Clear cell renal cell carcinoma

The Clear Cell Renal Cell Carcinoma (CCRCC) is a type of renal cell carcinoma.

Genetics

Cytogenetics

• Alterations of chromosome 3p segments occurs in 70 – 90% of CCRCCs
• Inactivation of von Hippel-Lindau disease (VHL) gene by gene mutation and promoter hypermethylation
• Gain of chromosome 5q
• Loss of chromosomes 8p, 9p, and 14q

Molecular genetics

Several frequently mutated genes were discovered in CCRCC: VHL, KDM6A/UTX, SETD2, KDM5C/JARID1C and MLL2. PBRM1 is also commonly mutated in CCRCC.

Histogenesis

CCRCC is derived from the proximal convoluted tubule.

Microscopy

Generally, the cells have a clear cytoplasm, are surrounded by a distinct cell membrane and contain round and uniform nuclei.

Microscopically, CCRCCs are graded by the ISUP/WHO as follows:[1][2]

• Grade 1: Inconspicuous and basophilic nucleoli at ×400 magnification
• Grade 2: Clearly visible and eosinophilic nucleoli at ×400 magnification
• Grade 3: Clearly visible nucleoli at ×100 magnification
• Grade 4: Extreme pleomorphism or rhabdoid and/or sarcomatoid morphology

Epidemiology

• Most commonly affects male patients in their sixties and seventies.
• Majority of CCRCC arise sporadically.
• Only 2 – 4% of the cases presenting as part of an inherited cancer syndrome, such as von Hippel-Lindau syndrome.

Images

• 
  Clear cell renal cell carcinoma. Macroscopy.
• 
  Clear cell renal cell carcinoma. HE, x100.
• 
  Clear cell renal cell carcinoma. Führman Grade = 1. HE, x400.
• 
  Grade 3: Arrows point at a clearly visible nucleolus

References

1. YiFen Zhang. "What is the ISUP/WHO grading system for renal cell carcinoma (RCC)?". Medscape. Updated: Jul 02, 2019
2. Moch, H. (2016). "WHO-ISUP-Graduierungssystem für Nierenkarzinome". Der Pathologe. 37 (4): 355–360. doi:10.1007/s00292-016-0171-y. ISSN 0172-8113.