Cases
60-year-old man with sudden weight loss   

Discussion

Chromophobe RCC

Pathophysiology

Chromophobe RCC arises from intercalated cells of the renal cortex.

Epidemiology

It is the third most common subtype of renal cell carcinoma. It comprises 5%-11% of renal epithelial tumors. Mean age is 59 years and men are affected more than women.

Clinical presentation

Most patients are asymptomatic, and a unilateral tumor is found incidentally on imaging.  Chromophobe RCC is associated with Birt-Hogg-Dube syndrome. Grossly, the tumor is circumscribed, light brown, and may have a central scar.

Microscopic features

Classic tumors are composed of large cells with an abundant pale cytoplasm with prominent cell borders. Binucleation is common. The pattern of growth is predominantly solid, separated by thin, incomplete fibrovascular septa. In the classic type, the predominant cell type has a pale, clear-appearing cytoplasm. The eosinophilic variant is composed of cells with an abundant granular, eosinophilic cytoplasm. Hale’s colloidal iron shows diffuse staining in the cytoplasm. The most characteristic feature is hyperchromatic nuclei showing irregular wrinkled outlines with perinuclear halos. Most tumors are positive for CK 7, CD117, and E-Cadherin. Ultrastructurally, the cells contain abundant microvesicles and degenerating mitochondria.

Prognostic and molecular features

Prognosis is determined by tumor size, small-vessel invasion, presence of necrosis, and sarcomatoid change. Sarcomatoid features (2%-8% of cases) and perinephric extension are associated with aggressive behavior. Grading is not recommended due to a lack of association with outcome. There can be loss of multiple chromosomes including 1, 6, 10, 13, 17, and 21. TP53 mutations are seen in 20%-32% of cases and PTEN mutations are seen in 6%-9%.

References

  1. Amin MB, Paner GP, Alvarado-Cabrero I, et al. Chromophobe renal cell carcinoma: Histomorphologic characteristics and evaluation of conventional pathologic prognostic parameters in 145 cases. Am J Surg Pathol. 2008;32(12):1822-1834. doi:10.1097/PAS.0b013e3181831e68.
  2. Przybycin CG, Cronin AM, Darvishian F, et al. Chromophobe renal cell carcinoma: A clinicopathologic study of 203 tumors in 200 patients with primary resection at a single institution. Am J Surg Pathol. 2011;35(7):962-970. doi:10.1097/PAS.0b013e31821a455d.
  3. Davis CF, Ricketts CJ, Wang M, et al. The somatic genomic landscape of chromophobe renal cell carcinoma. Cancer Cell. 2014;26(3):319-330. doi:10.1016/j.ccr.2014.07.014.
  4. Steffens S, Janssen M, Roos FC, et al. The Fuhrman grading system has no prognostic value in patients with nonsarcomatoid chromophobe renal cell carcinoma. Hum Pathol. 2014;45(12):2411-2416. doi:10.1016/j.humpath.2014.08.002.
  5. Cheville JC, Lohse CM, Sukov WR, Thompson RH, Leibovich BC. Chromophobe renal cell carcinoma: The impact of tumor grade on outcome. Am J Surg Pathol. 2012;36(6):851-856. doi:10.1097/PAS.0b013e3182496895.