Have you seen skin metastases in rare cases of bladder cancer?

The skin is an extremely rare metastatic area of ​​bladder urothelial cancer
.

Simple skin metastasis without systemic metastasis is very rare, and less than 10 cases have been reported in the literature
.

In this case, pelvic lymphadenectomy and radiotherapy were performed for cervical cancer, which resulted in various lymphatic fistulas in the skin
.

Researchers believe that the most likely mechanism for skin metastasis in this case is lymphatic spread through lymphatic fistula
.

For patients who cannot receive cisplatin, immunotherapy is one of the most important treatment options
.

Background The incidence and mortality of bladder cancer in men are higher, about four times that of women
.

According to reports, the incidence of skin involvement in all malignant tumors of the urinary system is 1.
1%~2.
5%
.

The incidence of skin metastasis of bladder cancer was 0.
84%
.

The most common metastatic sites of bladder cancer are the liver, lungs and bones
.

Case status: A female, 80 years old, presented to the doctor with hematuria for 6 to 7 months
.

Complaints of dysuria, groin pain, and urgency
.

Chronic medical history includes hypertension, anemia, atherosclerotic heart disease, first-degree mitral and tricuspid regurgitation
.

Both KPS score and ECOG score are 2
.

Past medical history includes left nephrectomy, cervical cancer radiotherapy, pelvic lymph node dissection, and lymphatic drainage skin fistula
.

Physical examination revealed tenderness of the right costal vertebral angle, and multiple skin fistulas that had existed for about 20 years were visible on the skin
.

A cystoscopy was performed for suspected tumors, and tumor lesions were found in the triangle of the bladder
.

Pathology after transurethral resection of bladder tumor (TURBT) showed pT2G3 urothelial carcinoma
.

CT of the chest and abdomen for radiological staging, no metastasis was shown
.

The patient underwent radical cystectomy + urethral resection + right ureterocutaneostomy (ureterocutaneostomy)
.

Postoperative pathological results showed that urothelial carcinoma (T4aN0M0)
.

Immunohistochemistry showed that cytokeratin (CK) 7 and GATA3 were positive
.

The patient was not suitable for a cisplatin-containing treatment regimen and therefore received pembrolizumab treatment
.

About two months after radical cystectomy, the patient complained of a red, painful, and tender mass on the abdomen, manifested as erythema nodule (Figure 1)
.

A needle biopsy of the skin nodules revealed extensive infiltration from CK7 GATA3 YMA CK-positive high-grade transitional cell bladder cancer (Figure 2)
.

Figure 1 Multiple skin metastases in the abdominal wall Figure 2 a) Hematoxylin and eosin staining shows superficial dermal urethral cancer infiltration; b) Hematoxylin and eosin staining shows deep dermal urethral cancer infiltration; c) Immunohistochemical staining shows nuclear GATA3 positive ; D) Immunohistochemical staining showed positive cytoplasmic CK7
.

Discussion Bladder cancer is one of the malignant tumors that are difficult and time-consuming to treat
.

According to data from the American Cancer Society (ACS), the 5-year relative survival rate for patients with bladder cancer is about 77%, but the 5-year survival rate for patients with metastatic bladder cancer has dropped significantly, only 5%
.

Most patients with bladder cancer die from metastatic disease
.

The study by Mueller et al.
found that the total incidence of skin metastasis of primary solid visceral malignancies was 2.
9%, the incidence of skin metastasis of urinary system malignancies was 1.
3%, and the incidence of skin metastasis of bladder cancer was less than 1%
.

The prognosis of patients with skin metastases of bladder cancer is poor
.

Studies have shown that after being diagnosed with skin metastases of urinary tumors, more than 98% of patients survive less than one year
.

In addition, from the first appearance of skin metastasis, the median disease-specific survival period is less than 6 months
.

The literature shows that there may be four different mechanisms for skin metastasis: 1) hematogenous; 2) lymphatic; 3) spread from the underlying tumor; 4) iatrogenic implantation
.

The patient has a history of pelvic lymph node dissection and radiotherapy
.

Physical examination showed that there was a lymphatic fistula on the skin for 20 years
.

Researchers believe that the most likely mechanism for skin metastasis in this patient is the lymphatic spread of tumor cells through the lymphatic fistula
.

Based on the patient's existing comorbidities and KPS and ECOG scores, there are not many treatment options
.

Chemotherapy is the preferred option
.

The MVAC regimen (methotrexate + vinblastine + doxorubicin hydrochloride + cisplatin) or gemcitabine + cisplatin is a known treatment regimen, and the remission rate is reported to be as high as 70%
.

But the prognosis is still very poor
.

The FDA has approved six drugs for metastatic bladder cancer (Avirulumab, Nivolumab, Pembrolizumab, Atelizumab, Enfortumab vedotin, Erdatinib)
.

For patients with platinum intolerance, immunotherapy is one of the most important options
.

Due to adverse events, chemotherapy could not be continued, so the researchers changed the treatment plan to immunotherapy
.

So far, this is the second case of using immunotherapy for skin metastasis of bladder cancer
.

Conclusion: Skin metastasis of bladder urothelial carcinoma is extremely rare
.

Skin metastasis has been proven to be a poor prognostic factor
.

All clinicians need to pay attention to skin lesions, which may be the early symptoms of metastatic disease
.

To avoid misdiagnosis, skin biopsy should be performed
.

In most cases, due to the advanced stage of the disease and poor prognosis for skin metastases, palliative treatment is usually used
.

References: Öztürk H, Yurtsever S, Özer A, et al.
Cutaneous metastasis of bladder urothelial carcinoma; A rare conditions, Urology Case Reports (2021), doi: https:// doi.
org/10.
1016/j.
eucr.
2021.
101955 .