Pancreatic Neuroendocrine Tumor (PNET)

Henry William Taylor, MD, Forest Washington, MD, and Michael D. Smith, MD
The Operative Review of Surgery. 2023; 1:189-196.

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Table of Contents

Definitions and Tumors
Functional PNET Comparisons
Staging
Diagnosis
Treatment

Mnemonics
References

Definitions and Tumors

Definitions

  • Pancreatic Neuroendocrine Neoplasia (PNEN) – Any Neuroendocrine Neoplasia of the Pancreas
    • Previously Known as “Islet Cell Tumors”
  • Pancreatic Neuroendocrine Tumor (PNET) – Well-Differentiated PNEN
  • Pancreatic Neuroendocrine Carcinoma (PNEC) – Poorly-Differentiated PNEN with High-Proliferative Rate

Non-Functional PNET (NF-PNET) 1,2

  • The Majority of PNETs are Nonfunctional (60-90%)
  • Can Secrete Substances but Do Not Present with Hormonal Syndromes
    • Ex: Chromogranin, Pancreatic Polypeptide, Ghrelin, etc.
  • Generally Present Later with a More Indolent and Protracted Course
  • Symptoms are Generally Related to Mass Effect:
    • Abdominal Pain
    • Weight Loss
    • Anorexia
    • Nausea and Vomiting
    • Obstructive Jaundice

Functional PNET (F-PNET)

Resection of a Nonfunctional PNET 3

Functional PNET Comparisons

PNET

Percentage of All
Functional PNETs 4

General Presentation
Insulinoma

35-40%
(Most Common)

Whipple’s Triad

  • Fasting Hypoglycemia
  • Symptoms of Hypoglycemia
  • Symptomatic Relief with Glucose
Gastrinoma16-30%Peptic Ulcer Disease
Glucagonoma< 10%

4-D Syndrome

  • Diabetes/Glucose Intolerance
  • Dermatoses (NME)
  • DVT
  • Depression
VIPoma< 10%

WDHA Syndrome

  • Watery Diarrhea
  • Hypokalemia
  • Achlorhydria
Somatostatinoma< 5%
  • Diabetes/Glucose Intolerance
  • Cholelithiasis
  • Diarrhea/Steatorrhea

Size and Malignancy

  • Most are Large (> 3 cm) and Malignant (60-90%) 5-8
    • 75% Present as Advanced Disease
  • Conversely, Insulinomas are Generally Small (< 3 cm) and Benign (93%) 9,10

Association with Multiple Endocrine Neoplasia Type 1 (MEN-1)

  • Most are Sporadic
  • Insulinoma: 6% 11
  • Gastrinoma: 20-30% – The Most Common PNET Associated with MEN-1 12
  • Glucagonoma: 3-10% 6,13,14
  • VIPoma: 5% 15
  • Somatostatinoma: 35-45% 16
    • Although MEN-1 is Common in Somatostatinoma, Somatostatinoma is Overall One of the Least Common PNETS in MEN-1 (< 1%) 16

Most Common Location in the Pancreas Mn

  • Insulinoma: Even Distribution Throughout the Pancreas 17
  • Gastrinoma: Head 18
  • Glucagonoma: Body and Tail 19
  • VIPoma: Body and Tail 20
  • Somatostatinoma: Head 8

Staging

TNM Staging (AJCC 8) 21

 TNM
1Limited to the Pancreas (< 2 cm)Any Regional Lymph Node Involvement

M1a – Liver
M1b – Extrahepatic
M1c – Both Liver and Extrahepatic

2Limited to the Pancreas (2-4 cm)  
3Limited to the Pancreas (> 4 cm) or Invades the Duodenum/CBD  
4Invades Adjacent Organs or Large Vessels  
  • For T Stage – Multiple Tumors are Designated as T(#) (Example: T3(4))
    • If Number or Tumors is Too Numerous or Unavailable – T(m)
  • *Note: This System Does Not Apply to High-Grade, Poorly Differentiated Neuroendocrine Carcinoma (PNEC) – These are Staged as an Exocrine Pancreatic Cancer

TNM Stage 21

StageTNM
IT1N0M0
IIT2-3N0M0
IIIT4N0M0
Any TN1M0
IVAny TAny NM1

WHO 2010 Grading 22

GradeDifferentiationKi-67 Index

Mitotic Count

(/10 HPF)

G1 (Low)Well≤ 2%< 2
G2 (Intermediate)Well3-20%2-20
G3 (High)Poorly> 20%> 20

Diagnosis

Diagnosis

Localization

  • Initial Imaging: Noninvasive (CT or MRI)
  • Somatostatin Receptor Imaging
    • Consider if Initial Imaging Fails to Localize
    • Options:
      • Somatostatin (Octreotide) Receptor Scintigraphy (SRS) – Classic Test Used
      • Functional PET Scan (Ga-68 DOTATATE) – Becoming More Prevalent with Higher Sensitivity
    • Insulinomas Demonstrate Relatively Low Somatostatin Receptor Expression (May Be More Difficult to Detect than Other PNETs) 28,29
  • If Noninvasive Imaging Fails: Invasive Imaging
    • Endoscopic Ultrasound (EUS) – Generally Preferred Next Step
    • Selective Arterial Stimulation with Hepatic Venous Sampling
      • Use: Insulinoma (Calcium Stimulation) or Gastrinoma (Secretin Stimulation)
    • Selective Visceral Angiography
  • For Gastrinoma, Consider Surgical Exploration with Palpation or Intraoperative Ultrasound if High Suspicion but All Imaging Negative

PNET on Imaging: (A) CT, (B) EUS, (C) SRS, (D) Functional PET 30

Treatment

Surgical Resection (Treatment of Choice)

  • Small (< 2-3 cm): Enucleation
    • *Enucleation is Controversial for the More Malignant PNETs (VIPoma, Somatostatinoma, or Glucagonoma)
  • Large (> 2-3 cm): Surgical Resection

See Individual Pages for Specifics on Management

Pancreatic Neuroendocrine Carcinoma (PNEC)

  • Poor Prognosis with Rapid Disease Progression
  • Resectable Disease: Surgical Resection with Adjuvant Chemotherapy
  • Unresectable Disease: Palliative Chemotherapy

Mnemonics

Most Common Site of PNET’s 31

  • “6: The Number of the Pancreas”
    • Pancreas Looks Like a #6
    • *Used in Other Mnemonics: Pseudocyst and Chronic Pancreatitis
  • “SIX” Written on Pancreas:
    • “S” in Head: gaStrin and SomatoStatin
    • “I” Anywhere: Insulin
    • “X” in Body/Tail: Glucagon and VIP

References

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