Stanford School of Medicine

Surgical Pathology Criteria

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Papillary Renal Cell Carcinoma


  • Carcinoma of the kidney with a predominantly papillary growth pattern

Covered Separately (as discrete entities)

Diagnostic Criteria

  • Predominantly papillary pattern
    • May have tubular areas
    • Papillae have fibrovascular cores
    • May be intracystic
    • Rare cases of apparent solid pattern
      • Formed by collapsed tubules and papillae
  • 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
      • Nuclei frequently pseudostratified or apical
      • Large spherical nuclei
        • Prominent nucleoli
      • Macrophages, edema, psammoma bodies, glomeruloid papillae infrequent
      • Most cases high grade (3), many higher stage
  • Papillary carcinoma with low grade spindle cell features has been described (Argani)
    • Predominantly solid
      • 4 of 5 reported cases had papillary areas
      • All appear to be Type 1
    • Nuclear grade 2
    • Lacks mucinous stroma of mucinous tubular and spindle cell carcinoma
      • May be distinguishable only by FISH for trisomy 7 or 17
  • If under 0.5 cm and grade 1 or 2, designate as papillary adenoma

John P Higgins MD
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting:: January 24, 2011

Supplemental studies


Low MW keratin, CD10 >90%
CK7 Type 1 80%, Type 2 20%
EMA, S100 50%
High MW keratin neg
PAX2, PAX8 >85%
See also markers in table below

Immunohistologic markers useful for distinguishing major types of renal cell carcinoma
  CA-IX Vim CD117 AMACR Racemase PN15 /PNRA/ gp200 CK7
Clear Cell 100% >85% <5% 15-25% 85% neg or focal
Papillary 50 >90 <20 >80 >85 20-80%
Chromophobe 0 0 >90 <15 0-45 >70% strong
Oncocytoma 0 0 >90 <15 0 neg to scattered
CA-IX = Carbonic Anhydrase IX; Vim = Vimentin; Clone PN15 anti-gp200 is sold as Renal Cell Carcinoma Marker, a unfortunately chosen, non-specific name

References for general IPOX of major types of RCC

  • Truong LD, Shen SS. Immunohistochemical diagnosis of renal neoplasms. Arch Pathol Lab Med. 2011 Jan;135(1):92-109.
  • 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
    • Not commonly used for diagnosis

Differential Diagnosis

Papillary Renal Cell Carcinoma Papillary Adenoma
>1.5 cm diameter Papillary lesion ≤1.5 cm REQUIRED
May have any nuclear grade Nuclear grade 1 or 2 REQUIRED

Papillary Renal Cell Carcinoma Conventional Clear Cell Renal Cell Carcinoma with Papillary Foci
Papillary pattern usually predominates Usually has conventional areas with sheets and clusters of cells with extensive vascular network
Fibrovascular cores in papillae Lacks fibrovascular cores in papillae
Frequent foamy macrophages and psammoma bodies Lacks foamy macrophages and psammoma bodies
May show intracystic growth pattern Does not show intracystic growth
CK7 and Racemase/AMACR/P504S usually strong positive CK7 and Racemase/AMACR/P504S usually negative to weak/focal

Papillary Renal Cell Carcinoma Clear Cell Papillary Renal Cell Carcinoma
Clear cell cytoplasm, if present, is focal Widespread clear cell cytoplasm, frequently subnuclear/basal
Frequently has foamy macrophages, psammoma bodies, stromal hemosiderin Lacks foamy macrophages, psammoma bodies, stromal hemosiderin
May have high grade nuclear features and necrosis Low grade nuclear features, no necrosis
CD10 pos, Racemase/AMACR pos CD10 neg, Racemase/AMACR neg

Papillary Renal Cell Carcinoma Collecting Duct Carcinoma
Lacks desmoplasia Prominent desmoplasia
Circumscribed Infiltrative
Frequently low grade nuclear features High grade nuclear features
CD10, AMACR/Racemase, PN15/gp200 positive CD10, AMACR/Racemase, PN15/gp200 negative

Type 2 Papillary Renal Cell Carcinoma Oncocytic Papillary Renal Cell Carcinoma
Nuclei usually pseudostratified Nuclei usually linear, frequently apical
Cytoplasm eosinophilic but not abundant and granular Abundant granular eosinophilic cytoplasm
The distinction might be significant since oncocytic papillary carcinomas may have a better prognosis, but more data is needed.

Mucinous Tubular and Spindle Cell Carcinoma of the Kidney Papillary Renal Cell Carcinoma with Low Grade Spindle Cell Foci
Lacks areas of classic papillary carcinoma Areas of classic papillary carcinoma usually present
Mucinous stroma present Mucinous stroma generally absent
Lacks trisomy 7 and 17 Trisomy 7 and/or 17 present

  • Mucinous tubular and spindle cell carcinoma may show morphologic and immunophenotypic overlap with papillary renal cell carcinoma (Paner 2006)
    • Features that may be shared
      • Papillary growth
      • Mucin production
      • Foam cells
      • AMACR expression
    • We diagnose borderline cases as papillary carcinoma
      • Urologists are much more familiar with that diagnosis
      • That diagnosis will probably elicit more extensive followup
    • Genetic studies can separate the two but are rarely indicated

MiT Family Translocation Renal Cell Carcinoma Papillary Renal Cell Carcinoma
Frequently occurs under age 20 Mean age 60
Mixed papillary and clear cell areas Clear cell areas focal to absent
Voluminous cytoplasm Moderately abundant cytoplasm at most
Typically high grade nuclear features May have any grade nuclear features
TFEB or TPE3 immunostain or FISH positive Lacks TFEB or TPE3 translocations
CK7 & EMA negative to weak CK7 & EMA frequently strong positive (but may be negative)

Hereditary Leiomyomatosis RCC Papillary Renal Cell Carcinoma

FH Negative, 2SC Overexpressed

FH intact, No 2SC over expression

CK7 negative

CK7 positive

Prominent eosinophilic nucleoli
with a clear perinucleolar halo

May have prominent nucleoli

Foamy macrophages uncommon

Foamy macrophages common

Average age 36

Average age 60

  • Both may show predominantly papillary architecture
  • HLRCC-associated RCC more likely to resemble Type 2 PRCC with larger tumor cells, often with higher nuclear grade and eosinophilic cytoplasm
  • Grading / Staging


    • WHO/ISUP grading system for clear cell and papillary renal cell carcinomas
    • Grade 1 Nucleoli are absent or inconspicuous and basophilic at 400x magnification
      Grade 2 Nucleoli are conspicuous and eosinophilic at 400x and visible but not prominent at 100x
      Grade 3 Nucleoli are conspicuous and eosinophilic at 100x
      Grade 4 Extreme nuclear pleomorphism, multinucleate giant cells, and/or rhabdoid and/or sarcomatoid differentiation
    • 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)


    • 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)
        • Note that oncocytomas can infiltrate fat and exhibit vascular invasion without affecting prognosis (Perez-Odonez)
    • Critical/controversial points in staging of RCC include:
      • pT3a is defined as extension into perirenal fat
        • This requires actual touching of fat, preferably 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)


    • Type 2 has worse overall prognosis than Type 1
      • Type 2 presents at higher stage
      • When controlled for stage and grade, behavior is similar
    • 30-40% of cases multiple
    • Frequently coexists with adenomas

    Classification / Lists

    Renal epithelial neoplasms


    • 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.
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