Sarcomatoid carcinoma of the renal pelvis: Experience of multiple cases over a ten-year period

Sarcomatoid carcinoma of the renal pelvis is a rare clinical entity. To the best of our knowledge, only 14 cases of this type of neoplasm have been reported in the literature to date. In the present study, the records at The First Affiliated Hospital, Medicine School of Zhejiang University (Hangzhou, Zhejiang, China) between 2000 and 2010 were reviewed to identify patients with primary renal pelvis sarcomatoid carcinoma (RPSC). A particular emphasis was placed on the treatment, recurrence and survival outcome. Eight patients with RPSC were identified and treated with nephrectomy or nephroureterectomy. All of the patients presented with Grade 3 RPSC. According to the TNM classification system, 2 patients were in stage pT2, 5 in stage pT3 and 1 in stage pT4. Adjuvant chemotherapy was administered to four patients, and the mean follow-up period was 27.5±41.0 months. In total, 6 patients succumbed to the disease with a mean survival time of 7.7±5.3 months (range, 1–18 months), while 2 patients were free of disease at 54 and 120 months, respectively, following treatment. The mean disease-specific survival time was 27.5±41.0 months and the 1-year recurrence-free survival, 1-year survival and overall survival rates were 37.5, 37.5 and 25%, respectively. The present analysis suggests a poor prognosis for the majority of RPSC patients, most likely resulting from the advanced stage of the disease at diagnosis and a poor response to systemic therapy. To improve the survival rate of RPSC, it is therefore essential to perform an early diagnosis and early radical surgery. Intravesical instillation is not essential following surgery.


Introduction
Transitional cell carcinoma is the most common histological type of urinary tract cancer. Squamous cell carcinoma and adenocarcinoma form the second and third most common histological types, respectively. Renal pelvis sarcomatoid carcinoma (RPSC) is an extremely rare variant of urinary tract cancer, which possesses a high-grade malignant neoplasm and a poor prognosis. To the best of our knowledge, only 14 cases of RPSC have been reported in the literature to date, usually as case reports or small series (1)(2)(3)(4)(5)(6)(7)(8)(9). In the present study, we report our experience with 8 cases of RPSC. A particular emphasis was placed on the treatment, recurrence and survival outcome of RPSC.

Patients and methods
Patients and methods. Between January 2000 and December 2010, 8 males with RPSC (age range, 38-78 years; mean age, 65.3±14.0 years) were registered in the surgical pathology files at The First Affiliated Hospital, Medicine School of Zhejiang University (Hangzhou, Zhejiang, China), including 1 previously reported case (10). Formalin-fixed paraffin-embedded tissue sections stained with hematoxylin and eosin were available for examination for each case. The sarcomatoid carcinoma in each instance consisted of a spindle cell malignancy with or without coexistent overt urothelial carcinoma. Light microscopical or immunohistochemical evidence of epithelial differentiation in the spindle cells was also observed. The patient records were reviewed to assess the tumor type, treatment modalities, recurrence and survival parameters. Tumor recurrence was detected by routine follow-up imaging performed at 3-6-month intervals. The pathological features were retrospectively evaluated and confirmed by a urological pathologist. The institutional review board of the The First Affiliated Hospital, Medicine School of Zhejiang University approved the retrospective study. Written informed consent was obtained from the patient or patient's family.

Results
Diagnosis. Of the 342 evaluated patients that were treated for tumors of the renal pelvis, 8 (2.3%) were diagnosed with primary RPSC. The tumor characteristics and patient outcomes are shown in Table I. Among the 8 patients diagnosed with sarcomatoid carcinoma, the male-to-female ratio was 8:0. The symptoms observed in the 8 patients included hematuria in 7 cases and abdominal pain in 1 case. A tumor of the renal pelvis was identified in all patients by contrast-enhanced computed tomography. Malignancy was diagnosed cytologically with renal pelvis lavage in 2 cases (including 1 case with sarcomatoid carcinoma) prior to surgery. Immunohistochemical studies confirmed the diagnosis of sarcomatoid carcinoma. Prior to surgery, 3 patients were in stage pT2 and 5 were in stage pT3, according to the TNM classification system.
Of the 8 patients diagnosed with RPSC, 3 patients were treated with nephrectomy (2 patients with nephrectomy plus chemotherapy) and 5 patients with nephroureterectomy (2 patients with nephroureterectomy plus chemotherapy). The gross appearance of the sarcomatoid carcinoma was described in 8 cases. The mean tumor size was 5.8±4.5 cm (range, 1.5-16.0 cm) at the greatest dimension. In total, 5 lesions were polypoid and 3 were nodular. A pure spindle cell carcinoma without any apparent epithelial components was noted in 1 case, spindle and transitional cell carcinoma in 4 cases and spindle and squamous cell carcinoma in 3 cases. According to the TNM classification system, 2 patients were now diagnosed with stage pT2, 5 with stage pT3 and 1 with stage pT4.
Survival. The mean follow-up time was 27.5±41.0 months. A total of 6 patients succumbed to the disease with a mean survival time of 7.7±5.3 months (range, 1-18 months; Table I), while 2 patients (cases 4 and 7) were free of disease at 54 and 120 months, respectively. The mean disease-specific survival time was 27.5±41.0 months. The 1-year recurrencefree survival, 1-year survival and overall survival rates were 37.5, 37.5 and 25%, respectively. A comparison between the patients who underwent surgery alone and those who underwent surgery plus chemotherapy demonstrated no evident difference in survival (Table II).
The characteristics of the 22 reported patients (including the patients examined in the present study) with RPSC are shown in Table I and Table III. RPSC was more common in males than females (4:1 ratio in previously reported studies, 8:0 ratio in the present study) and more common in the right side compared with the left side (5:2 ratio in previously reported studies, 5:3 ratio in the present study). The most common symptom of RPSC was gross hematuria.
The prognosis for patients diagnosed with RPSC is poor. Several factors contribute to this poor prognosis, including diagnosis at an advanced stage of the disease, high-grade features, a large tumor and a short progression time despite additional therapy. The previously reported 13 cases of RPSC were of metastatic disease or advanced tumor involvement Table I. Patient characteristics of the cases of RPSC reported in the present study. of the renal parenchyma, which had an extremely poor prognosis (1)(2)(3)(4)(5)(6)(7)(8)   biology compared with urothelial carcinoma. Therefore, intravesical instillation is not essential following surgery. As RPSC is known for its aggressive nature, insensitivity to adjuvant therapy and adverse outcomes, it is essential to conduct an early diagnosis and early radical surgery to improve the survival outcome (7,8). In the present study, the 2 cases of urothelial-confined and organ-confined RPSC (cases 4 and 7) did not recur for >4 years following radical surgery. Efforts aimed at improving the accuracy of diagnosis at presentation and the consequent treatment strategies are required. The main obstacle for the accurate diagnosis and treatment of RPSC is that the presentation of non-urothelial tumors is usually similar to that of urothelial tumors. Any findings that suggest the possibility of RPSC should subsequently invoke a more thorough investigation implementing a repeat biopsy with specific immunohistochemical stains. These findings may include the following: abnormal cytology results that are incongruent with tumors of the renal pelvis (as in the present study, immunocytochemistry with markers of sarcomatoid carcinoma aids discrimination); atypical radiological characteristics or any evidence of metastatic disease despite the radiological appearance of small-volume disease. Following a clinical presentation that suggests RPSC, neoadjuvant strategies may aid in the identification of those patients who are the best candidates for surgery and also aid in avoiding unnecessary surgery in patients where it is likely that their disease will progress rapidly. Patients with TNM stage pT2 should be treated with nephroureterectomy, patients with TNM stage pT3 should be treated with nephrectomy and patients with TNM stage T4 should avoid surgery. However, this hypothesis remains to be verified.
In conclusion, RPSC is rare. The present study analysis suggests a poor prognosis for the majority of patients with RPSC, most likely as a result of the advanced stage of the disease at diagnosis and the poor response to systemic therapy. It is essential to conduct an early diagnosis and early radical surgery to improve the survival outcome. Intravesical instillation is not essential following surgery.