The precursor lesions of
renal cell carcinoma (RCC) are unknown. The purpose of this study is to determine the incidence, histomorphological features, and immunohistochemical features of
papillary adenoma and elucidate its potential relationship to RCC. We reviewed 542 consecutive
nephrectomy specimens over an 8-year period. Immunohistochemistry was carried out with
antibodies specific for alpha-methyl-
coenzyme A racemase (AMACR) and
glutathione S-transferase alpha (clear-cell RCC marker). Thirty-eight (7%)
nephrectomy specimens showed histologic evidence of
papillary adenoma. Of these 38 cases, 18 (47%) arose in the setting of papillary RCC (PRCC). Seven
papillary adenomas (18%) occurred in the setting of acquired
polycystic kidney disease (APKD), 6 in clear-cell RCCs, 3 in chromophobe RCCs, 2 in
end-stage kidney disease, 1 in
oncocytoma, 1 in
angiomyolipoma, and 1 in renal
schwannoma. Furthermore,
papillary adenomas were more commonly found in kidneys removed for PRCC (25%, 18/71) than in kidneys harboring clear-cell RCC (1.9%, 6/318). Histomorphologically,
papillary adenomas were characterized by varying proportions of papillae and tubules formed by cuboidal cells with scant basophilic cytoplasm similar to those in type 1 PRCC.
Adenomas associated with PRCC tend to be multiple in number (61% [11/18] of cases had >2
adenomas; mean, 5). In contrast, 100% of
papillary adenomas arising in other conditions had less than 2
adenomas. Most of the
adenomas (82%, 31/38) stained strongly for AMACR in a fashion similar to that of PRCC. The 7 AMACR-negative cases all arose in the setting of APKD. In this study of surgical specimens, the high coincidence, multifocality, and histologic and immunohistochemical similarities between
papillary adenoma and PRCC suggest that the 2 are strongly associated and may represent a continuum of 1 biologic process. In contrast,
adenomas associated with APKD exhibit distinct morphological and immunohistochemical features and, therefore, may have an entirely different pathogenesis.