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
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Pancytokeratin KL-1
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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
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34bE12
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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
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Cam5.2
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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
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CK7
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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
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EMA
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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, 55/10216
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MOC31
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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
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BerEP4
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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
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RCC Ma
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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, 36/4217
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CD10
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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)4,
58/62(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
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E-cadherin
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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
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CD15
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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
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Vimentin
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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, 67/10216
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CD117
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4/817,
0/6(granular [eosinophilic] variants)13
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b defensin-1
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3/238
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parvalbumin
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5/238, 0/759
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RON
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3/6(granular [eosinophilic] variants: focal membrane or cytoplasmic positivity)13
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anti-mitochondrial antibody
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diffuse in eosinophilic variant11
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Colloidal iron
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0/6(granular [eosinophilic] variants)13
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kidney-specific cadherin
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6/36(staining focal membranous)15,
0/102(ncludes 19 granular cell variants)16, 6/4217, 10/3318
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P504S
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13/5219
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Cytogenetics
Deletions of chromosome 3p are common, the site of the von Hippel-Lindau gene.
Differential diagnosis of primary renal tumours:
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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.
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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.
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Renal oncocytoma
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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.
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metastatic renal carcinoma:
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coexpression of cytokeratin and vimentin
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versus
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most other carcinomas:
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cytokeratin positive, vimentin negative
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metastasis to adrenal:
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EMA positive, cytokeratin positive
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versus
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primary adrenal cortical carcinoma:
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EMA negative, only weakly cytokeratin positive.
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metastasis to thyroid
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thyroglobulin negative
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versus
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primary clear cell carcinoma of thyroid:
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thyroglobulin positive
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metastasis to brain:
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EMA positive
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versus
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primary capillary haemangioblastoma or CNS:
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EMA negative
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metastasis to pleura
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versus
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renal cell carcinoma
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Angioleiomyoma-like proliferations have been reported adjacent to renal clear cell carcinoma14, with a differential diagnosis that includes:
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
14 Kuhn E, De Anda J, Manoni S, et al. Renal cell carcinoma associated with prominent angioleiomyoma-like proliferation: Report of 5 cases and review of the literature. Am J Surg Pathol 2006; 30:1372-81
15 Kuehn A, Paner GP, Skinnider BF, et al. Expression analysis of kidney-specific cadherin in a wide spectrum of traditional and newly recognized renal epithelial neoplasms: diagnostic and histogenetic implications. Am J Surg Pathol 2007; 31:1528-33
16 Mazal PR, Exner M, Haitel A, et al. Expression of kidney-specific cadherin distinguishes chromophobe renal cell carcinoma from renal oncocytoma. Hum Pathol 2005; 36:22-8
17 Shen SS, Krishna B, Chirala R, et al. Kidney-specific cadherin, a specific marker for the distal portion of the nephron and related renal neoplasms. Mod Pathol 2005; 18:933-40 FULL TEXT
18 Adley BP, Gupta A, Lin F, et al. Expression of kidney-specific cadherin in chromophobe renal cell carcinoma and renal oncocytoma. Am J Clin Pathol 2006; 126:79-85
19 Tretiakova MS, Sahoo S, Takahashi M, et al. Expression of alpha-methylacyl-CoA racemase in papillary renal cell carcinoma. Am J Surg Pathol 2004; 28:69-76
This page last revised 2.2.2008.
©SMUHT/PW Bishop