Neuroendocrine tumors, particularly carcinoid tumors, are low-grade malignancies commonly found in the gastrointestinal tract, primarily in the appendix and ileum. These tumors arise from endocrine cells and can lead to carcinoid syndrome when metastasizing to the liver, resulting in symptoms like diarrhea and flushing. Prognosis varies by location, with foregut tumors rarely metastasizing while midgut carcinoids are often aggressive.

1. NEUROENDOCRINE
TUMORS

2. • Carcinoid tumors are low grade malignancy
• Commonly located in the submucosa of intestinal tract,
• Appendix(40%), terminal ileum(25%),colon, rectum(20%)
• Multicentric in stomach and ileum
• sixth decade,
• Means, Carcinoma- like
• Arise from diffusely distributed endocrine cells,
• Called as well differentiated neuroendocrine tumors,
• Most arise in gut,(lungs are second in frequency),

3. • The cells of origin are responsible for hormone secretion that
coordinate gut function,
• Associated with endocrine cell hyperplasia, autoimmune chronic
atrophic gastritis, MEN-I, Zollinger –Ellison syndrome,
• follow a more indolent course than do carcinoma,

4. • MORPHALOGY
• GROSS
• Yellow-tan intramural or submucosal masses
• small polypoid lesions
• intense desmoplastic response -firm
• bowel obstruction,

5. • M/E
• Islands to sheets of tumor cells
• Uniform cohesive cells having scant, granular cytoplasm, with oval
stippled nuclei,
• Cells are typically positive for neuroendocrine markers(chromogranin
A, synaptophysin)

6. • Neuroendocrine cells
• utilize amino acids, or derivatives of amino acids, as
chemical messengers mediating paracrine and neuroendocrine
effects.
• are known as APUD (Amine precursor uptake and
decorboxylation)

7. • Enterochromaffin cells
• named after for their staining with chromate fixation.
• in groups at the bases of the intestinal crypts small
intestine ,
• synthesize 5HT( 5HYDROXYTRYPTAMINE) and Kallikrein.

8. • Categories
• into three grades (G1,G2 andG3) according to mitotic count
and Ki67 proliferative index.
• is reserved for poorly differentiated neuroendocrine tumor
with marked nuclear atypia and high mitotic rate(> 20/ HPF)

9. • Histochemical staining
• silver staining demonstrates black granules in the
cytoplasm,
• Electron microscopy
• cells show cytoplasmic granules, stained red with eosin,
yellowish brown with chrome salts, black with iron-haematoxylin
and metallic black with silver salts.

10. • Metastases
• Carcinoid of appendix and rectum are seldom malignant.
• invade submucosa and muscularis and penetrate bowel wall,
• large carcinoid >2 cm size in ileum and appendix has tendency
to spread to regional lymph nodes and liver, lungs and bones.

11. • Carcinoid syndrome
• tumors metastasizing to the liver can lead to carcinoid
syndrome as a result of synthesis of 5HT, Serotonin, and bradykinin.
• 5HT increases gut motility resulting in diarrhea, excessive
bowl sounds (borborygmi) and abdominal pain.
• kallikrein produces flushing of skin, bronchospasm.
• 5HT is inactivated in the liver by mono amine oxidase to
form 5hydroxyindole acetic acid and excreted in the urine.

12. • Marked by flushing, diarrhea, dermatitis, and bronchoconstriction,
caused by released mediators,

13. • Carcinoid heart disease
products enter into hepatic veins and affect the right side of
heart,
-develops tricuspid valve incompetence and pulmonary valve
stenosis as a result of formation of fibrous plaques.
- smooth muscle cells within endocardium may undergo
proliferation as a result of kallikrein.

14. • Prognosis
• Foregut tumors(esophagus, stomach, and duodenum) rarely
metastasize and are cured by resection.
• Midgut carcinoids(jejunum and ileum) are usually multiple and
aggressive.
•
• Hindgut trs (appendix and colon) are usually found incidentally.

15. • Appendiceal carcinoids found at the tip, are <2 cm,
• usually benign,
• Colonic carcinoids- large and metastasize,
• Rectal carcinoids- secrete polypeptide hormones and /or cause
pain , do not metastasize.

16. NEUROENDOCRINE PROLIFERATIONS
• Normal lung contains NE cells within the epithelium as single cells
or
as clusters
diffuse idiopathic pulmonary neuroendocrine cell hyperplasia---
precursor to the development of multiple tumorlets, typical or
atypical carcinoids,
tumorlets—small, benign hyperplastic nest of neuroendocrine
cells, seen adjacent to chronic inflammation or scarring.

17. • CARCINOID TUMORS—LUNG
• Low grade malignancies classified as typical or atypical;
high mitotic rates, focal necrosis, increased pleomorphism,
lymphatic invasion.

18. • Morphology
• Gross—intrabronchial, highly vascular, polypoid masses less than
• 3 to 4cm, collar button lesion.
• M/E-nest, cords of uniform, small, round cells,