Pancreas
Other tumors
Pancreatoblastoma
Authors: Ryan Kendziora, M.D., Lizhi Zhang, M.D.
Editorial Board Member: Aaron R. Huber, D.O.
Deputy Editor-in-Chief: Catherine E. Hagen, M.D.
Topic Completed: 22 July 2021
Minor changes: 22 July 2021
Copyright: 2002-2021, PathologyOutlines.com, Inc.
PubMed Search: Pancreatoblastoma[TI] free full text[SB]
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Kendziora R, Zhang L. Pancreatoblastoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/pancreaspancreatoblastoma.html. Accessed October 25th, 2021.
Definition / general
- Rare pancreatic malignancy that is seen most often in children and displays multiple lines of differentiation
Essential features
- Displays at least 2 pancreatic lines of differentiation, including acinar, ductal and neuroendocrine elements
- Presence of squamoid nests is a defining diagnostic feature
- Tumors are aggressive, with complete surgical resection being the most important prognostic factor
Terminology
- Infantile pancreatic carcinoma
- Pancreatic carcinoma in childhood (Cancer Cytopathol 2019;127:708)
ICD coding
Epidemiology
- Children > adults
- Most common pancreatic tumor of children < 10 years old
- Median age in this group is 4 - 5 years (Pediatr Surg Int 2019;35:1231)
- Mean age of presentation of adult tumors is 41 years
- M = F (Gland Surg 2015;4:322)
- Most common pancreatic tumor of children < 10 years old
- Only about 200 cases reported in the literature
Sites
- About 50% occur in pancreatic head, with the rest relatively equally split between tail and body (Gland Surg 2015;4:322)
- 1 reported case found in ampulla of Vater (Arch Pathol Lab Med 2003;127:1501)
Pathophysiology
- Unknown
- Loss of chromosome 11p or mutations in APC / B catenin pathway possibly implicated in pathogenesis (Gland Surg 2015;4:322)
Etiology
- Unknown
- Some cases associated with Beckwith-Wiedemann syndrome, familial adenomatous polyposis (Gland Surg 2015;4:322)
Clinical features
- Generally nonspecific presentation; most common symptom is abdominal pain (Sci Rep 2020;10:11285)
- Commonly advanced at presentation with local extension and metastases
- Commonly metastasizes to liver > lymph nodes > lung
- Associated with Beckwith-Wiedemann syndrome, familial adenomatous polyposis (Gland Surg 2015;4:322)
Diagnosis
- Can be identified on CT or MRI
- Difficult to diagnose by FNA due to variety of cell lines expressed (Gland Surg 2015;4:322)
Laboratory
- Up to 50% of pediatric patients can show elevations in carcinoembryonic antigen (CEA) and alpha fetoprotein (AFP); less helpful in adults (Gland Surg 2015;4:322)
- 66% of children will have AFP > 1000 μg/L
- Some tumors reported to secrete adrenocorticotropic hormone (ACTH), resulting in Cushing syndrome (J Cancer Res Ther 2015;11:1027)
Radiology description
- Generally solid, irregular lesion but can be cystic or degenerative
- Can grow outward, as branches growing from a tree trunk (Sci Rep 2020;10:11285)
Radiology images
Images hosted on other servers:
Pancreatoblastoma, CT scan
Prognostic factors
- Prognosis largely dependent on resectability of tumor (Pancreatology 2004;4:441)
- 5 year survival for resectable tumors: 65%
- 5 year survival for nonresectable tumors: 0%
- Presence of distant metastases portends poorer prognosis
- Prognosis worse in adults, as children tend to have well encapsulated tumors without metastases
Case reports
- 4 year old boy with multiple pancreatic and liver masses (Ecancermedicalscience 2018;12:861)
- 27 year old woman with a 3.6 cm pancreatic mass and metastasis to the liver and lungs (JOP 2012;13:301)
- 69 year old man with a pancreatic head mass (BMJ Case Rep 2020;13:e233884)
Treatment
- Complete surgical resection is critical to prognosis
- Chemotherapy or radiotherapy may be used to ensure complete resection
Gross description
- Large (average size is 10 cm), lobulated, fleshy mass
- Can have cystic components or soft areas of necrosis
- Predominantly cystic tumors can be seen in Beckwith-Wiedemann syndrome (Gland Surg 2015;4:322)
Gross images
Images hosted on other servers:
Pancreatoblastoma,
body / tail mass
Encapsulated heterogeneous mass with cystic components
Microscopic (histologic) description
- Multilineage components resembling embryologic pancreas
- Geographic hypercellular solid tumor lobules separated by fibrous bands
- Acinar differentiation is the predominant pattern, mimicking acinar cell carcinoma:
- Acinar appearances resembling normal acini, with small lumen and luminal secretion
- Focal solid, trabecular or pseudoglandular patterns
- Cells with eosinophilic or amphophilic granular cytoplasm, mild atypical nuclei and small nucleoli
- Squamoid nests:
- Defining feature, present in every case
- Plump to spindle shaped cells with abundant eosinophilic / clear cytoplasm arranged in whorls or nests
- Typically bland cytology
- May show keratinization
- Neuroendocrine component:
- More than 50% of cases show focal neuroendocrine differentiation
- Neuroendocrine cells diffusely intermix with acinar component, being highlighted by immunostains or form focal organoid or trabecular growth
- Ductal component:
- Very focal glandular formation
- May be highlighted by a mucicarmine stain
- Primitive component:
- Solid sheets of immature small round cells
- Stroma:
- Variable cellularity
- Sometimes showing heterologous elements (e.g. bone, cartilage)
- Reference: Am J Surg Pathol 1995;19:1371
Microscopic (histologic) images
Contributed by Lizhi Zhang, M.D.
Geographic tumor lobules
Lobulated tumor nests
Acinar differentiation
Squamoid nests
Squamoid nests with keratinization
Neuroendocrine component
Ductal component
Primitive component
Stroma
Keratin immunostain
Trypsin immunostain
Beta catenin immunostain
CK5 immunostain
Synaptophysin immunostain
Cytology description
- Loosely cohesive, blast-like tumor cells are small, with fine chromatin, granular cytoplasm and atypia with nucleoli (Cancer Cytopathol 2019;127:708)
- Mimic acinar cell carcinoma
- Squamoid nest cells can be well defined, whorled clusters or syncytial appearing groups (Cancer Cytopathol 2019;127:708)
- Better appreciated on cell block preparations
Positive stains
- Pancytokeratin
- Squamoid nests positive for beta catenin (nuclear staining), CK5 and EMA
- Acinar markers (Gland Surg 2015;4:322):
- Ductal markers (positive in up to 65% of cases) (Gland Surg 2015;4:322):
- CEA
- B72.3
- DUPAN-2
- CK19
- Mucicarmine
- Neuroendocrine markers (if present) (Gland Surg 2015;4:322):
- Synaptophysin
- Chromogranin
- INSM1
- AFP, if serum levels are elevated
Negative stains
- Germ cell markers
- p53
- Rare cases loss of DPC4 expression (Am J Pathol 2001;159:1619)
Electron microscopy description
- All showing zymogen granules (400 - 800 nm) for acinar differentiation (Am J Surg Pathol 1995;19:1371)
- Some with neuroendocrine granules (125 - 250 nm) and mucigen granules (500 - 900 nm)
Molecular / cytogenetics description
- Loss of chromosome 11p (Gland Surg 2015;4:322)
- Alterations in the APC / beta catenin pathway (Am J Pathol 2001;159:1619)
Sample pathology report
- Pancreas, duodenum and gallbladder, Whipple procedure:
- Pancreatoblastoma, forming an 8 x 6 x 4 cm mass in the pancreatic head (see comment)
- Tumor is confined within the pancreas without extension to peripancreatic soft tissue, common bile duct and duodenum
- Tumor necrosis is present
- Angiolymphatic and perineural invasion are present
- All surgical margins are negative for tumor
- Background pancreatic parenchyma is unremarkable
- Multiple (3 of 14) regional lymph nodes are positive for metastatic tumor
- Gallbladder is without diagnostic abnormality
- Comment: Immunoperoxidase stains show the tumor cells are positive for trypsin with beta catenin nuclear staining in the scattered squamoid nests, confirming the diagnosis. Focal area is also positive for synaptophysin and chromogranin, representing a minor component of neuroendocrine tumor. No convincing component of ductal adenocarcinoma is seen.
Differential diagnosis
- Acinar cell carcinoma:
- No squamoid nests or other lines of differentiation
- No nuclear beta catenin staining
- Neuroendocrine tumor / carcinoma:
- May have focal acinar appearance but no squamoid nests
- Nested or trabecular growth patterns
- Diffuse positive staining of neuroendocrine markers (synaptophysin, chromogranin, INSM1)
- No nuclear beta catenin staining
- Solid pseudopapillary neoplasm:
- No acinar differentiation
- No squamoid nests
- Pseudopapillary structures
- Diffuse nuclear beta catenin staining
- Undifferentiated carcinoma or anaplastic carcinoma:
- No acinar differentiation
- No squamoid nests
- Highly atypical and pleomorphic tumor cells
- May have multinucleated giant tumor cells or osteoclast-like giant cells
Additional references
Board review style question #1
A 40 year old man presents with abdominal pain and unintentional weight loss. Subsequent imaging reveals an 8 cm mass in the pancreatic head invading into the duodenum and a likely metastasis in the liver. The patient undergoes neoadjuvant chemoradiation and a pancreaticoduodenectomy. A representative histology section is shown above. The cell population that most definitively identifies this diagnosis would be most specifically highlighted by which of the following immunohistochemical stains?
- Alpha fetoprotein
- Beta catenin
- Chromogranin
- Trypsin
Board review style answer #1
B. Beta catenin. Nuclear staining of beta catenin is a marker of alterations in the APC / beta catenin pathway, which commonly occurs in pancreatoblastoma associated with loss of chromosome 11p.
Comment Here
Reference: Pancreatoblastoma
Comment Here
Reference: Pancreatoblastoma
Board review style question #2
A 5 year old boy presents with weight loss, abdominal pain and distention and hepatomegaly. An abdominal ultrasound reveals a pancreatic mass and multiple liver masses. A pancreas biopsy is performed. Based on the findings in the image shown above, what is the most likely diagnosis?
- Acinar cell carcinoma
- Malignant germ cell tumor
- Pancreatic neuroendocrine tumor
- Pancreatoblastoma
Board review style answer #2
D. Pancreatoblastoma. The characteristic squamoid nest shown in the image is a defining feature of pancreatoblastoma, present in every case.
Comment Here
Reference: Pancreatoblastoma
Comment Here
Reference: Pancreatoblastoma
