LGCmain
Indian Journal of Pathology and Microbiology
Home About us Instructions Submission Subscribe Advertise Contact e-Alerts Ahead Of Print Login 
Users Online: 953
Print this page  Email this page Bookmark this page Small font sizeDefault font sizeIncrease font size


 
  Table of Contents    
ORIGINAL ARTICLE  
Year : 2022  |  Volume : 65  |  Issue : 3  |  Page : 551-557
Clinical and pathological profile of gastric neuroendocrine tumors


Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India

Click here for correspondence address and email

Date of Submission15-Aug-2021
Date of Decision06-Sep-2021
Date of Acceptance13-Sep-2021
Date of Web Publication21-Jul-2022
 

   Abstract 


Background: Gastric neuroendocrine tumors (G-NETs) are classified into well-differentiated NETs with three grades and poorly differentiated neuroendocrine carcinomas based on morphology and the Ki-67 index. Besides, G-NETs are broadly classified into four types based on clinical and pathophysiological features. Aim: To study clinical and pathological features of different types and grades of G-NET. Materials and Method: All G-NETs, diagnosed from January 2011 to December 2020, were included. Clinical presentation, peritumoral findings, lymph node status, and liver involvement were obtained and correlated with different grades and types of G-NETs. Results: NET was diagnosed in 88 cases. Tumors were graded as I, II, III, and carcinoma in 58, 14, 12, and 4 cases, respectively. Type I NET (49.2%) in the background of chronic atrophic gastritis was the most common type followed by type III (33.3%). Type I tumors were predominantly graded I (91.1%) and limited to the mucosa and submucosa. MEN-1-associated G-NET (type II) was seen in eight cases. All except one type II tumor was associated with ZES syndrome. Remarkably, peritumoral mucosa showed atrophy and intestinal metaplasia in 52.1% and 24.6% cases, respectively. Two cases were associated with adenocarcinoma. Lymph node metastasis was seen in all carcinoma and grade III cases. All carcinoma cases and 58.3% of grade III tumors showed liver metastasis. Conclusion: Biological behavior of G-NET varies with different types and grades of tumor. Typing and grading of G-NET should be done whenever possible to predict the aggressiveness of the tumor.

Keywords: Atrophic gastritis, gastric neuroendocrine tumor, MEN syndrome

How to cite this article:
Sekar A, Vaiphei K. Clinical and pathological profile of gastric neuroendocrine tumors. Indian J Pathol Microbiol 2022;65:551-7

How to cite this URL:
Sekar A, Vaiphei K. Clinical and pathological profile of gastric neuroendocrine tumors. Indian J Pathol Microbiol [serial online] 2022 [cited 2022 Aug 15];65:551-7. Available from: https://www.ijpmonline.org/text.asp?2022/65/3/551/351621





   Introduction Top


Gastric neuroendocrine tumors (G-NETs) are neoplasms, most commonly derived from enterochromaffin-like cells (ECL) and rarely from D cells, G cells, and enterochromaffin cells (EC) present in the stomach.[1] It constitutes 8.7% of all gastrointestinal neuroendocrine tumor and 2% of all gastric cancer.[2] Due to advanced diagnostic strategies and widespread use of upper gastrointestinal endoscopy, the detection of G-NET is steadily increasing in recent years.[3] The incidence of gastric carcinoids has increased 10-fold in the last 35 years as per the Surveillance, Epidemiology, and End Results Program conducted in the United States.[4]

G-NETs have a heterogenous presentation in terms of clinical, histopathological, and functional characteristics. Most gastric tumors, except those associated with Zollinger–Ellison syndrome (ZES), do not cause specific symptoms and are discovered during endoscopic evaluation for dyspepsia or abdominal pain.[5] In 2018, World Health Organization (WHO) proposed the new classification of neuroendocrine neoplasms (NENs) in different sites. NENs in the gastrointestinal tract and pancreas are broadly classified into well-differentiated NETs and poorly differentiated neuroendocrine carcinomas based on morphology.[6] Further, NETs are graded into three tiers (G1, G2, and G3) based on the proliferation assessed by mitotic count and the Ki-67 index. Besides, based on clinical, pathophysiological, and histomorphology characteristics, G-NETs are broadly classified into four types.[7] Type I is the most common and constitutes about 70%-80% of G-NETs. It is associated with hypergastrinemia in the background of hypochloridria due to chronic atrophic gastritis (CAG).[8] CAG may result from either antiparietal cell antibody or H-pylori infection. However, approximately in 50% of CAG cases, there was no underlying etiology identified.[9] Type II is also a gastrin-dependent tumor and is associated with hypergastrinemia due to ZES in the background of MEN-1 syndrome.[10] Type III G-NET is a sporadic solitary tumor and not associated with autoimmune gastritis or MEN syndrome. It is a gastrin-independent high-grade tumor, usually accompanied by angioinvasion with lymph node and liver metastases.[11] Type IV G-NET is a recently added type and is usually a solitary, large, and highly malignant tumor with either small cell or large cell neuroendocrine morphology on histology.[12] Types I to III G-NETs are frequently of ECL origin, while type IV tumor arises from endocrine cells other than ECL.[13] Only a few studies in the literature describe clinical and pathological characteristics of different types of G-NETs.[14],[15] We intend to put forward our last 10 years of institutional experience in different G-NETs diagnosed on biopsy or resected specimens.


   Materials and Methods Top


All cases with a diagnosis of G-NETs, diagnosed from January 2011 to December 2020 in the Department of Histopathology, were retrieved. Hematoxylin and eosin and immunohistochemistry (IHC)-stained sections of all these cases were reviewed. Cases with a suspicious diagnosis of the NET due to lack of material for immunochemistry were excluded from the study. Clinical details and endoscopic findings were recorded from the request forms and records in the Medical registry Department. Histological findings such as the predominant pattern of tumor, extent of invasion, mitotic activity, the Ki-67 index, the status of immunoreactivity to chromogranin, synaptophysin, and gastrin in available cases were noted. Grading of tumors was done as per WHO 2018 criteria with the help of the Ki-67 index.[6] If peritumoral mucosal fragment also available in the biopsy, the presence or absence of findings such as atrophy, intestinal metaplasia, enterochromaffin hyperplasia activity, and H. pylori were recorded and graded as per the updated Sydney classification system.[16] In resected specimens, additional parameters such as location, size, number, the extent of invasion, lymph node, and liver involvement were also recorded. In cases of a specimen with only biopsies, lymph node and liver involvement status were noted from clinical records.

Based on clinical features and histopathological findings observed in tumor and peritumoral fragments, G-NET tumors were subtyped into four categories, as shown in [Figure 1]. Continuous data were expressed as mean, and category data were expressed as number (percentage) for analysis.
Figure 1: Algorithmic approach used in classifying gastric neuroendocrine tumors

Click here to view



   Results Top


From 2011 to 2020, NET in the stomach was diagnosed in 88 cases. It includes biopsies (n = 53, 60.2%), resected specimen without prior biopsies (n = 19, 21.7%), block submitted from elsewhere for review (n = 16, 18.1%).

Clinical characteristics

The age ranged from 16 to 102 years with M:F ratio of 2.1:1. Most cases presented with nonspecific symptoms such as dyspepsia (79.5%), abdominal pain (18.1%), followed by melena (4.5%), and diarrhea (2.3%). In three cases, NET was diagnosed on evaluation for anemia (3.4%). ZES due to gastrinoma was seen in seven out of eight cases of G-NET associated with MEN-1 syndrome. In all cases, gastrinoma was seen in the duodenum, and in three cases, it was seen in both pancreas and duodenum. The diagnosis of the second NET in the gastric body was made during endoscopic evaluation for gastric manifestation.

Location and nature of the tumor

Commonest location observed was body (n = 70, 79.6%) followed by fundus (n = 13, 14.8%), and antrum (n = 5, 5.6%). Of the five antral located tumors, four showed immunoreactivity to gastrin. In 19 resected specimens, lesions were of multiple and nodular in 11 cases (57.8%). Solitary nodule with size ranged 1–6 cm was seen in eight cases (42.1%). [Figure 2]
Figure 2: (Gross photograph): (a) Total gastrectomy specimen of MEN-1 associated G-NET case showing multiple nodules of variable size in the body. (b) Gastrectomy specimen of case categorized as type III tumor showing large solitary nodule measuring 8 cm in maximum dimension and firm cut surface with areas of hemorrhage

Click here to view


Histopathology

The pattern of tumor

Most cases showed mixed pattern. The predominant pattern observed was nests admixed with cords and trabeculae (n = 79, 89.7%), acini (n = 3, 3.4%), papillae (n = 2, 2.3%), and solid pattern (n = 4, 4.5%). [Figure 3]
Figure 3: Histopathology of neuroendocrine tumors depicting different patterns such as nests (a), cords and trabeculae (b), acinar (c), papillae (d), rosettes (e) and diffuse pattern (f). (H and E, 200×)

Click here to view


Grades of tumor

Based on morphology and the Ki-67 index, tumors were classified. Grade I, grade II, grade III, and neuroendocrine carcinoma were seen in 58 (65.9%), 14 (15.9%), 12 (13.6%), and 4 (4.5%) cases, respectively. Large cell neuroendocrine morphology was observed in all carcinoma cases.

The extent of invasion

Tumor was limited to muscularis mucosa in four cases (21%) and extended to the submucosa, muscularis propria, and serosa in six (31.5%), three (15.7%), six (31.5%) cases, respectively.

Adjacent fragments

Adjacent peritumoral mucosa for evaluation was available in 69 cases (78.4%). Observed findings were atrophy (n = 36, 52.1%), intestinal metaplasia (n = 17, 24.6%), enterochromaffin hyperplasia (n = 25, 36.2%), Helicobacter pylori (n = 9, 13.1%), and activity (n = 5, 7.2%). [Figure 4]
Figure 4: Histopathology of adjacent nontumorous fragment depicting marked atrophy of glands (a, H and E, 200×), intestinal metaplasia (b, H and E, 200×), linear and nodular endocrine cell hyperplasia highlighted by IHC for chromogranin (c, immunoperoxidase, 200×). Adjacent fragment in one case showing adenomatous polyp with low-grade dysplasia. (d, H and E, 200×)

Click here to view


Other tumors of epithelial origin

Adenocarcinoma was seen in two cases, of which one also showed mucinous component. A single case was associated with adenomatous polyp with low-grade dysplasia.

Regional lymph node metastasis

Status of lymph node involvement was available in 80 cases. Lymph node metastasis was seen in all carcinoma and grade III cases, whereas 3.7% and 40% of grade I and grade II tumors showed regional lymph node involvement.

Liver metastasis

Status of liver metastasis was available in 80 cases. All carcinoma cases, 3.7%, 10%, and 58.3% of grade I, grade II, and grade III tumors, respectively, showed liver metastasis.

IHC

Immunoreactivity for chromogranin, synaptophysin, and gastrin was observed in 76 out of 88 cases (86.3%), 30 out of 43 (69.7%), 4 out of 63 cases (63.4%), respectively.

Types of NET

Based on the clinical features and histological findings in the tumorous and peritumoral fragment, we could categorize the tumor into four types in 69 cases (78.4%). Most common type of tumor observed was type 1 (n = 34, 49.2%), followed by type III (n = 23, 33.3%), type II (n = 8, 11.5%) and type IV (n = 4, 5.7%) tumors.

Serum gastrin

Serum gastrin was available in all eight cases of MEN syndrome-associated NET. Of the eight cases, seven cases showed a marked rise in serum gastrin levels (>10000 pg/ml) and a single case with normal gastrin levels.

Clinical and histological findings of different types of NETs

The mean age of type I, II, III, and IV tumors were 51.8, 44.8, 47.4, and 56, respectively. Males were frequently affected of all types except in type II, in which there was no sex predilection observed. Lesions were predominantly multiple in all types. The distribution of different grades of the tumor, various peritumoral findings, the extent of invasion of the tumor, IHC findings, lymph node, and liver involvement in each type are shown in [Table 1].
Table 1: Clinical and histological findings of different types of NETs

Click here to view


Clinical and histological findings of different grades of NETs

The mean age of grade I, II, III, and carcinoma cases was 51.4, 47.3, 46.6, and 56.8, respectively. The distribution of various peritumoral findings, IHC findings, lymph node, and liver involvement in different grades, and carcinoma are shown in [Table 2].
Table 2: Clinical and histological findings of different grades of NETs

Click here to view



   Discussion Top


In the stomach, 88 cases were diagnosed as a NET based on morphology and with the help of IHC. It constitutes 4.6% of all gastric tumors reported in our institute. Comparable to other studies, tumors were commonly seen in the body (79.6%) and fundus (14.8%), followed by antrum (5.6%). Type I NET (49.2%) in the background of CAG was the most common type in our study. The mean age of type I NET in this study was 51.8 years. Contrary to the other studies, male predilection (70.6%) was observed for type I G-NET.

CAG can be due to autoimmune etiology with antibody formation against H+/K+-ATPase antigen in the parietal cells or due to chronic H-pylori infection.[17],[18] In autoimmune etiology, atrophy is restricted to the body and fundus, whereas H-pylori-mediated CAG is multifocal and involves both body and antrum. The underlying pathophysiological mechanism leading to the development of type I NET in atrophic gastritis is hypersecretion of gastrin by G cell in the antrum in response to achlorhydria developed due to loss of parietal cells.[19] Besides hypergastrinemia, multiple factors such as age >50 years, pangastritis, the severity of intestinal metaplasia, and enterochromaffin hyperplasia were documented as risk factors for the progression of atrophic gastritis to NETs.[20] In a Swedish cohort study, during the 20-year follow-up period of atrophic gastritis cases, there was a 13-fold increase in the occurrence of gastric carcinoid.[21]

Multifocal atrophic gastritis, enterochromaffin hyperplasia, and intestinal metaplasia were present in 58.8%, 64.7%, and 41.2%, respectively, of type I G-NET cases. H-pylori organism was observed in 17.6% of cases. The possibility of prior anti-H-pylori treatment administration in the remaining cases was not excluded in this study. In a study by Asaka et al.,[22] the overall prevalence of atrophic gastritis and intestinal metaplasia in H-pylori infection was 82.9% and 43.1%, respectively. Though H. pylori eradication may modify the natural history of atrophy, the lesion may persist in the tissue even after many years following treatment.[23]

Though the status of antiparietal cell antibody was not known in all type I G-NET cases, the observations such as male predominance, relatively a more significant number of cases with multifocal atrophy and presence of H-pylori organisms favor atrophic gastritis of nonautoimmune etiology were common in the present study. Comparable to studies done by Chung et al.,[14] type I NETs followed an indolent course in most cases. In the present study, type I tumors were predominantly graded I (91.2%) followed by grade II (8.8%) and limited to the mucosa and submucosa. Though rare, lymph node and liver metastasis were seen in 8.5% and 5.8% cases, respectively.

MEN 1-associated type II NET occurred in a relatively younger age group (mean age = 44.8 years), with no sex predilection and tumors were predominantly limited to the mucosa and submucosa (71.4%). Type II NET is also gastrin dependent and occurs mainly in ZES due to gastrinoma in the background of MEN-1 syndrome. Interestingly, in our study, a single case of MEN-1-associated NET was not associated with ZES and hypergastrinemia. This similar rare observation was also observed by Hosoya et al.[24] and Bordi et al.[25] In a study by Berna et al.,[26] on long-term follow-up of sporadic ZES, NETs were developed only in less than 2% of cases. So, loss of heterozygosity in the MEN-1 gene is also required for the pathogenesis of G-NETs in addition to hypergastrinemia. Remarkably, in MEN-associated NET, multifocal atrophy was seen in two cases, with the presence of H-pylori in one of them. Though the eradication of H-pylori does not affect the degree of ECL hyperplasia in MEN-1 syndrome, the presence of concomitant H-pylori infection may accelerate the development of type I NET in MEN-1 syndrome.[27] In this study, MEN-associated NETs showed lymph node and liver metastasis in 75% and 25% cases, respectively. In all except one case, metastasis was from gastrinoma rather than type II NET arising from EC. IHC for gastrin in the metastatic site is necessary to determine the type of tumor that get metastasized in MEN-1 cases. The metastatic rate of type II NET reported in the literature was from 3 to 12%.[28]

Type III NETs are sporadic tumors, and their occurrence is not related to atrophic gastritis or MEN-1 syndrome. It was seen in 33.3% of cases with a mean age of 47.4 years and male predominance (69.5%). Though resected specimens were less for the type III category, the serosa involvement, the lymph node, and the liver metastasis were seen in 75%, 39.1%, and 26.1% cases, respectively. These findings highlight the aggressive behavior of type III tumors as documented in other studies.[11],[24]

Newly described type IV neuroendocrine cancers are poorly differentiated with the solid pattern on histology. It was seen in four cases with male predominance, and all were solitary with infiltration up to serosa and showed metastasis to regional lymph node and liver. Notably, three cases failed to show expression for CG in immunostaining. IHC for other neuroendocrine markers such as synaptophysin may be required for diagnosis.[29] Of the four carcinoma cases, two were seen in the antrum and showed immunoreactivity to gastrin, indicating its origin from G cells. La Rosa et al.[30] observed that vacuolated parietal cells in peritumoral mucosa of type IV tumor. However, in this study, vacuoles in the parietal cells were not specific for type IV as it was also observed in type III and type II tumors. Though the aggressive nature of the tumor is related to the Ki-67 index and high-grade morphology, a small proportion of grade I tumors (3.7%) with a size more than 1 cm also showed regional lymph node and liver metastasis. Though the size of tumors was not available in all cases in the present study, none of the tumors with a size less than 1 cm in resected specimens showed nodal or distant metastasis. A similar observation was also made by Chung et al.[14] and suggested that endoscopic resection can be used as a curative treatment for grade I and grade II G-NETs with a size less than 1 cm.

Due to the retrospective plan, there are some limitations in this study. It includes nonavailability of diagnostic workup such as antiparietal cell antibody, serum gastrin in all cases, and intragastric pH. In spite of limitations, we attempted to classify gastric NETs with clinical and histological findings in a relatively good number of cases (78.4%). As prognosis differs with types and grades, one should also attempt to categorize the tumor in addition to grade based on clinical information and histological findings observed in the tumorous and peri-tumorous fragment.

Ethical approval

This study was in accordance with the ethical standards of the institutional and national research committee.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Roberto GA, Rodrigues CMB, Peixoto RD, Younes RN. Gastric neuroendocrine tumor: A practical literature review. World J Gastrointest Oncol 2020;12:850-6.  Back to cited text no. 1
    
2.
Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer 2003;97:934-59.  Back to cited text no. 2
    
3.
Scherübl H, Cadiot G, Jensen RT, Rösch T, Stölzel U, Klöppel G. Neuroendocrine tumors of the stomach (gastric carcinoids) are on the rise: Small tumors, small problems? Endoscopy 2010;42:664-71.  Back to cited text no. 3
    
4.
Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, et al. One hundred years after “carcinoid”: Epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol 2008;26:3063-72.  Back to cited text no. 4
    
5.
Kidd M, Gustafsson B, Modlin IM. Gastric carcinoids (neuroendocrine neoplasms). Gastroenterol Clin North Am 2013;42:381-97.  Back to cited text no. 5
    
6.
Rindi G, Klimstra DS, Abedi-Ardekani B, Asa SL, Bosman FT, Brambilla E, et al. A common classification framework for neuroendocrine neoplasms: An International agency for research on cancer (IARC) and World health organization (WHO) expert consensus proposal. Mod Pathol 2018;31:1770-86.  Back to cited text no. 6
    
7.
Li T-T, Qiu F, Qian ZR, Wan J, Qi X-K, Wu B-Y. Classification, clinicopathologic features and treatment of gastric neuroendocrine tumors. World J Gastroenterol 2014;20:118-25.  Back to cited text no. 7
    
8.
Vannella L, Sbrozzi-Vanni A, Lahner E, Bordi C, Pilozzi E, Corleto VD, et al. Development of type I gastric carcinoid in patients with chronic atrophic gastritis. Aliment Pharmacol Ther 2011; 33:1361-9.  Back to cited text no. 8
    
9.
La Rosa S, Inzani F, Vanoli A, Klersy C, Dainese L, Rindi G, et al. Histologic characterization and improved prognostic evaluation of 209 gastric neuroendocrine neoplasms. Hum Pathol 2011;42:1373-84.  Back to cited text no. 9
    
10.
Kamilaris CDC, Stratakis CA. Multiple endocrine neoplasia type 1 (MEN1): An update and the significance of early genetic and clinical diagnosis. Front Endocrinol (Lausanne) 2019;10:339.  Back to cited text no. 10
    
11.
Rindi G, Bordi C, Rappel S, La Rosa S, Stolte M, Solcia E. Gastric carcinoids and neuroendocrine carcinomas: Pathogenesis, pathology, and behavior. World J Surg 1996;20:168-72.  Back to cited text no. 11
    
12.
Otsuji E, Yamaguchi T, Taniguchi H, Sakakura C, Kishimoto M, Urata Y, et al. Malignant endocrine carcinoma of the stomach. Hepatogastroenterology 2000;47:601-4.  Back to cited text no. 12
    
13.
Latta E, Rotondo F, Leiter LA, Horvath E, Kovacs K. Ghrelin- and serotonin-producing gastric carcinoid. J Gastrointest Cancer 2012;43:319-23.  Back to cited text no. 13
    
14.
Chung C-S, Tsai C-L, Chu Y-Y, Chen K-C, Lin J-C, Chen B-C, et al. Clinical features and outcomes of gastric neuroendocrine tumors after endoscopic diagnosis and treatment: A Digestive endoscopy society of Tawian (DEST). Medicine (Baltimore) 2018;97:e12101.  Back to cited text no. 14
    
15.
Zhang X, Ma L, Bao H, Zhang J, Wang Z, Gong P. Clinical, pathological and prognostic characteristics of gastroenteropancreatic neuroendocrine neoplasms in China: A retrospective study. BMC Endocr Disord 2014;14:54.  Back to cited text no. 15
    
16.
Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis. The updated Sydney system. International workshop on the histopathology of Gastritis, Houston 1994. Am J Surg Pathol 1996;20:1161-81.  Back to cited text no. 16
    
17.
Nehme F, Rowe K, Palko W, Tofteland N, Salyers W. Autoimmune metaplastic atrophic gastritis and association with neuroendocrine tumors of the stomach. Clin J Gastroenterol 2020;13:299-307.  Back to cited text no. 17
    
18.
Lahner E, Zagari RM, Zullo A, Di Sabatino A, Meggio A, Cesaro P, et al. Chronic atrophic gastritis: Natural history, diagnosis and therapeutic management. A position paper by the Italian society of hospital gastroenterologists and digestive endoscopists [AIGO], the Italian society of digestive endoscopy [SIED], the Italian society of gastroenterology [SIGE], and the Italian society of internal medicine [SIMI]. Dig Liver Dis 2019;51:1621-32.  Back to cited text no. 18
    
19.
Bordi C, D'Adda T, Azzoni C, Ferraro G. Pathogenesis of ECL cell tumors in humans. Yale J Biol Med 1998;71:273-84.  Back to cited text no. 19
    
20.
Vannella L, Lahner E, Annibale B. Risk for gastric neoplasias in patients with chronic atrophic gastritis: A critical reappraisal. World J Gastroenterol 2012;18:1279-85.  Back to cited text no. 20
    
21.
Hsing AW, Hansson LE, McLaughlin JK, Nyren O, Blot WJ, Ekbom A, et al. Pernicious anemia and subsequent cancer. A population-based cohort study. Cancer 1993;71:745-50.  Back to cited text no. 21
    
22.
Asaka M, Sugiyama T, Nobuta A, Kato M, Takeda H, Graham DY. Atrophic gastritis and intestinal metaplasia in Japan: Results of a large multicenter study. Helicobacter 2001;6:294-9.  Back to cited text no. 22
    
23.
Rocco A, Suriani R, Cardesi E, Venturini I, Mazzucco D, Nardone G. Gastric atrophy and intestinal metaplasia changes 8 years after Helicobacter pylori eradication. A blind, randomised study. Minerva Gastroenterol Dietol 2002;48:175-8.  Back to cited text no. 23
    
24.
Hosoya Y, Fujii T, Nagai H, Shibusawa H, Tsukahara M, Kanazawa K. A case of multiple gastric carcinoids associated with multiple endocrine neoplasia type 1 without hypergastrinemia. Gastrointest Endosc 1999;50:692-5.  Back to cited text no. 24
    
25.
Bordi C, Falchetti A, Azzoni C, D'Adda T, Canavese G, Guariglia A, et al. Aggressive forms of gastric neuroendocrine tumors in multiple endocrine neoplasia type I. Am J Surg Pathol 1997;21:1075-82.  Back to cited text no. 25
    
26.
Berna MJ, Annibale B, Marignani M, Luong TV, Corleto V, Pace A, et al. 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 2008;93:1582-91.  Back to cited text no. 26
    
27.
Kidd M, Modlin IM, Eick GN, Camp RL, Mane SM. Role of CCN2/CTGF in the proliferation of Mastomys enterochromaffin-like cells and gastric carcinoid development. Am J Physiol Gastrointest Liver Physiol 2007;292:G191-200.  Back to cited text no. 27
    
28.
Ito T, Igarashi H, Jensen RT. Zollinger-Ellison syndrome: Recent advances and controversies. Curr Opin Gastroenterol 2013;29:650-61.  Back to cited text no. 28
    
29.
Rindi G, Klöppel G. Endocrine tumors of the gut and pancreas tumor biology and classification. Neuroendocrinology 2004;80(Suppl 1):12-5.  Back to cited text no. 29
    
30.
La Rosa S, Solcia E. New insights into the classification of gastric neuroendocrine tumours, expanding the spectrum of ECL-cell tumours related to hypergastrinaemia. Histopathology 2020;77:862-64.  Back to cited text no. 30
    

Top
Correspondence Address:
Kim Vaiphei
Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpm.ijpm_824_21

Rights and Permissions


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2]



 

Top
 
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  


    Abstract
   Introduction
    Materials and Me...
   Results
   Discussion
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed402    
    Printed20    
    Emailed0    
    PDF Downloaded33    
    Comments [Add]    

Recommend this journal