Medical Case Reports

Keywords

Bladder; Melanin; Malignant; Bladder pigmentation

Introduction

Melanosis of the bladder is defined as a rare benign lesion caused by melanin deposits in bladder tissue. It can be seen in any organ but more frequently in the skin and oral mucosa [1-3]. It is required for its diagnosis to prove melanin pigment. We present a typical case of melanosis of the bladder with immunohistochemical characterization and we make a review of the English literature thus far. We highlight its benign aetiopathogenesis [1-16].

Case Report

A 69-year-old man presented with a history of urinary obstruction with urgency to void. He had hypertension without other personal antecedents. Urine cytological exam and all complementary analysis were negative. Cystoscopy revealed trabecular wall of the bladder and diffuse black discoloration of the bladder mucosa (Figure 1). No focal lesions were identified. Several biopsies were realized. Biopsy specimens were processed and stained with Haematoxylin Eosine (H and E), which revealed abundant intracytoplasmic brown-black pigment granules deposit in urothelial cells and lamina propria (Figure 2). There was no inflammatory or cytological atypia.

Histochemical stain for iron reaction (Perls´ Prussian blue stain) and Periodic Acid Schiff (PAS) ruled out hemosiderin and lipofuscin deposits, respectively. Neither, melanocytes were detected by immunohistochemical with Melan-A (Figure 3). Brown pigment deposit was positive for Fontana-Masson stain, which was hand tested in our laboratory (Figure 4). Our diagnosis was of melanosis of the bladder. Nowadays, the patient successfully follows periodic reviews by urologist through cystourethroscopy.

Discussion

Brown-black granules in the bladder can be the result of three different pigments: hemosiderin, lipofuscin, and melanin. Hemosiderin is an iron-containing intermediate product of hemoglobin degradation, and it is distinguished by its positive reaction with Perls´ stains. Lipofuscin is a degradation membrane product that is accumulated on lysosomes and positive for PAS stain. Bladder urothelial cells have telolysosomes, which are rich in lipids, and have lipofuscin-like morphology and are positive with PAS stain [1-16]. Furthermore, Lipofuscin deposits have been reported in patients with phenacetin abuse [17,18] and ciprofloxacin treatment by interstitial cystitis [7]. However, the aetiology of melanosis is unclear. Some hypotheses talk about an aberrant migration from the neural crest cells during embryological development or transdifferentiating of urothelial stem cells. None of the hypotheses about deposit origin to date have been conclusive. Symptoms are nonspecific, such as haematuria, dysuria, difficulty voiding, cystitis or urinary incontinence. Therefore, its diagnosis is based on suggestive brown-like cystoscopy images from the bladder wall and thorough histopathological analysis. Atypia cytological should be ruled out for its diagnosis. And granules must be positive with melanic stain and negative with Perls´ and PAS stains.

We have made a review of the English literature about bladder melanosis (Table 1). We have found fifteen cases in all. The age of the patients ranges from 50 to 86 years. There were nine men and seven women. Twelve of them were individual cases of unspecific clinic and diagnostic of urinary bladder melanosis. Three reports (#6#10 and #13)2,5,16 was associated with tumoral pathology. In the 6th and 10th case, the diagnosis was made during follow up contacts. And in the 13th case, both detections were made simultaneously. Also, in two reports (#11 and #14), the lesions had completely resolved in six months and eight years after the diagnosis, respectively [16-19].

The connection between bladder melanosis and malignancy is unknown, currently. Some authors believe melanosis is a premalignant lesion [2-20] and other ones believe both entities are a continuum. Despite this, we suggest that there is no existing relationship between both entities. Being that: (1) the real incidence of only melanosis vesical is not known because it is a diagnosis by chance, on patients with unspecific urinary symptoms, (2) as a rule, bladder biopsy lacks melanocytes and (3) not all cases with melanosis and bladder tumour might have been published.

Conclusion

Melanosis of the bladder has an unknown incidence for this reason should be known considered by urologists and pathologists to avoid a potential malignant misdiagnosis. Demonstrating the melanin pigment in the absence of atypia cytological is the diagnostic key. The scientific community believes melanosis is a benign entity, what we support. However, melanocytes within the urothelial mucosa could have malignant potential. For this reason, its presence should be reported by the pathologist. Demonstrating the melanic pigment in the absence of atypia cytological is the diagnostic key. In short, the published cases are few and lack follows up, what explains the lack of management guidelines for this disease, beyond routine urethrocystoscopy although it may not be able to be considered to large-scale health program.

Acknowledgment

In this work, María Inmaculada Pastora, Ph.D., participated in the monitoring and reporting of cystoscopy images. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

References

1. Alroy J, Ucci AA, Heaney JA, Mitcheson HD, Gavris VE, Woods W. Multifocal pigmentation of prostatic and bladder urothelium. J Urol. 1986;136(1):96â??7.
2. Sanborn SL, MacLennan G, Cooney MM, Zhou M, Ponsky LE. High-Grade Transitional Cell Carcinoma and Melanosis of Urinary Bladder: Case Report and Review of the Literature. Urology. 2009;73(4):928.e13-928.e15.
3. Kerley SW, Blute ML, Keeney GL. Multifocal malignant melanoma arising in vesicovaginal melanosis. Arch Pathol Lab Med [Internet]. 1991 Sep [cited 2019 Dec 7];115(9):950â??2. Available from: http://www.ncbi.nlm.nih.gov/pubmed/1929794
4. Chong FK, Wolfe GZ, Coukos WJ. Melanosis vesica urinaria: Is it a premalignant lesion? J Urol. 1999;161(6):1904â??5.
5. Wieringa RE, Blaauwgeers HJ, Van Andel G. Pseudomelanosis of the bladder: A case report. Acta Cytol. 2006;50(4):473â??5.
6. Di Fiore F, Pone D, Domizio S, Uricchio F, Tufano A, Testa G, et al. Melanosis of the bladder: A rare endoscopic and histopathological finding. Urol Int. 2007;78(2):185â??7.
7. Jin B, Zaidi SY, Hollowell M, Hollowell C, Saleh H. A unique case of urinary bladder simple melanosis: A case report and review of the literature. Diagn Pathol. 2009;4(1).
8. Talmon GA, Khan AU, Koerber RK, Johansson SL. Simple melanosis of the bladder: A rare entity. Int J Surg Pathol. 2010;18(6):547â??9.
9. Willys CB, Winkle DC, Kerr KM. Urinary bladder melanosis: Case report of a rare mucosal lesion. Pathology. 2011;43(2):164â??6.
10. Stuhldreher PP, Ponsky LE, MacLennan GT. Melanosis of the bladder. J Urol. 2011;185(5):1908â??9.
11. Harikrishnan JA, Chilka S, Jain S. Urinary tract transitional cell carcinoma and melanosis of the bladder: A case report and review of the literature. Ann R Coll Surg Engl. 2012;94(4):152â??4.
12. SS P. Melanosis of the Urinary Bladder â?? A Case Report and Review of the Literature. Urol Nephrol Open Access J [Internet]. 2016;Volume 3(Issue 5). Available from: http://medcraveonline.com/UNOAJ/UNOAJ-03-00093.php
13. Yau SE, Singer EJ, Sun Y, Johnson MH. Bladder melanosis with concurrent urothelial carcinoma. Urol Case Reports [Internet]. 2017;15:30â??2. Available from: https://doi.org/10.1016/j.eucr.2017.09.001
14. Lightowlers S, Sengupta A. A Case of Bladder Melanosis Associated with Recurrent Urinary Tract Infections. UroToday Int J [Internet]. 2011;04(06). Available from: http://www.urotoday.com/index.php?option=com_content&catid=1182&id=48749&lang=en&view=article&Itemid=0
15. Godinho R, Tavares E, Oliveira R, Conceição P. Bladder Melanosis: A rare case report. J Case Rep Images Urol [Internet]. 2016 [cited 2019 Dec 7];11:8â??11. Available from: www.edoriumjournals.com/ej/crj/jcriu
16. Mera Z, Patel S, Qassid O, England R. Unusual case of simple urinary bladder melanosis with complete resolution. BMJ Case Rep [Internet]. 2018 Apr 25 [cited 2019 Dec 7];2018. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29695392
17. Berneis K, Korteweg E, Mihatsch MJ. Characterization of the brown pigment of the mucosa of the urinary tract. Vol. 402, Virchows Archiv A, Pathol Anat. 1983. p. 203â??7.
18. Munck A, Lindlar F, Masshoff W. The pigmentation of the renal papillae and the mucosa of the urinary tract in chromic sclerosing interstitial nephritis (â??Phenacetin-Niereâ?). Virchows Arch A, Pathol Anat [Internet]. 1970 [cited 2019 Dec 14];349(4):323â??31. Available from: http://www.ncbi.nlm.nih.gov/pubmed/5310021
19. Lightowlers S, Sengupta A. A case of Bladder melanosis associated with recurrent urinary tract infections. UroToday Int J. 2011;4(6).
20. Yau SE, Singer EJ, Sun Y, Johnson MH, Kerley SW, Blute ML, et al. Bladder melanosis with concurrent urothelial carcinoma. Urol Case Reports [Internet]. 2017 [cited 2019 Nov 23];15:30â??2. Available from: www.edoriumjournals.com/ej/crj/jcriu