Renal clear cell carcinoma, conventional renal cell carcinoma

Epidemiology

Renal clear cell carcinomas form 75% of all renal cell carcinomas.

This type of tumour arises in patient with the von Hippel-Lindau syndrome.

Macroscopic appearances

Histopathology

Cytoplasm may be clear or granular. There may be vacuolation, with the vacuoles sited peripherally. There is copious cytoplasm with a central nucleus with a prominent nucleolus. Sometimes the nuclei are eccentric, giving a plasmacytoid appearance.

Immunohistochemistry

	Pancytokeratin KL-1	218/256 (diffuse positivity of more than 80% of tumour cells; 129, strong positivity of 50-80% of tumour cells; 23, heterologous positivity of less than 50% of tumour cells; 66: study by tissue microarray)4
	34bE12	4/256 (strong positivity of 50-80% of tumour cells; 2,heterologous positivity of less than 50% of tumour cells; 2: study by tissue microarray)4
	Cam5.2	223/256 (diffuse positivity of more than 80% of tumour cells; 104, strong positivity of 50-80% of tumour cells; 69, heterologous positivity of less than 50% of tumour cells; 50: study by tissue microarray)4
	CK7	16/256 (diffuse positivity of more than 80% of tumour cells; 6, strong positivity of 50-80% of tumour cells; 5, heterologous positivity of less than 50% of tumour cells; 5: study by tissue microarray)4, 1/18 (one case showed weak focal staining)5
	EMA	197/256 (diffuse positivity of more than 80% of tumour cells; 112, strong positivity of 50-80% of tumour cells; 54, heterologous positivity of less than 50% of tumour cells; 31: study by tissue microarray)4
	MOC31	11/256 (diffuse positivity of more than 80% of tumour cells; 3, strong positivity of 50-80% of tumour cells; 5, heterologous positivity of less than 50% of tumour cells; 3: study by tissue microarray)4
	BerEP4	68/256 (diffuse positivity of more than 80% of tumour cells; 11, strong positivity of 50-80% of tumour cells; 28, heterologous positivity of less than 50% of tumour cells; 29: study by tissue microarray)4
	RCC Ma	123/256 (diffuse positivity of more than 80% of tumour cells; 38, strong positivity of 50-80% of tumour cells; 54, heterologous positivity of less than 50% of tumour cells; 31: study by tissue microarray)4, 53/62 (low grade; 35/38, high grade; 18/24)6, 5/6 (granular [eosinophilic] variants: diffuse positivity. The negative case was Fuhrman grade IV.)13
	CD10	209/256 (diffuse positivity of more than 80% of tumour cells; 84, strong positivity of 50-80% of tumour cells; 89, heterologous positivity of less than 50% of tumour cells; 36: study by tissue microarray)458/62 (low grade; 36/38, high grade; 22/24)6, 124/129 (extensive; 105, moderate; 13, focal; 6: extensive positivity in grade I or II; 72/81, grade III or IV; 33/48: study by tissue microarray)12, 6/6 (granular [eosinophilic] variants: membrane and granular cytoplasmic positivity)13
	E-cadherin	132/256 (diffuse positivity of more than 80% of tumour cells; 18, strong positivity of 50-80% of tumour cells; 37, heterologous positivity of less than 50% of tumour cells; 77: study by tissue microarray)4
	CD15	153/250 (diffuse positivity of more than 80% of tumour cells; 66, strong positivity of 50-80% of tumour cells; 66, heterologous positivity of less than 50% of tumour cells; 21: study by tissue microarray)4
	Vimentin	164/256 (diffuse positivity of more than 80% of tumour cells; 56, strong positivity of 50-80% of tumour cells; 85, heterologous positivity of less than 50% of tumour cells; 23: study by tissue microarray)4, 19/238
	CD117	4/817, 0/6 (granular [eosinophilic] variants)13
	b defensin-1	3/238
	parvalbumin	5/238, 0/759
	RON	3/6 (granular [eosinophilic] variants: focal membrane or cytoplasmic positivity)13
	anti-mitochondrial antibody	diffuse in eosinophilic variant11
	Colloidal iron	0/6 (granular [eosinophilic] variants)13

Cytogenetics

Deletions of chromosome 3p are common, the site of the von Hippel-Lindau gene.

Differential diagnosis of primary renal tumours:

• The granular variant of clear cell renal cell carcinoma may be confused with the eosinophilic variant of chromophobe renal cell carcinoma: the latter is negative for renal cell carcinoma marker but more often positive for CD117 and MOC31⁴.

• Papillary renal cell carcinoma, particularly its solid variant. There is less cytoplasm, which is more basophilic, and the nuclear chromatin is more granular. Conventional cell carcinoma may develop a focal pseudopapillary architecture. Papillary renal cell carcinoma is more often BerEP4+/RCC Ma+/CD10-⁴.

• Renal oncocytoma

• Benign cyst. Conventional cell carcinoma may be cystic: a single layer of cells with the right cytological appearance is sufficient to make the diagnosis of carcinoma.

Differential diagnosis of metastatic clear cell renal cell carcinoma²:

Usually coexpress pancytokeratin and vimentin, unlike most other carcinomas. Most are EMA positive but negative for CEA and for both CK7 and CK20³. However, there is considerable overlap with other tumours which constitute differentials of renal cell carcinoma. The "Renal cell carcinoma marker" has a promising specificity for renal cell carcinoma.

metastatic renal carcinoma:   coexpression of cytokeratin and vimentin		versus	most other carcinomas: cytokeratin positive, vimentin negative
metastasis to adrenal:   EMA positive, cytokeratin positive		versus	primary adrenal cortical carcinoma: EMA negative, only weakly cytokeratin positive.
metastasis to thyroid   thyroglobulin negative		versus	primary clear cell carcinoma of thyroid: thyroglobulin positive
metastasis to brain:   EMA positive		versus	primary capillary haemangioblastoma or CNS: EMA negative
metastasis to pleura		versus	renal cell carcinoma

Prognosis

There is a propensity to metastasis to unusual sites. The prognosis of the cystic variant is excellent¹.

References

¹ Renshaw, A. A. (2002). "Subclassification of renal cell neoplasms: an update for the practising pathologist." Histopathology 41(4): 283-300.

² Diagnostic histopathology of tumors. Edited by CDM Fletcher. 2nd edition. Churchill Livingstone. Page 485.

³ McGregor, D. K., Khurana, K. K., Cao, C. Diagnosing primary and metastatic renal cell carcinoma: the use of the monoclonal antibody 'Renal Cell Carcinoma Marker'. Am J Surg Pathol 2001;25:1485-1492.

⁴ Pan CC, Chen PC,Ho DM. The diagnostic utility of MOC31, BerEP4, RCC marker and CD10 in the classification of renal cell carcinoma and renal oncocytoma: an immunohistochemical analysis of 328 cases. Histopathology 2004; 45:452-9

⁵ Mathers ME, Pollock AM, Marsh C, et al. Cytokeratin 7: a useful adjunct in the diagnosis of chromophobe renal cell carcinoma. Histopathology 2002; 40:563-7

⁶ Avery, A.K., Beckstead, J., Renshaw, A.A. and Corless, C.L. Use of antibodies to RCC and CD10 in the differential diagnosis of renal neoplasms. Am J Surg Pathol 2000;24:203-10.

⁷ Ono, Y., Ito, T., Tsujino, S., Aizawa, S. and Suzuki, M. [A study of papillary renal cell carcinoma. Clinicopathological, immunohistochemical features and its typing]. Nippon Hinyokika Gakkai Zasshi 1997;88:587-95.

⁸ Young, A.N., de Oliveira Salles, P.G., Lim, S.D., Cohen, C., Petros, J.A., Marshall, F.F., Neish, A.S. and Amin, M.B. Beta defensin-1, parvalbumin, and vimentin: a panel of diagnostic immunohistochemical markers for renal tumors derived from gene expression profiling studies using cDNA microarrays. Am J Surg Pathol 2003;27:199-205.

⁹ Martignoni, G., M. Pea, et al. (2001). "Parvalbumin is constantly expressed in chromophobe renal carcinoma." Mod Pathol 14(8): 760-7.

^{10 11} Abrahams, N. A., G. T. Maclennan, et al. (2004). "Chromophobe renal cell carcinoma: a comparative study of histological, immunohistochemical and ultrastructural features using high throughput tissue microarray." Histopathology 45(6): 593-602.

¹² Langner, C., M. Ratschek, et al. (2004). "CD10 is a diagnostic and prognostic marker in renal malignancies." Histopathology 45(5): 460-7.

¹³ Wang HY,Mills SE. KIT and RCC are useful in distinguishing chromophobe renal cell carcinoma from the granular variant of clear cell renal cell carcinoma. Am J Surg Pathol 2005; 29:640-6

This page last revised 17.7.2005.

©SMUHT/PW Bishop