a) Renal Cell Carcinoma


Renal cell carcinoma is increasing in incidence, about 10/100,000 per year. The median age of diagnosis is 65 and it is rare in those under 40 without an underlying genetic condition. It is more common in men 1.5 : 1. It is more common in developed countries.
Of the five variants of renal cell carcinoma:

  • Clear cell carcinoma is most common (~70%)
  • Papillary carcinoma is next most common (~15%)
  • Chromophobe carcinoma is uncommon (< 10%)
  • Renal cell carcinoma with Xp11.2 translocation and multicystic renal cell carcinoma are rare.

Aetiology and Pathogenesis

Smoking, hypertension and obesity are the most common predisposing factors. Exposure to arsenic is another factor, more commonly in developing countries. Analgesic abuse is more of a historical concern.
In clear cell carcinoma, an important step in the pathogenesis appears to be loss of part of chromosome 3 which contains the Von Hippel Lindau gene (VHL). In patients with VHL syndrome there is an earlier onset of disease as well as multifocal and bilateral disease.

Natural History

No known precursor lesions exist.
Tumours typically grow locally prior to metastasis. Small tumours rarely metastasise. Clear cell carcinomas and type II papillary tumours tend to be more locally and distantly aggressive. Metastasis most often occurs to the lung and axial skeleton.

Clinical Presentation

A common mode of presentation is of an incidental renal mass on CT or US for another condition. This has led to an earlier stage of diagnosis overall. Alternatively, patients may present with haematuria (most common), or alternatively flank pain, mass, symptoms of IVC compression (lower leg oedema, DVT). In men, patients may develop scrotal varicocoele due to obstruction of the testicular vein (10%).
Imaging findings are important for renal masses and cysts:

  • On CT, a simple cyst should be uniform and non-enhancing with contrast, with a density matching water. Suspicious lesions enhance, have a heterogenous appearance or have a density other than water.
  • On US, a simple cyst should be anechoic with a strong signal on the distant edge.

Bloods should evaluate for distant metastases and electrolyte abnormalities.

Tumour Features

The appearance and behaviour of renal cell carcinomas is dependent on the histological subtype. It is important to avoid fine needle or core biopsy of a renal mass due to the potential for seeding along the biopsy tract.

Clear Cell Carcinoma

Cells that are contain clear or eosinophilic cytoplasm within a fine vascular network.


The tumours are usually encapsulated and pushing; they are classically yellow in colour due to high lipid content.


Microscopically, the tumour cells are arranged in a variety of patterns (solid, alveolar, acinar). The cells themselves vary in size (see grading) but the classical finding is of a clear cytoplasm due to artefact from the fixation process.


Renal cell carcinomas are staged through the Fuhrman system which has 4 grades.


Usually this is not necessary, but tumours stain positively for the Renal Cell Carcinoma Marker (RCC Ma).


An important finding is abnormalities in the hypoxia response pathways, the most important molecule being HIF1

Papillary Cell Carcinoma

Cells are arranged in a papillary pattern.


Tumours are tan, often with a pseudocapsule. They are typically smaller and less advanced than clear cell carcinomas.


Malignant cells line papillary fronds. The malignant cells are one of two types:

  • Type I have better prognosis, containing small cells with a high N/C ratio that form a simple epithelium.
  • Type II tumours have larger cells with larger nuclei, arranged in a pseudostratified pattern

Chromophobe renal cell carcinoma

Macroscopically the tumours are light brown and may have areas of haemorrhage or necrosis.
Contain two cell types:

  • Chromophobe cells, containing well defined cell borders with light cytoplasms and perinuclear halos
  • Eosinophilic cells, containing intensively staining cytoplasm that resemble oncocytoma

One or both cell types may be present or dominant within a tumour. A small minority show sarcomatoid differentiation which is a poor prognostic feature.
On cytogenetics, there is often hypodiploidy with losses of entire chromosomes.
These tumours rarely metastasise in the absence of a high grade component.

Multilocular Cystic Renal Cell Carcinoma

Large cysts lined by cells that resemble grade I clear cell carcinoma. The cysts are visible macroscopically.

Renal Cell Carcinoma with Xp11.2 translocation

Renal cell carcinoma containing a translocation involving the X chromosome (Xp11.2, containing the TFE transcription factor). Fusion of this transcription factor with other genes may lead to dysregulation of cell cycle control. This translocation is frequently seen in childhood renal cell carcinoma.

Staging / Classification

Renal cell carcinomas are staged using the TNM system; grade is also important.

T Stage

T1: < 7 cm
T2: > 7 cm
T3: Invasion into perinephric fat, renal vein/IVC
T4: Invasion into Gerota's fascia (dense connective tissue lying around the perinephric fat)

Furhman Grade

The Furhman Grade is used to predict prognosis, and is based on the size of the nuclei and nucleoli.
Grade 1: Small dense nuclei
Grade 2: Larger nuclei (15 um)
Grade 3: Visible nucleoli
Grade 4: Large nuclei, Sarcoid or rhabdoid differentiation

  • Rhabdoid cells contain an eccentric nucleus with intracytoplasmic hyaline granules

Leibovich Score

This is a score that combines the T stage, N stage, tumour size, nuclear grade and presence of necrosis. Higher scores are associated with worse metastasis free survival.