Pathology of Renal Cancer

Malignant renal cell tumours

Clear cell renal cell carcinoma

Multilocular clear cell renal cell carcinoma

Papillary renal cell carcinoma

Chromophobe renal cell carcinoma

Carcinoma of the collecting ducts of Bellini

Renal medullary carcinoma

Xp11 translocation carcinomas

Carcinoma associated with neuroblastoma

Mucinous tubular and spindle cell carcinoma

Renal cell carcinoma unclassified

Adapted from Algabaa et al. [4]. With permission from Elsevier

The pathology of familial renal cancers is summarised in Table 19.2.

Table 19.2

Pathology of hereditary RCC

Syndrome	Chromosomes involved	Gene	Protein	Histological type	Involvement of other organs
Von Hippel-Lindau	3p25	VHL	pVHL	Bilateral, cystic renal lesions and clear cell	Cysts in other organs, phaeochromocytoma neuroendocrine tumours
Von Hippel-Lindau	3p25	VHL	pVHL	Carcinoma
Hereditary papillary Ca	7p 31	c-MET	HGF-R	Bilateral & multiple	None
Hereditary papillary Ca	7p 31	c-MET	HGF-R	Papillary RCC	None
HLRC (Hereditary leiomyomatosis RCC	1q 42	FH	FH	Papillary RCC (non type 1)	Uterine leiomomyoma/leiomyosarcoma
Familial papillary thyroid carcinoma	1q 21	Not known	Not known	Papillary RCC & oncocytoma
Hyperparathyroidism jaw tumour (HP-JT)	1q 25	HRPT2	–	Epithelial stromal mixed tumours, papillary RCC
Birt-Hogg-Dube	17p 11	BHD	Folliculin	Multiple chromophobe RCC, oncocytic adenoma, papillary RCC	Pulmonal cysts; spontaneous
Birt-Hogg-Dube	17p 11	BHD	Folliculin	Multiple chromophobe RCC, oncocytic adenoma, papillary RCC	Pneumothorax, facial fibrofolliculoma
Constitutional translocation chromosome 3	3p13-14			Multiple, bilateral clear cell RCC	–

Adapted from Algabaa et al. [4]. With permission from Elsevier

Table 19.3 outlines rare tumours in the kidney in WHO classification [5].

Table 19.3

Benign and other rare malignant tumours

1. Benign: papillary adenoma, oncocytoma

2. Metanephric tumours (metanephric adenoma, metanephric adenofibroma, metanephric stromal tumours)

3. Nephroblastic tumours (cystic nephroma, mixed epithelial and stromal tumours, synovial sarcoma)

4. Nephroblastic tumours (nephrogenic rests, nephroblastoma, cystic partially differentiated nephroblastoma)

5. Neuroendocrine tumours (carcinoid, neuroendocrine carcinoma, primitive neuroectodermal tumour, Neuroblastoma, pheochromocytoma)

6. Miscellaneous (mesenchymaltumours, haemopoetic & lympoidtumours, germ cell tumours, metastatictumours)

Adapted from et al. [5]. With permission from Elsevier

Table 19.4 summarizes the grouping of the tumours according to the prognosis: good prognosis, intermediate and poor prognosis.

Table 19.4

Clinical classification according to prognosis

Good prognosis	Papillary adenoma (benign); oncocytoma (benign)
	Metanephric adenoma; angiomyolipoma
	Multilocular clear cell renal cell carcinoma (malignant)
	Mucinous tubular and spindle cell carcinoma (malignant)
Intermediate prognosis	Papillary carcinoma (malignant), chromophobe renal cell carcinoma
Poor prognosis	Clear cell carcinoma, metastatic cancers, collecting duct carcinoma
	Renal medullary carcinoma, Xp11 translocation carcinomas
	Sarcomas

Clear Cell RCC (ccRCC)

The cells of ccRCC have a clear cytoplasm due to the high content of glycogen and lipid but may have an eosinophilic or granular appearance when the mitochondrial content is high (Fig. 19.1). The ccRCC accounts for more than 60 % of all malignant renal tumours with 4 % being multifocal and 3 % bilateral [4]. Compared to other RCCs, they tend to be more aggressive in men, progress to metastatic disease twice as frequently after nephrectomy and have lower overall survival [6].

Fig. 19.1

Clear cell carcinoma (×100)

Macroscopically, the cut surface has yellowish appearance often with areas of haemorrhage, scarring and calcification, ossification and extension to renal vein. They maybe solid, tubular or cystic, the latter of which has given rise to a subtype known as multilocular cystic RCC when the there is a complete cystic appearance. Sarcomatoid changes are seen in 5 % of tumours, which represents high-grade transformation and carries a poor prognosis.

Papillary RCC (PRCC)

These are the second most common type, with a male predominance and accounting for up to 15 % of all RCCs [7] (Fig. 19.2).

Fig. 19.2

Papillary RCC (×100)

Tumours less than 5 ml are considered to be adenomas and those greater than 5 ml to be carcinomas [7]. The underlying genetic abnormalities are trisomy of chromosomes 3q, 7, 8, 12, 16, 17 and 20 with loss of the Y chromosome [8]. Macroscopically, they are round and white or beige in colour and may contain central necrosis or haemorrhagic areas. The cells are usually small containing scanty cytoplasm and foamy macrophages. The growth pattern is predominantly papillary but may also be tubular or solid. Two morphological types are typically described, although recently a third group has emerged composed entirely of oncocytes and shows different clinic-pathological features [9].

Type I

The papillae and tubular structures are lined by cuboidal cells with small oval nuclei, inconspicuous nucleoli and pale cytoplasm. The papillary cores often contain foamy macrophages and psammoma bodies are common. These patients have a longer survival.

Type II

The papillae contain large cells with higher nuclear grade, copious eosinophilic cytoplasm and large nuclei with prominent nucleoli. Foamy macrophages within the papillary cores and psammoma bodies are uncommon. In general, the type 2 tumours are larger and present in younger patients with advanced stage.

Type III

Oncocytic PRCC – Rarely, PRCC can display extensive areas of solid and non-papillary architecture and extensive areas with oncocytic cytoplasm. The oncocytic features in PRCC may pose a diagnostic problem in differentiating oncocytic PRCC from oncocytoma. Papillae and trabeculae are present with fibro-vascular cores covered with cells containing an eosinophilic cytoplasm packed with mitochondria and aggregates of foamy macrophages, round nuclei and a low nuclear-cytoplasmic ratio. There are no cytogenetic or molecular tests for this variant of PRCC [10].

Chromophobe RCC (CRCC)

They account for 5 % of RCC and are characterised by a combination loss of chromosomes 1, 2, 6, 10, 13, 17 and 21 [4]. Macroscopically, the tumour appears lobulated; the cut surface containing one or more solid tumour nodules but well circumscribed. The cells are large and pale and polygonal usually with a clear but sometimes eosinophilic cytoplasm containing condensed, hyperchromatic and sometimes bifid nuclei. The growth pattern is typically solid although rarely maybe cribiform (Fig. 19.3).

Fig. 19.3

Chromophobe RCC

Rare Types of Renal Cell Carcinomas

Multilocular Clear Cell RCC (MCRCC)

This accounts for an estimated 3.5 % of RCCs and whilst it may be considered as a separate entity it is essentially a well-differentiated ccRCC [7]. The cysts are lines by a single layer of clear cells with fibrous septations containing epithelial cells [7]. They present as a Bosniak type II or III cystic lesion although this type of Bosniak lesion can also be due to a benign cystic nephroma, multilocular cyst or mixed epithelial and stromal tumor of the kidney. Biopsy or frozen section of the lesion often cannot distinguish between these lesions and the usual management is surgical excision. The clinical outcome in these cases is excellent.

Collecting Duct (of Bellini) Carcinoma (CDC)

These rare tumours are derived from the cells of collecting ducts in the renal medulla and account for less than 1.8 % of RCCs [11]. There is a male predominance and poor prognosis with up to 40 % having metastatic disease on clinical presentation [12]. The most frequent genetic abnormality is deletion of chromosome 1q32 [13]. Macroscopically, they have a whitish grey appearance with a solid growth pattern. There is dilation of the tubules and papillae, which are lined by cuboidal cells, giving a cobblestone appearance under microscopy. At presentation they are usually advanced with metastasis with Fuhrman grade 3 or 4 nuclear features (Fig. 19.4 [14], Fig. 19.5).