Selective Immunohistochemical Markers to Distinguish Between Metastatic High-Grade Urothelial Carcinoma and Primary Poorly Differentiated Invasive Squamous Cell Carcinoma of the Lung

Context.-Distinction between primary lung carcinomas and metastases from other sites, especially the urinary tract, is a common diagnostic dilemma. As urothelial carcinomas can demonstrate a broad range of morphology and frequently demonstrate squamous differentiation, discerning metastatic urothelial carcinoma to the lung from primary pulmonary squamous cell carcinoma can be challenging. Objective.-To investigate immunostains that may aid in the distinction of urothelial carcinoma metastatic to the lung. Design.-Staining patterns of 14 markers in primary urothelial carcinoma of the bladder and primary squamous cell carcinoma of the lung were examined to establish a diagnostic panel. These antibodies were subsequently tested on tumors taken from 30 patients with a paired urinary tract and metastatic lung lesion. Results.-The best markers to distinguish poorly differentiated metastatic urothelial carcinoma from primary pulmonary squamous cell carcinoma were CK7, CK20, GATA-3, CK14, desmoglein-3, and uroplakin III, with the utility of the latter dependent upon the quantity of tissue available for analysis. The observed percentage positive staining in nonmetastatic urothelial carcinoma versus primary pulmonary squamous cell carcinoma with these antibodies was as follows: CK7 (100% versus 33%), CK20 (54% versus 7%), GATA-3 (78% versus 23%), CK14 (32% versus 77%), desmoglein-3 (11% versus 87%), and uroplakin III (14% versus 0%). Similar expression patterns were observed among the paired cases. Conclusion.-When interpreted in correlation with clinical history and histomorphology, a panel of immunostains including CK7, CK20, GATA-3, CK14, desmoglein-3, and uroplakin III may be a useful adjunct in the distinction of metastatic urothelial carcinoma to the lung. (Arch Pathol Lab Med. 2012;136:1339-1346; doi: 10.5858/arpa.2011-0575-OA)