Introduction: Cutaneous metastasis of urinary 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 even years after the primary cancer
Material and Methods: A retrospective review of the literature
Conclusion: 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
Keywords: Cutaneous metastases; Bladder; Urothelial Cancer
Bladder cancer is the most common genitourinary tract cancer, and the 9th most common cancer in the world with over 330,000 new cases/year, over 30,000 deaths/year and a 3.8:1 rate between men and women [1,2]. The most common bladder cancer is Urothelial Carcinoma (UC), also known as Transitional Cell Carcinoma (TCC). Other much common types are adenocarcinoma, leiomyosarcoma, sarcomatoid carcinoma etc. The progression of normal cells to a tumorigenic and metastatic state involves the accumulation of mutations in multiple key signalling proteins, encoded by oncogenes and tumor suppressor genes. Recently, members of the transient receptor potential (TRP) channel family have been included in the oncogenic and tumor suppressor protein family. TRPM1, TRPM8, and TRPV6 are tumor suppressors and oncogenes in localized melanoma and prostate cancer, respectively . Changes in TRPV1 expression occur during the development of transitional cell carcinoma (TCC) of human bladder. A progressive decrease in TRPV1 expression as the TCC stage increases triggers the development of a more aggressive gene phenotype and invasiveness . The most common sites for metastases from urothelial carcinoma are liver, lung and bone. Cutaneous metastases are very rare andonly few cases have been published in the literature. 17% of all cutaneous metastases derive from urothelial carcinoma of the bladder .
In all the cases we revised in the literature, cutaneous metastases were preceded by bladder urothelial carcinoma. All patients presented with symptoms of cutaneous lesions. The age ranged between 50 and 80 years and all were males. Some presented with multiple reddish nodules on the neck and chest wall, resembling Herpes Zoster . Others presented with swelling of a limb and well-demarcated macular-nodular rash on the thigh . One presented with disseminated pigmented skin lesions , while another had multiple nodular swelling over the body with no lymphadenopathy and no other manifestations . The time interval between the original tumor and the skin metastases ranged between 3 week and 8 years.
All skin lesions were biopsied and on the classical Hematoxylin & Eosin stain a metastatic epithelial tumor wasfound. Immunohistochemical stains were performed in order
to prove the origin of the tumor. The tumors showed strong
positivity to cytokeratin 7, cytokeratin 20 and p-63. Tumor
cells were negative for PSA and thyroid transcription factor 1
(TTF1). The above cytokeratin immunoprofile is consistent with
metastatic urothelial carcinoma.
The first reported case of cutaneous metastasis of urothelial
carcinoma of the urinary bladder was in 1909 . From the
published literature cutaneous metastases occur most often
within 18 months of the primary diagnosis, and only very
few some years later . Metastatic infiltration of the skin
or subcutaneous tissue can occur due to the direct tumor
invasion, hematogenous or lymphatic spread or as a result
of iatrogenic implantation of the tumor cells . It is notable
that even superficial, non-invasive, urothelial carcinoma show
dissemination in 20% of the cases. There may be cutaneous
metastases even in absence of muscle invasive disease .
Cutaneous metastases are a poor prognostic factor with
generally less than 1-year median survival .
Cutaneous metastases may mimic dermatological disorders.
Clinicians and pathologists should be aware of this entity and
consider performing a biopsy. Metastatic lesions often preserve
histological similarities with the primary lesion, but they may
as well be in a poorer differentiated state. In such cases the
immunohistochemical stains can aid the diagnosis and exclude
metastases from other sites.