STEPTRACKERGASTROINTESTINAL + ENDOCRINE | PATHOLOGY | HIGH-YIELD REVIEW

Pancreatic Neoplasms

The deadly ductal adenocarcinoma, the cystic tumors you must tell apart, and the islet-cell tumors defined by what they secrete.

FOCUS ON
Adenocarcinoma: smoking, head of pancreas → painless jaundice + palpable nontender gallbladder (Courvoisier), weight loss, migratory thrombophlebitis (Trousseau), CA 19-9; KRAS, CDKN2A. Cystic: serous (benign, older women) vs mucinous / IPMN (premalignant). Islet tumors: insulinoma, glucagonoma, VIPoma, somatostatinoma, gastrinoma; MEN1.
TUMOR
MECHANISM · RISK
FEATURES
CLUE
Pancreatic adenocarcinoma
Smoking (top modifiable risk), chronic pancreatitis, obesity, diabetes, age, BRCA2, hereditary syndromes; PanIN precursor; KRAS, CDKN2A (p16), SMAD4, TP53
Ductal glands in a desmoplastic stroma; perineural invasion; head 60–70%
CA 19-9 (monitoring) · Whipple resection · very poor prognosis
Head-of-pancreas tumor
Compresses the common bile duct
Painless obstructive jaundice, pruritus, pale stools, dark urine; Courvoisier sign
Double duct sign on imaging
Body/tail tumor
Grows silently, invades celiac plexus
Epigastric pain radiating to the back, weight loss; late diagnosis
New-onset diabetes in an older adult
Trousseau syndrome
Tumor mucins and tissue factor → hypercoagulability
Migratory superficial thrombophlebitis
Pancreatic and other adenocarcinomas
Serous cystadenoma
Benign; older women; von Hippel-Lindau
Many small cysts lined by glycogen-rich clear cells; central sunburst scar/calcification
Clear watery fluid, low CEA
Mucinous cystic neoplasm
Premalignant; almost always women
Body/tail; mucin-producing epithelium over ovarian-type stroma; no duct connection
Thick fluid, high CEA · resect
IPMN
Intraductal papillary mucinous neoplasm; premalignant; older men
Dilated duct filled with mucin; communicates with the duct; "fish-mouth" ampulla oozing mucin
Main-duct type has highest cancer risk
Solid pseudopapillary neoplasm
Low-grade malignant; β-catenin (CTNNB1) mutation
Young women; large solid-cystic hemorrhagic mass
Cured by resection usually
Insulinoma
β-cell tumor; most common functional islet tumor; MEN1
Whipple triad: hypoglycemia symptoms, low glucose, relief with glucose
↑ insulin + ↑ C-peptide (vs exogenous insulin: ↓ C-peptide)
Glucagonoma
α-cell tumor
Necrolytic migratory erythema, diabetes, DVT, depression, weight loss
"4 Ds": dermatitis, diabetes, DVT, depression
VIPoma
VIP → ↑ intestinal secretion, ↓ gastric acid
Watery diarrhea, hypokalemia, achlorhydria (WDHA)
Large-volume secretory diarrhea despite fasting
Somatostatinoma
δ-cell tumor; somatostatin inhibits everything
Diabetes, gallstones (↓ CCK), steatorrhea, achlorhydria
Rare

Mechanism — PanIN to adenocarcinoma

Normal duct
→
PanIN-1KRAS (earliest)
→
PanIN-2CDKN2A (p16)
→
PanIN-3TP53, SMAD4
→
Invasive carcinomaDesmoplasia, nerves
Tumor in head
→
CBD obstruction
→
Conjugated hyperbilirubinemiaDistended, nontender gallbladder

Cystic lesions of the pancreas

LESION
WHO
LINING
RISK
Pseudocyst
After pancreatitis
None (granulation)
None
Serous cystadenoma
Older women, VHL
Clear glycogen cells
Benign
Mucinous cystic
Middle-aged women
Mucinous + ovarian stroma
Premalignant
IPMN
Older men
Mucinous papillae in duct
Premalignant
Solid pseudopapillary
Young women
Solid + cystic
Low-grade malignant

How it's tested

COMMON CONFUSIONPainless jaundice with a big gallbladder = pancreatic head tumor. Painful jaundice with a shrunken, scarred gallbladder = gallstones (Courvoisier's law).
THE TRAPHypoglycemia with high insulin and LOW C-peptide is exogenous insulin, not an insulinoma. Sulfonylureas raise both, so check a drug screen too.
YOUR APPROACHSolid vs cystic → location (head/body/tail) → patient profile (age, sex, VHL, MEN1) → secretory syndrome → marker (CA 19-9, C-peptide, hormone level).

If you see… think…

Older smoker, painless jaundice, palpable nontender gallbladder → pancreatic head adenocarcinoma
Weight loss + new diabetes + back pain → pancreatic body/tail cancer
Migratory thrombophlebitis → Trousseau sign — occult adenocarcinoma
Earliest mutation in pancreatic cancer → KRAS
Older woman, cyst with central sunburst calcification → serous cystadenoma
Woman with a mucinous tail cyst and ovarian-type stroma → mucinous cystic neoplasm
Mucin oozing from the ampulla, dilated main duct → IPMN
Fasting hypoglycemia, ↑ insulin, ↑ C-peptide → insulinoma
Migratory red blistering rash + diabetes → glucagonoma
Watery diarrhea, low K⁺, no stomach acid → VIPoma