STEPTRACKERGASTROINTESTINAL + ONCOLOGY | PATHOLOGY + ANATOMY | HIGH-YIELD REVIEW

Neuroendocrine, Stromal & Other GI Tumors

Carcinoid tumors and the syndrome that needs a liver metastasis, GIST, GI lymphomas, appendiceal and anal tumors.

FOCUS ON
Carcinoid syndrome appears only when serotonin bypasses the liver (usually liver metastases): flushing, diarrhea, wheezing, right-sided valve disease; ↑ urine 5-HIAA; octreotide. GIST = KIT (CD117), stomach, imatinib. Anal SCC = HPV-16; the dentate line decides drainage.
TUMOR
MECHANISM · ORIGIN
FEATURES
CLUE · TREATMENT
GI carcinoid (neuroendocrine) tumor
Enterochromaffin cells; chromogranin A, synaptophysin ⁺; nests of uniform cells, salt-and-pepper chromatin
Most common in the small bowel (ileum); also appendix, rectum; often silent
Ileal tumors metastasize more than appendiceal ones
Carcinoid syndrome
Serotonin, histamine, kinins reach the systemic circulation — needs liver metastases (or a bronchial/ovarian primary)
Episodic flushing, watery diarrhea, wheezing, hypotension
↑ urine 5-HIAA · octreotide; telotristat (blocks serotonin synthesis)
Carcinoid heart disease
Serotonin → fibrous plaques on valves on the right side; the lungs (MAO) protect the left heart
Tricuspid regurgitation, pulmonic stenosis → right heart failure
"TIPS": tricuspid insufficiency, pulmonic stenosis
Niacin deficiency in carcinoid
Tumor diverts tryptophan to serotonin → less niacin made
Pellagra: dermatitis, diarrhea, dementia
Also seen in Hartnup disease
Appendiceal neuroendocrine tumor
Arises at the tip of the appendix
Incidental at appendectomy; most < 2 cm
Small ones cured by appendectomy
Gastrointestinal stromal tumor (GIST)
Interstitial cells of Cajal (pacemaker cells); gain-of-function KIT or PDGFRA
Stomach most common, then small bowel; submucosal spindle-cell mass; bleeding
CD117, DOG1 ⁺ · imatinib (tyrosine kinase inhibitor) · NF1, Carney triad
GI lymphomas
Stomach: MALT (H pylori), DLBCL · small bowel: EATL (celiac) · ileocecal: Burkitt (children) · mantle cell: multiple polyps
Mass, obstruction, intussusception, bleeding
Stomach is the most common extranodal site
Small bowel adenocarcinoma
Rare; celiac, Crohn, FAP, Lynch, Peutz-Jeghers
Duodenum (periampullary) most often
Obstruction, jaundice, bleeding
Appendiceal mucinous neoplasm
Mucin-producing epithelium; rupture spreads mucin
Pseudomyxoma peritonei: gelatinous ascites ("jelly belly")
Also from ovarian mucinous tumors
Anal squamous cell carcinoma
HPV-16; risk ↑ with HIV, receptive anal intercourse, immunosuppression; precursor: anal intraepithelial neoplasia
Bleeding, mass, pain; below the dentate line → superficial inguinal nodes
Chemoradiation (Nigro protocol), not surgery first

Mechanism — why liver metastases unmask carcinoid

Tryptophan
→
Serotonin (5-HT)Made by the tumor
→
Portal vein
→
Liver MAO5-HT → 5-HIAA
→
No symptoms
Liver metastasesDrain into hepatic veins
→
Systemic serotoninFlushing, diarrhea, bronchospasm
→
Right heart valvesFibrosis

Above vs below the dentate line

FEATURE
ABOVE
BELOW
Origin
Endoderm (hindgut)
Ectoderm
Epithelium
Columnar
Stratified squamous
Nerve
Visceral — painless
Somatic (pudendal) — painful
Venous
Superior rectal → portal
Inferior rectal → caval
Lymph
Internal iliac
Superficial inguinal
Lesion
Internal hemorrhoid, adenocarcinoma
External hemorrhoid, fissure, SCC

How it's tested

COMMON CONFUSIONA carcinoid tumor confined to the bowel is usually silent. The syndrome needs serotonin to skip the liver — liver metastases or a primary outside the portal system.
THE TRAPCarcinoid heart disease involves right-sided valves. Left-sided lesions are rare because the lungs inactivate serotonin.
YOUR APPROACHNeuroendocrine markers (chromogranin) vs CD117 vs lymphoid → site → secretory syndrome → targeted drug (octreotide, imatinib).

If you see… think…

Flushing + diarrhea + wheezing + liver masses → carcinoid syndrome
Best diagnostic test for carcinoid syndrome → 24-hour urine 5-HIAA
Tricuspid regurgitation in a patient with flushing → carcinoid heart disease
Diarrhea, dermatitis and dementia in a carcinoid patient → niacin deficiency
Small yellow nodule at the appendix tip at appendectomy → appendiceal carcinoid
Gastric submucosal spindle-cell tumor, CD117⁺ → GIST — imatinib
Child with an ileocecal mass and intussusception → Burkitt lymphoma
Gelatinous ascites after appendiceal tumor rupture → pseudomyxoma peritonei
HIV-positive man with anal mass and inguinal nodes → anal SCC (HPV-16)
Painless bleeding above the dentate line → internal hemorrhoid