patoloji-ders-notlari

Title

Serdar Balcı

Gastrointestinal and Pancreas Neuroendocrine Tumors

Serdar BALCI, MD

GASTROINTESTINAL NEUROENDOCRINE TUMORS

Carcinoid

Dr. Oberndorfer

Learn his life and his contribution to “Istanbul” and “Karzinoide”

Carcinoid vs Neuroendocrine Tumor

• Carcinoid is now only used in lung tumors
• In GIS and pancreas
  • Well Differentiated Neuroendocrine Tumor (NET)

Well Differentiated Neuroendocrine Tumor

• Most in GI Tract
  • 40% in small intestine
• Tracheobroncial tree, lungs

Neuroendocrine Tumors

• May be associated with
  • Endocrine cell hyperplasia
  • Chronic atrophic gastritis
  • Zollinger-Ellison syndrome
• Grade
  • based on mitotic activity
  • fraction of cells immunohistochemcially positive for Ki67, a mitotic marker
• Localization, extent and presence of atrophy and intestinal metaplasia are important prognostically
• High-grade neuroendocrine tumors
  • neuroendocrine carcinoma

Neuroendocrine Neoplasms

• Hyperplasia
  • In the setting of chronic gastritis
• <0.5 cm microNET, microadenoma
• Well differentiated NET
  • Grade
    • Mitotic activity
    • Ki-67 index
  • G1, G2, G3
• Small cell carcinoma, Large cell carcinoma

Grade

Endocr Pathol. 2014 Mar;25(1):65-79

Neuroendocrine Tumor

intramural or submucosal masses

small polypoid lesions

yellow or tan in appearance

form intense desmoplastic reaction that may cause kinking of the bowel and obstruction

Robbins Basic Pathology

Neuroendocrine Tumor

islands, trabeculae, strands, glands, or sheets of uniform cells

Robbins Basic Pathology

Neuroendocrine Tumor

scant, pink granular cytoplasm

round to oval stippled nucleus

salt and pepper chromatin

Robbins Basic Pathology

Cytology

Endocr Pathol. 2014 Mar;25(1):65-79

Clinical Features of GI NET

Peak incidence in the sixth decade, may appear at any age

Symptoms by the hormones produced

Zollinger-Ellison syndrome

NET produce gastrin

Gastrinomas of small intestine or pancreas

Increase oxyntic mucosa, increased acid production

Ulcer formation in stomach

Carcinoid syndrome

Ileal tumors

Cutaneous flushing, sweating, bronchospasm, colicky abdominal pain, diarrhea, and right-sided cardiac valvular fibrosis

If confined to intestine, the secretions are metabolised in liver

If large tumor, in nonportal circulation, metastasis to liver → carcinoid syndrome

Location is important for prognosis

• Foregut
  • Stomach, duodenum proximal to the ligament of Treitz, and esophagus
  • Rarely metastasize, generally cured by resection
  • Gastric NET without predisposing factors (atrophic gastritis) are often more aggressive

• Midgut
  • jejunum and ileum
  • Often multiple
  • Tend to be aggressive
  • Greater depth of local invasion, increased size, and the presence of necrosis and mitoses are associated with a worse outcome
• Hindgut
• Appendix and colorectum
• Discovered incidentally
• Appendix
  • occur at any age
  • Generally located at the tip
  • Rarely more than 2 cm in diameter and are almost always benign
• Rectal
  • Produce polypeptide hormones
  • Abdominal pain and weight loss
  • Discovered when small, metastasis is uncommon

PANCREATIC NEUROENDOCRINE TUMORS

Pancreatic Neuroendocrine Tumors

• Islet cell tumors
• 2% of all pancreatic neoplasms
• Most common in adults
• Single or multifocal
• Liver is the most common site of organ metastases
• Produce and secrete pancreatic hormones, but some are nonfunctional
• Nonfunctional are larger lesions at diagnosis
  • no symptoms related to excessive hormone production

Autopsy Pathology: A Manual and Atlas

Endocr Pathol. 2014 Mar;25(1):65-79

Ankara Atatürk Eğitim ve Araştırma Hastanesi Arşivi

Endocr Pathol. 2014 Mar;25(1):65-79

• All PanNETs are regarded as having malignant potential
• Insulinomas are detected earlier and they are regarded as “benign”
• 65-80% of PanNETs manifest with overtly malignant features of biologic aggressiveness
  • invasion into local tissues or distant metastases
• Grade
  • Mitosis
  • proliferation marker Ki-67
• Genetics:
  • Familial MEN syndrome, type 1
    • MEN1
  • Loss-of-function mutations in tumor suppressor genes
    • PTEN and TSC2
      • negative regulators of the oncogenic mammalian TOR (mTOR) signaling pathway
  • Inactivating mutations
    • ATRX and DAXX

Endocr Pathol. 2014 Mar;25(1):65-79

Insulinomas

• **Beta cell tumors **
• Most common type of PanNET
• Whipple triad
  • Low blood glucose
  • Symptoms and signs of hypoglycemia
  • Resolve with blood glucose elevation
• Favorable biologic behavior
  • Possibly because the vast majority are identified while they are small
    • <2 cm in diameter
  • localized to the pancreas
• Most are solitary lesions
  • multifocal tumors or tumors ectopic to the pancreas may be encountered
• Malignancy in insulinomas
  • <10% of cases
  • Local invasion or metastases

Look remarkably like giant islets

Preservation of the regular cords of monotonous cells and their orientation to the vasculature

Not even malignant lesions present much evidence of anaplasia, and they may be deceptively encapsulated

Deposition of amyloid in the extracellular tissue is a characteristic feature of many insulinomas

Robbins Basic Pathology

Under the electron microscope, neoplastic beta cells, like their normal counterparts, display distinctive round granules

Robbins Basic Pathology

Gastrinomas

• **Marked hypersecretion of gastrin **
• Likely to arise in the duodenum and peripancreatic soft tissues as in the pancreas
  • gastrinoma triangle
• Zollinger-Ellison syndrome
  • Pancreatic islet cell lesions with hypersecretion of gastric acid and severe peptic ulceration
    • 90-95% of patients with gastrinomas
  • Duodenal and gastric ulcers often are multiple
  • Unusual locations such as the jejunum
    • intractable jejunal ulcers
• More than half of the affected patients have diarrhea

Over half of gastrin-producing tumors are locally invasive or have already metastasized at the time of diagnosis

25% of patients, arise in conjunction with other endocrine tumors

MEN-1 associated gastrinomas frequently are multifocal

Sporadic gastrinomas usually are single

Histologically bland and rarely exhibit marked anaplasia

α-cell tumors (glucagonomas)

• Increased serum levels of glucagon
• Mild diabetes mellitus
• A characteristic skin rash
  • Necrolytic migratory erythema
• Anemia
• Perimenopausal and postmenopausal women

δ-cell tumors (somatostatinomas)

Associated with diabetes mellitus, cholelithiasis, steatorrhea, and hypochlorhydria

Difficult to localize preoperatively

High plasma somatostatin levels are required for diagnosis

VIPoma

• WDHA syndrome
  • Watery diarrhea, hypokalemia, achlorhydria
• Some are locally invasive and metastatic
• Associated neural crest tumors
  • neuroblastomas, ganglioneuroblastoma, ganglioneuromas, pheochromocytomas

Rare pancreas NET

Serotonin and an atypical carcinoid syndrome are exceedingly rare

Pancreatic polypeptide-secreting endocrine tumors present as mass lesions as even high plasma levels of this hormone fail to cause symptoms

Multihormonal tumors

Endocr Pathol. 2014 Mar;25(1):65-79

Endocr Pathol. 2014 Mar;25(1):65-79

Endocr Pathol. 2014 Mar;25(1):65-79

Endocr Pathol. 2014 Mar;25(1):65-79

Endocr Pathol. 2014 Mar;25(1):65-79