Pancreatic Tumours
Surgery · Hepatobiliary · lean revision notes
Pancreatic Tumours
Pancreatic neoplasms span an aggressive exocrine carcinoma (ductal adenocarcinoma) and a fascinating family of functioning neuroendocrine tumours. For NEET PG, the high-yield axis is surgical anatomy of the Whipple resection, the double-duct sign, and the clinical syndrome-to-hormone matching of pancreatic neuroendocrine tumours (PanNETs).
Classification
Pancreatic tumours divide broadly into exocrine (≈95%) and endocrine (≈5%) origins.
| Category | Tumour | Notes |
|---|---|---|
| Exocrine — malignant | Ductal adenocarcinoma | ~85–90% of all pancreatic cancers; arises from duct epithelium |
| Exocrine — cystic | Serous cystadenoma | Benign; central scar, "honeycomb"/microcystic |
| Mucinous cystic neoplasm (MCN) | Premalignant; "ovarian-type stroma"; body/tail; women | |
| IPMN (intraductal papillary mucinous neoplasm) | Main-duct type high malignant potential; "fish-mouth" papilla | |
| Solid pseudopapillary tumour (Frantz tumour) | Young women; low-grade malignant; good prognosis | |
| Exocrine — others | Acinar cell carcinoma, pancreatoblastoma | Pancreatoblastoma is the commonest pancreatic tumour in children |
| Endocrine (PanNET) | Insulinoma, gastrinoma, glucagonoma, VIPoma, somatostatinoma, non-functioning | Functioning tumours secrete hormones |
High-yield: Ductal adenocarcinoma is the commonest pancreatic malignancy and ~60–70% arise in the head of the pancreas. Solid pseudopapillary (Frantz) tumour is the classic "young woman, large encapsulated tumour, good prognosis" answer.
Carcinoma Head of Pancreas (Ductal Adenocarcinoma)
Risk factors & pathology
- Smoking is the single most important modifiable risk factor (≈2–3× risk).
- Others: chronic pancreatitis, diabetes mellitus (both risk factor and presenting feature), obesity, high-fat diet.
- Hereditary syndromes: BRCA2, Peutz–Jeghers (STK11), familial atypical multiple mole melanoma (CDKN2A/p16), hereditary pancreatitis (PRSS1), Lynch syndrome.
- Molecular hits (commonest → rarest): KRAS (~90%, earliest), CDKN2A/p16, TP53, SMAD4/DPC4. Precursor lesion = PanIN (pancreatic intraepithelial neoplasia).
High-yield: KRAS is the most frequently mutated oncogene; SMAD4 (DPC4) loss correlates with widespread metastatic disease and poor prognosis.
Clinical features
- Painless progressive obstructive jaundice is the hallmark of head tumours (compression of the intrapancreatic CBD).
- Courvoisier's law: in a jaundiced patient, a palpable, non-tender gallbladder is unlikely to be due to stones (because chronic stone disease produces a fibrotic, non-distensible gallbladder) — it suggests malignant distal biliary obstruction (periampullary/pancreatic head cancer).
- Weight loss, anorexia, pruritus (bile salt deposition), pale stools, dark urine, steatorrhoea.
- Trousseau's sign of malignancy: migratory thrombophlebitis.
- New-onset diabetes in an older adult can be a paraneoplastic harbinger.
- Virchow's node (left supraclavicular), Sister Mary Joseph nodule (umbilical), Blumer's shelf (rectal-shelf metastasis) indicate dissemination.
High-yield: Courvoisier-positive (palpable gallbladder + painless jaundice) ⇒ think periampullary/pancreatic head carcinoma, not gallstones. Exception: a double impaction (cystic + CBD stone) can rarely mimic this.
Investigations
Imaging flow: USG (initial, may show dilated ducts/mass) → Triple-phase (pancreatic protocol) contrast CT (investigation of choice for diagnosis AND resectability/staging) → EUS ± FNA (best for small lesions and tissue) → ERCP/MRCP (ductal anatomy, stenting) → staging laparoscopy (occult peritoneal disease).
- Double-duct sign: simultaneous dilatation of the common bile duct and the main pancreatic duct seen on MRCP/ERCP/CT — classic for a periampullary / pancreatic head carcinoma obstructing both ducts at the ampulla.
- Tumour marker: CA 19-9 — used for prognosis and monitoring recurrence/response, not for screening (falsely low in Lewis-antigen-negative individuals; falsely raised in cholestasis).
- CEA may be mildly elevated.
High-yield: Double-duct sign = pancreatic head/periampullary carcinoma. Investigation of choice for diagnosis & staging = contrast-enhanced (triple-phase) CT abdomen.
Resectability criteria (NCCN concept)
| Status | Arterial involvement | Venous (SMV/portal) |
|---|---|---|
| Resectable | No contact with coeliac axis, SMA, common hepatic | ≤180° contact, no vein contour irregularity |
| Borderline resectable | ≤180° SMA/coeliac contact; reconstructable hepatic artery | >180° SMV/portal contact but reconstructable |
| Unresectable / locally advanced | >180° SMA or coeliac encasement | Unreconstructable SMV/portal occlusion |
Distant metastases (liver, peritoneum, lung) = unresectable regardless of local anatomy.
Management — surgery
Whipple's procedure (pancreaticoduodenectomy) is the operation for resectable head/periampullary cancers.
Structures removed in classical Whipple:
- Head of pancreas (and neck)
- Duodenum (whole)
- Distal stomach (antrum) — preserved in pylorus-preserving variant (PPPD)
- Gallbladder
- Distal common bile duct
- Proximal jejunum
- Regional lymph nodes
Three anastomoses reconstructed: pancreaticojejunostomy + hepaticojejunostomy + gastrojejunostomy (or duodenojejunostomy in PPPD).
High-yield: The commonest and most dreaded complication of Whipple's = pancreatic anastomotic leak / postoperative pancreatic fistula, which can cause sepsis and erosive haemorrhage. Delayed gastric emptying is the commonest cause of prolonged hospital stay.
- Adjuvant chemotherapy: mFOLFIRINOX (fit patients) or gemcitabine ± capecitabine.
- Neoadjuvant therapy is increasingly used for borderline-resectable disease.
- Palliation (for unresectable/jaundiced patients): endoscopic biliary stenting (SEMS) or surgical triple bypass (choledochojejunostomy + gastrojejunostomy + a coeliac plexus block for pain). Coeliac plexus neurolysis relieves the deep boring back pain.
Carcinoma Body & Tail of Pancreas
- Presents late because there is no early ductal obstruction → no jaundice early.
- Features: dull boring epigastric pain radiating to the back (retroperitoneal/coeliac plexus invasion), relieved by leaning forward; marked weight loss.
- Often unresectable at diagnosis (>50–60%).
- Resectable body/tail tumours ⇒ distal pancreatectomy with splenectomy (the splenic vessels run along the tail, mandating splenectomy). Radical antegrade modular pancreatosplenectomy (RAMPS) improves margins.
- Worse prognosis than head tumours due to delayed presentation.
High-yield: Body/tail carcinoma → distal pancreatectomy + splenectomy; head/periampullary → Whipple's. Remember post-splenectomy vaccination against encapsulated organisms (pneumococcus, meningococcus, Hib).
Pancreatic Neuroendocrine Tumours (PanNETs / Islet cell tumours)
Functioning PanNETs produce striking clinical syndromes. Memorise the hormone → cell → syndrome → diagnostic test mapping.
| Tumour | Cell | Hormone | Key syndrome | Diagnosis |
|---|---|---|---|---|
| Insulinoma | β-cell | Insulin | Whipple's triad, hypoglycaemia | ↑Insulin, ↑C-peptide, ↑proinsulin during 72-h fast; ↓glucose |
| Gastrinoma | non-β (G-type) | Gastrin | Zollinger–Ellison (recurrent/refractory PUD, diarrhoea) | ↑Fasting gastrin >1000; secretin stimulation test |
| Glucagonoma | α-cell | Glucagon | Necrolytic migratory erythema, diabetes, weight loss | ↑Glucagon (>500–1000) |
| VIPoma | non-β (D1) | VIP | WDHA syndrome (Verner–Morrison) | ↑VIP; secretory diarrhoea |
| Somatostatinoma | δ-cell | Somatostatin | Diabetes, gallstones, steatorrhoea | ↑Somatostatin |
High-yield mnemonic for VIPoma = "WDHA" → Watery Diarrhoea, Hypokalaemia, Achlorhydria (also called Verner–Morrison or pancreatic cholera). VIP inhibits gastric acid → achlorhydria.
High-yield mnemonic for glucagonoma "4 Ds" → Dermatitis (necrolytic migratory erythema), Diabetes, DVT, Depression (+ weight loss, anaemia, glossitis).
Insulinoma (most common functioning PanNET)
- Whipple's triad: (1) symptoms of hypoglycaemia on fasting, (2) documented blood glucose <50 mg/dL, (3) relief of symptoms with glucose administration. (Note: this is a different "Whipple" from the operation — a classic NEET trick.)
- ~90% benign, ~90% solitary, ~90% intrapancreatic, ~90% <2 cm ("rule of 90s").
- Gold-standard diagnosis: supervised 72-hour fast showing inappropriately elevated insulin, C-peptide, and proinsulin with hypoglycaemia.
- Localisation: EUS, CT, intra-arterial calcium stimulation; intra-operative USG is best for small lesions.
- Distinguish from exogenous insulin abuse: high insulin with LOW C-peptide = factitious insulin injection (exogenous insulin suppresses endogenous C-peptide). Sulfonylurea abuse: high insulin and high C-peptide (mimics insulinoma) → check sulfonylurea screen.
- Treatment: enucleation if small/benign; diazoxide controls symptoms medically.
Gastrinoma & Zollinger–Ellison Syndrome (ZES)
- Recurrent, multiple, atypical-site peptic ulcers (e.g., distal duodenum/jejunum), diarrhoea, GERD, refractory to standard therapy.
- Most arise in the gastrinoma triangle (Passaro's triangle): bounded by the junction of cystic & common bile duct (superior), junction of 2nd–3rd part of duodenum (inferior), junction of neck & body of pancreas (medial). Duodenum is the commonest primary site.
- Diagnosis: fasting serum gastrin (markedly ↑); if equivocal, secretin stimulation test → paradoxical rise in gastrin (normal G-cells are inhibited by secretin, gastrinoma cells are stimulated). Gastric pH <2 must be confirmed.
- ~25% associated with MEN-1 (look for hyperparathyroidism + pituitary tumours).
- Treatment: high-dose PPIs control acid; surgical resection of localised tumour.
High-yield: Insulinoma is the commonest functioning PanNET overall; gastrinoma is the commonest in MEN-1. Most common pancreatic NET is actually the non-functioning type (presents as a mass/metastasis with raised chromogranin A).
MEN-1 association ("3 Ps")
Parathyroid (hyperplasia — commonest, earliest), Pancreas (gastrinoma > insulinoma), Pituitary (prolactinoma). Gene = MENIN on chromosome 11. Always screen a young patient with multiple/recurrent PanNETs or ZES for MEN-1.
General PanNET work-up & treatment
- General marker: Chromogranin A (best overall PanNET marker; raised in functioning and non-functioning tumours).
- Functional localisation: Ga-68 DOTATATE PET (somatostatin-receptor imaging) — superior to older octreotide (¹¹¹In) scintigraphy.
- Medical: somatostatin analogues (octreotide/lanreotide) control symptoms and slow growth in well-differentiated tumours; PRRT (¹⁷⁷Lu-DOTATATE), everolimus, sunitinib for advanced disease.
- Surgical: enucleation for small benign tumours; formal resection (Whipple/distal pancreatectomy) for larger/malignant ones.
Complications
- Of the cancer: biliary obstruction & cholangitis, gastric outlet obstruction, duodenal invasion/bleeding, portal vein thrombosis, malabsorption, cachexia, migratory thrombophlebitis, depression.
- Of Whipple's surgery: postoperative pancreatic fistula (most feared), delayed gastric emptying (most common), bile leak, intra-abdominal abscess, post-pancreatectomy haemorrhage (often from a pseudoaneurysm of the gastroduodenal artery stump — sentinel bleed warning), endocrine & exocrine insufficiency (diabetes, steatorrhoea).
- Of PanNETs: hormone-mediated effects — refractory hypoglycaemia (insulinoma), severe peptic disease (gastrinoma), profound dehydration & hypokalaemia (VIPoma), thromboembolism (glucagonoma).
Key Differentials
- Painless obstructive jaundice: pancreatic head Ca, ampullary carcinoma, cholangiocarcinoma (distal CBD), choledocholithiasis (usually painful), enlarged porta hepatis nodes.
- Periampullary tumours (better prognosis than pancreatic head Ca): ampullary, distal CBD, duodenal, and pancreatic head — all resected by Whipple's; ampullary carcinoma presents earliest (intermittent "silver stools" — combined obstructive jaundice + GI bleed) and has the best prognosis.
- Cystic pancreatic lesions: pseudocyst (history of pancreatitis, no epithelial lining), serous cystadenoma (benign), MCN (premalignant, women, body/tail), IPMN (ductal communication).
- Hypoglycaemia DDx for insulinoma: factitious insulin/sulfonylurea, non-islet-cell tumour hypoglycaemia (IGF-2), Addison's, alcohol.
Recently asked / exam angle
- Double-duct sign → periampullary/pancreatic head carcinoma (recurrent single-best-answer).
- Structures removed in Whipple's procedure (gallbladder is removed; tail of pancreas and spleen are NOT).
- Courvoisier's law statement and its exception.
- Whipple's triad of insulinoma vs Whipple's operation — the deliberate name-clash trick.
- Hormone–syndrome matching: VIPoma → WDHA/Verner–Morrison, glucagonoma → necrolytic migratory erythema, gastrinoma → ZES.
- Secretin stimulation test → paradoxical gastrin rise in gastrinoma.
- High insulin with low C-peptide = exogenous insulin (factitious), not insulinoma.
- Gastrinoma triangle (Passaro's triangle) boundaries.
- Commonest functioning PanNET = insulinoma; commonest PanNET in MEN-1 = gastrinoma; most common PanNET overall = non-functioning.
- Commonest mutation in ductal adenocarcinoma = KRAS; poor-prognosis marker = SMAD4/DPC4 loss.
- CA 19-9 is for monitoring, not screening; falsely low in Lewis-negative patients.
- Body/tail carcinoma management = distal pancreatectomy + splenectomy.
- Commonest pancreatic tumour in children = pancreatoblastoma; "young woman, encapsulated, good prognosis" = solid pseudopapillary (Frantz) tumour.
Rapid revision
- Ductal adenocarcinoma = commonest pancreatic malignancy; ~70% in the head; smoking is the top risk factor.
- KRAS earliest/most common mutation; SMAD4 (DPC4) loss = poor prognosis; precursor = PanIN.
- Painless obstructive jaundice + palpable gallbladder = Courvoisier-positive → periampullary/head carcinoma.
- Double-duct sign (dilated CBD + main pancreatic duct) = pancreatic head/periampullary cancer.
- Triple-phase contrast CT = investigation of choice for diagnosis & resectability; EUS-FNA for tissue.
- CA 19-9 for prognosis/monitoring only; falsely low in Lewis-antigen-negative individuals.
- Whipple's removes head of pancreas, duodenum, distal stomach, gallbladder, distal CBD, proximal jejunum; spares tail & spleen.
- Most feared Whipple complication = pancreatic fistula/leak; commonest = delayed gastric emptying.
- Body/tail Ca → late presentation, back pain → distal pancreatectomy + splenectomy.
- Insulinoma = commonest functioning PanNET; Whipple's triad; ↑insulin + ↑C-peptide (low C-peptide = factitious insulin).
- Gastrinoma → ZES, secretin test causes paradoxical gastrin rise; commonest PanNET in MEN-1; site = duodenum/Passaro's triangle.
- VIPoma → WDHA (Verner–Morrison); glucagonoma → necrolytic migratory erythema + diabetes; Chromogranin A = best general PanNET marker; Ga-68 DOTATATE PET for localisation.