A rare case of bladder cancer with skin metastases, have you seen it?

Introduction The skin is an extremely rare metastatic site for bladder urothelial carcinoma
.

Pure skin metastases without systemic metastases are very rare, with less than 10 cases reported in the literature
.

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

The investigators believe that the most likely mechanism for skin metastases in this case is lymphatic spread through lymphatic fistulas
.

Immunotherapy is one of the most important treatment options for patients who cannot receive cisplatin
.

Background Bladder cancer incidence and mortality are higher in men, about four times higher than in women
.

The reported incidence of skin involvement in all urological malignancies is 1.
1% to 2.
5%
.

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

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

The case is a female, 80 years old, who presented with hematuria for 6 to 7 months
.

Complaints of dysuria, groin pain, and urgency
.

Chronic medical history included hypertension, anemia, atherosclerotic heart disease, and primary mitral and tricuspid regurgitation
.

Both KPS score and ECOG score were 2
.

Past medical history included left nephrectomy, radiation therapy for cervical cancer and pelvic lymph node dissection, and lymphatic drainage skin fistula
.

Physical examination revealed tenderness in the right costovertebral angle, and multiple cutaneous fistulas that had existed for approximately 20 years were seen in the skin
.

Cystoscopy was performed because of suspected tumor, and tumor lesions were found in the bladder triangle
.

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

CT of the chest and abdomen for radiological staging showed no metastases
.

The patient underwent radical cystectomy + urethrectomy + right ureterocutaneostomy
.

Postoperative pathological results showed urothelial carcinoma (T4aN0M0)
.

Immunohistochemistry showed positive for cytokeratin (CK) 7 and GATA3
.

The patient was ineligible for a cisplatin-containing regimen and received pembrolizumab
.

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

Skin nodule biopsy revealed extensive infiltration from CK7 GATA3 YMA CK-positive high-grade transitional cell bladder cancer (Figure 2)
.

Fig 1 Multiple skin metastases on the abdominal wallFig 2 a) Hematoxylin and eosin staining showed infiltration of superficial dermis urethral carcinoma; b) Hematoxylin and eosin staining showed infiltration of urethral carcinoma in deep dermis; c) Immunohistochemical staining showed positive GATA3 nuclei ;d) Immunohistochemical staining showed positive cytoplasmic CK7
.

Discussion Bladder cancer is one of the most difficult and time-consuming malignancies to treat
.

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

Most bladder cancer patients die from metastatic disease
.

The study by Mueller et al found that the overall incidence of skin metastases from primary solid visceral malignancies was 2.
9%, the incidence of skin metastases from urological malignancies was 1.
3%, and the incidence of skin metastases from bladder cancer was less than 1%
.

The prognosis for patients with skin metastases from bladder cancer is poor
.

Studies have shown that more than 98% of patients who are diagnosed with skin metastases from urinary tumors survive less than 1 year
.

In addition, median disease-specific survival was less than 6 months from the first appearance of skin metastases
.

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

The patient had a history of pelvic lymphadenectomy and radiotherapy
.

Physical examination revealed a lymphatic fistula in the skin for 20 years
.

The researchers believe that the most likely mechanism responsible for skin metastases 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
.

MVAC regimens (methotrexate + vinblastine + doxorubicin hydrochloride + cisplatin) or gemcitabine + cisplatin are known regimens with reported remission rates as high as 70%
.

But the prognosis remains poor
.

The FDA has approved six drugs for metastatic bladder cancer (avelumab, nivolumab, pembrolizumab, atezolizumab, enfortumab vedotin, erdatinib)
.

Immunotherapy is one of the most important options for platinum-intolerant patients
.

Due to adverse events, chemotherapy could not be continued, and the investigators changed the treatment regimen to immunotherapy
.

To date, this is the second case where immunotherapy has been used for bladder cancer skin metastases
.

Conclusion Skin metastases from bladder urothelial carcinoma are extremely rare
.

Skin metastases have been shown to be a poor prognostic factor
.

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

To avoid misdiagnosis, a skin biopsy should be performed
.

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

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 .