Chromophobe renal cell carcinoma, CRCC
Epidemiology
Chromophobe renal cell carcinoma constitutes 3-5% of all renal cell carcinomas
Clinical features
Macroscopic appearances
Histopathology
The tumour cells form broad trabeculae. The cells have flocculent cytoplasm with distinct cell borders. The cytoplasm may be clear (classical variant) or eosinophilic. There are frequent binucleate forms. Nuclei are dark and irregular. These features give the cells are resemblance to koilocytes. The cells stain with Hale's colloidal iron. Accentuated cell borders, and a combination of hyperchromatic wrinkled nuclei with perinuclear halos are particularly useful in diagnosing CRCC2.
Immunohistochemistry
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Pancytokeratin KL-1
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28/28(diffuse positivity of more than 80% of tumour cells; 13, strong positivity of 50-80% of tumour cells; 12, heterologous positivity of less than 50% of tumour cells; 3: study by tissue microarray)4
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34bE12
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0/28
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Cam5.2
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28/28(diffuse positivity of more than 80% of tumour cells; 22, strong positivity of 50-80% of tumour cells; 3, heterologous positivity of less than 50% of tumour cells; 3: study by tissue microarray)4
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CK7
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20/242,
18/28(diffuse positivity of more than 80% of tumour cells; 13, strong positivity of 50-80% of tumour cells; 5: study by tissue microarray)4,
8/11(in addition, one case showed focal positivity)5,
12/12(all showed membrane staining. There is no cytoplasmic staining in the classical variant; there is weak cytoplasmic staining in the eosinophilic variant)6,
6/6(strong cytoplasmic with peripheral accentuation)7, 27/3015
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CK20
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0/242, 0/115
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EMA
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18/242,
28/28(diffuse positivity of more than 80% of tumour cells; 22, strong positivity of 50-80% of tumour cells; 3, heterologous positivity of less than 50% of tumour cells; 3: study by tissue microarray)4, 30/3015
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MOC31
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23/28(diffuse positivity of more than 80% of tumour cells; 13, strong positivity of 50-80% of tumour cells; 7, heterologous positivity of less than 50% of tumour cells; 3: study by tissue microarray)4
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BerEP4
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26/28(diffuse positivity of more than 80% of tumour cells; 19, strong positivity of 50-80% of tumour cells; 6, heterologous positivity of less than 50% of tumour cells; 1: study by tissue microarray)4
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RCC Ma
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1/28(strong positivity of 50-80% of tumour cells in 1 case: study by tissue microarray)4, 0/198, 0/1113, 2/1316
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CD10
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9/28(diffuse positivity of more than 80% of tumour cells; 2, strong positivity of 50-80% of tumour cells; 2, heterologous positivity of less than 50% of tumour cells; 5: study by tissue microarray)4,
0/19(all negative for surface staining: a minority showed focal cytoplasmic staining)8,
11/23(extensive; 7, moderate; 2, focal; 2: study by tissue microarray)11,
8/11(both membrane and diffuse granular cytoplasmic staining, diffuse in 6 cases, focal in 2 cases. In one case with a sarcomatoid component, only the sarcomatoid component was positive.)13
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E-cadherin
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28/28(diffuse positivity of more than 80% of tumour cells; 15, strong positivity of 50-80% of tumour cells; 4, heterologous positivity of less than 50% of tumour cells; 9: study by tissue microarray)4
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CD15
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3/28(diffuse positivity of more than 80% of tumour cells; 1, strong positivity of 50-80% of tumour cells; 1, heterologous positivity of less than 50% of tumour cells; 1: study by tissue microarray)4
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Vimentin
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0/242,
6/28(diffuse positivity of more than 80% of tumour cells; 2, strong positivity of 50-80% of tumour cells; 4: study by tissue microarray)4, 0/810, 0/3015
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Parvalbumin
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22/242, 32/323 8/810
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Antimitochondrial antibody
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6/24(peripheral staining)2
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CD117
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11/369,
11/11(diffusely positive with both membrane and finely granular cytoplasmic staining. A sarcomatoid component in one case was negative.)13
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RON
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11/11(either cell membrane or cytoplasmic, diffuse in 6 cases, focal in 5 cases. In one case with a sarcomatoid component, the chromophobe component was positive but the sarcomatoid component was negative.)13
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b defensin-1
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8/810
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Epcam
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18/20 strongly membrane positive12
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kidney-specific cadherin
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23/25(staining typically strong and membranous with lesser cytoplasmic staining: the cytoiplasmic staing dominates in some eosinophilic variants)14,
29/30(staining is membranous)15,
13/13(staining ws membranus with basolateral accentuation)16, 31/3617
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Colloidal iron
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9/11(diffuse finely granular cytoplasmic staining)13, 26/3015
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P504S
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0/1818
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Cytogenetics
There are numerous associated chromosomal deletions.
Ultrastructure
Abundant microvesicles are present and characteristic.
Differential diagnosis
In two studies, positivity for parvalbumin has a high sensitivity and specificity for CRCC2,3: it is also positive in renal oncocytoma but not in conventional renal cell carcinoma or papillary renal cell carcinoma.
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The classical variant needs to be distinguished from conventional cell carcinoma. Chromophobe carcinomas show more variation in cell and nuclear size with darker irregular nuclei, lacking nucleoli.
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Oncocytomas show less nuclear variation. Like CRCC, they may show cell membrane staining with colloidal iron.
Prognosis
The prognosis is excellent, unless the tumour is large or multifocal. Metastases, when they occur, are often to liver.
References
1 Renshaw, A. A. (2002). "Subclassification of renal cell neoplasms: an update for the practising pathologist." Histopathology 41(4): 283-300.
2 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.
3 Martignoni, G., M. Pea, et al. (2001). "Parvalbumin is constantly expressed in chromophobe renal carcinoma." Mod Pathol 14(8): 760-7.
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 Wu SL, Kothari P, Wheeler TM, et al. Cytokeratins 7 and 20 immunoreactivity in chromophobe renal cell carcinomas and renal oncocytomas. Mod Pathol 2002; 15:712-7
6 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
7 Leroy, X., Moukassa, D., Copin, M.C., Saint, F., Mazeman, E. and Gosselin, B. Utility of cytokeratin 7 for distinguishing chromophobe renal cell carcinoma from renal oncocytoma. Eur Urol 2000;37:484-7.
8 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.
9 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.
10 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.
11 Langner, C., M. Ratschek, et al. (2004). "CD10 is a diagnostic and prognostic marker in renal malignancies." Histopathology 45(5): 460-7.
12 Went P, Dirnhofer S, Salvisberg T, et al. Expression of epithelial cell adhesion molecule (EpCam) in renal epithelial tumors. Am J Surg Pathol 2005; 29:83-8
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 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
15 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
16 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
17 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
18 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