Neuroendocrine neoplasms, also commonly known as neuroendocrine tumors (NETs) or carcinoid tumors, comprise a large heterogeneous group of benign and malignant tumors derived from multipotent stem cells found in both endocrine and non-endocrine organs, as well as the diffuse neuroendocrine system ⁹.

Terminology

The World Health Organization has proposed a universal definition for neuroendocrine neoplasms as carcinoid, meaning "carcinoma-like" or "carcinoid syndrome", was considered an inaccurate descriptor for many of these tumors ⁸. Neoplasms with neuroendocrine differentiation have thus been classified as ⁸:

• neuroendocrine tumor (NET): well-differentiated; grade 1-3

• neuroendocrine carcinoma (NEC)

  • poorly differentiated; high-grade

  • can be further subtyped into

    • small cell neuroendocrine carcinoma (SCNEC)

    • large cell neuroendocrine carcinoma (LCNEC)

However, these neoplasms have variable names, which are acceptable (but not preferred) terminology per the WHO Classification of Tumors, depending on location:

• carcinoid tumor, particularly for those NETs arising in the thorax and gonads ^8,10

• adenoma, e.g. parathyroid adenoma ¹¹

• carcinoma, e.g. medullary thyroid carcinoma ¹¹

• paraganglioma, including pheochromocytoma ¹¹

Historically, these tumors were called APUDomas or APUD tumors because they were thought to arise from what was known at the time as the APUD cell system, which was renamed the neuroendocrine system in the late 1970s ⁹.

Pathology

Neuroendocrine neoplasms arise from two cell groups ^8,11:

• epithelial type

  • orginate in both endocrine and non-endocrine organs

  • have morphological/molecular features of normal neuroendocrine cells

• neuronal/para-neuronal type

  • orginate in neural structures

  • paragangliomas

Location

Neuroendocrine tumors can occur in a wide range of locations ^10,11:

• head and neck

  • medullary thyroid carcinoma

  • paraganglioma

  • parathyroid adenoma

  • pituitary neuroendocrine tumor (pituitary adenoma)

• thorax

  • pulmonary neuroendocrine tumors

  • thymic carcinoid

• abdomen and pelvis

  • digestive system neuroendocrine tumors

    • hepatic neuroendocrine tumor

    • pancreatic neuroendocrine tumors (pNET)

    • small bowel neuroendocrine tumor

  • ovarian carcinoid

  • pheochromocytoma and extra-adrenal paraganglioma

  • primary renal carcinoid tumor: extremely rare ¹⁷

  • well-differentiated neuroendocrine tumor of the prostate

• spine

  • cauda equina neuroendocrine tumor

• skin

  • Merkel cell carcinoma

Classification

Depending on whether peptides/hormones are produced NETs can be classified as ^8,16:

• non-functional: more common

• functional: e.g. carcinoid syndrome; Zollinger-Ellison syndrome; hormonal syndrome related insulinomas, glucagonomas, somatostatinomas, or VIPomas

Markers

Biohemical markers, such as 24-hour urinary 5-HIAA metabolite of serotonin and serum chromogranin A (CgA), are considered helpful in the diagnosis of neuroendocrine neoplasms in general ⁸.

Genetics

The vast majority (~90%) neuroendocrine neoplasms occur sporadically, around 10% are linked to genetic germline mutations ¹⁵.

Radiographic features

CT/MRI

Refer to specific articles (above) for imaging characteristics.

Nuclear medicine

• gallium-68 octreotide PET-CT (e.g. Ga-68 DOTATATE) has shown improved accuracy for detection of NETs relative to indium-111 pentetreotide (Octreoscan) SPECT/CT ^12,13

• iodine-123 MIBG will also concentrate on NETs, including the low percentage (~15%) that are negative with indium-111 octreotide ¹⁴

Treatment and prognosis

Complications

• cardiac valve lesions from carcinoid

History and etymology

This lesion was initially coined “karzinoide” by Oberndorfer in 1907 to denote its resemblance to carcinoma ^4,8.