Pancreatic Serous Neoplasm and Metastatic Clear Cell Renal Cell Carcinoma: Diagnostic Pitfalls Resolvable by a Panel of Immunohistochemical Stains to Include PAX8 and CK7 But Not CAIX.

Pancreatic serous neoplasms can morphologically resemble metastatic clear cell renal cell carcinoma (ccRCC) and may present a diagnostic dilemma, particularly if the solid variant is in small biopsy specimens and/or in patients with von Hippel Lindau (VHL) syndrome. We investigate the utility of immunohistochemical staining in this differential diagnosis by performing head-to-head comparisons of commonly used immunohistochemical markers for these 2 tumor types. We examined 16 pancreatic serous neoplasms and 24 ccRCCs (12 metastatic to pancreas and 12 primaries in patients with VHL). All pancreatic serous neoplasms stained positive for CK7, and most were positive for CAIX (15/16) and GLUT1 (15/16), variable for alpha-inhibin and vimentin (each 8/16 weak/focal; and 7/16 and 8/16, respectively, positive), and weak/focal for synaptophysin (14/16). All pancreatic serous neoplasms were negative for PAX8 and Periodic acid-Schiff without diastase. In contrast, ccRCC, both metastatic and in VHL patients, were mostly positive for PAX8 (18/24; 6/24 were weak/focal), negative for CK7 (15/24; 8/24 were weak/focal, one case diffuse positive), and negative for alpha-inhibin (100%) and synaptophysin (22/24). Like pancreatic serous neoplasms, all ccRCC showed weak/focal or positive staining for GLUT1, CAIX, and vimentin, and were negative for PAS-D. In conclusion, CK7 and PAX8 are the most useful stains in distinguishing between pancreatic serous neoplasm and ccRCC; however, weak/focal CK7 or PAX8 staining can be seen in a minority of ccRCC, thereby presenting a diagnostic pitfall. Alpha-inhibin was at least weak/focal in most pancreatic serous neoplasms and negative in all ccRCC and may be useful as an adjunct stain in difficult cases.