Definition/General
Introduction:
Acinar cell carcinoma (ACC) is a rare malignant tumor comprising 1-2% of all pancreatic neoplasms
Derives from pancreatic acinar cells
Shows aggressive behavior with poor prognosis
Characterized by acinar differentiation and enzyme production
FNAC can be diagnostic with proper technique.
Origin:
Arises from pancreatic acinar cells responsible for enzyme production
Maintains some enzyme synthetic capacity
May arise from multipotent stem cells with acinar differentiation
Shows zymogen granule formation
Rarely associated with genetic syndromes.
Classification:
WHO classification: Acinar cell carcinoma
Considered high-grade malignancy
Variants include pure acinar type
Mixed acinar-ductal carcinoma
Mixed acinar-neuroendocrine carcinoma
Pancreatoblastoma (pediatric variant).
Epidemiology:
Male predominance (M:F = 2:1)
Peak incidence in 6th-7th decades
No racial predilection
Associated with lipase hypersecretion syndrome
Rare familial cases reported
May be associated with Lynch syndrome.
Clinical Features
Presentation:
Abdominal pain (most common symptom)
Weight loss and cachexia
Jaundice (if head involvement)
Lipase hypersecretion syndrome (10-15%)
Subcutaneous fat necrosis
Polyarthralgia
Eosinophilia.
Symptoms:
Abdominal pain (80-90%)
Weight loss (60-70%)
Nausea and vomiting (50%)
Jaundice (30-40%)
Subcutaneous nodules (fat necrosis)
Joint pain and swelling
Peripheral eosinophilia.
Risk Factors:
Male gender
Advanced age (>60 years)
Lynch syndrome (rare association)
Familial adenomatous polyposis
No smoking association
No alcohol association
Previous pancreatitis (controversial).
Screening:
No established screening protocols
Lipase levels may be markedly elevated
Alpha-fetoprotein normal
CA 19-9 variable
EUS-FNAC for tissue diagnosis
CT/MRI for staging.
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Gross Description
Appearance:
Large, well-circumscribed mass with lobulated surface
Soft, tan-gray cut surface
Areas of hemorrhage and necrosis common
May show cystic degeneration
Calcification uncommon
Pseudocapsule may be present.
Characteristics:
Solid tumor with soft consistency
Tan to gray coloration
Hemorrhagic areas frequent
Necrosis common in larger tumors
May be multinodular
Well-demarcated from surrounding pancreas.
Size Location:
Typically large tumors (5-15 cm average)
Pancreatic tail most common (40-50%)
Head involvement (30-40%)
Body involvement (20%)
May involve multiple regions in large tumors.
Multifocality:
Usually unifocal at presentation
Multifocal disease suggests metastases
Liver metastases common at diagnosis
Peritoneal seeding frequent
Lymph node involvement common.
Microscopic Description
Histological Features:
Cells arranged in acinar/glandular pattern
Solid sheets also present
Zymogen granules in cytoplasm (PAS-positive)
Nuclear pleomorphism moderate to marked
Prominent nucleoli
Mitotic activity increased
Desmoplastic stroma variable.
Cellular Characteristics:
Large polygonal cells with abundant cytoplasm
Eosinophilic, granular cytoplasm
Round to oval nuclei with coarse chromatin
Prominent nucleoli
Nuclear pleomorphism present
PAS-positive, diastase-resistant granules
Apical cytoplasmic blebbing.
Architectural Patterns:
Acinar pattern with central lumina
Solid nests and sheets
Trabecular arrangement
Pseudoacinar formation
Loss of normal acinar architecture
Infiltrative growth pattern
Vascular invasion common.
Grading Criteria:
Generally high-grade tumors
Nuclear grade 2-3 (moderate to high)
Mitotic count >10 per 10 HPF
Ki-67 index typically >20%
Necrosis common
Aggressive behavior regardless of grade.
Immunohistochemistry
Positive Markers:
Trypsin (highly specific, >90% positive)
Chymotrypsin (highly specific)
Lipase (specific for acinar cells)
BCL10 positive
Carboxypeptidase A positive
Amylase variable
CK8/18 positive.
Negative Markers:
Chromogranin A negative (helps exclude NET)
Synaptophysin negative
CK19 negative (helps exclude ductal)
TTF-1 negative
CDX2 negative
Insulin, glucagon negative.
Diagnostic Utility:
Trypsin and chymotrypsin are diagnostic markers
Help distinguish from ductal adenocarcinoma
Exclude neuroendocrine tumors
Combined panel essential for diagnosis
BCL10 emerging as useful marker.
Molecular Subtypes:
No established molecular subtypes
Microsatellite instability in Lynch-associated cases
BRCA2 mutations occasionally
APC mutations rare
TP53 mutations common
SMAD4 loss frequent.
Molecular/Genetic
Genetic Mutations:
TP53 mutations (60-70% cases)
SMAD4 alterations (40-50%)
APC mutations (20-30%)
BRCA2 mutations (10-15%)
CDKN2A deletions
RB1 alterations
Microsatellite instability (Lynch cases).
Molecular Markers:
Complex genomic alterations
High mutation burden
Chromosomal instability
p53 pathway dysfunction
TGF-beta pathway alterations
DNA repair defects in some cases.
Prognostic Significance:
BRCA2 mutations may predict platinum sensitivity
Microsatellite instability predicts immunotherapy response
SMAD4 loss associated with worse prognosis
Overall poor prognosis regardless of molecular features.
Therapeutic Targets:
PARP inhibitors for BRCA2-mutated tumors
Immunotherapy for MSI-high tumors
Platinum-based chemotherapy
Targeted therapies under investigation
Clinical trials recommended.
Differential Diagnosis
Similar Entities:
Pancreatic ductal adenocarcinoma (most important)
Pancreatic neuroendocrine tumor
Solid pseudopapillary neoplasm
Pancreatoblastoma (pediatric)
Metastatic carcinoma to pancreas.
Distinguishing Features:
ACC: Trypsin/chymotrypsin positive
ACC: Large cell size
ACC: Granular cytoplasm
Ductal: CK19 positive
Ductal: Mucin production
NET: Chromogranin/synaptophysin positive
NET: Smaller uniform cells.
Diagnostic Challenges:
Mixed acinar-ductal carcinomas challenging
Poorly differentiated cases difficult
Loss of acinar differentiation
Immunohistochemistry essential
May require extensive sampling
Distinguish from metastases.
Rare Variants:
Mixed acinar-ductal carcinoma
Mixed acinar-neuroendocrine carcinoma
Acinar cell cystadenocarcinoma
Pancreatoblastoma (adults)
Pure acinar type most common.
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
Highly cellular smears showing [describe cell population]
Cell Morphology
Large polygonal cells with [cytoplasmic] and [nuclear features]
Architecture
Cells show [acinar/solid] arrangement
Background
Background shows [necrosis/blood/inflammatory cells]
Immunocytochemistry
Trypsin: [result], Chymotrypsin: [result], Chromogranin: [result]
Differential Diagnosis
Differential includes [list conditions]
Final Diagnosis
FNAC pancreas: [diagnosis]