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Well-differentiated neuroendocrine tumors of the appendix: Diagnosis, differentials, and disease progression.

Well-differentiated neuroendocrine tumors are the most common neoplasm of the appendix. They are graded and staged using World Health Organization and American Joint Committee on Cancer criteria, respectively. They may be invisible grossly or form rounded yellow nodules, sometimes in the appendiceal tip. They show classic neuroendocrine tumor features microscopically, forming nests and cords of monotonous cells with salt-and-pepper chromatin and amphophilic cytoplasm. They are positive for neuroendocrine markers by immunohistochemistry, but their molecular characteristics are not well defined. pT-category staging relies primarily on tumor size, though higher-stage cases may involve the subserosa or mesoappendix. Few entities enter the differential diagnosis, but lesions such as goblet cell adenocarcinoma, poorly differentiated neuroendocrine carcinoma, and mixed neuroendocrine-non-neuroendocrine neoplasm may be considered. Appendiceal neuroendocrine tumors may metastasize to regional lymph nodes, but farther spread is rare. The most consistently proven risk factor for such spread is tumor size, though different studies have proposed different cutoffs. Other potential risk factors include lymphovascular invasion and margin positivity. Tumors smaller than 1 cm can be treated by appendectomy, while hemicolectomy is recommended for tumors larger than 2 cm. Proper treatment for cases measuring 1-2 cm remains a matter of debate.

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