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Renal Cell Carcinoma Associated with End Stage Renal Disease

Definition

  • Two types of distinctive renal cell carcinomas associated with end stage renal disease

Diagnostic Criteria

  • Classical types of renal cell tumors can occur with end stage renal disease (ESRD)
    • Clear cell, papillary, chromophobe carcinomas
    • Collecting duct, tubulocystic, translocation carcinomas
    • Oncocytoma, angiomyolipoma also reported
  • More common are two distinctive patterns:
    • Aquired cystic disease associated renal cell carcinoma
      • Surrounded by pseudocapsule with frequent dystrophic calcification
      • Frequently can be seen to arise in and fill a cyst
      • Solid or acinar patterns, may be micro or macrocystic
        • Papillary foci may be present
      • Abundant to voluminous granular eosinophilic cytoplasm, occasionally focally clear
      • Microcribriform appearance due to frequent intracytoplasmic and intercellular microlumens
      • Large nuclei with prominent nucleoli, Fuhrman grade 3
      • Frequent oxalate crystals and calcifications
      • Occurs only in patients with ESRD with cystic disease
    • Clear cell tubulopapillary renal cell carcinoma of end stage kidneys
      • Predominantly tubulopapillary pattern
      • Frequently cystic
      • Clear cytoplasm
      • Cytologically low grade, Fuhrman 1 or 2
      • Frequently apically polarized nuclei
        • Separated from base by clear cytoplasm
          • Reminiscent of early secretory endometrium
      • Primarily occurs in ESRD but rarely same tumor appears sporadically (Aydin)
  • Incidence of carcinoma in ESRD is elevated 100x compared to general population
    • Especially elevated with aquired cystic disease
      • Also elevated in familial polycystic disease
    • Less frequently seen in ESRD in the absence of cystic disease, but does happen

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
Updates: 11/11/11

Supplemental studies

Immunohistology

  • Aquired cystic disease associated renal cell carcinoma
    • Racemase/AMACR/P504S, AE1/3 keratin, CD10, vinculin positive
    • Vimentin variable
    • EMA, CK7, high molecular weight keratin negative or focal
  • Clear cell papillary renal cell carcinoma of end stage kidneys
    • CK7 positive
    • Racemase negative
    • TFE3 and TFEB negative

Differential Diagnosis

  • The diagnosis typically is made easily in the context of ESRD
  • Both distinctive types of carcinoma may be separated from conventional types of renal cell carcinoma using standard criteria
    • Acquired cystic disease associated renal cell carcinoma
      • Distinguished by abundant/voluminous eosinophilic cytoplasm
      • Cribriform pattern formed by intra- and intercellular lumens
    • Clear cell tubulopapillary renal cell carcinoma of end stage kidneys

Xp11 Translocation Renal Cell Carcinoma Clear Cell Tubulopapillary Renal Cell Carcinoma
Frequently occurs under age 20 Mean age 60
Typically high grade nuclear features Low grade nuclear features
Voluminous cytoplasm Moderate amount of clear cytoplasm
TPE3 immunostain or FISH positive in >80% Lacks Xp11 translocations
CK7 and other keratins negative to weak, CD10 pos, Racemase/AMACR pos CK7 strong pos, CD10 neg, Racemase/AMACR neg

  • Renal papillary adenoma also appears in end stage kidneys with increased frequency
    • Neither clear cells nor high grade cytology are permitted for the diagnosis of adenoma

Grading / Staging

Grading

  • Use Fuhrman grading, but clinical correlation is not clear (see below)

Staging

  • Use TNM for renal cell carcinoma

  • Most commonly cited grading scheme is that of Fuhrman
    • Requires simultaneous assessment of three features: nuclear size, shape and nucleoli
      • Nuclear size may be subject to fixation variables and difficult to measure
      • No provision for cases with discrepant grade features
      • Poor interobserver agreement
  • We and others find a simplified version based primarily on nucleolar prominence to be more practical
    • This approach has been shown to have predictive value for clear cell and papillary carcinomas (Lohse; Sika-Paotonu; Delahunt)
    • Grade based on worst high powered field
    • Does not apply to chromophobe carcinoma or oncocytomas
    • Is provisionally applied to various other types and variants of RCC but has not been validated
      • Complete Fuhrman grading has not been validated on other types either
    Simplified Fuhrman Grading
  • Grade 1 Small, round, dark lymphocyte-like nuclei with without visible nucleoli
    Grade 2 Inconspicuous nucleoli, visible only at 200-400X (nuclei usually small and uniform with open, finely granular chromatin)
    Grade 3 Prominent nucleoli, easily visible at 100X (nuclei usually mildly to moderately pleomorphic)
    Grade 4 Markedly pleomorphic, bizarre nuclei, giant cells, multiple nucleoli
    • 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.

    Clinical

    • Prevalence of 1.64% in ESRD
    • Behavior uncertain

    Classification / Lists

    Renal epithelial neoplasms

    Bibliography

    • Srigley JR, Delahunt B. Uncommon and recently described renal carcinomas. Mod Pathol. 2009 Jun;22 Suppl 2:S2-S23.
    • Nouh MA, Kuroda N, Yamashita M, Hayashida Y, Yano T, Minakuchi J, Taniguchi S, Nomura I, Inui M, Sugimoto M, Kakehi Y. Renal cell carcinoma in patients with end-stage renal disease: relationship between histological type and duration of dialysis. BJU Int. 2010 Mar;105(5):620-7.
    • 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.
    • Pan CC, Chen YJ, Chang LC, Chang YH, Ho DM. Immunohistochemical and molecular genetic profiling of acquired cystic disease-associated renal cell carcinoma. Histopathology. 2009 Aug;55(2):145-53.
    • 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.
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