Stanford School of Medicine

Surgical Pathology Criteria
http://surgpathcriteria.stanford.edu/

 use browser back button to return

Clear Cell Papillary Renal Cell Carcinoma

Definition

  • Renal neoplasm composed of bland clear epithelial cells with tubular and papillary pattern

Alternate/Historical Names

  • Clear cell papillary and cystic renal cell carcinoma
  • Clear cell tubulopapillary renal cell carcinoma
  • Clear cell papillary renal cell carcinoma of end stage kidneys
  • Renal angiomyoadenomatous tumor
  • Sporadic renal cell carcinoma with diffuse CK7 reactivity

Diagnostic Criteria

  • Most tumors exhibit mixtures of tubular, cystic, acinar and papillary patterns
    • Branching tubules and anastomosing ribbons
      • Lumens may contain eosinophilic secretion
      • Lumens may be compressed by sclerosis
    • Multicystic with variably sized cysts
      • Frequent intracystic papillae
    • Papillae ranging from coarse to fine
      • No foamy macrophages or psammoma bodies
  • All patterns lined by a single layer of cuboidal to low columnar cells
    • Scant eosinophilic or moderate clear cytoplasm
    • Nuclei apical to mid-cytoplasmic orientation
      • Nuclei typically uniformly separated from base of cell by clear cytoplasm (pseudoendometrial appearance)
  • Low grade and stage
    • WHO/ISUP grade 1 or 2
    • Over 95% pT1a
      • No vascular or renal sinus invasion
    • May be multifocal
  • Frequent prominent partial to complete capsule
    • Most cases have at least focal smooth muscle in capsule
    • Occasional cases have at least focal smooth muscle in the tumor stroma
  • Immunophenotype CK7 strong, diffuse positive, CA9 basal or cup-like, CD10 negative to focal, Racemase negative
  • Small solid foci of clear cells reminiscent of conventional clear cell renal cell carcinoma may be seen
    • These may be formed by compressed aggregates of tubules
    • There is no immunohistochemical or genetic evidence that they are precursors of conventional carcinoma
  • May be seen in sporadic patients and in those with end stage renal disease (Tickoo)
  • Relationship to clear cell renal cell carcinoma with angioleiomyomatous stroma is not clear (Kuhn; Shannon; Mai 2010)
    • Reported cases are CK7+ but CD10+ also (small numbers tested)
    • Three cases studied with FISH show chromosome 3 abnormalities consistent with conventional clear cell RCC (Shannon)

Kurt Schaberg MD
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
Last update: 11/11/16

Supplemental studies

Immunohistology

CK7, EMA, PAX2, PAX8 100% pos
Carbonic anhydrase IX (CA9) 100% pos, basal or cup-like
CD10 neg to focal (<10% of cells)
AMACR/racemase/P504S neg
TFE3

neg

Genetic Studies

  • While not typically used for diagnosis, clear cell tubulopapillary carcinomas are distinct from both conventional clear cell and papillary carcinomas

Differential Diagnosis

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

Conventional Clear Cell Renal Cell Carcinoma Clear Cell Papillary Renal Cell Carcinoma
Sheets and clusters of cells with extensive vascular network Nearly all have branched tubules and anastomosing ribbons
Solid areas have clusters more than two cells wide Solid areas usually formed by compressed tubules, each only two cells wide
May have high grade nuclear features, vascular invasion and necrosis Low grade nuclear features, no invasion or necrosis
Cysts frequently due to degeneration, lined in areas by multiple layers of cells Uniformly lined by single layer of cells
Clear cytoplasm apical or diffuse, non-localized Linear arranged apical to mid cell, frequent regular basal clearing, resembling interval endometrium
Usually CK7 neg, CD10 pos, CA9 diffuse CK7 pos, CD10 neg to focal, CA0 basal/cup-like

MiT Family Translocation Renal Cell Carcinoma Clear Cell Papillary Renal Cell Carcinoma
Frequently occurs under age 20 Mean age 60
Typically high grade nuclear features Low grade nuclear features, nuclei linear, apical
Voluminous cytoplasm Moderate amount of clear cytoplasm
TFEB or TPF3 immunostain or FISH positive Lacks TFEB or TPF3 translocations
CK7 and other keratins negative to weak, CD10 pos, Racemase/AMACR pos CK7 strong pos, CD10 neg, Racemase/AMACR neg
Variable expression of melanocytic markers Melanocytic markers neg
CA9 negative CA9 s basolateral positive

Multilocular Renal Cell Neoplasm of Low Malignant Potential Clear Cell Papillary Renal Cell Carcinoma
No tubules, ribbons or papillae Nearly all have branched tubules, anastomosing ribbons and papillae
Clear cytoplasm apical or diffuse, non-localized Frequent regular basal clearing, resembling interval endometrium
Nests of clear cells in septa Nests of clear cells if present are formed by compressed tubules, each of which is only two cells wide
CK7 neg, CD10 pos CK7 pos, CD10 neg to focal

Grading / Staging

Grading

  • By definition they have grade 1 or 2 nuclei
  • Grade should be assigned based on the siingle high power field showing the greatest degre of nuclear pleomorphism
  • 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

Staging

  • Use TNM for renal cell carcinoma
    • 95% are pT1a

Clinical

  • Mean age about 60
    • Range 26-85
  • No aggressive behavior or metastases reported
  • Althouogh originally described ih end stage renal disease it is now recognized more commonlly sporadically
    • Same appearance and indolent behavior

Classification / Lists

Renal epithelial neoplasms

Bibliography

  • Aydin H, Chen L, Cheng L, Vaziri S, He H, Ganapathi R, Delahunt B, Magi-Galluzzi C, Zhou M. Clear cell tubulopapillary renal cell carcinoma: a study of 36 distinctive low-grade epithelial tumors of the kidney. Am J Surg Pathol. 2010 Nov;34(11):1608-21.
  • Srigley JR, Delahunt B. Uncommon and recently described renal carcinomas. Mod Pathol. 2009 Jun;22 Suppl 2:S2-S23.
  • Kuhn E, De Anda J, Manoni S, Netto G, Rosai J. Renal cell carcinoma associated with prominent angioleiomyoma-like proliferation: Report of 5 cases and review of the literature. Am J Surg Pathol. 2006 Nov;30(11):1372-81.
  • Shannon BA, Cohen RJ, Segal A, Baker EG, Murch AR. Clear cell renal cel carcinoma with smooth muscle stroma. Hum Pathol. 2009 Mar;40(3):425-9. Epub 2008 Sep 11.
  • Mai KT, Faraji H, Desantis D, Robertson SJ, Belanger EC, Levac J. Renal cell carcinoma with mixed features of papillary and clear cell cytomorphology: a fluorescent in situ hybridization study. Virchows Arch. 2010 Jan;456(1):77-84.
  • Mai KT, Kohler DM, Belanger EC, Robertson SJ, Wang D. Sporadic clear cell renal cell carcinoma with diffuse cytokeratin 7 immunoreactivity. Pathology. 2008 Aug;40(5):481-6.
  • Michal M, Hes O, Nemcova J, Sima R, Kuroda N, Bulimbasic S, Franco M, Sakaida N, Danis D, Kazakov DV, Ohe C, Hora M. Renal angiomyoadenomatous tumor: morphologic, immunohistochemical, and molecular genetic study of a distinct entity. Virchows Arch. 2009 Jan;454(1):89-99.
  • Tickoo SK, dePeralta-Venturina MN, Harik LR, Worcester HD, Salama ME, Young AN, Moch H, Amin MB. Spectrum of epithelial neoplasms in end-stage renal disease: an experience from 66 tumor-bearing kidneys with emphasis on histologic patterns distinct from those in sporadic adult renal neoplasia. Am J Surg Pathol. 2006 Feb;30(2):141-53.
  • Gobbo S, Eble JN, Grignon DJ, Martignoni G, MacLennan GT, Shah RB, Zhang S, Brunelli M, Cheng L. Clear cell papillary renal cell carcinoma: a distinct histopathologic and molecular genetic entity. Am J Surg Pathol. 2008 Aug;32(8):1239-45.
  • Adam J, Couturier J, Molinié V, Vieillefond A, Sibony M. Clear-cell papillary renal cell carcinoma: 24 cases of a distinct low-grade renal tumour and a comparative genomic hybridization array study of seven cases. Histopathology. 2011 Jun;58(7):1064-71.
  • Rohan SM, Xiao Y, Liang Y, Dudas ME, Al-Ahmadie HA, Fine SW, Gopalan A, Reuter VE, Rosenblum MK, Russo P, Tickoo SK. Clear-cell papillary renal cell carcinoma: molecular and immunohistochemical analysis with emphasis on the von Hippel-Lindau gene and hypoxia-inducible factor pathway-related proteins. Mod Pathol. 2011 Sep;24(9):1207-20.
  • Moch H, Humphrey PA, Ulbright TM, Reuter VE eds. World Health Organization Classification of Tumors. Pathology and genetics of tumors of the Urinary System and Male Genital Organs, 4th edition,. IARC Press: Lyon 2016.
Printed from Surgical Pathology Criteria: http://surgpathcriteria.stanford.edu/
© 2010  Stanford University School of Medicine