Goblet cell adenocarcinoma (GCA) of the appendix is a rare but clinically significant neoplasm characterized by infiltrative nests of mucin-rich goblet-like cells that may exhibit minimal cytologic atypia. During routine sign-out, we observed a reproducible alteration of the resection margin in appendectomy specimens that closely mimicked low-grade GCA. Following institutional review board approval, we retrospectively reviewed 33 appendectomy specimens to characterize this finding and assess associated clinicopathologic factors. A goblet cell-like artifact was identified in 12 of 33 cases (36%). The altered areas consisted of optically clear, vacuolated profiles arranged in linear arrays or small clusters within the appendiceal wall, often associated with thermal-type tissue injury. AE1/AE3 immunohistochemistry was performed in all artifact-positive cases, which were negative, supporting a non-epithelial, non-neoplastic interpretation. The finding was strongly associated with appendiceal base management using endoloop ligation with energy-assisted transection (12/12 artifact cases, 100%), whereas stapler-only transection was observed exclusively in non-artifact cases (p = 0.001). Thermal injury (p < 0.001), mucin depletion (p = 0.009), marked wall edema (p < 0.001), and receipt of an open proximal margin (p = 0.031) were also significantly associated. Clinical follow-up (median 6.2 months in artifact cases) demonstrated no subsequent neoplasms, additional surgery, or oncologic therapy. These findings support a reproducible, procedure-related artifact that can mimic GCA, particularly in specimens managed with endoloop ligation and energy-assisted transection. Awareness of the associated morphologic constellation and operative context may help prevent overinterpretation of this benign alteration as infiltrative neoplasia.
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