A 55-year-old female presented with recurrent hematuria and urinary tract infections. Evaluations with computed tomography urogram, flexible cystoscopy, and urine cytology revealed an extensive bladder tumor with a vesicovaginal fistula. The TNM pathologic stage of the tumor was pT3a N0 M0. Histological evaluation showed that there were cohesive epithelioid malignant cells suggestive of urothelial carcinoma in few areas. However, most of the neoplasm consisted of singly dispersed cells with eccentric, abundant eosinophilic cytoplasm and bizarre, spindly nuclei characteristic of sarcomatoid urothelial carcinoma (SUC). The patient had anterior pelvic exenteration and adjuvant chemotherapy. No evidence of metastasis was found in preoperative or postoperative imaging. However, the patient presented with a rare axillary mass 3 months after surgery. Biopsy of the mass showed sarcomatous differentiation similar to the SUC primary tumor in the bladder. A CT scan of the chest and a whole body scan revealed lung, liver, abdominal, and mesenteric lymph node metastases. She died approximately 6 months after the initial diagnosis. The authors compare this case of axillary metastasis from sarcomatoid variant of urothelial cancer with other reports in the literature.
KEYWORDS: Sarcomatoid urothelial carcinoma; Axillary metastasis; Survival rate.
CITATION:UroToday Int J. 2010 Jun;3(3). doi:10.3834/uij.1944-5784.2010.06.01
ABBREVIATIONS AND ACRONYMS: CS, carcinosarcoma; CT, computed tomography; SUC, sarcomatoid urothelial carcinoma; TCC, transitional cell carcinoma; UC, urothelial carcinoma.
The incidence of sarcomatoid urothelial carcinoma (SUC) is 0.3% of all histologic subtypes, making it a rare malignant neoplasm of the urinary bladder. Typically, it is a transitional cell carcinoma (TCC) with predominant sarcomatoid spindle and giant cell components. It contains epithelial and mesenchymal elements, and may portend a worse prognosis than conventional urothelial carcinoma. Although SUC is widely considered to have a poor prognosis [1,2], the body of literature characterizing the tumor type is limited to case reports and small, single-institution series [3,4,5,6]. The present authors report a case of SUC with axillary metastasis and review the literature to examine the survival of patients with this rare variant.
A 55-year-old female presented with recurrent urinary tract infections and gross hematuria that began 10 days before the examination. A computed tomography (CT) urogram showed a soft tissue mass occupying the dome and right lateral wall of the bladder, with no immediate evidence of metastatic lesions (Figure 1; Figure 2). Further imaging with a voiding cystourethrogram revealed a vesicovaginal fistula. Cystoscopy showed a large, ulcerated, polypoid fleshy tumor on the dome and right lateral bladder wall. The patient underwent transurethral resection of the tumor. Histologic examination indicated a high-grade urothelial carcinoma (UC) with sarcomatoid differentiation.
The patient underwent pelvic anterior exenteration with urinary diversion and extensive lymph node dissection; 38 lymph nodes were removed and all were negative. The TNM pathologic stage was pT3a N0 M0. The tumor showed cohesive epithelioid malignant cells suggestive of UC in few areas. However, most of the neoplasm consisted of singly dispersed cells with eccentric, abundant eosinophilic cytoplasm and bizarre, spindly nuclei characteristic of SUC (Figure 3; Figure 4).
The patient had adjuvant chemotherapy with MVAC regimen: methotrexate, vinblastine, doxorubicin (Adriamycin; Bedford Laboratories, Bedford, OH, USA) and cisplatin. She was followed closely for 6 months. Despite the negative preoperative metastatic workup, she presented with an axillary mass 3 months after her initial diagnosis (Figure 5). Biopsy of the mass showed sarcomatous differentiation similar to the primary SUC tumor in the bladder. A CT scan of the chest and a whole body scan revealed lung, liver, abdominal, and mesenteric lymph node metastases. She died of systemic disease approximately 6 months after the initial diagnosis. The rapid deterioration of patient status despite preoperative negative metastatic workup emphasizes the nature of the disease.
More than 90% of tumors in the urinary bladder are UC. UC has a propensity for divergent differentiation, with squamous and glandular variants being the first and second most common, respectively. SUC refers to all biphasic malignant neoplasms that exhibit morphologic and/or immune histochemistry evidence of both epithelial and mesenchymal differentiation, with or without heterologous elements . SUC is commonly associated with a history of carcinoma treated by radiation or prior therapy with cyclophosphamide , neither of which applied to the present case.
SUCs are often polypoid, with large intraluminal masses that are observed macroscopically. They are characteristically sarcoma-like and dull gray, with infiltrative margins. Microscopically, SUC almost always contains a urothelial, glandular, or small-cell component with variable degrees of differentiation. These characteristics and the mesenchymal component most frequently observed in an undifferentiated, high-grade, spindle cell neoplasm were seen in the present case. The 2 most important differential diagnostic considerations for sarcomatoid UC are pseudosarcomatous stroma (a rare entity with reactive stroma) and carcinosarcoma (CS). Pathologists generally distinguish SUC from CS by phenotypic differences, in accordance with World Health Organization (WHO) guidelines . A more rigorous distinction can also be based on immune histochemical markers and electron microscopic ultrastructure. The mesenchymal element of CS lacks epithelial markers and is considered a true heterologous sarcoma, while the mesenchymal element in sarcomatoid carcinoma retains the expression of epithelial markers such as E-cadherin [9,10]. Any malignant spindle cell tumor in the urinary bladder in an adult should be considered SUC until proven otherwise. As evident in the present case, both epithelial and sarcomatoid elements reacted with cytokeratin and vimentin characterstics of SUC. Moreover, high-grade TCC and CS coexisted, as described in many reports of SUC of the urinary bladder [5,6,11].
Patients with sarcomatoid carcinoma have been reported to have recurrent urothelial carcinoma as a common antecedent, as well other irritative lesions such as recurrent cystitis, diabetes, neurogenic bladder, and bladder diverticulum . However, the patients usually present with a high-stage malignancy [12,13], requiring cystectomy with urinary diversion followed by chemotherapy or radiotherapy (as in the present case). Patients rarely have prolonged survival with conservative management.
Various studies in the literature have demonstrated that survival of SUC depends on the pathological stage, but poor outcomes were generally observed (Table 1). In a Dutch series of 18 patients , 8 (44%) had pT2 disease and the remaining 56% had pT3/4 disease; 61% of the patients died within 12 months and only 2 patients survived in the long term. In a Mayo Clinic study of 26 patients with sarcomatoid carcinoma , only 1 patient (4%) presented with a pT2 tumor and the remaining 25 patients (96%) presented with pT3/4 disease. Of 21 patients with adequate follow-up, 17 patients died of the disease at a mean of 9.8 months. Survival was shorter for those with SUC than for those with CS. Wright et al  conducted a survival analysis based on Surveillance, Epidemiology, and End Results (SEER) data. The analysis showed that the unadjusted survival rates of 46 515 patients with urothelial carcinoma, 135 patients with SUC, and 166 patients with CS were 77%, 54%, and 48% at 1 year, and 47%, 37%, and 17% at 5 years, respectively. Survival for patients with CS was significantly worse than for those with SUC. The Wright et al study was the first to describe relevant survival data on SUC and CS compared with UC. It confirmed commonly held beliefs that patients with these entities have higher rates of mortality. The present case report is additional evidence of the rapid progression of SUC, despite negative preoperative metastatic workup.
The present case is the first known report of SUC with axillary metastasis in the literature. Previous reports show that patients with SUC present at a more advanced stage and are at greater risk for death than patients with UC, even after adjusting for pathologic stage at presentation.