Clear cell adenocarcinoma of the urethra: review of the literature

Abstract

Background: Clear cell adenocarcinoma of the urethra (CCAU) is extremely rare and a number of clinicians may be unfamiliar with its diagnosis and biological behaviour.

Aims: To review the literature on CCAU.

Methods: Various internet databases were used.

Results/literature review: (i) CCAU occurs in adults and in women in the great majority of cases. (ii) It has a particular association with urethral diverticulum, which has been present in 56% of the patients; is indistinguishable from clear cell adenocarcinoma of the female genital tract but is not associated with endometriosis; and probably does not arise by malignant transformation of nephrogenic adenoma. (iii) It is usually, readily distinguished from nephrogenic adenoma because of greater cytological a-typicality and mitotic activity and does not stain for prostate-specific antigen or prostatic acid phosphatase. (iv) It has been treated by anterior exenteration in women and cystoprostatectomy in men and at times by radiotherapy; chemotherapy has rarely been given. (v) CCAU is aggressive with low 5-year survival rates. (vi) There is no consensus opinion of treatment options that would improve the prognosis.

Conclusions: Few cases of CCAU have been reported. Urologists, gynaecologists, pathologists, and oncologists should report cases of CCAU they encounter and enter them into a multicentric trial to determine the best treatment options that would improve the prognosis.

Figure 1

Haematoxylin and eosin staining, original magnification ×4, showing complex papillary architecture with abundant fibrovascular stroma; minimal tubular structures and focal solid areas are also seen. The figure was reproduced from [4, 7] with permission granted by Dr. Eddie Fridman. Copyright to Dr. Eddie Fridman. This permission is exclusive to this request specifically for this paper. Additional usage of any printed or electronic material for which Dr. Eddie Fridman holds would require copyright permission from Dr. Eddie Fridman.

Figure 2

Haematoxylin and eosin staining, original magnification ×10, showing papillary and tubular structures, with cytologically atypical epithelial lining with clear cells and focal hob-nail appearance. The figure was reproduced from [4, 7] with permission granted by Dr. Eddie Fridman. Copyright to Dr. Eddie Fridman. This permission is exclusive to this request specifically for this paper. Additional usage of any printed or electronic material for which Dr. Eddie Fridman holds would require copyright permission from Dr. Eddie Fridman.

Figure 3

Haematoxylin and eosin staining, original magnification ×10, showing areas of solid growth pattern composed of atypical clear cells. The figure was reproduced from [4, 7] with permission granted by Dr. Eddie Fridman. Copyright to Dr. Eddie Fridman. This permission is exclusive to this request specifically for this paper. Additional usage of any printed or electronic material for which Dr. Eddie Fridman holds would require copyright permission from Dr. Eddie Fridman.

Figure 4

Haematoxylin and eosin staining, original magnification ×40, high magnification, showing prominent cytological nuclear atypia and few eosinophilic globules. The figure was reproduced from [4, 7] with permission granted by Dr. Eddie Fridman. Copyright to Dr. Eddie Fridman. This permission is exclusive to this request specifically for this paper. Additional usage of any printed or electronic material for which Dr. Eddie Fridman holds would require copyright permission from Dr. Eddie Fridman.

Figure 5

Haematoxylin and eosin staining, original magnification ×40, showing prominent cytological pleomorphism in clear cells and atypical mitotic figures. The figure was reproduced from [4, 7] with permission granted by Dr. Eddie Fridman. Copyright to Dr. Eddie Fridman. This permission is exclusive to this request specifically for this paper. Additional usage of any printed or electronic material for which Dr. Eddie Fridman holds would require copyright permission from Dr. Eddie Fridman.

Figure 6

Immunohistochemical staining of clear cell adenocarcinoma showing strongly positive staining for CK7. The figure was reproduced from [4, 7] with permission granted by Dr. Eddie Fridman. Copyright to Dr. Eddie Fridman. This permission is exclusive to this request specifically for this paper. Additional usage of any printed or electronic material for which Dr. Eddie Fridman holds would require copyright permission from Dr. Eddie Fridman.

Figure 7

Immunohistochemical staining for clear cell adenocarcinoma showing positive staining for CD15. The figure was reproduced from [4, 7] with permission granted by Dr. Eddie Fridman. Copyright to Dr. Eddie Fridman. This permission is exclusive to this request specifically for this paper. Additional usage of any printed or electronic material for which Dr. Eddie Fridman holds would require copyright permission from Dr. Eddie Fridman.

Figure 8

Immunohistochemical staining of clear cell adenocarcinoma showing positive staining for Ki-67 (original magnification ×10). The figure was reproduced from [4, 7] with permission granted by Dr. Eddie Fridman. Copyright to Dr. Eddie Fridman. This permission is exclusive to this request specifically for this paper. Additional usage of any printed or electronic material for which Dr. Eddie Fridman holds would require copyright permission from Dr. Eddie Fridman.

Figure 9

Immunohistochemical staining of clear cell adenocarcinoma showing positive staining for Ki-67 (original magnification ×40). The figure was reproduced from [4, 7] with permission granted by Dr. Eddie Fridman. Copyright to Dr. Eddie Fridman. This permission is exclusive to this request specifically for this paper. Additional usage of any printed or electronic material for which Dr. Eddie Fridman holds would require copyright permission from Dr. Eddie Fridman.

Figure 10

Immunohistochemical staining of clear cell adenocarcinoma showing positive staining for p53 (original magnification ×10). The figure was reproduced from [4, 7] with permission granted by Dr. Eddie Fridman. Copyright to Dr. Eddie Fridman. This permission is exclusive to this request specifically for this paper. Additional usage of any printed or electronic material for which Dr. Eddie Fridman holds would require copyright permission from Dr. Eddie Fridman.

Figure 11

Immunohistochemical staining of clear cell adenocarcinoma showing positive staining for p53 (original magnification ×40). The figure was reproduced from [4, 7] with permission granted by Dr. Eddie Fridman. Copyright to Dr. Eddie Fridman. This permission is exclusive to this request specifically for this paper. Additional usage of any printed or electronic material for which Dr. Eddie Fridman holds would require copyright permission from Dr. Eddie Fridman.

Figure 12

This figure shows architectural patterns of clear cell adenocarcinomas and granular cytoplasmic reactivity with P504S. (a) Tubulocystic pattern with tubules lined by cells with clear cytoplasm component (bladder case 1). (b) Positive staining with P504S bladder case 1). (c) Diffuse growth of clear cells (bladder, case 2). (d) Positive staining with P504S (bladder, case 2). (e) Tubulocystic pattern with tubules lined by hobnail cells showing moderate to severe nuclear atypia (urethra, case 3). (f) Positive staining with P504S (urethra, case 3). (g) Papillary growth pattern with papillae lined by hobnail cells with severe nuclear atypia and mitoses (urethral diverticulum, case 4). (h) Positive staining with P504S (urethral diverticulum, case 4). Haematoxylin-eosin and immunoperoxidase original magnification ×200. Reprinted from [8] Sun et al. Clear cell adenocarcinoma of the urinary bladder and urethra: another urinary tract lesion immunoreactive for P504S. Arch Pathol Lab Med 2008 Sep; 132(9): 1417–1422 reprinted with permission from Archives of Pathology and Laboratory Medicine Copyright 2008 College of American Pathologists. This permission is exclusive to this request specifically for this paper. Additional usage of any printed or electronic material for which the Archives of Pathology and Laboratory Medicine owns copyright would require permission from the editorial office.

Figure 13

This figure shows immunoreactivity of cytokeratin (CK) 7, CK 20, K903, and p63 in clear cell adenocarcinoma. (a) Positive staining with CK7 (bladder, case 1). (b) Focally positive staining with CK20 (bladder, case 1). (c) Positive staining with CK 7 (urethra, case 3). (d) Negative staining with CK 20 (urethra, case 3). (e) Positive staining with K 903 (bladder, case 2). (f) Negative staining with p63 (bladder, case 2). Immunoperoxidase, original magnification ×200 ((a) to (e)) and ×100 (f). Reprinted from [8] Sun et al. Clear cell adenocarcinoma of the urinary bladder and urethra: another urinary tract lesion immunoreactive for P504S. Arch Pathol Lab Med 2008 Sep; 132(9): 1417–1422 reprinted with permission from Archives of Pathology and Laboratory Medicine Copyright 2008 College of American Pathologists. This permission is exclusive to this request specifically for this paper. Additional usage of any printed or electronic material for which the Archives of Pathology and Laboratory Medicine owns copyright would require permission from the editorial office.