Utility of Islet 1, PAX8, CDX2 and TTF1 in Fine Needle Aspiration Workup of Metastatic Neuroendocrine Tumors
Claudia Velosa, Jacqueline Nunez, Jan Silverman. Allegheny General Hospital, Pittsburgh, PA
Background: Determining the origin of a metastatic neuroendocrine tumor (NET) can be challenging since primary NET from various sites share similar cytologic features. CDX2 and TTF1 have been found helpful identifying well-differentiated primary NET of gastrointestinal (GI) and pulmonary origin, respectively. Islet1 and PAX8 are useful markers for pancreatic endocrine neoplasia (PEN). We evaluated a panel of markers to determine the origin of metastatic NET on fine needle aspiration (FNA) cytology.
Design: FNA of 20 cases of primary NET (16 pancreatic, 5 pulmonary, 1 ileal, 1 duodenal, 1 colonic, and 1 gastric) and 31 metastatic NET (13 pancreatic, 10 pulmonary, 6 ileal, 1 duodenal, and 1 rectal) were evaluated. Cell blocks were immunohistochemically (IHC) stained for PAX8, Islet 1, TTF1 and CDX2. Nuclear staining for all antibodies was independently scored by two investigators as negative (<5% positivity) or positive (>5% moderate strong positivity).
Results: Islet 1 and PAX8 were positive in 13/16 (81.2%) and 14/16 (87.5%), respectively, of primary PEN. 10/13 cases (76.9%) of metastatic PEN were positive for either Islet1 or PAX8. Coexpression of both was present in 12/16 (75.0%) and 9/13 (69.2%) primary and metastatic PEN, respectively. No cases of primary or metastatic ileal NET were positive Islet1 or PAX8. PAX8 was positive in 1/1 primary gastric, 1/1 primary duodenal and 1/5 primary pulmonary NET. Islet 1 was expressed in 1/1 primary duodenal and 1/5 primary pulmonary NET. CDX2 expression was present in all cases of primary duodenal, ileal, colonic and rectal NET and 5/6 (83.3%) metastatic ileal NET. 1/16 (6.25%) primary and 2/13 (15.4%) metastatic PEN were positive for CDX2. TTF1 was positive in all cases of primary and metastatic pulmonary NET.
Conclusions: 1.Islet 1 and PAX8 were specific and sensitive for metastatic PEN 2.Although there was no significant difference between Islet1 and PAX8 in sensitivities and specificities for primary and metastatic PEN, 18.7% primary and 15.3% metastatic PEN showed discordant staining, suggesting that the stains complement each other as part of IHC panel for the FNA work-up of PEN 3.Islet 1 and PAX8 expression was negative in primary and metastatic ileal NET compared with high expression in primary and metastatic PEN, suggesting that Islet 1 and PAX8 can be useful in the FNA cytology work-up of ileal versus pancreatic metastatic NET 4.CDX2 and TTF1 were specific for primary and metastatic GI and pulmonary NET 5. We recommend Islet 1, PAX8 in addition to TTF1, and CDX2 for the work-up of metastatic NET of unknown primary in FNA cytology.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 60, Monday Morning