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American Journal of Surgical Pathology:
doi: 10.1097/PAS.0b013e318275d1d7
Original Articles

Tumor Staging But Not Grading Is Associated With Adverse Clinical Outcome in Neuroendocrine Tumors of the Appendix: A Retrospective Clinical Pathologic Analysis of 138 Cases

Volante, Marco MD, PhD*; Daniele, Lorenzo MD; Asioli, Sofia MD; Cassoni, Paola MD; Comino, Alberto MD; Coverlizza, Sergio MD§; De Giuli, Paolo MD; Fava, Cristina MD; Manini, Claudia MD§,#; Berruti, Alfredo MD*; Papotti, Mauro MD*

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Abstract

Appendiceal neuroendocrine neoplasms (NENs) are rare and usually incidentally discovered. Most cases are clinically indolent, although the rare aggressive ones are poorly predictable. The aim of this study was to test the applicability and prognostic significance of the new World Health Organization (WHO) classification and to test the several pathologic features and TNM staging systems (American Joint Committee on Cancer and European Neuroendocrine Tumor Society) in these tumors. A multi-institutional retrospective series of 138 appendiceal NENs was selected on the basis of the availability of both pathologic material and clinical information, including follow-up data. All cases were reviewed to record pathologic features and to apply year 2000 and 2010 WHO classifications, as well as European Neuroendocrine Tumor Society and American Joint Committee on Cancer TNM stages. Clinical and pathologic characteristics were compared with disease outcome by contingency, univariate, and multivariate survival analyses. Although up to one third of cases presented several malignancy-associated pathologic features, only 4 patients died of the disease. Adverse outcome was significantly associated with extramural extension (including mesoappendix), well-differentiated carcinoma diagnosis (2000 WHO classification), pT3-4 stage, older age, and presence of positive resection margins, but not with tumor size, mitotic or proliferative indexes, and, consequently, 2010 WHO grading. In the appendix, at variance with midgut/hindgut NENs, the 2000 WHO classification performs better than the grading-based 2010 WHO scheme and, together with tumor stage, is the most relevant parameter associated with clinical aggressiveness.

© 2013 Lippincott Williams & Wilkins, Inc.

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