
The tumor can differentiate along both exocrine (acinar) and endocrine (islet cell) lines, which can
be demonstrated by special studies [Cooper 1989, Morohoshi 1987]. Expression of a-FP by tumor cells is
consistent with the embryonal nature of this tumor [Iseki 1986]. Cytokeratin is expressed by the
epithelial cells. Zymogen granules, indicative of acinar cell differentiation, are periodic acid-Schiff
positive. These can also be demonstrated by electron microscopy [Kakudo 1976, Silverman 1990b, Zhu 2005]
or by immunochemistry. Zymogen granules contain various digestive enzymes such as trypsin, chymotrypsin,
or lipase. General neuroendocrine immunomarkers, such as synaptophysin and chromogranin, are usually
positive. Specific endocrine (islet cell) differentiation is indicated by expression of insulin,
gastrin, somatostatin, etc [Hua 1996]. CEA may also be positive. Like solid pseudopapillary neoplasms
and acinar cell carcinoma, pancreatoblastoma can express b-catenin (nuclear) [Tanaka 2003].
Pancreatoblastomas is associated with loss of heterozygosity at chromosome 11p and IGF2 overexpression
The correct diagnosis is rarely made preoperatively, in part owing to the rarity of the
tumor. The differential diagnosis includes other tumors with small blue cells, such as lymphoma,
Ewing/PNET [Bulchmann 2000, Danner 1994, Movahedi-Lankarani 2002, Perek 2003] , and other "blastomas"
such as neuroblastoma, hepatoblastoma, and nephroblastoma (Wilms tumor). The differential diagnosis with
acinar cell carcinoma, which can affect young children, can be difficult because acinar cell
differentiation occurs in both tumors. Similarly, the differential diagnosis also includes pancreatic
endocrine neoplasms because of possible endocrine differentiation in pancreatoblastoma. Squamous pearls
and stromal elements (particularly heterologous elements) favor pancreatoblastoma, although
hepatoblastoma and nephroblastoma (Wilms tumor) can also have stromal elements [Pitman 2004, 2007].
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