Pancreatitis & Pancreatic Tumours
Pathology · GIT & Liver · lean revision notes
Pancreatitis & Pancreatic Tumours
A high-frequency Pathology cluster spanning acute and chronic pancreatitis through to exocrine carcinoma and the islet-cell endocrine tumours. NEET PG loves the morphology pivots here — fat saponification, double-duct sign, CA 19-9 — so anchor your revision to the named facts and cut-offs.
Classification overview
The pancreas produces both exocrine (acinar + ductal) and endocrine (islet) disease. Organise the topic as four buckets:
| Category | Prototype lesion | Signature exam clue |
|---|---|---|
| Acute inflammation | Acute pancreatitis | Fat necrosis + calcium soaps, raised lipase |
| Chronic inflammation | Chronic pancreatitis | Ductal calcification, "chain of lakes", steatorrhoea |
| Exocrine malignancy | Pancreatic ductal adenocarcinoma (PDAC) | Double-duct sign, CA 19-9, Trousseau sign |
| Endocrine (islet) tumours | Insulinoma, gastrinoma | Whipple triad / ZES (intractable ulcers) |
High-yield: The two single most-tested morphological facts are (1) fat saponification (calcium soap) in acute pancreatitis and (2) the double-duct sign + CA 19-9 in pancreatic head adenocarcinoma.
Acute pancreatitis
Definition
Reversible, acute inflammation of the pancreas due to autodigestion by inappropriately activated pancreatic enzymes, ranging from mild interstitial oedema to severe necrotising disease.
Etiology
The classic mnemonic is "I GET SMASHED":
- I — Idiopathic
- G — Gallstones (commonest cause in India, esp. women)
- E — Ethanol/alcohol (commonest in men)
- T — Trauma (steering-wheel injury, ERCP)
- S — Steroids
- M — Mumps / Malignancy
- A — Autoimmune, Ascaris (duct obstruction — relevant in India), Anatomic (pancreas divisum)
- S — Scorpion sting (Tityus trinitatis; classic but rare)
- H — Hypercalcaemia / Hypertriglyceridaemia (>1000 mg/dL)
- E — ERCP
- D — Drugs (azathioprine, sulfonamides, thiazides, valproate, didanosine, GLP-1 agonists)
High-yield: Gallstones and alcohol together account for ~80% of cases. Hypertriglyceridaemia must usually exceed 1000 mg/dL to trigger pancreatitis; serum amylase may be falsely normal/low because the lipid interferes with the assay.
Pathophysiology
The unifying event is intra-acinar activation of trypsinogen to trypsin, which then activates the entire zymogen cascade. Three proposed initiating mechanisms:
- Duct obstruction (gallstone, tumour) → increased intraductal pressure → enzyme-rich fluid leaks into interstitium.
- Primary acinar injury (alcohol, drugs, ischaemia, viruses) → direct cellular damage releasing enzymes.
- Defective intracellular transport → zymogens delivered to lysosomes → cathepsin B activates trypsinogen.
Flow: Trypsin activation → phospholipase A2 + elastase (vascular & tissue destruction) → fat necrosis → released free fatty acids bind calcium → saponification (calcium soaps) → hypocalcaemia.
High-yield: Phospholipase A2 and lipase drive fat necrosis. Liberated fatty acids chelate calcium to form chalky-white calcium soaps — this is why hypocalcaemia is a marker of severity (and a poor-prognosis Ranson criterion).
Morphology
- Microvascular leak and oedema (interstitial/oedematous pancreatitis).
- Fat necrosis of peri-pancreatic and intraperitoneal fat — grossly chalky-white foci.
- Proteolytic destruction of parenchyma.
- Vessel destruction → haemorrhage (haemorrhagic pancreatitis).
- Acute inflammatory infiltrate.
Clinical features
- Severe, constant epigastric pain radiating to the back, relieved by leaning forward.
- Nausea, vomiting, abdominal distension (ileus).
- Grey-Turner sign (flank ecchymosis) and Cullen sign (periumbilical ecchymosis) indicate retroperitoneal haemorrhage — late, severe disease.
- Tetany/Chvostek sign if marked hypocalcaemia.
Diagnosis & investigation of choice
Diagnosis needs 2 of 3 (Revised Atlanta criteria):
- Characteristic abdominal pain.
- Serum lipase or amylase >3× upper limit of normal.
- Characteristic imaging (CECT/MRI/USG).
| Marker | Rise | Peak | Normalises | Notes |
|---|---|---|---|---|
| Amylase | 6–12 h | 24–48 h | 3–5 days | Less specific; raised in salivary disease, perforation |
| Lipase | 4–8 h | 24 h | 8–14 days | More sensitive & specific — investigation of choice |
High-yield: Lipase is the more specific marker and stays elevated longer than amylase. Enzyme magnitude does not correlate with severity. CECT abdomen is the imaging investigation of choice, ideally done after 72 h to assess necrosis (CT Severity Index / modified Balthazar).
Severity scoring — Ranson criteria (at admission): GA-LAW → Glucose >200, Age >55, LDH >350, AST >250, WBC >16,000. At 48 h: fall in haematocrit >10%, BUN rise >5, Ca²⁺ <8, PaO₂ <60, base deficit >4, fluid sequestration >6 L. BISAP and APACHE-II are also used.
Management / treatment
Largely supportive — there is no specific drug of choice:
- Aggressive isotonic fluid resuscitation (Ringer's lactate preferred) — the single most important intervention.
- Analgesia (opioids).
- Early enteral nutrition (within 24–72 h; nasogastric/nasojejunal) — superior to prolonged NPO/TPN.
- Treat the cause: urgent ERCP + sphincterotomy for gallstone pancreatitis with cholangitis/obstruction; cholecystectomy before discharge in mild biliary pancreatitis.
- Antibiotics only for proven infected necrosis (carbapenems penetrate well) — not prophylactically.
- Step-up approach for infected/walled-off necrosis: percutaneous/endoscopic drainage → minimally invasive necrosectomy.
Complications
- Pseudocyst — collection of enzyme-rich fluid walled off by granulation tissue (no true epithelial lining — that is why it is a "pseudo" cyst), typically >4 weeks.
- Pancreatic abscess, infected necrosis.
- ARDS (phospholipase destroys surfactant), shock, DIC.
- Hypocalcaemia, hyperglycaemia.
- Pancreatic ascites, splenic vein thrombosis → gastric varices.
High-yield: A pseudocyst lacks an epithelial lining and is the commonest cystic lesion of the pancreas after acute pancreatitis. ARDS results from phospholipase A2 degrading pulmonary surfactant.
Chronic pancreatitis
Definition
Irreversible, progressive destruction of pancreatic parenchyma with fibrosis, leading to permanent loss of exocrine and (later) endocrine function.
Etiology
- Chronic alcoholism — commonest cause in adults.
- Tropical (tropical calcific) pancreatitis — important in India, affects young non-alcoholics, presents with diabetes + ductal calculi; associated with SPINK1 mutations and cassava (dietary).
- Hereditary (PRSS1 cationic trypsinogen gene — autosomal dominant).
- Cystic fibrosis (CFTR), autoimmune (IgG4-related), obstructive, idiopathic.
- Mnemonic TIGAR-O: Toxic-metabolic, Idiopathic, Genetic, Autoimmune, Recurrent severe acute, Obstructive.
Pathophysiology & morphology
Recurrent injury → activation of stellate cells → dense fibrosis, acinar atrophy, ductal dilatation with intraductal protein plugs that calcify (calculi), and a chronic inflammatory infiltrate. Islets are relatively preserved until late.
Clinical features
- Recurrent/persistent epigastric pain.
- Steatorrhoea & malabsorption (exocrine insufficiency — loss of lipase) → fat-soluble vitamin deficiency.
- Diabetes mellitus (endocrine failure — late).
- Weight loss.
Diagnosis
- CECT / MRCP — pancreatic calcification, ductal dilatation ("chain of lakes" appearance), atrophy.
- Faecal elastase-1 low (best test of exocrine function); secretin stimulation test (gold standard, rarely done).
- Amylase/lipase often normal (burnt-out gland).
High-yield: Pancreatic calcification on plain film/CT is virtually diagnostic of chronic pancreatitis; the dilated beaded duct is the "chain of lakes". Tropical pancreatitis = young Indian patient + large ductal calculi + diabetes, with a markedly raised risk of pancreatic carcinoma.
Management
- Abstinence (alcohol, smoking), analgesia.
- Pancreatic enzyme replacement for steatorrhoea; insulin for diabetes.
- Endoscopic/surgical drainage (Puestow lateral pancreaticojejunostomy) for dilated ducts; coeliac plexus block for pain.
Pancreatic ductal adenocarcinoma (PDAC)
Definition & epidemiology
Highly lethal malignancy arising from the exocrine ductal epithelium; accounts for ~85% of pancreatic neoplasms. Peak 60–80 yrs; one of the worst 5-year survivals of any solid tumour (~5–8%).
Risk factors
Smoking (strongest modifiable), chronic pancreatitis (esp. hereditary & tropical), diabetes mellitus, obesity, advanced age, family history (BRCA2, Peutz-Jeghers/STK11, FAMMM, Lynch).
Molecular pathogenesis
Stepwise progression through PanIN (pancreatic intraepithelial neoplasia):
Flow: Normal duct → PanIN-1 (KRAS mutation, ~95%) → PanIN-2 (p16/CDKN2A loss) → PanIN-3 (TP53, SMAD4/DPC4 loss) → invasive carcinoma.
High-yield: KRAS is the earliest and commonest mutation; SMAD4 (DPC4) loss is characteristic and prognostic. Tumours are intensely desmoplastic (dense stroma), explaining their firm consistency and chemoresistance.
Clinical features
| Tumour site (% ) | Hallmark presentation |
|---|---|
| Head (~60–70%) | Painless obstructive jaundice, palpable non-tender gallbladder (Courvoisier sign), pale stools/dark urine |
| Body & tail (~25%) | Insidious epigastric/back pain, weight loss, late presentation |
Other features: weight loss, new-onset diabetes in the elderly, migratory thrombophlebitis (Trousseau sign) from a hypercoagulable state.
High-yield: Courvoisier's law — a palpable, non-tender gallbladder with jaundice is unlikely to be due to stones (because chronic stone disease scars/contracts the gallbladder); suspect malignant obstruction. Trousseau sign = migratory superficial thrombophlebitis, a paraneoplastic clue.
Diagnosis & investigation of choice
- Contrast (pancreatic-protocol) CT — investigation of choice for diagnosis & staging/resectability.
- MRCP/ERCP shows the "double-duct sign" — simultaneous dilatation of the common bile duct and pancreatic duct from a head mass.
- EUS-guided FNA for tissue diagnosis (most sensitive for small lesions).
- CA 19-9 — the tumour marker; used for prognosis and monitoring recurrence, not screening. Falsely low in Lewis-antigen-negative individuals (~5–10%); also raised in cholangitis/biliary obstruction.
High-yield: Double-duct sign + raised CA 19-9 in an elderly patient with painless jaundice = pancreatic head adenocarcinoma until proven otherwise. CA 19-9 is not a screening test.
Management
- Whipple procedure (pancreaticoduodenectomy) for resectable head tumours; distal pancreatectomy + splenectomy for body/tail. Only ~15–20% are resectable at diagnosis.
- Adjuvant FOLFIRINOX or gemcitabine-based chemo.
- Palliative biliary stenting, coeliac plexus block.
Pancreatic endocrine (islet-cell) tumours
Arise from islet cells; may be functional (hormone-secreting) or non-functional. Associated with MEN-1 (parathyroid, pituitary, pancreas — "3 Ps").
| Tumour | Cell | Hormone | Classic syndrome |
|---|---|---|---|
| Insulinoma | β | Insulin | Whipple triad; commonest, usually benign |
| Gastrinoma | non-β (G) | Gastrin | Zollinger-Ellison syndrome (ZES) |
| Glucagonoma | α | Glucagon | Necrolytic migratory erythema, diabetes, 4 D's |
| VIPoma | — | VIP | WDHA / Verner-Morrison (watery diarrhoea, hypokalaemia, achlorhydria) |
| Somatostatinoma | δ | Somatostatin | Diabetes, gallstones, steatorrhoea |
Insulinoma
- Commonest functional islet tumour; ~90% benign and solitary.
- Whipple triad: (1) symptoms of hypoglycaemia on fasting, (2) low blood glucose (<50 mg/dL), (3) relief with glucose.
- Diagnosis: raised insulin, raised C-peptide, raised proinsulin during a supervised 72-h fast.
High-yield: High C-peptide distinguishes insulinoma from exogenous (factitious) insulin administration, where C-peptide is suppressed/low. Sulfonylurea abuse mimics insulinoma but is detected on a urine drug screen.
Gastrinoma / Zollinger-Ellison syndrome
- Gastrin-secreting tumour, often in the "gastrinoma triangle" (junction of cystic/CBD, 2nd/3rd part duodenum, neck/body of pancreas).
- Multiple, refractory, atypical (distal duodenal/jejunal) peptic ulcers + secretory diarrhoea (acid inactivates lipase).
- Fasting gastrin markedly raised; secretin stimulation test paradoxically increases gastrin (confirmatory).
- ~25% are part of MEN-1.
High-yield: Suspect gastrinoma when peptic ulcers are multiple, recurrent after eradication, or in unusual sites, or associated with diarrhoea. Treat with high-dose PPIs ± tumour resection.
Key differentials
| Presentation | Distinguishing test |
|---|---|
| Acute pancreatitis vs perforated peptic ulcer | Both raise amylase; free gas under diaphragm + lipase <3× favour perforation |
| Pancreatic head cancer vs chronic pancreatitis mass | EUS-FNA, SMAD4 loss, CA 19-9; calcification favours chronic pancreatitis |
| Pseudocyst vs cystic neoplasm (mucinous/IPMN/serous) | History of pancreatitis + no epithelial lining = pseudocyst; mural nodules/septae favour neoplasm |
| Insulinoma vs factitious hypoglycaemia | C-peptide high (insulinoma) vs low (exogenous insulin) |
| Obstructive jaundice — stone vs tumour | Courvoisier sign + painless + weight loss favours malignancy |
Recently asked / exam angle
- Fat necrosis with calcium soap (saponification) — directly named as the hallmark of acute pancreatitis; linked to hypocalcaemia and phospholipase A2/lipase.
- Lipase vs amylase — lipase more specific, stays elevated longer; enzyme level does NOT predict severity.
- Double-duct sign image-based question pointing to pancreatic head carcinoma.
- CA 19-9 — marker for monitoring (not screening) PDAC; false-low in Lewis-negative blood group.
- Pseudocyst lacks epithelial lining — one-liner factual MCQ.
- C-peptide to separate insulinoma from exogenous insulin in a hypoglycaemia work-up.
- Secretin stimulation test — increases gastrin in ZES (paradoxical), distinguishing it from other hypergastrinaemias.
- Tropical calcific pancreatitis / SPINK1 and PRSS1 hereditary pancreatitis genetics.
- KRAS earliest, SMAD4/DPC4 loss in PanIN→PDAC sequence.
- Courvoisier's law and Trousseau migratory thrombophlebitis as PDAC clues.
Rapid revision
- Acute pancreatitis: gallstones (women) + alcohol (men) = ~80% of cases.
- Lipase is the more specific enzyme; diagnose with 2 of 3 (pain, enzymes >3× ULN, imaging).
- Fat saponification → calcium soaps → hypocalcaemia (Ranson poor-prognosis marker).
- Phospholipase A2 destroys surfactant → ARDS in severe pancreatitis.
- Pseudocyst = enzyme collection with no epithelial lining, walls of granulation tissue, >4 weeks.
- Management of acute pancreatitis is supportive — Ringer's lactate, analgesia, early enteral feed; antibiotics only for infected necrosis.
- Chronic pancreatitis: calcification + chain-of-lakes duct + steatorrhoea; tropical type in young Indians (SPINK1).
- PDAC: smoking biggest risk; KRAS earliest mutation, SMAD4 loss prognostic; dense desmoplasia.
- Pancreatic head cancer → painless jaundice + Courvoisier sign + double-duct sign.
- CA 19-9 monitors PDAC (not screening); false-low in Lewis-antigen-negative patients.
- Insulinoma: Whipple triad + high C-peptide; commonest islet tumour, usually benign.
- Gastrinoma/ZES: multiple refractory ulcers + diarrhoea; secretin raises gastrin; treat with high-dose PPIs; ~25% MEN-1.