Allory Y, Bazille C, Vieillefond A, Molinié V, Cochand-Priollet B, Cussenot O, Callard P, Sibony M. Profiling and classification tree applied to renal epithelial tumours. Histopathology. 2008 Jan;52(2):158-66.
Molinié V, Balaton A, Rotman S, Mansouri D, De Pinieux I, Homsi T, Guillou L. Alpha-methyl CoA racemase expression in renal cell carcinomas. Hum Pathol. 2006 Jun;37(6):698-703.
Paner GP, Srigley JR, Radhakrishnan A, Cohen C, Skinnider BF, Tickoo SK, Young AN, Amin MB. Immunohistochemical analysis of mucinous tubular and spindle cell carcinoma and papillary renal cell carcinoma of the kidney: significant immunophenotypic overlap warrants diagnostic caution. Am J Surg Pathol. 2006 Jan;30(1):13-9.
Liu L, Qian J, Singh H, Meiers I, Zhou X, Bostwick DG. Immunohistochemical analysis of chromophobe renal cell carcinoma, renal oncocytoma, and clear cell carcinoma: an optimal and practical panel for differential diagnosis. Arch Pathol Lab Med. 2007 Aug;131(8):1290-7.
Memeo L, Jhang J, Assaad AM, McKiernan JM, Murty VV, Hibshoosh H, Tong GX, Mansukhani MM. Immunohistochemical analysis for cytokeratin 7, KIT, and PAX2: value in the differential diagnosis of chromophobe cell carcinoma. Am J Clin Pathol. 2007 Feb;127(2):225-9.
Avery AK, Beckstead J, Renshaw AA, Corless CL. Use of antibodies to RCC and CD10 in the differential diagnosis of renal neoplasms. Am J Surg Pathol. 200 Feb;24(2):203-10.
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 May;29(5):640-6.
McGregor DK, Khurana KK, Cao C, Tsao CC, Ayala G, Krishnan B, Ro JY, Lechago J, Truong LD. Diagnosing primary and metastatic renal cell carcinoma: the use of the monoclonal antibody 'Renal Cell Carcinoma Marker'. Am J Surg Pathol. 2001 Dec;25(12):1485-92.
Yoshida SO, Imam A. Monoclonal antibody to a proximal nephrogenic renal antigen: immunohistochemical analysis of formalin-fixed, paraffin-embedded human renal cell carcinomas. Cancer Res. 1989 Apr 1;49(7):1802-9.
Genetic Study
Most show deletions involving chromosomes 1, 2, 6, 10, 13, 17, 21
Not commonly used for diagnosis
Hale colloidal iron stain diffusely positive in cell cytoplasm
Clear cells usually prominent, frequently peripheral in nests
Clear cells only focally in hyalinized scars
CK7 usually diffuse, strong
CK7 usually negative or scattered positive cells
Hale colloidal iron stain diffusely positive
Hale colloidal iron stain may be apical, but not diffuse, confluent
This is one of the most problematic distinctions between renal neoplasms and may frequently be impossible
We consider a diagnosis of “oncocytic renal neoplasm” with a comment that chromophobe carcinoma cannot be completely excluded to be preferable to overdiagnosing a likely benign neoplasm as chromophobe carcinoma
Grading / Staging
Grading
Fuhrman and modified Fuhrman grading schemes do not apply to chromophobe carcinoma (Delahunt)
Paner et al. have proposed a grading scheme
Grade I
No nuclear crowding and anaplasia (see definitions below)
Grade 2
requires both criteria below:
Nuclear crowding
High geographic nuclear/cytoplasmic density detectable at 10x objective
Some nuclei in direct contact with each other when assessed at 40x objective
Nuclear pleomorphism
Size variation of ≥3-fold and
Distinct nuclear chromatin irregularities
Not smudged nuclear atypia of degenerate foci
Grade 3 requires either
Nuclear polylobation and tumor giant cells, or
Sarcomatoid change
At least two distinct areas required to have above features to determine the grade
Otherwise, use next lower grade
A large study (Przybycin 2011) does not find grading to predict behavior
Following features found to be predictive of adverse outcome
Angiolymphatic invasion
Microscopic necrosis
Tumor size (>7cm)
Sarcomatoid differentiation
Staging
Use TNM staging for all renal carcinomas at present
Remember that it is based predominantly on clear cell carcinomas
It has not been validated as applicable to other types of carcinoma (see Herrmann for an example)
Critical/controversial points in staging of RCC include:
pT3a is defined as extension into perirenal fat
This requires actual infiltration into and between fat cells
It does not include bulging tumor with stretched, thin capsule that appears to touch fat
Classically has been considered fat peripheral to the cortical capsule
It appears that renal sinus (peripelvic) fat should be considered equivalent
The renal sinus must be examined grossly and appropriately sampled
pT3 requires gross involvement of renal vein and or vena cava
This requires an adequate gross examination
Retraction of vascular wall around a lumenal tumor thrombus may falsely suggest a positive margin
Positive vascular margin requires involvement of the vessel wall at the margin
Direct (contiguous) invasion of the adrenal gland (pT4) should be distinguished from discontiguous (metastatic) involvement (pM1)
Bibliography (for Staging)
Murphy WM, Grignon DJ, Perlman EJ. Tumors of the Kidney, Bladder and Related Urinary Structures, Atlas of Tumor Pathology, AFIP Fourth Series, Fascicle 1, 2004
Delahunt B. Advances and controversies in grading and staging of renal cell carcinoma. Mod Pathol. 2009 Jun;22 Suppl 2:S24-36.
Bonsib SM. The renal sinus is the principal invasive pathway: a prospective study of 100 renal cell carcinomas. Am J Surg Pathol. 2004 Dec;28(12):1594-600.
Bonsib SM. Renal veins and venous extension in clear cell renal cell carcinoma. Mod Pathol. 2007 Jan;20(1):44-53.
Bonsib SM. T2 clear cell renal cell carcinoma is a rare entity: a study of 120 clear cell renal cell carcinomas. J Urol. 2005 Oct;174(4 Pt 1):1199-202; discussion 1202.
Herrmann E, Trojan L, Becker F, Wülfing C, Schrader AJ, Barth P, Stöckle M, Hammerschmied CG, Staehler M, Stief C, Haferkamp A, Hohenfellner M, Legal W, Wullich B, Bolenz C, Klein T, Noldus J, Bierer S, Hertle L, Brenner W, Roos F, Michel MS, Walter B, Wieland W, Gerss J, Otto W, Hartmann A. Prognostic factors of papillary renal cell carcinoma: results from a multi-institutional series after pathological review. J Urol. 2010 Feb;183(2):460-6.
Clinical
Predominantly seen in adults
Range 24-82, mean about 60
One report at 8 years of age (Katzman)
8% multifocal
95% 5 year survival
Poor survival in cases with sarcomatoid differentiation
Murphy WM, Grignon DJ, Perlman EJ. Tumors of the Kidney, Bladder and Related Urinary Structures, Atlas of Tumor Pathology, AFIP Fourth Series, Fascicle 1, 2004
Eble JN, Sauter G, Epstein JI, Sesterhenn IA eds. World Health Organization Classification of Tumors. Pathology and genetics of tumors of the Urinary System and Male Genital Organs. IARC Press: Lyon 2004.
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Kovacs G, Akhtar M, Beckwith BJ, Bugert P, Cooper CS, Delahunt B, Eble JN, Fleming S, Ljungberg B, Medeiros LJ, Moch H, Reuter VE, Ritz E, Roos G, Schmidt D, Srigley JR, Störkel S, van den Berg E, Zbar B. The Heidelberg classification of renal cell tumours. J Pathol. 1997 Oct;183(2):131-3.
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Paner GP, Amin MB, Alvarado-Cabrero I, Young AN, Stricker HJ, Moch H, Lyles RH. A novel tumor grading scheme for chromophobe renal cell carcinoma: prognostic utility and comparison with Fuhrman nuclear grade. Am J Surg Pathol. 2010 Sep;34(9):1233-40.
Delahunt B, Sika-Paotonu D, Bethwaite PB, McCredie MR, Martignoni G, Eble JN, Jordan TW. Fuhrman grading is not appropriate for chromophobe renal cell carcinoma. Am J Surg Pathol. 2007 Jun;31(6):957-60.
Amin MB, Paner GP, Alvarado-Cabrero I, Young AN, Stricker HJ, Lyles RH, Moch H. Chromophobe renal cell carcinoma: histomorphologic characteristics and evaluation of conventional pathologic prognostic parameters in 145 cases. Am J Surg Pathol. 2008 Dec;32(12):1822-34.
Liu L, Qian J, Singh H, Meiers I, Zhou X, Bostwick DG. Immunohistochemical analysis of chromophobe renal cell carcinoma, renal oncocytoma, and clear cell carcinoma: an optimal and practical panel for differential diagnosis. Arch Pathol Lab Med. 2007 Aug;131(8):1290-7.
Memeo L, Jhang J, Assaad AM, McKiernan JM, Murty VV, Hibshoosh H, Tong GX, Mansukhani MM. Immunohistochemical analysis for cytokeratin 7, KIT, and PAX2 value in the differential diagnosis of chromophobe cell carcinoma. Am J Clin Pathol. 2007 Feb;127(2):225-9.
Yusenko MV. Molecular pathology of chromophobe renal cell carcinoma: a review. Int J Urol. 2010 Jul;17(7):592-600.
Brunelli M, Delahunt B, Gobbo S, Tardanico R, Eccher A, Bersani S, Cossu-Rocca P, Parolini C, Balzarini P, Menestrina F, Cheng L, Eble JN, Martignoni G. Diagnostic usefulness of fluorescent cytogenetics in differentiating chromophobe renal cell carcinoma from renal oncocytoma: a validation study combining metaphase and interphase analyses. Am J Clin Pathol. 2010 Jan;133(1):116-26.
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Viswanathan S, Desai SB, Prabhu SR, Amin MB. Squamous differentiation in a sarcomatoid chromophobe renal cell carcinoma: an unusual case report with review of the literature. Arch Pathol Lab Med. 2008 Oct;132(10):1672-4.
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Petersson F, Gatalica Z, Grossmann P, Perez Montiel MD, Alvarado Cabrero I, Bulimbasic S, Swatek A, Straka L, Tichy T, Hora M, Kuroda N, Legendre B, Michal M, Hes O. Sporadic hybrid oncocytic/chromophobe tumor of the kidney: a clinicopathologic, histomorphologic, immunohistochemical, ultrastructural, and molecular cytogenetic study of 14 cases. Virchows Arch. 2010 Apr;456(4):355-65.
Katzman PJ, Schwartz JI. Chromophobe renal cell carcinoma in a child: case report and review of the literature. Pediatr Dev Pathol. 2007 Mar-Apr;10(2):125-8.
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Przybycin CG, Cronin AM, Darvishian F, Gopalan A, Al-Ahmadie HA, Fine SW, Chen YB, Bernstein M, Russo P, Reuter VE, Tickoo SK. Chromophobe renal cell carcinoma: a clinicopathologic study of 203 tumors in 200 patients with primary resection at a single institution. Am J Surg Pathol. 2011 Jul;35(7):962-70.
