Definition/General
Introduction:
Pancreatic acinar cell carcinoma (ACC) is a rare malignant epithelial tumor
It constitutes 1-2% of all pancreatic malignancies
It demonstrates acinar differentiation with enzyme production
It shows aggressive behavior with poor prognosis
It has characteristic morphology and immunoprofile.
Origin:
Arises from pancreatic acinar cells
Shows exocrine pancreatic differentiation
Retains capacity for digestive enzyme production
May arise from multipotent pancreatic progenitors
Involves loss of acinar cell polarity
Shows malignant transformation of acinar elements.
Classification:
WHO classifies as malignant epithelial tumor
Pure acinar cell carcinoma (most common)
Mixed acinar-neuroendocrine carcinoma
Mixed acinar-ductal carcinoma
Acinar cell cystadenocarcinoma
Mixed acinar-endocrine-ductal carcinoma.
Epidemiology:
Peak incidence in 6th-7th decades
Male predominance (2:1 ratio)
Most cases are sporadic
Familial adenomatous polyposis association (rare)
APC gene mutations in some cases
Indian population shows similar age distribution but lower overall incidence.
Clinical Features
Presentation:
Abdominal pain (80-90% of cases)
Weight loss (60-70%)
Nausea and vomiting (40-50%)
Palpable abdominal mass (30-40%)
Lipase hypersecretion syndrome (10-15%)
Jaundice (if head of pancreas).
Symptoms:
Lipase hypersecretion syndrome: Fat necrosis, polyarthropathy, eosinophilia
Metastatic fat necrosis (subcutaneous nodules)
Polyserositis
Bone lesions (osteoblastic)
Diabetes mellitus (pancreatic insufficiency)
Thrombotic complications.
Risk Factors:
Familial adenomatous polyposis (rare association)
APC gene mutations
Advanced age
Male gender
Smoking (possible)
Alcohol consumption (possible)
Most cases have no identifiable risk factors.
Screening:
Cross-sectional imaging (CT, MRI)
Serum lipase (may be markedly elevated)
Serum trypsin
CA 19-9 (usually normal or mildly elevated)
Endoscopic ultrasound
Fine needle aspiration for diagnosis.
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Gross Description
Appearance:
Large lobulated mass
Tan to gray-white cut surface
Soft to firm consistency
Size typically 5-10 cm at presentation
May show areas of necrosis
Hemorrhage may be present.
Characteristics:
Well-circumscribed to infiltrative margins
Multinodular appearance
Tan-pink color
Fleshy consistency
May show cystic degeneration
Cut surface appears lobulated
Encapsulation rare.
Size Location:
Size ranges from 2-25 cm (median 7 cm)
Pancreatic tail most common (50-60%)
Head of pancreas (30-40%)
Body of pancreas (10-20%)
Diffuse involvement possible
Often larger than ductal adenocarcinoma at presentation.
Multifocality:
Usually solitary lesions
Local invasion into surrounding structures
Lymph node metastases (50-70%)
Liver metastases common
Peritoneal seeding
Distant metastases (lung, bone).
Microscopic Description
Histological Features:
Acinar cell differentiation with enzyme-rich cytoplasm
Basophilic granular cytoplasm
Basal nuclei with prominent nucleoli
Acinar formation with central lumina
Zymogen granules in cytoplasm
High mitotic rate.
Cellular Characteristics:
Polygonal cells with abundant cytoplasm
Deeply basophilic cytoplasm (rich in RER)
Round to oval nuclei
Prominent nucleoli
Basal nuclear location (polarized)
Pleomorphic nuclei in high-grade areas
Mitotic figures frequent.
Architectural Patterns:
Acinar pattern (small lumina)
Solid pattern
Trabecular pattern
Ductal pattern (mixed tumors)
Microacinar pattern
Sheet-like growth
Mixed architectural patterns common.
Grading Criteria:
No standardized grading system
Well-differentiated: Prominent acinar formation
Moderately differentiated: Mixed patterns
Poorly differentiated: Solid growth, loss of acinar features
Mitotic activity variable
Necrosis common in large tumors.
Immunohistochemistry
Positive Markers:
Trypsin (85-95% positive)
Chymotrypsin (80-90%)
Lipase (70-80%)
Carboxyl ester lipase (85-95%)
CK8/18 (positive)
BCL10 (specific marker)
PTF1A (transcription factor).
Negative Markers:
Chromogranin A (usually negative)
Synaptophysin (usually negative)
CK19 (negative or focal)
CEA (negative)
CA 19-9 (negative)
CDX2 (negative)
TTF-1 (negative).
Diagnostic Utility:
Trypsin most specific and sensitive
Chymotrypsin supportive
BCL10 highly specific
Essential for differential diagnosis
Useful in poorly differentiated cases
Enzyme panel recommended.
Molecular Subtypes:
APC mutations (30-40%)
CTNNB1 mutations (rare)
SMAD4 loss (subset)
TP53 mutations (variable)
KRAS mutations (less common than PDAC)
Chromosomal instability.
Molecular/Genetic
Genetic Mutations:
APC mutations (30-40%)
TP53 mutations (20-30%)
SMAD4 loss (15-25%)
CTNNB1 mutations (10-15%)
KRAS mutations (10-20%)
RB1 mutations
ARID1A mutations.
Molecular Markers:
APC protein loss
Beta-catenin alterations
p53 accumulation
SMAD4 loss
Rb protein loss
Cyclin D1 overexpression
Ki-67 high proliferation index.
Prognostic Significance:
SMAD4 loss associated with worse prognosis
APC mutations may predict FAP association
TP53 mutations indicate aggressive behavior
Tumor size important prognostic factor
Stage at presentation critical
Resectability determines outcome.
Therapeutic Targets:
Surgery (only curative treatment)
Chemotherapy (gemcitabine, oxaliplatin)
Targeted therapy limited
mTOR inhibitors (investigational)
Immunotherapy (limited efficacy)
Supportive care for lipase syndrome.
Differential Diagnosis
Similar Entities:
Pancreatic ductal adenocarcinoma (most important)
Pancreatic neuroendocrine tumor
Pancreatoblastoma
Solid pseudopapillary neoplasm
Metastatic carcinoma
Chronic pancreatitis with atypical changes.
Distinguishing Features:
ACC: Trypsin/chymotrypsin positive
ACC: Acinar morphology
PDAC: CK19, CEA positive
NET: Chromogranin, synaptophysin positive
Pancreatoblastoma: Squamoid corpuscles
SPN: Beta-catenin nuclear positive.
Diagnostic Challenges:
Distinguishing from poorly differentiated PDAC
Mixed tumors with ductal components
Crush artifact in small biopsies
Enzyme negativity in poorly differentiated areas
Limited tissue for complete workup.
Rare Variants:
Acinar cell cystadenocarcinoma
Mixed acinar-ductal carcinoma
Mixed acinar-neuroendocrine carcinoma
Oncocytic variant
Clear cell variant
Pleomorphic variant.
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
Pancreatoduodenectomy/distal pancreatectomy, measuring [dimensions]
Diagnosis
Pancreatic Acinar Cell Carcinoma
Differentiation
Differentiation: [well/moderately/poorly] differentiated
Microscopic Features
Shows acinar cell differentiation with basophilic granular cytoplasm and [pattern description]
Size and Location
Size: [X] cm; Location: [head/body/tail] of pancreas
Margins
Margins: [involved/uninvolved], closest margin [X] mm
Lymphovascular Invasion
Lymphovascular invasion: [present/absent/suspicious]
Lymph Node Status
Lymph nodes: [X] positive out of [X] examined
Immunohistochemistry
Trypsin: [positive/negative]; Chymotrypsin: [positive/negative]; [other enzymes]: [results]
Clinical Correlation
Clinical correlation with serum lipase and fat necrosis syndrome recommended
TNM Staging
pT[X]N[X]: [staging based on size, invasion, nodes]
Final Diagnosis
Pancreatic Acinar Cell Carcinoma, [differentiation], [size] cm, pT[X]N[X]