1. Overview on Neuroendocrine tumors of pancreas
Sarah S. Al-Ghamdi
2013

2. Outlines: Basic Anatomy, Embryology and Histology Epidemiology
Classification
Overview on functional types of neuroendocrine tumors of pancreas

3. Basic Anatomy: - Gland of both Exocrine and Endocrine function
- Location: Retro-peritoneum, 2nd lumbar vertebral level
- Extends in an oblique, transverse position
- Parts of pancreas: head, neck, body and tail

4. Basic Anatomy:

5. Cell Origins:
The embryologic development of normal pancreatic tissue can be separated into three phases: 1- First: dorsal and ventral buds arise from foregut endoderm. 2- Second: cells differentiate into exocrine and endocrine cells. 3- Finally: morphogenesis occurs through growth and branching.

6. Cell Origins:
These events result in three distinct cell types derived from a common precursor: 1- Exocrine acinar cells: synthesize and secrete digestive proenzymes into pancreatic ducts 2- Ductal cells: line the pancreatic ducts and secrete alkaline fluid 3- Endocrine cells: primarily involved in glucose homeostasis, are clustered into structures called islets of Langerhans

7. Histology: Endocrine Pancreas Exocrine Pancreas
Nests of cells - islets of Langerhans
2 major components – Acinar cells and Ducts
Accounts for only 2% of the pancreatic mass
They constitute 80% to 90% of the pancreatic mass
Four major cell types
- Alpha (A) cells secrete glucagon
- Beta (B) cells secrete insulin
- Delta (D) cells secrete somatostatin
20 to 40 acinar cells coalesce into a unit called the acinus
Centroacinar cell (2nd cell type in the acinus) is responsible for fluid and electrolyte secretion by the pancreas

9. Pancreatic Cancer:
Pancreatic cancer is the fourth leading cause of cancer death in the United States.
Approximately individuals in the USA and over individuals worldwide die from the disease each year .
The incidence approximates the mortality rate, which reflects the poor prognosis of pancreatic cancer.
the 5-year survival rate for affected patients remains under 5%

10. WHO Classification: Lymphoma Epithelial Tumors benign
Premalignant lesion
Malignant
Neuroendocrine neoplasm
Mesenchymal tumours
Lymphangioma NOS
Lymphoma NOS
Solitary fibrous tumor
Lymphoma
Diffuse large B-cell lymphoma
Secondary Tumors

11. Neuroendocrine Tumors:
Pancreatic neuroendocrine tumors, also called islet cell tumors, are rare tumors that form from the hormone-producing cells in the pancreas called islet cells
It accounts for less than 5% of all pancreatic tumors. They tend to grow slower than the adenocarcinoma

12. Types: Pancreatic neuroendocrine microadenoma
Neuroendocrine tumor: G1 , G2 , NOS
- Large cell and Small cell neuroendocrine carcinoma
Gastrinoma
Glucagonoma
Insulin producing carcinoma (insulinoma)
Somatostatinoma
Vipoma

13. Neuroendocrine Tumors:
Functional or non-Functional
Benign Vs malignant
Considered malignant except microadenomas (less than 5 mm, usually incidental at autopsy), because no histologic criteria differentiates benign and malignant (except metastases)
Cell of origin ??
Can occur as part of 4 inherited disorders: MENI, VHL, NF-1 and TSC
80% occur in MEN1 patients, usually age 50-60

14. Neuroendocrine Tumors : (prognosis)
Tumor size > 3 cm
Invasion of stroma, capsule, vessels or adjacent organs
Glandular/solid pattern
Older age, high proliferation index (Ki-67 of 5% or more
Necrosis, vascular invasion, perineural invasion or CK19+

15. NET G1- G2
Rare, arise from serotonin secreting cells normally present in pancreas
Well-differentiated: cells with features similar to normal gut endocrine cell, expressing general markers of neuroendocrine differentiation and hormones according to site, with mild- to-moderate nuclear atypia and a low number of mitoses
G1 (NET G1): mitotic count <2/10 HPF or ≤2% Ki67 index
G2 (NET G2): mitotic count 2-20/10 HPF or 3-20% Ki67 index

17. Neuroendocrine carcinoma, NOS
- Poorly differentiated, high grade malignant neoplasm - Composed of small, intermediate or large cells, - diffusely expressing neuroendocrine markers (diffuse staining for synaptophysin; faint or focal staining for chromogranin A) - marked nuclear atypia, multifocal necrosis and a high number of mitoses (> 20 per 10 HPF)

18. Neuroendocrine carcinoma, NOS
- Represents less than 3% of pancreatic neuroendocrine tumors - May produce ACTH - Associated with hypercalcemia

19. Large number of poorly differentiated fusiform cells and focal necrosis

20. Pancreatic neuroendocrine carcinoma (NEC)
Pancreatic neuroendocrine carcinoma (NEC). Note the very high mitotic rate

21. Insulinoma (beta cell tumor)
Functionally active and commonly benign endocrine tumour of the pancreas with evidence of beta cell differentiation and clinical hypoglycemia due to inappropriate secretion of insulin
Only 7-10% have malignant behavior
Whipple’s triad

22. Insulinoma (beta cell tumor)

23. Insulinoma (beta cell tumor)

24. -Gastrinoma (G cell tumor)
Functionally active and usually malignant endocrine tumour with clinical symptoms due to inappropriate secretion of gastrin
ZES

25. Gastrinoma: C/P
Associated with hypersecretion of gastric acid and severe peptic ulceration
90% have ulcers; 85% in duodenum/jejunum, 15% in stomach
50% have diarrhea
Tumors usually in pancreas or duodenum peripancreatic soft tissue, gastric antrum
Also ovary, mesentery, liver, intra-abdominal lymph nodes (unclear if due to ectopic pancreatic tissue or metastases)
50% are locally invasive or metastatic at diagnosis

26. Gastrinoma:
Malignant tumor has trabecular pattern, hyaline and fibrous tissue between epithelial cell cords

27. Glucagonoma:
Rare
Arising from alpha cells of pancreas; often displays vascular invasion and may metastasize
Adult females, age 40+

28. Multiple small tumors with gyriform growth pattern
Types
Glucagonoma syndrome
Multiple small tumors with gyriform growth pattern
High incidence of malignancy
Nearly always benign
Necrolytic migratory erythema Sore red tongue, angular stomatitis Severe weight loss, depression Deep venous thromboses May develop overwhelming infection Normochromic, normocytic anemia
Strongly immunoreactive for glucagon
Typical granules on EM

29. EM-Glucagon granules:

30. Necrolytic migratory erythema

31. VIPoma
called Verner-Morrison tumors - tumors secrete vasoactive intestinal peptide (VIP)
90% of VIPomas arise from pancreas
Diarrhea (cholera-like), hypokalemia, achlorhydria
It contains pancreatic polypeptide, calcitonin, alpha chain of hCG

32. Interconnecting nests and trabeculae of uniform cuboidal cells with granular cytoplasm and central round nuclei

33. Somatostatinoma
Functionally active and usually malignant endocrine tumour with evidence of D-cell differentiation
Only rarely associated with somatostainoma syndrome (diabetes, cholecystolithiasis, steatorrhea, hypochlorhydria)
May be in duodenal wall
May have psammoma bodies

35. The endoscopic finding of the duodenal submucosal tumor

36. Thank You …