Neuroendocrine tumor G1 (NET G1) / Carcinoid
A neuroendocrine tumour (NET) is defined as a well-differentiated, neuroendocrine neoplasm composed of cells with features similar to those of the normal gut endocrine cell, expressing general markers of neuroendocrine differentiation (usually diffuse and intense chromogranin A and synaptophysin) and hormones (usually intense but not necessarily diffuse) according to site, with mild- to-moderate nuclear atypia and a low number of mitoses.
The proposed grading based on proliferation with the following definitions of mitotic count and Ki67 index:
– G1 (NET G1): mitotic count, <2 per 10 high power fields (HPF) and/or ≤2% Ki67 index;
– G2 (NET G2)
: mitotic count 2–20 per 10 HPF and/or 3–20% Ki67 index
Bosman FT, Carneiro F, Hruban RH, Theise ND (Eds.)
WHO Classification of Tumours of the Digestive System.
International Agency for Research on Cancer: Lyon 2010
Commentary: Neuroendocrine tumours of the digestive system
Endocrine tumours of the stomach are mostly well-differentiated, nonfunctioning enterochromaffin-like (ECL) cell carcinoids arising from oxyntic mucosa in the corpus or fundus. Three distinct types have are recognized:
> Type I, associated with autoimmune chronic atrophic gastritis (A-CAG)
> Type II, associated with muliple endocrine neoplasia type 1 (MEN-1)
and Zollinger-Ellison syndrome. The term gastrinoma is reserved for G-cell tumors that produce hypergastrinemia and are the source of the Zollinger-Ellison syndrome (ZES).
> Type III, sporadic, i.e. not associated with hypergastrinaemia or A-CAG.
> Histological subtypes
ECL cell, histamine-producing NET
EC cell, serotonin-producing NET
Gastrin-producing NET (gastrinoma)
> Precursor lesions
ECL cell NETs arising in hypergastrinaemic conditions (types I and II) develop through a sequence of hyperplasia–dysplasia-neoplasia that is well-documented
Solcia E, Bordi C, Creutzfeldt W, Dayal Y, Dayan AD, Falkmer S, Grimelius L, Havu N (1988)
. The successive stages of hyperplasia are termed simple, linear, micronodular, and adenomatoid. Dysplasia is characterized by moderately atypical cells with features of enlarging or fusing micronodules, microinvasion or newly formed stroma. When the nodules increase in size to > 0.5 mm or invade the submucosa, the lesion is classified as microcarcinoid(< 0.5 cm) or plain carcinoid (≥ 0.5 cm). The entire spectrum of ECL cell growth, from hyperplasia to dysplasia and neoplasia has been observed in MEN1-ZES and A-CAG. A similar sequence of lesions has been shown in experimental models of the disease, mostly based on hypergastrinaemia secondary to pharmacological inhibition of acid secretion in rodents
Histopathological classification of nonantral gastric endocrine growths in man.
Digestion 41: 185-200
Tang LH, Modlin IM, Lawton GP, Kidd M, Chinery R (1996)
. Linear hyperplasia or more advanced changes have been shown to represent a risk factor for the development of gastric ECL cell tumours in patients with MEN1-ZES
The role of transforming growth factor alpha in the enterochromaffin-like cell tumor autonomy in an African rodent mastomys.
Gastroenterology 111: 1212-23
Berna MJ, Annibale B, Marignani M, Luong TV, Corleto V, Pace A, Ito T, Liewehr D, Venzon DJ, Delle Fave G, Bordi C, Jensen RT (2008)
, while the presence of dysplastic lesions has been proven to markedly increase the risk of developing ECL cell tumours
A prospective study of gastric carcinoids and enterochromaffin-like cell changes in multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome: identification of risk factors.
J Clin Endocrinol Metab 93: 1582-91
Annibale B, Azzoni C, Corleto VD, di Giulio E, Caruana P, D'Ambra G, Bordi C, Delle Fave G (2001)
Atrophic body gastritis patients with enterochromaffin-like cell dysplasia are at increased risk for the development of type I gastric carcinoid.
Eur J Gastroenterol Hepatol 13: 1449-56