PATHOLOGY

Sarcomatoid renal cell carcinoma: an examination of underlying histologic subtype and an analysis of associations with patient outcome
Cheville JC, Lohse CM, Zincke H, Weaver AL, Leibovich BC, Frank I, Blute ML
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
Am J Surg Pathol. 2004; 28: 435-41

• A sarcomatoid component can occur in all histologic subtypes of renal cell carcinoma (RCC) and indicates an aggressive tumor. We studied 2381 patients treated with radical nephrectomy for RCC between 1970 and 2000. A urologic pathologist reviewed the microscopic slides from all tumor specimens for the presence of a sarcomatoid component, defined as a RCC with any malignant spindle cell component. All tumors with a sarcomatoid component were classified as nuclear grade 4. A total of 120 (5.0%) patients had RCC with a sarcomatoid component, including 94 who died of RCC at a mean of 1.4 years following nephrectomy (median 8 months; range 44 days to 10 years). Cancer-specific survival rates at 2 and 5 years following nephrectomy were 33.3% and 14.5%, respectively. The presence of distant metastases at the radical nephrectomy and histologic tumor necrosis were significantly associated with death from RCC among patients with sarcomatoid RCC. Patients with clear cell (conventional) RCC and chromophobe RCC were more likely to have tumors with a sarcomatoid component (5.2% and 8.7%, respectively) compared with patients with papillary RCC (1.9%). The presence of a sarcomatoid component was significantly associated with death from RCC for all three subtypes (P < 0.001). Even among patients with grade 4 clear cell RCC, the presence of a sarcomatoid component was significantly associated with outcome, both univariately (risk ratio 1.59; P = 0.010) and after adjusting for TNM stage, tumor size, and histologic tumor necrosis (risk ratio 1.46; P = 0.037).
  
  
• Editorial Comment
  The Heidelberg classification of renal cell tumors is based on genetic alterations and classifies malignant parenchymal neoplasms as: 1) - common or conventional renal cell carcinoma which includes tumors with clear and/or eosinophilic cytoplasm; 2) - papillary renal cell carcinoma; 3) - chromophobe renal cell carcinoma; 4) - collecting duct carcinoma which includes the variant medullary carcinoma associated to sickle cell trait; and, 5) - renal cell carcinoma, unclassified (1). From group 5 was separated a new entity named “low-grade mucinous tubular and spindle cell carcinoma” possibly originated from the loop of Henle (2).
  It is recognized that sarcomatoid change has been found to arise in all of these types of renal cell carcinoma in this classification. Sarcomatoid features thus do not constitute a type per se, but rather are an indication of progression in renal cell carcinoma.
  In the study by Cheville JC et al., patients with chromophobe renal cell carcinoma had a higher frequency of sarcomatoid transformation (8.7%) comparatively to conventional (clear cell) carcinoma (5.2%) and papilllary carcinoma (1.9%). This high frequency was also found by Akhtar M et al. (3) in Saudi Arabia where chromophobe renal cell carcinoma has the highest prevalence.
  Sarcomatoid change should always be reported by the pathologist. The presence of a sarcomatoid change has an important impact on prognosis. In the study by Cheville et al. the presence of a sarcomatoid component was significantly associated with death both univariately and after adjusting for TNM stage, tumor size, and histologic tumor necrosis.

REFERENCES
1. Kovacs G, Akhtar M, Beckwith BJ, Bugert P, Cooper CS, Delahunt B, et al.: The Heidelberg classification of renal cell tumours. J Pathol. 1997; 183: 131-3.
2. Srigley JR et al.: Mod Pathol. 1999; 12: 107A.
3. Akhtar M, Tulbah A, Kardar AH, Ali MA: Sarcomatoid renal cell carcinoma: the chromophobe connection. Am J Surg Pathol. 1997; 21: 1188-95.

Dr. Athanase Billis
Full-Professor of Pathology
State University of Campinas, Unicamp
Campinas, São Paulo, Brazil