Definition

• a malignant epithelial tumour arising in the kidney.

 Epidemiology

• accounts for ~2% of all cancers worldwide.

 • More common in developed countries, with an average incidence of ~10 per 100 000 in men and 3 per 100 000 in women.

Aetiology

• Recognized risk factors include smoking, hypertension, obesity, environmental chemicals, and long- term dialysis.

• Some genetic syndromes are associated with renal cell carcinoma (RCC) (e.g. von Hippel– Lindau and tuberous sclerosis).

 Presentation

 • about half of all cases present with painless haematuria.

• Most of the remainder is picked up incidentally on imaging.

 • a small proportion presents with metastatic disease.

Subtypes

• 70% clear cell RCC.

• 15% papillary RCC.

• 5% chromophobe RCC.

• a number of rare subtypes make up the remainder of cases.

Clear cell renal cell carcinoma

 • Macroscopically, heterogenous tumours with golden yellow and haemorrhagic areas (Fig. 1).

• histologically composed of epithelial cells with clear or eosinophilic cytoplasm, set within a delicate vascular network.

• immunohistochemically positive for ae1/ ae3, eMa, CD10, vimentin, Pax8, RCC, and CaiX.

• immunohistochemically negative for CK7 and CD117.

• Genetically demonstrates losses at chromosome 3p.

Papillary renal cell carcinoma

• Macroscopically, well- circumscribed, friable tumours with a surrounding f ibrous pseudocapsule.

• histologically composed of epithelial cells arranged in a papillary or tubulopapillary growth pattern and a size >15 mm.

 • immunohistochemically positive for ae1/ ae3, CK7, Pax8, and racemase.

 • Genetically shows trisomy of chromosomes 7 and 17 and loss of chromosome y in men.

Chromophobe renal cell carcinoma

• Macroscopically, well- circumscribed, solid light brown tumours.

 • histologically composed of sheets of large, round epithelial cells with distinct cell borders and finely reticulated cytoplasm. The vasculature within the tumour is thick- walled.

• immunohistochemically positive for CK7, Pax8, e- cadherin, and CD117.

• immunohistochemically negative for CaiX.

• Genetically shows extensive chromosomal losses.

 Prognosis

• Overall 5- year survival rate is ~60%.

• Stage and grade are the most important prognostic factors.

• The recommended grading system for clear cell RCC and papillary RCC is the ISUP (international Society of Urologic Pathologists) nucleolar grade. Grade 1 has the best prognosis, and grade 4 the worst. Chromophobe RCC is not graded.

• The Leibovich risk model may also be used for clear cell RCC to predict the likelihood of progression. Tumour stage, size, grade, and necrosis are each scored to give a maximum possible total of 11: 0– 2 = low risk, 3– 5 = intermediate risk, 6 or more = high risk.

Fig1 This patient presented with macroscopic haematuria and was found to have a solid renal mass on CT imaging. anephrectomy was performed and sent to pathology. The kidney has been sliced open by the pathologist to reveal a large tumour in the upper pole of the kidney. Subsequent microscopic examination of samples of the tumour revealed this to be a clear cell renal cell carcinoma (see Plate 32). Reproduced with permission from Clinical Pathology (Oxford Core Texts), Carton, James, Daly, Richard, and Ramani, Pramila, Oxford University Press (2006), p.233, Figure 11.6.

ISUP nucleolar grading system for clear cell and papillary RCC

Grade 1: nucleoli are inconspicuous or absent at high- power magnification.

Grade 2: nucleoli are clearly visible at high- power magnification but are not prominent.

Grade 3: nucleoli are prominent and are easily visualized at low- power magnification.

Grade 4: presence of tumour giant cells and/ or marked pleomorphism.