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Diagn Cytopathol. 2015 Jul;43(7):577-80. doi: 10.1002/dc.23236. Epub 2014 Nov 26.

Cytological findings of appendiceal mixed adenoneuroendocrine carcinoma in pleural effusion: Morphological changes evident after metastasis.

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Department of Diagnostic Pathology, Kanto Rosai Hospital, 1-1 Kizukisumiyoshi-cho, Nakahara, Kawasaki, Kanagawa, 211-8510, Japan.


Goblet cell carcinoid (GCC) of the appendix is now regarded as a malignant tumor, and mixed adenoneuroendocrine carcinoma (MANEC) is a carcinoma progressing from GCC. We describe a man initially diagnosed with GCC of the appendix who died 4 years after diagnosis. Pleural fluid due to metastasis was noted in the terminal phase. Histological findings of the initial tumor indicated that cells with signet-ring morphology were predominant, but the cytological morphology of the fluid was more atypical, making it difficult to diagnose as metastatic GCC by cellular morphology alone. The cells in the pleural fluid were immunopositive for synaptophysin, which was compatible with GCC, but p53 and ki67 staining indicated that the metastatic tumor was more aggressive. These findings suggested a final diagnosis of poorly differentiated adenocarcinoma-type MANEC, which we define as a tumor with typical GCC characteristics and foci that cannot be distinguished from a poorly differentiated adenocarcinoma. This case, which we believe is reported here for the first time, indicates the cytological features of GCC cells may change at metastatic sites to be more atypical and aggressive as the tumor progresses, and these changes should be considered in diagnosis.


goblet cell carcinoid; ki67; mixed adenoneuroendocrine carcinoma; p53; pleural fluid

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