Goblet cell carcinoids of the appendix - Immunophenotype and ultrastructural study

Background.-Goblet cell carcinoids of the appendix are pare neoplasms with uncertain biological behavior. Objective.-The aims of our study were to evaluate the immunophenotype of th is neoplasm with cell cycle/cell proliferation markers and to understand th eir histogenesis with ultrastructural analysis using conventional carcinoid s as a frame of reference. Methods.-Clinical data and archival pathologic material of all goblet cell carcinoids of the appendix recorded by the Saskatchewan Cancer Registry bet ween 1970 and 1998 were reviewed and evaluated by light microscopy, histoch emistry, immunohistochemistry, and electron microscopy. Results.-Seven cases of goblet cell carcinoids were identified among 110 ca ses of conventional carcinoids of the appendix. Histopathology revealed wid espread infiltration of the periappendiceal fat in all cases, with extensiv e perineural invasion. The cells stained strongly positive for mucicarmine, periodic acid-Schiff, periodic acid-Schiff diastase, Alcian blue, cytokera tin, and carcinoembryonic antigen. Most cases were positive for synaptophys in. Increased expression of cell proliferation markers and cell cycle marke rs was observed. Expression of p53 was strong in one case. Electron microsc opy demonstrated the presence of mucinous vacuoles of varying sizes and occ asional membrane-bound neuroendocrine granules. Conclusions.-Goblet cell carcinoids of the appendix arise from a pluripoten t cell with divergent neuroendocrine and mucinous differentiation. These ne oplasms are widely invasive; they demonstrate a high cellular proliferation rate and dysregulation of the cell cycle with up-regulation of cyclin D1 a nd p21, and down-regulation of p16. Complete removal of the tumor is recomm ended because of the unpredictable biological behavior of this tumor, which includes delayed local recurrences and lung metastases.