Gastroenterology

Gastroenterology

Volume 116, Issue 3, March 1999, Pages 532-542
Gastroenterology

Alimentary Tract
ECL cell tumor and poorly differentiated endocrine carcinoma of the stomach: Prognostic evaluation by pathological analysis,☆☆

https://doi.org/10.1016/S0016-5085(99)70174-5Get rights and content

Abstract

Background & Aims: Gastric endocrine tumors show a wide spectrum of clinical behavior, and prognostic assessement of individual tumors is difficult. The aims of this work were to identify predictors of tumor malignancy and patient outcome and to provide a rationale for treatment guidelines. Methods: Gastric endocrine tumors (86 enterochromaffin-like cell carcinoids and 16 poorly differentiated carcinomas) were investigated for 15 clinicopathologic variables and for expression of Ki67, P53, and BCL-2 proteins. Data were analyzed by univariate and multivariate statistics for evidence of tumor malignancy and patient survival. Results: Histological grades 2 and 3, size ≥3 cm, 9 or more mitoses, or ≥300 Ki67-positive cells per 10 high-power fields identified 26 of 33 (79%) malignant (metastatic or deeply invasive) tumors, and size <1 cm and/or growth restricted to the mucosa characterized 46 of 69 (67%) tumors with benign behavior during a median follow-up of 39 months. Malignancy-predictive models were developed using angioinvasion, size, clinicopathologic type, mitotic index, and Ki67 index. The same variables, in addition to deep gastric wall invasion and histological grade, predicted patient outcome. Conclusions: Criteria for the assessment of malignancy risk and patient outcome were developed for the different tumors, providing a basis for treatment guidelines.

GASTROENTEROLOGY 1999;116:532-542

Section snippets

Materials and methods

In the last three decades, 258 cases of gastric endocrine tumors were identified in the Departments of Pathology of Bayreuth, Parma, Pavia, and Varese. Of the 258 cases, 217 (84.1%) had been diagnosed as ECL cell tumors, 3 as pyloric gastrin cell tumors, 1 as a pyloric somatostatin cell tumor, 1 as a corpus serotonin cell microtumor, 20 (7.8%) as PDEC, 13 (5.0%) as associations of gastric endocrine tumor and nonendocrine carcinoma in a background of chronic atrophic gastritis (10 ECL cell

Overall description

The 102 patients selected for study had approximately equal sex distribution (55 female, 47 male), with a mean age of 59 years (SD, 13.7); 52% of patients (n = 53) were older than 58 years. However, 13 of 16 PDECs and 11 of 17 type III ECL cell tumors were in men, and 32 of 58 type I and 7 of 11 type II ECL cell tumors were in women.

Tumor features

The main pathological findings of the 102 tumors are outlined in Table 1 and Figures 1 and 2.

. (A and B) Grade 1a ECL cell tumor associated with corpus-fundus

Discussion

Extensive investigation of 102 gastric endocrine tumors allowed identification of 11 variables (tumor size, site, number, histological grade, mitotic index, Ki67 or P53 protein expression, angioinvasion, lymphoinvasion, clinicopathologic type, and patient's sex) that, upon univariate analysis, proved to be significant predictors of malignancy as defined by metastases and/or deep gastric wall invasion. Mitotic index, Ki67 index, histological grade, size, and clinicopathologic type were found to

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      The arbitrary choice to use a combined negative end-point including angioinvasion, developing of metastases and tumour-related death, may also affect risk factor analysis. Although angioinvasion may be considered a criterion of malignancy in NENs, as suggested by some studies, its role in gastric primaries is not well established [22–24]. Furthermore, a longer follow-up observation could improve the ability to detect unfavourable clinical outcomes in rare and indolent diseases such as gNENs.

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    Address requests for reprints to: Enrico Solcia, M.D., Department of Human Pathology, via Forlanini 16, 27100 Pavia, Italy. Fax: (39) 382-525866; e-mail: [email protected].

    ☆☆

    Supported by grants from the Italian Ministry of Health (to IRCCS Policlinico San Matteo), from Ministero dell'Universita e Ricerca Scientifica e Tecnologica (MURST) and University of Pavia (to G.R. and E.S.), and from MURST, University of Parma, and Associazione Italiana per la Ricerca sul Cancro (to C.B.). S.L.R. is supported by an Anna Villa Rusconi Foundation Fellowship.

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