Sarcomatoid renal cell carcinoma: biology, natural history and management

Sarcomatoid dedifferentiation is an uncommon feature that can occur in most histological subtypes of renal cell carcinomas (RCCs) and carries a decidedly poor prognosis. Historically, conventional treatments for sarcomatoid RCCs (sRCCs) have shown little efficacy, and median survival is commonly 6–13 months. Despite being first described in 1968, the mechanisms driving sarcomatoid dedifferentiation remain poorly understood, and information and treatment options available to physicians and patients are limited. When diagnosed at an early stage, surgical intervention remains the treatment of choice. However, preoperative identification through routine imaging or biopsy is unreliable and most patients present with advanced disease and systemic symptoms. For these patients, the role of cytoreductive nephrectomy is disputed. The expansion of immunotherapies approved for RCCs has generated a search for biomarkers that might be indicative of treatment response in sRCCs, although a proven effective systemic agent remains elusive. PDL1 expression is increased in sarcomatoid dedifferentiated renal tumours, which suggests that patients with sRCCs could benefit from PD1 and/or PDL1 immune checkpoint blockade therapy. Treatment outcomes for sarcomatoid tumours have remained relatively consistent compared with other RCCs, but further investigation of the tumour–immune cell microenvironment might yield insights into further therapeutic possibilities. In this Review, Blum et al. summarize the current knowledge on sarcomatoid renal cell carcinoma, a diagnosis characterized by the presence of sarcomatoid dedifferentiation and a poor prognosis. They discuss the origin, presentation, molecular biology and treatment of this disease. Key Points Sarcomatoid dedifferentiation is not considered to be a unique histological subtype of renal cell carcinomas (RCCs); rather, it can be present within any subtype of RCCs. Sarcomatoid dedifferentiation appears in ~4% of all RCCs, but is present in ~20% of all metastatic RCCs. According to WHO guidelines, any RCC with sarcomatoid dedifferentiation is a WHO–International Society of Urological Pathology grade 4 lesion. Sarcomatoid dedifferentiation is often heterogeneously present within RCCs, making routine imaging and biopsy unreliable for preoperative detection. Surgical resection for localized disease is the standard of care, with subsequent close monitoring of patients following surgery. In patients with metastatic disease, conventional