Definition/General

Introduction:
-Pancreatitis represents inflammatory disease of the pancreas with characteristic FNAC findings
-Can be acute or chronic in nature
-FNAC shows inflammatory cells and reactive changes
-Important to distinguish from neoplastic lesions
-May present as mass-forming pancreatitis.
Origin:
-Results from pancreatic enzyme activation within the gland
-Leads to autodigestion and inflammation
-Acute pancreatitis: reversible inflammatory process
-Chronic pancreatitis: progressive fibrosis and dysfunction
-Various etiologies trigger the inflammatory cascade.
Classification:
-Acute pancreatitis: interstitial edematous
-Acute pancreatitis: necrotizing
-Chronic pancreatitis: obstructive type
-Chronic pancreatitis: inflammatory type
-Autoimmune pancreatitis (IgG4-related)
-Hereditary pancreatitis.
Epidemiology:
-Common cause of pancreatic masses
-Peak incidence 4th-5th decades
-Male predominance in chronic pancreatitis
-Alcohol-related most common cause
-Gallstone pancreatitis in females
-Indian population: tropical pancreatitis seen.

Clinical Features

Presentation:
-Abdominal pain (most common symptom)
-Epigastric pain radiating to back
-Nausea and vomiting
-Weight loss (chronic cases)
-Steatorrhea (exocrine insufficiency)
-Diabetes mellitus (endocrine insufficiency).
Symptoms:
-Severe epigastric pain (acute cases)
-Chronic dull aching pain
-Post-prandial exacerbation
-Nausea and vomiting
-Weight loss and malnutrition
-Steatorrhea and flatulence
-New-onset diabetes.
Risk Factors:
-Alcohol abuse (most common cause)
-Gallstones
-Hypertriglyceridemia
-Hereditary factors (PRSS1, CFTR mutations)
-Medications
-Trauma
-Tropical pancreatitis (malnutrition-related).
Screening:
-Serum amylase and lipase (elevated acutely)
-CT scan for morphological assessment
-MRCP for ductal evaluation
-EUS for detailed pancreatic imaging
-Fecal elastase for exocrine function.

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Gross Description

Appearance:
-Acute: enlarged, edematous pancreas
-Hemorrhagic areas in necrotizing pancreatitis
-Chronic: firm, nodular surface
-Calcifications visible in chronic cases
-Ductal dilatation and strictures.
Characteristics:
-Acute: soft, edematous consistency
-Areas of fat necrosis
-Hemorrhage and necrosis
-Chronic: hard, fibrotic texture
-Gritty calcifications
-Dilated main pancreatic duct.
Size Location:
-Diffuse involvement common
-Head more affected in chronic disease
-Mass-forming pancreatitis may simulate tumor
-Can involve entire gland or be segmental.
Multifocality:
-Usually diffuse process
-Focal areas more severely affected
-Pseudocyst formation in severe cases
-Skip lesions in chronic pancreatitis
-Strictures and dilatations alternate.

Microscopic Description

Histological Features:
-Acute: interstitial edema and inflammatory infiltrate
-Neutrophilic infiltration predominant
-Fat necrosis and hemorrhage
-Chronic: chronic inflammatory cells
-Fibrosis and acinar atrophy
-Ductal proliferation.
Cellular Characteristics:
-Acute: neutrophils and macrophages
-Reactive ductal epithelium
-Chronic: lymphocytes and plasma cells
-Activated fibroblasts
-Reactive/regenerative epithelial changes
-Loss of acinar cells.
Architectural Patterns:
-Loss of normal acinar architecture
-Fibrotic replacement (chronic)
-Ductal dilatation and metaplasia
-Pseudocyst formation
-Vascular changes and thrombosis.
Grading Criteria:
-Acute: mild, moderate, severe based on necrosis extent
-Chronic: early, advanced stages
-Cambridge classification for chronic pancreatitis
-Functional assessment important.

Immunohistochemistry

Positive Markers:
-CK19 (ductal epithelium)
-CK7 (reactive ducts)
-Trypsin (residual acinar cells)
-Chromogranin A (islet cells)
-Smooth muscle actin (myofibroblasts)
-IgG4 (autoimmune pancreatitis).
Negative Markers:
-CEA (helps exclude adenocarcinoma)
-CA 19-9 (may be elevated but non-specific)
-p53 (typically negative, unlike carcinoma)
-SMAD4 (retained, unlike ductal adenocarcinoma).
Diagnostic Utility:
-IgG4 staining diagnostic for autoimmune pancreatitis
-p53 and SMAD4 help exclude carcinoma
-Ductal markers show reactive changes
-Combined clinical-pathological correlation essential.
Molecular Subtypes:
-Type 1 autoimmune pancreatitis (IgG4-related)
-Type 2 autoimmune pancreatitis (idiopathic)
-Hereditary pancreatitis (genetic mutations)
-Tropical pancreatitis (nutritional).

Molecular/Genetic

Genetic Mutations:
-PRSS1 mutations (hereditary pancreatitis)
-CFTR mutations (cystic fibrosis-related)
-SPINK1 mutations
-CTRC mutations
-CPA1 mutations
-CEL gene mutations.
Molecular Markers:
-Inflammatory cytokines elevated
-Oxidative stress markers
-Fibrosis-related genes upregulated
-Growth factors (PDGF, TGF-beta)
-Matrix metalloproteinases.
Prognostic Significance:
-Genetic testing important for hereditary cases
-Risk of pancreatic cancer in chronic pancreatitis
-Functional outcomes depend on extent of damage
-Early intervention improves prognosis.
Therapeutic Targets:
-Anti-inflammatory agents
-Antioxidants
-Enzyme replacement therapy
-Pain management
-Pancreaticoenteric drainage
-Total pancreatectomy with islet transplant (severe cases).

Differential Diagnosis

Similar Entities:
-Pancreatic ductal adenocarcinoma (most important)
-Autoimmune pancreatitis
-Neuroendocrine tumor
-Chronic pancreatitis vs carcinoma
-Groove pancreatitis.
Distinguishing Features:
-Pancreatitis: inflammatory cells predominant
-Pancreatitis: Reactive epithelial changes
-Carcinoma: malignant epithelial cells
-Carcinoma: p53 positive, SMAD4 loss
-Clinical correlation essential.
Diagnostic Challenges:
-Mass-forming pancreatitis vs carcinoma most difficult
-Sampling adequacy crucial
-May require multiple FNACs
-Core biopsy sometimes needed
-Clinical and imaging correlation mandatory.
Rare Variants:
-Autoimmune pancreatitis (IgG4-related)
-Groove pancreatitis
-Paraduodenal pancreatitis
-Tropical pancreatitis
-Hereditary pancreatitis.

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 lesion, [location], [number] passes

Adequacy

Specimen is adequate for evaluation

Cellular Findings

Smears show [inflammatory cell types] with [epithelial changes]

Inflammatory Pattern

Predominantly [acute/chronic] inflammatory pattern

Epithelial Changes

Reactive ductal epithelium showing [describe changes]

Background

Background shows [debris/necrosis/blood]

Malignant Cells

No malignant cells identified

Final Diagnosis

FNAC pancreas: Findings consistent with pancreatitis