Definition/General
Introduction:
Solid pseudopapillary neoplasm (SPN) is a rare pancreatic tumor with low malignant potential
Comprises 1-2% of all pancreatic tumors
Predominantly affects young women aged 10-30 years
Also called Frantz tumor or solid-cystic papillary tumor
Has unique cytological features that make FNAC diagnostic.
Origin:
Origin remains controversial with multiple theories proposed
May arise from multipotent stem cells
Some suggest acinar cell origin
Others propose ductal cell origin
Recent studies favor pancreatic progenitor cell origin
Shows both epithelial and mesenchymal differentiation.
Classification:
WHO classification: Solid pseudopapillary neoplasm
Considered low-grade malignant tumor
May occasionally metastasize
Benign behavior in most cases
Complete resection usually curative
Rare variants include malignant transformation.
Epidemiology:
Strong female predominance (90-95%)
Peak incidence 2nd-3rd decades
Male cases usually in older age group
Asian populations show higher incidence
No familial clustering
Associated with beta-catenin mutations in >90% cases.
Clinical Features
Presentation:
Abdominal mass (most common presentation)
Often asymptomatic or vague symptoms
Abdominal pain (dull, non-specific)
Early satiety
Nausea and vomiting
Palpable mass in larger tumors
Obstructive symptoms rare.
Symptoms:
Vague abdominal discomfort (50-70%)
Palpable abdominal mass
Early satiety and fullness
Nausea and vomiting
Weight loss (uncommon)
Jaundice (rare, only with head tumors)
Incidental finding on imaging in 30% cases.
Risk Factors:
Female gender (strongest risk factor)
Young age (<30 years)
Asian ethnicity
Beta-catenin pathway mutations
No known environmental factors
No association with smoking or alcohol
No hereditary syndromes identified.
Screening:
No specific screening guidelines available
Imaging surveillance for incidental findings
EUS-FNAC for tissue diagnosis
Consider in young women with pancreatic masses
Tumor markers usually normal.
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Gross Description
Appearance:
Well-encapsulated mass with smooth surface
Variegated cut surface with solid and cystic areas
Hemorrhage and necrosis common
Calcifications may be present
Pseudocapsule usually present
Color varies from tan to hemorrhagic.
Characteristics:
Encapsulated tumor with fibrous pseudocapsule
Solid areas alternate with cystic/hemorrhagic areas
Necrosis often extensive
Calcification in 30% cases
No invasion of surrounding structures
Friable consistency typical.
Size Location:
Size ranges from 2-20 cm (average 8-10 cm)
Most commonly in pancreatic tail (50-60%)
Head involvement in 20-30%
Body involvement in 15-20%
Large tumors may involve multiple regions.
Multifocality:
Usually solitary lesions
Multifocal disease extremely rare
No association with other pancreatic tumors
Rarely bilateral involvement
Complete encapsulation helps surgical planning.
Microscopic Description
Histological Features:
Alternating solid and pseudopapillary patterns
Cells arranged around delicate fibrovascular cores
Monomorphic cells with minimal pleomorphism
Tumor cells have clear to eosinophilic cytoplasm
Nuclear grooves commonly seen
Foamy macrophages and cholesterol clefts present.
Cellular Characteristics:
Monomorphic polygonal cells with well-defined borders
Round to oval nuclei with fine chromatin
Nuclear grooves in many cells
Moderate eosinophilic cytoplasm
Low nuclear-cytoplasmic ratio
Mitotic activity low
PAS-positive, diastase-resistant cytoplasmic inclusions.
Architectural Patterns:
Solid sheets of cells interrupted by pseudopapillae
Pseudorosette formation around blood vessels
Cystic degeneration common
Hemorrhage and necrosis frequent
Hyalinized fibrovascular cores
Calcification may be present.
Grading Criteria:
Generally low-grade tumors with uniform appearance
Nuclear grade usually 1-2
Mitotic count <2 per 10 HPF
Ki-67 index typically <3%
Rare high-grade areas with increased mitoses
Malignant potential based on size and invasive features.
Immunohistochemistry
Positive Markers:
Beta-catenin (nuclear positivity - diagnostic)
CD10 positive
Vimentin positive
Alpha-1-antitrypsin positive
PR positive (often)
CD56 positive
Synaptophysin (variable)
E-cadherin typically lost.
Negative Markers:
Chromogranin A negative
Trypsin negative
Chymotrypsin negative
CK19 negative
CDX2 negative
TTF-1 negative
Insulin and other hormones negative.
Diagnostic Utility:
Beta-catenin nuclear staining is pathognomonic
Helps distinguish from neuroendocrine tumors
CD10 positivity supports diagnosis
Absence of acinar markers excludes acinar cell carcinoma
Combined panel provides definitive diagnosis.
Molecular Subtypes:
Beta-catenin mutations in >90% cases
CTNNB1 exon 3 mutations most common
Wnt pathway activation
APC mutations rare
No other recurrent mutations identified
Microsatellite stability maintained.
Molecular/Genetic
Genetic Mutations:
CTNNB1 mutations (>90% cases)
Most mutations in exon 3
Point mutations or small deletions
Result in beta-catenin stabilization
APC mutations rare
No TP53 mutations typically.
Molecular Markers:
Wnt pathway activation (hallmark feature)
Beta-catenin nuclear accumulation
TCF/LEF target genes upregulated
Low proliferation markers
Stable genome with few alterations.
Prognostic Significance:
Beta-catenin mutation confirms diagnosis
Generally excellent prognosis with complete resection
Size >5 cm may indicate higher risk
Vascular invasion rare but indicates malignant potential
Age >35 years associated with worse prognosis.
Therapeutic Targets:
Complete surgical resection is curative
Wnt pathway potential therapeutic target
No established chemotherapy regimens
Targeted therapy under investigation
Long-term follow-up recommended.
Differential Diagnosis
Similar Entities:
Pancreatic neuroendocrine tumor (most important differential)
Acinar cell carcinoma
Pancreatoblastoma
Ductal adenocarcinoma (cystic variant)
Pseudocyst with solid components.
Distinguishing Features:
SPN: Beta-catenin nuclear positive
SPN: Young female patient
SPN: CD10 positive
NET: Chromogranin/synaptophysin positive
NET: Beta-catenin negative
Acinar: Trypsin/chymotrypsin positive
Acinar: Male predominance.
Diagnostic Challenges:
Distinction from neuroendocrine tumor most challenging
Both can show similar cytology
Immunohistochemistry essential
Beta-catenin staining diagnostic
Young age and female gender helpful clues.
Rare Variants:
Malignant SPN with metastases
SPN with anaplastic features
SPN with sarcomatous differentiation
Mixed SPN with NET components
Multicystic variant described.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
FNAC from pancreatic mass, [location], [number] passes
Adequacy
Specimen is adequate for diagnosis
Cellular Findings
Moderately cellular smears showing [describe cell population]
Cell Morphology
Monomorphic cells with [nuclear features] and [cytoplasmic features]
Background
Background shows [hemorrhage/necrosis/foamy macrophages]
Immunocytochemistry
Beta-catenin: [result], CD10: [result], Chromogranin: [result]
Differential Diagnosis
Differential includes [list conditions]
Final Diagnosis
FNAC pancreas: [diagnosis]