Neuroendocrine tumour of the pancreas

Neuroendocrine tumour of the pancreas, also pancreatic neuroendocrine tumour, is a relatively uncommon tumour.

Neuroendocrine tumour of the pancreas
Diagnosis in short
Pancreatic neuroendocrine tumour. H&E stain.
Synonyms	pancreatic islet cell tumour (obsolete term)
LM	nests of cells or cords, stippled chromatin, moderate quantity of cytoplasm, +/-hyaline globules
LM DDx	solid pseudopapillary neoplasm, acinar cell carcinoma, invasive ductal carcinoma of the pancreas
IHC	chromogranin +ve, synaptophysin +ve, insulin +/-ve, glucagon +/-ve, gastrin +/-ve, somatostatin +/-ve
Site	pancreas
Syndromes	Multiple endocrine neoplasia I, von Hippel-Lindau disease, neurofibromatosis type 1
Symptoms	dependent on subtype
Prevalence	uncommon
Radiology	pancreatic mass
Clin. DDx	invasive ductal carcinoma of the pancreas, other pancreatic tumours

It may be abbreviated PanNET.

Previously, it was referred to as pancreatic islet cell tumour or islet cell tumour; these terms are now considered to be outdated.

Neuroendocrine tumours in general are dealt with in the neuroendocrine tumours article.

General

• Rare ~ 1% of pancreatic tumours.
• Presentation depends on subtype, e.g. for insulinoma the typical presentation is hypoglycemia.
• May be part of a syndrome:
  • Multiple endocrine neoplasia I.
  • Von Hippel-Lindau disease.
  • Neurofibromatosis type 1.

WHO classification of 2017

Five categories:

• NET G1. Ki67 Index < 3%, Mitotic Index < 2/10HPF
• NET G2. Ki67 Index 3-20%, Mitotic Index 2-20/10HPF
• NET G3. Ki67 Index > 20%, Mitotic Index > 20/10 HPF AND well-differentiated, expressing neuroendocrine differentiation and hormones
• Neuroendocrine carcinoma (NEC G3). Ki 67 Index > 20%, Mitotic Index > 20/10 HPF Poorly differentiated, expressing neuroendocrine differentiation but lacking exocrine markers.
• MiNEN. mixed endocrine-nonendocrine neoplasm: components of a non-endocrine carcinoma (mostly ductal adenocarcinoma or acinar cell carcinoma) combined with a neuroendocrine neoplasm

Classification by product

Based on peptide produced in the pancreatic islets:

1. Glucagon from alpha cells (glucagonoma).
2. Insulin from beta cells (insulinoma) - most common ~ 50% of islet cell tumours.
3. Somatostatin from D cells (somatostatinoma).
4. Pancreatic polypeptide from PP cells.

Others:

1. Vasoactive intestinal peptide (VIPoma).
2. Gastrin (gastrinoma).
   • May be seen in Zollinger-Ellison syndrome.
     • Triad: pancreatic gastrinoma, gastric acid hypersecretion, marked peptic ulcers in the small bowel.

Gross

• Usually in the head of the pancreas - 68% in one series, and 50% in another series.

Microscopic

Features:

• Nests of cells or cords.
• Stippled chromatin - key feature.
• Moderate cytoplasm.
• +/-Hyaline globules.

DDx:

• Solid pseudopapillary neoplasm.
• Acinar cell carcinoma.
• Invasive ductal carcinoma of the pancreas.

Images

• 

  Insulinoma. (WC)

• 

  Insulinoma. (WC)

• 

  Insulinoma - chromogranin A. (WC)

• 

  Insulinoma - insulin IHC. (WC)

• 

  Pancreatic NET - very low mag. (WC/Nephron)

• 

  Pancreatic NET - low mag. (WC/Nephron)

• 

  Pancreatic NET - intermed. mag. (WC/Nephron)

• 

  Pancreatic NET - intermed. (WC/Nephron) mag.

• 

  Pancreatic NET - high mag. (WC/Nephron)

• 

  Pancreatic NET - very high mag. (WC/Nephron)

• 

  Pancreatic NET - intermed. mag. (WC/Nephron)

• 

  Pancreatic NET - high mag. (WC/Nephron)

Low grade pancreatic neuroendocrine tumor. A. Stromal trabeculums (black arrows) support the uniform, non-necrotic tumor that has sharp edges (green arrows). B. Modestly variable, rounded nuclei show open chromatin and nucleoli. Individual pyknotic nuclei (black arrows) are insufficient as evidence of necrosis sufficient to increase grade. C. Immunostain. Cytoplasm is diffusely synaptophysin positive. D. Immunostain. Cytoplasm shows stippled chromogranin positivity. E. Immunostain. Only scattered nuclei are Ki67 positive.

www:

• Islet cell tumour (upmc.edu).
• Pancreatic NET with features of SPT (upmc.edu).
• Pancreatic NET - another case (upmc.edu).

IHC

• CK19 +ve.
  • Considered a poor prognostic factor - disputed by an older paper.
• Chromogranin +ve.
• Synaptophysin +ve.
• CD56 +ve.
• PAX8 +ve (74% of cases).

Functional tumours:

• Insulin.
• Glucagon.
• Somatostatin.
• Gastrin.

A panel:

• Chromogranin, synaptophysin, CD10, PR, beta-catenin, CK7, pankeratin, Ki-67, CK19.

Notes:

• CK19 should not be confused with CA19-9.
• If the tumour is not functional (clinically) one can forgo the stains for functional tumours.

Sign out

TAIL OF PANCREAS AND SPLEEN, PARTIAL PANCREATECTOMY AND SPLENECTOMY:
- CYSTIC PANCREATIC NEUROENDOCRINE TUMOUR, pT1, pN0.
-- INTERMEDIATE GRADE (G2).
-- NARROWLY EXCISED.
-- PLEASE SEE TUMOUR SUMMARY.
- UNREMARKABLE SURROUNDING PANCREAS WITH FAT.
- SPLEEN WITHIN NORMAL LIMITS.
- FOUR BENIGN LYMPH NODES.

TAIL OF PANCREAS AND SPLEEN, PARTIAL PANCREATECTOMY AND SPLENECTOMY:
- CYSTIC PANCREATIC NEUROENDOCRINE TUMOUR, pT1, pN0.
-- LOW GRADE (G1).
-- SURGICAL MARGINS NEGATIVE.
-- PLEASE SEE TUMOUR SUMMARY.
- UNREMARKABLE SURROUNDING PANCREAS WITH FAT.
- SPLEEN WITHIN NORMAL LIMITS.
- FOUR BENIGN LYMPH NODES.

Micro

The sections show pancreas with a large well-circumscribed tumour that centrally has a large cyst-like cavity. The tumour cells have moderate pale grey cytoplasm and round nuclei with salt and pepper chromatin. The tumour cells are arranged in cords and nests. No cholesterol clefts are readily apparent. No hyaline globules are identified. No papillary structures are apparent.

No necrosis is identified. No degenerative changes are apparent. Mitotic activity is seen focally. There are 2 mitoses per 10 high power fields, were one high power field has an area of 0.2376 mm*mm.

See also

• Pancreas.
• Neuroendocrine tumours.