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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::1/24/11
Last update: 6/2/15

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

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

  • 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

  • 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)

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.
  • Srigley JR, Delahunt B, Eble JN, Egevad L, Epstein JI, Grignon D, Hes O, Moch H, Montironi R, Tickoo SK, Zhou M, Argani P; ISUP Renal Tumor Panel. The International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia. Am J Surg Pathol. 2013 Oct;37(10):1469-89. doi: 10.1097/PAS.0b013e318299f2d1. PubMed PMID: 24025519.
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