Two types, have been defined by the types of cells lining papillae and tubules
We do not routinely classify papillary carcinomas according to type
In our experience, many cases show a mixed pattern or do not clearly conform to either of these types
Nevertheless, familial cases associated with MET mutations tend to show a type 1 morphology whereas those associated with fumarate hydratase mutations tend to show a type 2 morphology
Type 1 is lined by small cells with clear to basophilic cytoplasm
Single layer of small oval nuclei
Inconspicuous nucleoli
Frequent findings
Foamy macrophages and/or edema in papillary cores
Psammoma bodies and calcium oxalate crystals
Glomeruloid papillae
Most cases low grade (1 or 2)and low stage
Type 2 is lined by large cells with abundant eosinophilic cytoplasm
If cytoplasm is extensively granular, consider papillary oncocytoma, see Differential Diagnosis
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 trisomy 7 and 17 and loss of Y chromosome
Sarcomatoid differentiation may be seen in many types of renal carcinomas
(de Peralta-Venturina; Cheville)
It no longer refers to a type of carcinoma
It is considered an adverse prognostic factor
Prognosis may be worse than simple grade 4 carcinoma
Defined as a spindle cell component measuring at least one low power (40x) field with either
Adjacent carcinoma, or
Evidence of epithelial differentiation in the spindle cells
Spindle cells usually show moderate to marked atypia
Frequent patterns include fibrosarcoma, malignant fibrous histiocytoma, rhabdomyosarcoma
Occasional cases have low grade atypia in spindle component
No clinical significance to type of differentation or degree of atypia
May arise in setting of many types of carcinoma
Clear cell RCC (reported 5-8% incidence of sarcomatoid foci, in our experience it is less frequent)
Papillary RCC (2-3% incidence)
Chromophobe RCC (9% incidence)
Collecting duct carcinoma (39% incidence)
Bibliography (for Grading)
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.
Delahunt B, Sika-Paotonu D, Bethwaite PB, William Jordan T, Magi-Galluzzi C, Zhou M, Samaratunga H, Srigley JR. Grading of clear cell renal cell carcinoma should be based on nucleolar prominence. Am J Surg Pathol. 2011 Aug;35(8):1134-9.
Delahunt B, Bethwaite PB, Nacey JN. Outcome prediction for renal cell carcinoma: evaluation of prognostic factors for tumours divided according to histological subtype. Pathology. 2007 Oct;39(5):459-65.
Lohse CM, Blute ML, Zincke H, Weaver AL, Cheville JC. Comparison of standardized and nonstandardized nuclear grade of renal cell carcinoma to predict outcome among 2,042 patients. Am J Clin Pathol. 2002 Dec;118(6):877-86.
de Peralta-Venturina M, Moch H, Amin M, Tamboli P, Hailemariam S, Mihatsch M, Javidan J, Stricker H, Ro JY, Amin MB. Sarcomatoid differentiation in renal cell carcinoma: a study of 101 cases. Am J Surg Pathol. 2001 Mar;25(3):275-84.
Cheville JC, Lohse CM, Zincke H, Weaver AL, Leibovich BC, Frank I, Blute ML. Sarcomatoid renal cell carcinoma: an examination of underlying histologic subtype and an analysis of associations with patient outcome. Am J Surg Pathol. 2004 Apr;28(4):435-41.
Sika-Paotonu D, Bethwaite PB, McCredie MR, William Jordan T, Delahunt B. Nucleolar grade but not Fuhrman grade is applicable to papillary renal cell carcinoma. Am J Surg Pathol. 2006 Sep;30(9):1091-6.
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..
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.
Fuhrman SA, Lasky LC, Limas C. Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol. 1982 Oct;6(7):655-63.
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
Type 2 has worse overall prognosis than Type 1
Type 2 presents at higher stage
When controlled for stage and grade, behavior is similar
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.
Störkel S, Eble JN, Adlakha K, Amin M, Blute ML, Bostwick DG, Darson M, Delahunt B, Iczkowski K. Classification of renal cell carcinoma: Workgroup No. 1. Union Internationale Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC). Cancer. 1997 Sep 1;80(5):987-9.
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.
Delahunt B, Eble JN. Papillary renal cell carcinoma: a clinicopathologic and immunohistochemical study of 105 tumors. Mod Pathol. 1997 Jun;10(6):537-44.
Sharma SG, Gokden M, McKenney JK, Phan DC, Cox RM, Kelly T, Gokden N. The utility of pax-2 and renal cell carcinoma marker immunohistochemistry in distinguishing papillary renal cell carcinoma from nonrenal cell neoplasms with papillary features. Appl Immunohistochem Mol Morphol. 2010 Dec;18(6):494-8.
Cantley R, Gattuso P, Cimbaluk D. Solid variant of papillary renal cell carcinoma with spindle cell and tubular components. Arch Pathol Lab Med. 2010 Aug;134(8):1210-4.
Klatte T, Said JW, Seligson DB, Rao PN, Martino MD, Shuch B, Zomorodian N, Kabbinavar FF, Belldegrun AS, Pantuck AJ. Pathological, Immunohistochemical and Cytogenetic Features of Papillary Renal Cell Carcinoma With Clear Cell Features. J Urol. 2010 Nov 11. [Epub ahead of print]
Klatte T, Anterasian C, Said JW, de Martino M, Kabbinavar FF, Belldegrun AS, Pantuck AJ. Fuhrman grade provides higher prognostic accuracy than nucleolar grade for papillary renal cell carcinoma. J Urol. 2010 Jun;183(6):2143-7.
Sika-Paotonu D, Bethwaite PB, McCredie MR, William Jordan T, Delahunt B. Nucleolar grade but not Fuhrman grade is applicable to papillary renal cell carcinoma. Am J Surg Pathol. 2006 Sep;30(9):1091-6.
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. Epub 2009 Dec 14.
Amin MB, Corless CL, Renshaw AA, Tickoo SK, Kubus J, Schultz DS. Papillary (chromophil) renal cell carcinoma: histomorphologic characteristics and evaluation of conventional pathologic prognostic parameters in 62 cases. Am J Surg Pathol. 1997 Jun;21(6):621-35.
Argani P, Netto GJ, Parwani AV. Papillary renal cell carcinoma with low-grade spindle cell foci: a mimic of mucinous tubular and spindle cell carcinoma. Am J Surg Pathol. 2008 Sep;32(9):1353-9.
