2021-02 / January 11
Contributors: Aiswarya Irri, G. Kenneth Haines III, Li Li

A man in his 50s presented with significant debilitating left flank pain and was found to have an asymmetrically-enlarged left kidney (16.5 cm) with a soft tissue mass involving the pararenal fascia and hilum concerning for malignancy.


1. What is the correct diagnosis?

A. Papillary renal cell carcinoma with sarcomatoid features

B. High-grade urothelial cell carcinoma

C. Chromophobe renal cell carcinoma with sarcomatoid features

D. Clear cell papillary renal cell carcinoma

E. Clear cell renal cell carcinoma with sarcomatoid features


2. Which immunohistochemical phenotype is most consistent with this diagnosis?

A. Positive for CA IX and CK7; negative for AMACR or CD10

B. Positive for vimentin, CA IX, and PAX8; negative for CK7, desmin, or uroplakin

C. Positive for CK7, GATA3, and uroplakin; negative for PAX8, CD10, or CD117

D. Positive for CK7 and CD117; negative for CA IX or vimentin

E. Positive for CK7 and AMACR; negative for CD117, PAX8, or CA IX

1. e
2. b

1. Clear cell carcinoma with sarcomatoid features, WHO/ISUP Grade 4

Most cases of clear cell renal cell carcinoma (ccRCC) are asymptomatic and are detected incidentally from radiology. This neoplasm is one of the most aggressive types of renal cell carcinoma with a 5-year survival rate of 75%. Clear cell RCC accounts for 80-90% of all RCCs. It is associated with mutations of the VHL gene (3p23-26) or chromosome 3p loss, found in 98% of these tumors, whether familial, sporadic, or associated with cases of von Hippel-Lindau (VHL) syndrome. This tumor is typically managed with surgical nephrectomy.

Grossly, the tumor is usually unencapsulated but well circumscribed, with the cut surface showing a characteristic golden-yellow appearance (due to abundant intracytoplasmic lipids), often with cystic changes, fibrosis, necrosis, and areas of hemorrhage. Our case showed a pale-tan fleshy mass, occupying 90% of the renal parenchyma with an adjacent hemorrhagic, cystic, golden-yellow lesion (only 10% of total lesion) (image 1). Clear cell RCC frequently is confined to the renal parenchyma, but note that tumors larger than 7 centimeters often extend into the renal vein and the sinus fat, as is seen in this case (image 4).

Microscopically, ccRCC is composed of cells arranged into nests, micro- or macrocysts, or solid sheets surrounded by delicate, interconnecting fibrovascular septations. This vascular framework (CD31 positive) is lost in high-grade and sarcomatoid areas. Lower-grade cells are identified as clear cells with abundant intracytoplasmic glycogen and fat, while higher-grade cells may display an eosinophilic, granular cytoplasm. The World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading system is applied, with Grades 1-3 based primarily on nucleolar prominence, while Grade 4 applies to the presence of rhabdoid and/or sarcomatoid features, or significantly pleomorphic nuclei with lobulations or multinucleation.

Differential diagnoses that must be considered for this malignancy include papillary renal cell carcinoma with sarcomatoid features, clear cell papillary renal cell carcinoma, renal medullary carcinoma, collecting duct carcinoma, angiomyolipoma, chromophobe renal cell carcinoma with sarcomatoid features, and clear cell sarcoma of the kidney. By immunohistochemical staining (IHC), the sarcomatoid component of our case stained for PAX8, CA IX, CD10, vimentin, and INI-1 (retained), but were negative for CK7, CK20, GATA3, uroplakin, AMACR, HMWCK, TLE1, and HMB-45. This staining profile supports that of a ccRCC malignancy and proves that the sarcomatoid component of the tumor differentiated from the original ccRCC; this is consistent with our gross examination (image 1). The negative CK7 and AMACR stains helped to rule out papillary RCC, chromophobe RCC, and clear cell papillary RCC. The retained INI-1 stain rules out renal medullary carcinoma. Synovial sarcoma and angiomyolipoma were removed from the differential when TLE1 and HMB-45 were negative, respectively. Taking into account the patient’s clinical history, radiological findings, gross and microscopic morphologies, and immunohistochemical profile, one can deduce the diagnosis of clear cell renal cell carcinoma with sarcomatoid differentiation.

1. Alpers, C. E., & Chang, A. (2015). The Kidney. In V. Kumar, A. K. Abbas, & J. C. Aster (Authors), Robbins and Cotran Pathologic Basis of Disease (9th ed., pp. 897-957). Philadelphia, PA: Elsevier Saunders.
2. Amin, M. B., & Tickoo, S. K. (2016). Clear Cell Renal Cell Carcinoma. In Genitourinary (pp. 54-57). Philadelphia, PA: Elsevier.
3. Pichler, R., Compérat, E., Klatte, T., Pichler, M., Loidl, W., Lusuardi, L., & Schmidinger, M. (2019). Renal Cell Carcinoma with Sarcomatoid Features: Finally New Therapeutic Hope?. Cancers, 11(3), 422.
4. Tickoo, S. K., & Reuter, V. E. (2016). Clear Cell Renal Cell Carcinoma. Retrieved October 20, 2020, from

Aiswarya Irri (PGY1) and G. Kenneth Haines III
Icahn School of Medicine/Mount Sinai Hospital

Li Li
Thomas Jefferson University Hospital
Philadelphia, PA 19107


Kidney, clear cell carcinoma, sarcomatoid