Bladder Cancer That Metastasized to the Skin: A Unique Presentation That Signifies Poor Prognosis

Case Review Bladder Cancer That Metastasized to the Skin: A Unique Presentation That Signifies Poor Prognosis Tal Cohen, BS,1 Daniel Ricchiuti, MD,1,2 Mark Memo, DO2 1Department of Urology, Northeast Ohio Medical University, Rootstown, OH; 2N.E.O. Urology Associates, Boardman, OH In the United States in 2015, an estimated 74,000 new cases of bladder cancer were diagnosed and approximately 16,000 deaths were due to bladder cancer. We present a rare case of a patient with aggressive bladder cancer who presented with multiple inguinal and scrotal skin lesions that were proven to be metastatic urothelial malignancy. Bladder malignancy can involve the skin by direct tumor invasion, hematogenous routes, lymphatic spread, and direct seeding due to iatrogenic implantation. The cutaneous lesions have an extremely variable appearance, are resistant to therapies, and signify a dismal prognosis. [Rev Urol. 2017;19(1):68-71 doi: 10.3909/riu0740] ® © 2017 MedReviews , LLC Key words Bladder cancer • Cutaneous metastasis • Urothelial malignancy A 75-year-old white man presented to the urology clinic with a chief complaint of gross hematuria with clots. The patient had a past medical history significant for laryngectomy for laryngeal cancer, depression, glaucoma, seizure disorder, arthritis, thyroid disease, hypertension, diabetes, and history of gastrointestinal hemorrhage. The patient was a heavy smoker for 53 years. A computed tomography (CT) three-dimensional (3D) urogram 68 • Vol. 19 No. 1 • 2017 • Reviews in Urology was ordered at the initial consultation; however, the patient was admitted to the hospital prior to finalization of results. The patient’s chief complaint was gross hematuria and he was found to be anemic, with a hemoglobin level of 5 g/dL. The patient underwent cystoscopy and bilateral retrograde pyelogram, which identified normal ureteral anatomy and a large tumor on the dome of the bladder. Transurethral resection was performed. Pathologic Bladder Cancer That Metastasized to the Skin analysis revealed high-grade urothelial cell carcinoma invading subepithelial tissue without involvement of smooth muscle. Review of the CT 3D urogram ordered prior smooth muscle. The patient was seen in the office afterward, but was then lost to follow-up; he presented 3 months after his last visit to the emergency room with altered The patient underwent cystoscopy and repeat transurethral resection of bladder tumor for accurate staging; pathologic analysis revealed high-grade urothelial carcinoma with submucosal invasion. to admission demonstrated a large anterior bladder mass. The patient underwent a secondary bladder biopsy 2 months later to ensure accurate staging as per the standard of care, which identified remnants of high-grade urothelial carcinoma invasive into the lamina propria; no underlying muscularis propria was identified. The patient followed-up 1 month after the bladder biopsy and complained of gross hematuria, frequency, nocturia, urgency, and dysuria. The decision was made to proceed to the operating room for cystoscopy and clot evacuation. The patient was seen 2 months later for cystoscopy, which identified a few posterior wall tumors. The patient underwent cystoscopy and repeat transurethral resection of bladder tumor (TURBT) for accurate staging; pathologic analysis revealed high-grade urothelial carcinoma with submucosal invasion. No involvement of smooth muscle was noted. After this recurrence, the patient was offered a cystectomy, but he refused. The patient then underwent induction Bacillus Calmette-Guérin (BCG) immunotherapy with six bladder instillations. The patient had a follow-up visit 1 month after the BCG treatment, during which he complained of episodic gross hematuria. The patient then underwent another cystoscopy and TURBT; pathologic analysis demonstrated high-grade urothelial carcinoma with invasion into the lamina propria without involvement of the mental status and anemia. Upon physical examination, a series of approximately 8 to 10 cutaneous lesions located in the right inguinal region and scrotum was observed. The lesions were nodular, fibrotic, and hemorrhagic. A bedside biopsy of a skin lesion was performed and sent for pathologic analysis, which identified a poorly differenti- urothelial origin. The patient died shortly after diagnosis. Results of the CT of the abdomen and pelvis performed during the patient’s final hospital admission did not demonstrate any metastatic disease and no bone metastases were present. A thorough physical examination and review of imaging and pathology results demonstrated that the patient developed these cutaneous lesions without smooth muscle involvement or metastatic involvement of visceral organs, lymph nodes, or bony structures. Figure 1 is the CT of the abdomen and pelvis performed during the patients last hospital stay, which showed that cutaneous involvement was not achieved by direct invasion. The lesion had large anaplastic cells; test results were positive for pankeratin and CK7, but negative for CK20 and p63, which was consistent with a metastatic carcinoma of urothelial origin. ated neoplasm involving the dermis and subcutaneous tissue. The lesion had large anaplastic cells; test results were positive for pankeratin and CK7, but negative for CK20 and p63, which was consistent with a metastatic carcinoma of Figure 2 is an image of the lesions taken prior to the skin biopsy demonstrating multiple, actively bleeding, and umbilicated nodules. This case illustrates a rare instance of cutaneous metastases of bladder cancer, the variety in the lesion Figure 1. Computed tomography of the abdomen and pelvis demonstrating that involvement of the skin was not achieved through direct invasion. Vol. 19 No. 1 • 2017 • Reviews in Urology • 69 Bladder Cancer That Metastasized to the Skin continued glutathione-S-transferase.2 Although genetic changes have been identified as a risk factor, exposure to environmental carcinogens, smoking, radiation, and chemotherapy have a stronger association with the development of urothelial malignancy. Figure 2. Image demonstrating multiple umbilicated, actively bleeding lesions in the abdominal/inguinal area. characteristics, the role of histologic subtyping in identifying the tissue of origin, and the poor prognosis associated with cutaneous metastasis. Discussion Bladder Cancer Epidemiology A total of 90% of all bladder cancers are transitional cell carcinoma, 5% are squamous cell carcinoma, and 2% are adenocarcinoma or other variants. In the United States in 2015, an estimated 74,000 new cases of bladder cancer were diagnosed and approximately 16,000 deaths were due to bladder cancer.1 Genetic changes that predispose individuals to bladder cancer development include polymorphisms within detoxifying enzymes N-acetyltransferase and Cutaneous Metastasis Bladder cancer commonly metastasizes to regional lymph nodes, liver, lung, and bone.3 Only 5.3% of all malignancies lead to cutaneous metastasis. Out of these, 1.34% are linked to underlying genitourinary malignancy; bladder cancer accounts for 0.84% of these.4 The prognosis of any cancer with cutaneous metastasis is poor; with regard to bladder cancer with cutaneous metastasis, median survival time is  12 months. In previous studies, treatments such as local excision, radiotherapy, chemotherapy, and immunologic and combination therapy were applied with poor response.5,6 Cutaneous involvement from bladder cancer is achieved by direct tumor invasion, hematogenous routes, lymphatic spread, and direct seeding due to iatrogenic implantation. Iatrogenic Main Points • A total of 90% of all bladder cancers are transitional cell carcinoma, 5% are squamous cell carcinoma, and 2% are adenocarcinoma or other variants. Although genetic changes have been identified as a risk factor, exposure to environmental carcinogens, smoking, radiation, and chemotherapy have a stronger association with the development of urothelial malignancy. • Bladder cancer commonly metastasizes to regional lymph nodes, liver, lung, and bone. Only 5.3% of all malignancies lead to cutaneous metastasis. Out of these, 1.34% are linked to underlying genitourinary malignancy; bladder cancer accounts for 0.84% of these. • The prognosis of any cancer with cutaneous metastasis is poor; with regard to bladder cancer with cutaneous metastasis, median survival time is  12 months. Cutaneous involvement from bladder cancer is achieved by direct tumor invasion, hematogenous routes, lymphatic spread, and direct seeding due to iatrogenic implantation. Iatrogenic implantation is due to surgical treatment of these tumors, including cystectomy, partial cystectomy, transurethral resection of bladder tumor, and other procedures. • The lesions are typically poorly differentiated and identifying the origin usually requires immunohistochemical investigation. 70 • Vol. 19 No. 1 • 2017 • Reviews in Urology Bladder Cancer That Metastasized to the Skin implantation is due to surgical treatment of these tumors, including cystectomy, partial cystectomy, TURBT, and other procedures. and identifying the origin usually requires immunohistochemical investigation.6,7 Cutaneous involvement from bladder cancer is achieved by direct tumor invasion, hematogenous routes, lymphatic spread, and direct seeding due to iatrogenic implantation. Iatrogenic implantation is the most common cause of seeding outside of the urinary tract.4,6,7 The clinical appearance of these lesions varies and may mimic other dermatologic diseases. The lesions can be solitary or multiple, and can have Conclusions be evaluated for the possibility of metastatic involvement. In the rare case of bladder malignancy involving the skin, the main cause is iatrogenic implantation during surgical management of the tumor. References 1. 2. Metastatic lesions involving the skin are rare occurrences and extremely variable in presentation, and can mimic other dermatologic disorders. The lesions are typically resistant to local therapy and indi- 3. 4. 5. The lesions can be solitary or multiple, and can have a nodular, fibrotic, and inflammatory appearance. 6. a nodular, fibrotic, and inflammatory appearance. The lesions are typically poorly differentiated 7. cate a poor prognosis. Any patient with new-onset cutaneous lesions and a history of malignancy should Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5-29. García-Closas M, Malats N, Silverman D, et al. NAT2 slow acetylation, GSTM1 null genotype, and risk of bladder cancer: results from the Spanish Bladder Cancer Study and meta-analyses. Lancet. 2005;366:649-659. Weizer AZ, Shariat SF, Haddad JL, et al. Metastatic transitional cell carcinoma of the urinary bladder to the shoulder girdle. Rev Urol. 2002;4:97-99. Narayana MA, Patnayak R, Rukmangadha N, et al. Cutaneous metastasis of transitional cell carcinoma of the urinary bladder: Cytological aspect. J Cytol. 2014;31:50-52. Chang CP 1st, Lee Y, Shih HJ. Unusual presentation of cutaneous metastasis from bladder urothelial carcinoma. Chin J Cancer Res. 2013;25:362-365. Salemis NS, Gakis C, Zografidis A, Gourgiotis S. Cutaneous metastasis of transitional cell bladder carcinoma: A rare presentation and literature review. J Can Res Ther. 2011;7:217-219. Campanati A, Brisigotti V, Dusi D, et al. Bladder urothelial cell carcinoma metastatic to the skin. Clin Dermatol. 2013;1:22-25. Vol. 19 No. 1 • 2017 • Reviews in Urology • 71