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Cutaneous metastasis of transitional cell carcinoma of the urinary bladder eight years after the primary: a case report
© Lees; licensee BioMed Central. 2015
Received: 28 November 2014
Accepted: 2 April 2015
Published: 6 May 2015
Cutaneous metastasis of bladder carcinoma is extremely rare with a limited number of published cases. An awareness of this rare clinical entity and high index of suspicion is needed for diagnosis, as it can occur months or rarely as in this case, even years, after the primary cancer.
An 81-year-old Caucasian man presented with a one-year history of increasing left leg swelling and a two-month history of a macular-nodular rash on the anterior thigh, on a background of a high-grade (WHO Grade 2 of 3) papillary and invasive transitional cell carcinoma of the bladder in 2006. Following investigations, he was diagnosed as having probable locoregional recurrence of previously resected urothelial cancer of the bladder with extensive retrograde lymphatic permeation into the left thigh with cutaneous eruptions of malignancy. He completed a planned course of palliative radiation therapy to the left thigh lesions (30Gy divided over 10 fractions) as well as the left pelvic node (a total dose of 18Gy divided over six fractions). The disease ran an aggressive course and our patient died six months after the diagnosis of cutaneous metastases.
Metastatic disease should always be considered in the differential diagnosis in patients with a previous history of bladder cancer who present with cutaneous nodules, even many years after the initial diagnosis at the primary site.
In 2009, there were 2,316 new cases of bladder cancer in Australia, accounting for 2% of all new cancers . Bladder cancer is four times more common in men than women . However, in 2010, relative survival rates for bladder cancer were higher for men than for women in Australia : the five-year relative survival for bladder cancer for the period 2006 to 2010 was 60.0% for men and 49.6% for women . Approximately 50% of the patients will develop local recurrence and/or metastatic disease after radical cystectomy . Cutaneous metastasis of transitional cell carcinoma (TCC) is rare. The incidence is reported to be less than 1%, and ranges from 0.18% to 2% for TCC of the urinary bladder . Of the cutaneous metastasis from genitourinary organs, TCC of the bladder accounts for 17% of cases . It may occur at the time of diagnosis, or appear months or even years after the primary lesions are found . Rarely, it may present as the first symptom of the disease . We present the case of a patient with a rare cutaneous metastasis of TCC in the absence of generalized recurrent disease.
An 81-year-old Caucasian man presented with a one-year history of increasing left leg swelling, initially in the calf and subsequently extending to the thigh. The general practitioner requested a venous Doppler ultrasound of the left leg and a computed tomography (CT) scan of the abdomen and pelvis, which failed to discover any underlying cause. He had developed multiple lesions on the left anterior thigh, which increased significantly in number and size over two months.
Eight years before this presentation, in 2006, he underwent a cystectomy and ileostomy for high-grade TCC of the bladder. The cystoprostatectomy specimen showed invasive TCC extending into the inner half of his muscularis propria (Stage pT2a) but with a single focus of advential intralymphatic tumor, arising in a background of high-grade transitional cell carcinoma in situ mainly involving the left bladder wall. Ureteric and urethral margins were clear and there was no significant prostatic pathology. Histopathology of the resected trigone and lateral bladder wall was graded 2 of 3 in the WHO classification. An abdominal and pelvic CT scan demonstrated no para-aortic or pelvic lymphadenopathy, and no distant metastasis. It was hoped that the cystoprostatectomy was curative and, therefore, he did not require adjuvant treatments.
He completed a planned course of palliative radiation therapy to the left thigh lesions (30Gy divided over 10 fractions) as well as the left pelvic node (a total dose 18Gy divided over six fractions). Methotrexate was excluded as a treatment option in our patient in light of the potential for accumulation in the ‘third space’ comprising the lymphedema in his left leg. Our patient became too unwell to undergo a subsequent planned course of chemotherapy (carboplatin and gemcitabine). The disease ran an aggressive course and our patient died six months after the diagnosis of cutaneous metastases.
Since the first recorded case of cutaneous metastases of TCC of the urinary bladder in 1909 , infrequent reports have reached the world literature. Skin metastases may occur at any time after the initial diagnosis at the primary site . From the published literature, cutaneous metastases most often occur within 18 months of the primary diagnosis, and only one documented case occurring 10 years after the primary diagnosis . The incidence of metastatic TCC of the bladder is directly related to depth of penetration of the bladder wall, tumor grade and tumor size, with depth of tumor penetration being the single most important factor in predicting prognosis in TCC [11,12]. However, metastases may be associated with superficially invasive primary disease [13,14]. Urologic malignancies most commonly metastasize to regional lymph nodes, liver, lung and bones [5,15]. Metastatic infiltration of the skin or subcutaneous tissues can occur due to direct tumor invasion, hematogenous or lymphatic spread, or as a result of iatrogenic implantation of tumor cells . Gross appearance of cutaneous metastases is not distinctive and may mimic many common dermatologic disorders [16,17]. These lesions can be solitary or multiple in appearance [14,15,18]. Brownstein et al. described three clinical features of metastatic cutaneous lesions, including a nodular type, inflammatory type, and sclerodermoid type . In addition, a rarer zosteriform lesion has also been documented [20-22]. Metastatic skin lesions from genitourinary TCC are reported to be always located on the head, face, neck, trunk, abdomen, suprapubic region or extremities, as well as occasionally on scrotal skin and the ocular region .
Diagnosis requires clinical suspicion of metastases as well as histological evaluation. Diagnosis is usually established by microscopic examination of excisional biopsy specimens . Among reported cases, cutaneous metastases of TCC almost exclusively show high-grade differentiation of histological grading at the primary genitourinary sites . Wang et al. discovered that coordinated expression of cytokeratins 7 and 20 are positive in 89% of transitional cell bladder cancer .
The prognosis for patients with cutaneous TCC is typically poor, with a median survival of fewer than 12 months . However, very rare cases of extended survival (up to 23 years) have been reported . The treatment of choice for metastatic bladder cancer is either chemotherapy, with the combination of gemcitabine and cisplatin or the methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) scheme; or palliative care . Chemotherapy has reported tumor remission rates up to 70% , but survival does not exceed 14 months . Symptomatic patients may benefit from surgical resection of metastases in terms of tumor-related symptoms and performance status . Local radiation therapy has also been reported to resolve cutaneous lesions, which did not respond to chemotherapy .
This is a rare case of late presentation cutaneous metastasis of transitional cell carcinoma. Metastatic disease should always be considered in the differential diagnosis in patients with a previous history of bladder cancer who present with cutaneous nodules. This disease has a broad clinical impact across medicine, in particular for urologists, dermatologists, medical and radiation oncologists, general physicians, geriatricians and palliative care specialists. In many cases, as in our patient, treatment is mainly supportive and prognosis is poor. Due to its rarity and poor survival rate, management strategies have been difficult to define. Therefore, it is important for the medical community to have access to each case, through case reports, so as to advance our understanding of this particular disease.
Written informed consent was obtained from the patient’s next of kin for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
We thank the patient on whom the case report is based, his wife and Shaun Donovan, Staff Specialist Pathology, Royal Hobart Hospital, for the photographs of the histology.
- Australian Institute of Health and Welfare & Australasian Association of Cancer Registries. Cancer in Australia: an overview, 2012, Cancer series no. 74. Cat. No. CAN 70. Canberra: AIHW; 2012.Google Scholar
- Australian Institute of Health and Welfare. Cancer survival and prevalence in Australia: period estimates from 1982 to 2010, Cancer Series no. 69. Cat. No. CAN 65. Canberra: AIHW; 2012.Google Scholar
- Jaske G, Stockle M, Lehmann J, Otto T, Krege S, Rubben H. Metastatic bladder carcinoma. Dtsch Arztebl. 2007;104:A1024–1028.Google Scholar
- Fujita K, Sakamoto Y, Fujime M, Kitagawa R. Two cases of inflammatory skin metastasis from transitional cell carcinoma of the urinary bladder. Urol Int. 1994;53:114–6.View ArticlePubMedGoogle Scholar
- Mueller TJ, Wu H, Greenberg RE, Hudes G, Topham N, Lessin SR, et al. Cutaneous metastases from genitourinary malignancies. Urology. 2004;63:1021–6.View ArticlePubMedGoogle Scholar
- Chitale SV, Morrow DR, Patel R, Gaches CGC, Ball RY. Cutaneous metastases from transitional cell carcinomas of the bladder and renal pelvis. Br J Urol. 1997;79:292–3.View ArticlePubMedGoogle Scholar
- Serel TA, Ozdemir G, Yaman LS, Ozdemir H. Skin metastasis of bladder carcinoma. A case report. Mater Med Pol. 1994;26:113–4.PubMedGoogle Scholar
- Azua D. J Informaciones dermo-sitilografricas: carcinosis secondaria cutanea. Rev Clin Madrid. 1909;6:201–9.Google Scholar
- Lin CY, Lee CT, Huang JS, Chang LC. Transitional cell carcinoma metastasis to arm skin from the renal pelvis. Chang Gung Med J. 2003;26:525–9.PubMedGoogle Scholar
- Schmiedecke R, Perry A, Satter EK. Cutaneous metastasis of a transitional cell carcinoma. Dermatol Online J. 2014; 20.Google Scholar
- Beautyman EJ, Garcia CJ, Sibulkin D, Snyder PB. Transitional cell bladder carcinoma metastatic to the skin. Arch Dermatol. 1983;119:705–7.View ArticlePubMedGoogle Scholar
- Hinshaw M, Stratman E, Warner T, Sharata H. Metastatic transitional cell carcinoma of the bladder presenting as genital edema. J Am Acad Dermatol. 2004;51:143–5.View ArticlePubMedGoogle Scholar
- Swick BL, Gordon JRS. Superficially invasive transitional cell carcinoma of the bladder associated with distant cutaneous metastases. J Cutan Pathol. 2010;37:1245–50.View ArticlePubMedGoogle Scholar
- Akman Y, Cam K, Kavak A, Alper M. Extensive cutaneous metastasis of transitional cell carcinoma of the bladder. Int J Urol. 2003;10:103–4.View ArticlePubMedGoogle Scholar
- Atmaca AF, Akbulut Z, Demirci A, Belenli O, Alici S, Balbay DM. Multiple subcutaneous nodular metastases from transitional carcinoma of the bladder. Pathol Oncol Res. 2007;13:70–2.View ArticlePubMedGoogle Scholar
- Krathen RA, Orengo IF, Rosen T. Cutaneous metastasis: a meta-analysis of data. South Med J. 2003;96:164–7.View ArticlePubMedGoogle Scholar
- Block CA, Dahmoush L, Konety BR. Cutaneous metastases from transitional cell carcinoma of the bladder. Urology. 2006;67:846.View ArticlePubMedGoogle Scholar
- Narayana MA, Patnayak R, Rukmangadha N, Chowhan AK, Kottu R, Phaneendra BV. Cutaneous metastasis of transitional cell carcinoma of the urinary bladder: cytological aspect. J Cytol. 2014;31:50–2.View ArticlePubMedPubMed CentralGoogle Scholar
- Brownstein MH, Helwig EB. Spread of tumours to the skin. Arch Dermatol. 1973;107:80–6.View ArticlePubMedGoogle Scholar
- Ando K, Goto Y, Kato K, Murase T, Matsumoto Y, Ohashi M. Zosteriform inflammatory metastatic carcinoma from transitional cell carcinoma of the renal pelvis. J Am Acad Dermatol. 1994;31:284–6.View ArticlePubMedGoogle Scholar
- Somani BK, Prita D, Grant S, Nabi G, N’Dow J. Herpetiform cutaneous metastases from transitional cell carcinoma of the urinary bladder: immunohistochemical analysis. J Clin Pathol. 2006;59:1331–3.View ArticlePubMedPubMed CentralGoogle Scholar
- Jaworsky C, Bergfeld WF. Metastatic transitional cell carcinoma mimicking zoster sine herpete. Arch Dermatol. 1986;122:1357–8.View ArticlePubMedGoogle Scholar
- Wang NP, Zee S, Zarbo RJ, Bacchi CE, Gown AM. Coordinate expression of cytokeratins 7 and 20 defines unique subsets of carcinomas. Appl Immunhistochem. 1995;3:99–107.Google Scholar
- Gowardhan B, Mathers ME, Feggetter JG. Twenty-three years of disease-free survival following cutaneous metastasis from a primary bladder transitional cell carcinoma. Int J Urol. 2004;11:1031–2.View ArticlePubMedGoogle Scholar
- 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;7:217–9.View ArticleGoogle Scholar
- Otto T, Krege S, Suhr J, Rubben H. Impact of surgical resection of bladder cancer metastases refractory to systemic therapy on performance score: a phase II trial. Urology. 2001;57:55–9.View ArticlePubMedGoogle Scholar
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