The pagetoid variant of bladder urothelial carcinoma in situ

Abstract

Pagetoid urothelial carcinoma in situ (CIS) is a rare variant of bladder cancer that is characterized by an intraepithelial proliferation of large cells arranged singly or in clusters and randomly distributed. These neoplasms deserve recognition and attention, chiefly because they may be overlooked or misdiagnosed as urothelial dysplasia, then causing unsuspected tumor recurrence after surgery. We report on the clinicopathological features and immunohistochemical findings of 11 (14.86%) cases of pagetoid CIS in a retrospective study of 74 cases of conventional carcinoma in situ. Most patients were male ( n=10). Their ages ranged from 31 years to 78 years. The lesion can be present with primary ( n=2) or secondary ( n=9) CIS. Pagetoid CIS is usually a focal lesion occurring in a clinical and histological setting of conventional CIS, and these patients essentially have the same progression and survival rates as patients without pagetoid changes and are treated in the same way. In cases with extensive urothelial denudation, pagetoid CIS may be focally present in otherwise normal-looking urothelium, thus alerting the pathologist to search for additional CIS elsewhere in the bladder. Given that primary extramammary Paget disease of the external genitalia and of the anal canal may extend to the bladder and, conversely, some bladder cases of pagetoid CIS may extend to the urethra, ureter, and beyond to the external genitalia, the differential diagnoses between these two entities represent an important therapeutic consideration. Our data suggest that a panel of immunostains including CK7+/CK20+/TM+ may assist in differentiating urothelial pagetoid CIS from extramammary Paget disease which is known to be CK7+/CK20-.

Preneoplastic non-papillary lesions and conditions of the urinary bladder: an update based on the Ancona International Consultation

“…In denuded areas, CIS may only be present in Von Brunn nests, a useful clue in the diagnosis of residual CIS [40]. Rarely, CIS exhibits pagetoid growth [37,51], characterized by large single cells or small clusters of cells within otherwise normal urothelium in the bladder, ureter, urethra, or within prostatic ducts, but also pagetoid cells can be present within squamous metaplasia of the urinary bladder [36]. This variant of CIS is frequently overlooked and may be responsible for unsuspected recurrent disease after surgery.…”

Precursor Lesions of Urologic Malignancies

“…While several groups have described morphologic subtypes of UCIS, these have generally not been shown to have clinical or prognostic significance, and we do not specify the UCIS subtype(s) in our pathology reports. [88][89][90] The most common lesions included in the differential diagnosis of UCIS are reactive atypia (which we report as ''reactive epithelial changes'' to avoid any confusion for our clinical colleagues by using the word ''atypia'' or ''atypical'') and urothelial dysplasia (discussed in the next section). In cases of reactive change, the architecture is typically undisturbed or only minimally altered with the cells maintaining their polarity and showing no nuclear crowding or overlap.…”

Flat urothelial carcinoma in situ of the bladder with glandular differentiation

“…Primary or isolated CIS accounts for less than 10% of cases of CIS, and 1% of bladder tumors [10,11,13,19,20]. Secondary or concomitant CIS is more common than primary CIS, accounting for 90% of cases [19,20].…”

“…Carcinoma in situ (high-grade intraurothelial neoplasia) refers to a flat noninvasive neoplastic change of the urothelium with substantial architectural and cytological abnormalities, the latter being indistinguishable from those of carcinoma [10,11,13,19,20]. Primary or isolated CIS accounts for less than 10% of cases of CIS, and 1% of bladder tumors [10,11,13,19,20].…”

“…None of the reported cases had immunohistochemical evaluation, therefore making the immunophenotype of CISg virtually unknown [1,2]. Hence, more reports on larger series are needed to elucidate the clinical significance, immunophenotype and differential diagnostic implications of this morphologic variant of bladder CIS [1][2][3][4][5][6][7][8][9][10][11][12][13][14].…”