Elsevier

Human Pathology

Volume 41, Issue 4, April 2010, Pages 594-601
Human Pathology

Original contribution
Clear cell adenocarcinoma of the bladder and urethra: cases diffusely mimicking nephrogenic adenoma

https://doi.org/10.1016/j.humpath.2009.10.011Get rights and content

Summary

Although clear cell adenocarcinoma have been described focally mimicking nephrogenic adenoma, we have identified a subset of clear cell adenocarcinoma that diffusely resembles nephrogenic adenoma (nephrogenic adenoma-like clear cell adenocarcinoma). Twelve classic clear cell adenocarcinomas of the bladder and urethra and 7 nephrogenic adenoma-like clear cell adenocarcinomas were compared to 10 nephrogenic adenomas. Classic clear cell adenocarcinomas and nephrogenic adenoma-like clear cell adenocarcinomas comprised 4 men and 15 women. The following features were seen in classic clear cell adenocarcinomas: nephrogenic adenoma-like clear cell adenocarcinomas: predominantly solid pattern (7/12:0/7), marked nuclear pleomorphism (7/12:1/7), prominent nucleoli (5/12:1/7), clear cytoplasm in 50% or greater of tumor (7/12:0/7), and necrosis (8/12:3/7), although the necrosis in nephrogenic adenoma-like clear cell adenocarcinomas was often focal and intraluminal. Both patterns of clear cell adenocarcinomas showed prominent hobnail features, although more pronounced in nephrogenic adenoma-like clear cell adenocarcinomas. Muscularis propria invasion was seen in 5 of 9 classic clear cell adenocarcinomas and 6 of 6 nephrogenic adenoma-like clear cell adenocarcinomas, where evaluable. Classic clear cell adenocarcinoma was associated with urothelial carcinoma (n = 2) and endometriosis (n = 1). The Ki-67 rate in clear cell adenocarcinomas ranged from 10% to 80% compared with 0% to 5% in nephrogenic adenoma. The following antibodies were not helpful in distinguishing nephrogenic adenoma-like clear cell adenocarcinoma from nephrogenic adenoma: CD10, estrogen receptor, p63, high-molecular-weight cytokeratin, and α-methylacyl coenzyme-A racemase. PAX2 expression was more frequent in nephrogenic adenoma (89%) compared to both patterns of clear cell adenocarcinoma (29%-32%). The key features discriminating between nephrogenic adenoma-like clear cell adenocarcinoma and nephrogenic adenoma include occasional clear cells, more prominent pleomorphism especially hyperchromatic enlarged nuclei, and extensive muscular invasion. Presence of mitoses and a high rate of Ki-67 expression in lesions resembling nephrogenic adenoma require clinical correlation, close follow-up, and repeat biopsy with more extensive sampling.

Introduction

Clear cell adenocarcinomas (CCA) of the lower urinary tract are rare neoplasms that classically are comprised of solid areas and tubulopapillary architecture with prominent hobnail cytology [1], [2], [3], [4], [5]. It is recognized that focally within a CCA, there may be areas mimicking nephrogenic adenomas (NA), comprised primarily of tubules and papillae without significant cytological atypia [1], [3], [4], [6], [7], [8]. A distinction is usually possible by examining other areas of the tumor which show more obvious malignant features of CCA [3], [4], [6], [9]. We have identified a subset of CCA of the urinary tract where either the entire lesion or the overwhelming component of the lesion strikingly resembles NA. This subset demonstrates no significant solid growth pattern typical of classic CCA and has a more pronounced hobnail pattern. In addition, the cytological atypia seen in these lesions is less pronounced compared to classic CCA. Consequently, this nephrogenic adenoma-like CCA (NA-like CCA) may be misdiagnosed as NA, even with more extensive tissue sampling. In the current study, we present a series of NA-like CCA and compare their microscopic and immunohistochemical features with a series of classic CCA and NA.

Section snippets

Materials and methods

Twelve classic CCA of the bladder (n = 6) and urethra (n = 6) and 7 NA-like CCA arising in the urethra (n = 4) or bladder (n = 3), were studied histologically and immunophenotypically and compared to 10 NA. All but 2 cases were from either the surgical pathology archive files at The Johns Hopkins Hospital or from the personal consult files of the senior author. One case was contributed by the author P.A.D. and another by the author C.C.P. Routine formalin-fixed paraffin embedded hematoxylin and

Clinical features

Four men and 15 women with CCA had a mean age of 62 years (range, 36-91 years). Nine CCA were located in the bladder and 10 in the urethra. In contrast, with NA, there was a male predominance (8 men, 2 women) with a mean age of 53 years (range, 31 to 72 years). NA primarily involved the bladder (n = 9) with only 1 case in the urethra. Presenting symptoms, available in 12 of 19 of the CCA cases, were gross hematuria (n = 10) and urinary hesitancy (n = 2).

Patients with classic CCA consisted of 2

Discussion

CCA of the lower urinary tract is a rare type of carcinoma that arises in the urethra or bladder, predominantly in women and, in general, is regarded as an aggressive neoplasm with an associated poor prognosis [4], [5], [10]. CCA is characterized by an admixture of tubulopapillary and solid components which can focally resemble NA, especially on limited biopsy [1], [2], [6], [11]. However, a combination of features, including areas of diffuse growth pattern, abundant clear cytoplasm, and

Acknowledgment

The authors thank Luis Chiriboga, PhD, from Kaplan Comprehensive Cancer Center, New York University Medical Center, New York, NY, and Ming-Yuan Lee, MD, from Department of Pathology and Laboratory Services, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan for their contribution in PAX2 antibody workup and follow-up contribution, respectively.

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