TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system

Rindi, Guido; Klöppel, G.; Alhman, H.; Caplin, Martyn; Couvelard, Anne; Herder, Wouter W. de; Erikssson, B.; Falchetti, Alberto; Falconi, Massimo; Komminoth, Paul; Körner, Meike; Lopes, José Manuel; McNicol, A. M.; Nilsson, Ola; Perren, Aurel; Scarpa, Aldo; Scoazec, J.Y.; Wiedenmann, Bertram

doi:10.1007/s00428-006-0250-1

Cited by 1,375 publications

(1,130 citation statements)

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“…The authors used TNM and grading parameters modified with respect to those of ENETS 15 and propose several models that combine histological and clinicopathological data in the attempt to stratify pancreatic endocrine tumor patients into groups with increasing malignant potential. The paper reaches no definitive or consistent conclusion on the best mixture of different histological and clinicopathological parameters to determine prognosis.…”

Section: Discussionmentioning

confidence: 99%

“…15 The proliferative index was expressed as a percentage based on the count of Ki67-positive cells in 2000 tumor cells in areas of the highest immunostaining, using the MIB1 antibody (DBA, Milan, Italy).…”

Section: Who Classification Tnm Staging and Grading Of The Seriesmentioning

confidence: 99%

“…15 The ENETS-TNM system classifies tumors limited to the pancreas as T1, T2 or T3 based primarily on dimensions (o2, 2-4, 44 cm). T3 also includes cases with invasion of the duodenum or bile duct, whereas T4 cases are those with invasion of adjacent organs or large vessels.…”

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confidence: 99%

“…The ENETSgrading system is based on the assessment of the proliferative activity measured by either the mitotic count or Ki67 immunohistochemistry and assigns neoplasms to one of the three categories: G1 if proliferative index is r2%; G2 if 42 to 20%; G3 if 420%. 15 The validation of these TNM and grading systems has been variably addressed in four recent studies that all evidenced clear-cut distinctions only between higher and lower stages while they were of little help for intermediate-stage diseases. [16][17][18][19] There is clearly the need of a system permitting the prognostic stratification of all pancreatic endocrine tumor patients, including both those who may benefit from radical surgery and those with more advanced disease that cannot be resected.…”

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confidence: 99%

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Pancreatic endocrine tumors: improved TNM staging and histopathological grading permit a clinically efficient prognostic stratification of patients

et al. 2010

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Pancreatic endocrine tumors are rare diseases and devising a clinically effective prognostic stratification of patients is a major clinical challenge. This study aimed at assessing whether the tumor-node-metastasis (TNM)-based staging and proliferative activity-based grading recently proposed by the European NeuroEndocrine Tumors Society (ENETS) have clinical value. TNM was applied to 274 patients with histologically diagnosed pancreatic endocrine tumors operated from 1991 to 2005, with last follow-up at December 2007. According to World Health Organization (WHO) classification, 246 were well-differentiated neoplasms (51 benign, 56 uncertain behavior, 139 carcinomas) and 28 poorly differentiated carcinomas. Grading was based on Ki67 immunohistochemistry. Survival analysis not only ascertained the prognostic value of the TNM system but also highlighted that in the absence of nodal and distant metastasis, infiltration and tumor dimensions over 4 cm had prognostic significance. T parameters were then appropriately modified to reflect this weakness. The 5-year survival for modified TNM stages I, II, III and IV were 100, 93, 65 and 35%, respectively. Multivariate analysis identified TNM stages as independent predictors of death, in which stages II, III and IV showed a risk of death of 7, 29 and 58 times higher than stage I tumors (Po0.0001). Ki67-based grading resulted an independent predictor of survival with cut-offs at 5 and 20%. In conclusion, WHO classification assigns clinically significant diagnostic categories to pancreatic endocrine tumors that need prognostic stratification by applying a staging system. The ENETS-TNM provides the best option, but it requires some modifications to be fully functional. The modified TNM described in this study ameliorates the clinical applicability and prediction of outcome of the ENETS-TNM; it (i) assigns a risk of death proportional to the stage at the time of diagnosis, and (ii) allows a clinically based staging of patients, as the T parameters as modified permit their clinical-radiological recognition. Ki67-based grading discerns prognosis of patients with same stage diseases. Modern Pathology (2010) 23, 824-833; doi:10.1038/modpathol.2010 published online 19 March 2010 Keywords: pancreas; tumors; endocrine; staging; TNM; grading; prognosis Pancreatic endocrine tumors are rare and clinically taxing diseases, as their natural history is largely unknown. 1-4 Affected patients seek medical assistance due to symptoms resulting from either hormonal hypersecretion or mass. Thus, pancreatic endocrine tumors are clinically defined as functioning or nonfunctioning depending on the presence of a syndrome related to inappropriate hormone secretion. Such distinction, however, does not provide prognostic information. Pancreatic endocrine tumors are histologically divided into well-

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Section: Discussionmentioning

confidence: 99%

Section: Who Classification Tnm Staging and Grading Of The Seriesmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Pancreatic endocrine tumors: improved TNM staging and histopathological grading permit a clinically efficient prognostic stratification of patients

et al. 2010

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“…To date, at least three formal staging systems have been proposed by three different major organizations, including the World Health Organization (WHO), the European Neuroendocrine Tumor (ENETS), and the American Joint Commission on Cancer (AJCC) [41][42][43]. Although each of these staging systems utilizes slightly different criteria, their ability to predict survival is quite similar [44][45][46].…”

Section: Stagingmentioning

confidence: 99%

Pancreatic Neuroendocrine Tumors: an Update

2015

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Pancreatic neuroendocrine tumors (pNETs) are rare and comprise only 1-2 % of all pancreatic neoplastic disease. Although the majority of these tumors are sporadic (90 %), pNETs can arise in the setting of several different hereditary genetic syndromes, most commonly multiple endocrine neoplasia type 1 (MEN1). The presentation of pNETs varies widely, with over 60 % having malignant distant disease at the time of initial diagnosis involving the liver or other distant sites. Functioning pNETs represent approximately 10 % of all pNETs, secrete a variety of peptide hormones, and are responsible for several clinical syndromes caused by profound hormonal derangement. Surgery remains the cornerstone of therapy and the only curative approach. It should be pursued for localized disease and for metastatic lesions amenable to resection. Multimodality therapies, including liver-directed therapies and medical therapy, are gaining increasing favor in the treatment of advanced pNETs. Their utility is multifold and spans from ameliorating symptoms of hormonal excess (functional pNETs) to controlling the local and systemic disease burden (non-functional pNETs). The recent introduction of target molecular therapy has promising results especially for the treatment of progressive well-differentiated G1/G2 tumor. In this review, we summarize the current knowledge and give an update on recent advancements made in the therapeutic strategies for pNETs.

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Neuroendocrine Tumors of the Ampulla of Vater

Carter¹

2009

Arch Surg

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This is one of the largest series of neuroendocrine tumors of the ampulla. Preoperative biopsy was accurate, but computed tomographic scans were insensitive in detecting nodal metastases. Unlike duodenal carcinoid tumors, hypersecretion syndromes were absent and small tumor size did not preclude locoregional metastases. Tumor grade predicted survival. We recommend pancreaticoduodenectomy for this disease, with local resection reserved for mobile, superficial lesions.

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TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system

Cited by 1,375 publications

References 28 publications

Pancreatic endocrine tumors: improved TNM staging and histopathological grading permit a clinically efficient prognostic stratification of patients

Pancreatic endocrine tumors: improved TNM staging and histopathological grading permit a clinically efficient prognostic stratification of patients

Pancreatic Neuroendocrine Tumors: an Update

Neuroendocrine Tumors of the Ampulla of Vater

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