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A 58-year-old man presented for routine physical examination. His urine analysis showed numerous red blood cells. A subsequent ultrasound revealed a left renal mass.
Archive Case and Diagnosis:
This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2010, case 10, and is a renal cell carcinoma with sarcomatoid component.
Criteria for Diagnosis and Comments:
In the past, sarcomatoid renal cell carcinoma was considered a unique subtype of renal cell carcinoma (RCC). The findings were first described in 1968 by Farrow. The tumor exhibited marked cytologic atypia reminiscent of sarcoma with large pleomorphic or malignant spindle cells. Since this initial description sarcomatoid change has been reported in the common types (clear cell, chromophobe, papillary and collecting duct) of RCC. Recent molecular studies suggest that sarcomatoid change is progression or dedifferentiation of a specific type of RCC. No evidence supports the notion that RCC develops ‘de novo’ as sarcomatoid carcinoma, hence the entity was dropped from the 1997 UICC, AJCC, and Heidelberg classifications as well as 2004 WHO classification.
Approximately 5-10% of common types of RCCs contain areas of sarcomatoid morphology. Some reports indicate that sarcomatoid change is more common in chromophobe RCC (9%) as compared to clear cell RCC (8%) or papillary RCC (3%). While the incidence of sarcomatoid features may be higher among chromophobe RCC, the majority of RCC containing sarcomatoid features will have underlying clear cell RCC given the predominance of this RCC subtype. The current case had a focal area of residual clear cell RCC. Those tumors without any remaining subtype of RCC are best classified as RCC, unclassified.
Sarcomatoid change within a RCC is important to note as these tumors have been associated with an adverse prognosis. RCC with sarcomatoid change shows higher proliferative activity than other RCCs and usually exhibits highly malignant behavior with a predilection for increased local invasiveness and distant metastasis. Although the results are variable, some large series have reported that the greater the volume of sarcomatoid changes compared to recognizable RCC, the poorer the prognosis. Tumor stage is also a valuable predictor of prognosis in advanced tumors (T3-4).
The morphologic features of RCC with sarcomatoid change are diverse. On gross examination, the sarcomatoid component is a soft to fibrous, bulging, lobulated, gray-white, fleshy area with infiltrative borders. Histologically this tumor has a spindle cell component growing in fascicles with marked nuclear pleomorphism and frequent mitoses. This spindle cell component may range from 1-99% of the tumor and may be intermediate or high grade. It has been suggested that the sarcomatoid spindle cell component should occupy at least one low power field (4x), however others have advocated reporting any sarcomatoid areas with an estimate of the percentage of total tumor.
The differential diagnosis of spindle cell elements in a renal neoplasm include both benign and malignant neoplasms. If the smooth muscle component of an angiomyolipoma predominates or is hypercellular with atypia, it can present a diagnostic challenge. However thorough sampling (1 block/ cm) in search for the other elements (adipose tissue and malformed vascular channels) usually resolves the dilemma. If there is still a question, immunohistochemical stains can aid in the separation. Angiomyolipomas are HMB45 and MART 1 positive, AE1/AE3 negative, EMA negative, and RCC with sarcomatoid component are CD10, AE1/AE3 positive (94%) and EMA positive (50%). High grade urothelial carcinoma may occur in the renal pelvis and have a prominent spindle component. Distinguishing between RCC with sarcomatoid component and a high grade urothelial carcinoma with spindled elements could be aided by careful histologic examination of the perimeter of the mass and the immunoprofile of the tumor cells. High grade urothelial carcinoma may stain with Uroplakin III which is specific although not particularly sensitive. The majority of the more common markers (AE1/AE3) are often shared by these two carcinomas. The RCC marker is usually absent within the sarcomatoid component of RCC and therefore not helpful in distinguishing it from urothelial carcinoma. The finding of adjacent carcinoma in situ of the renal pelvis would favor a high grade urothelial carcinoma.
Primary renal sarcoma, although rare, may also enter the differential diagnosis.
Leiomyosarcoma represents approximately 47% of primary renal sarcomas and is composed of spindled cells. A thoroughly sampled RCC with sarcomatoid component should contain areas of a recognizable epithelial component. If there is further question of the appropriate diagnosis, then judicious use of immunohistochemical stains (leiomyosarcoma is positive for smooth muscle actin and desmin) should aid in arriving at the correct diagnosis. Sarcomatoid urothelial carcinoma arising in the renal pelvis could also be considered in the differential diagnosis particularly if the tumor is in the hilum of the kidney or the size prohibits assessment of the tumor epicenter. Often urothelial hyperplasia or urothelial carcinoma in situ can be identified within the renal pelvis or ureter adjacent to the sarcomatoid urothelial carcinoma. Sarcomatoid urothelial carcinoma is variably keratin positive.