title: Prognostic significance of atypical papillary urothelial hyperplasia.
abstract: Typical papillary hyperplasia, a recently recognized precursor lesion to low-grade papillary urothelial neoplasms, consists of undulating folds of cytologically benign urothelium. Well-developed, branching fibrovascular cores of a papillary neoplasm are not evident. We have noted lesions with the architectural pattern of papillary hyperplasia; however, the overlying urothelium demonstrated varying degrees of cytologic atypia. We identified 15 cases of atypical papillary hyperplasia (13 males, 2 females, age 55 to 92) with overlying urothelium showing cytologic atypia. Of these cases, 8 (53%) were received in consultation. Of the 15 cases, 8 exhibited overlying flat carcinoma in situ (CIS), 4 had overlying dysplasia, and 3 were transitional between papillary hyperplasia with atypia and the earliest lesions of papillary neoplasia. Of these cases, 5 patients had multiple specimens with atypical papillary hyperplasia (range, 2 to 8) over time. Concurrent to the diagnosis of atypical papillary hyperplasia, there were 25 different urothelial lesions: CIS (n = 11), papilloma (n = 1), papillary neoplasm of low malignant potential with CIS (n = 1), high-grade papillary urothelial carcinoma (n = 10; 3 with CIS), small-cell carcinoma (n = 1), and infiltrating urothelial carcinoma (n = 1). Of 11 patients with known prior history, 2 had 12 prior urothelial neoplasms (9 low-grade papillary neoplasms, 2 papillary urothelial neoplasms of low malignant potential, and 1 high-grade papillary cancer). Of 10 patients with atypical papillary hyperplasia and a minimum of 1 year of follow-up, 9 had 19 recurrences: CIS (n = 4), papilloma (n = 1), papillary neoplasm of low malignant potential (n = 1), infiltrating urothelial carcinoma (n = 3; 1 with CIS), and high-grade papillary urothelial carcinoma (n = 10; 5 with invasion and 2 with CIS). Whether the papillary hyperplasia had overlying CIS or dysplasia did not affect the correlation with urothelial neoplasms. Immunohistochemical analysis of p53 and Ki-67 expression in 8 cases demonstrated overexpression of p53 (n = 2; 1 with overlying dysplasia and 1 with overlying CIS), and Ki-67 (n = 5; 2 with overlying dysplasia and 3 with overlying CIS). Taken together, these results suggest that atypical papillary hyperplasia is most frequently associated with CIS and high-grade papillary cancer. In some cases, CIS or dysplasia may evolve into atypical papillary hyperplasia, with further progression to high-grade papillary cancer. This process may be analogous to papillary hyperplasia without cytologic atypia progressing to low-grade papillary urothelial neoplasms.
authors.affiliation: Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD 21231, USA.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Swierczynski
authors.forename: Jonathan I
authors.initials: JI
authors.lastname: Epstein
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002278:Carcinoma in Situ / Q000473:pathology*; D002291:Carcinoma, Papillary / Q000473:pathology; D002452:Cell Count; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010212:Papilloma / Q000473:pathology; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology*; D019459:Urothelium / Q000378:metabolism / Q000473:pathology
chemical_list: D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53