Kidney tumor

Benign adult tumors

Clear cell papillary renal cell tumor


Editorial Board Member: Debra L. Zynger, M.D.
Deputy Editor-in-Chief: Maria Tretiakova, M.D., Ph.D.
Daniel L. Shen, M.D.
Gregory MacLennan, M.D.

Last author update: 21 November 2022
Last staff update: 28 November 2022

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PubMed search: Clear cell papillary renal cell tumor

Daniel L. Shen, M.D.
Gregory MacLennan, M.D.
Page views in 2022 to date: 269
Cite this page: Shen DL, MacLennan G. Clear cell papillary renal cell tumor. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneytumorclearcellpapillary.html. Accessed December 3rd, 2022.
Definition / general
  • Indolent tumor with clear glycogen rich cytoplasm, luminal nuclear polarization, inconspicuous nucleoli and with papillary architecture with fibrovascular stroma
  • Distinctive immunohistochemical profile: positive CK7 and CAIX, with negative or patchy CD10 and AMACR
Essential features
  • Renamed in WHO 5th edition to reflect indolent behavior (previously was designated as a renal cell carcinoma)
  • Clear cytoplasm, luminal nuclear polarization, low nuclear grade (histologic grade 1 - 2)
  • Papillary architecture with fibrovascular stroma
  • CK7 / CAIX positive; CD10 / AMACR patchy or negative
  • Lacks features of high grade malignancies, including necrosis and vascular invasion
  • No reported metastasis or recurrence following adequate resection
Terminology
ICD coding
  • ICD-O: 8323/1 - clear cell papillary renal cell carcinoma
Epidemiology
Sites
  • Renal cortex; predominately unifocal, with multifocality in 25% of cases (multifocality is predominantly seen in ESRD patients)
Pathophysiology
  • Unknown at this time
Etiology
  • Etiology is unclear; lacks genetic modifications and driver mutations frequently associated with other renal cell carcinomas (RCC)
  • First described in association with ESRD, particularly acquired cystic disease of the kidney (ACDK) (Am J Surg Pathol 2006;30:141)
  • It is now known that most cases arise sporadically, with no evidence of somatic VHL gene inactivation or chromosome 3p loss, unlike clear cell renal cell carcinoma (CCRCC) (Arch Pathol Lab Med 2019;143:1154)
  • Believed to be associated with upregulation of the hypoxia inducible factor 1 pathway, similar to other RCCs but through a non-VHL dependent mechanism
    • Evidence suggests a shift away from respiratory metabolism, toward sorbitol pathway of tumorigenesis (Elife 2019;8:e38986)
Clinical features
Diagnosis
  • Usually initially identified by radiographic imaging (CT or ultrasound)
  • Diagnosis confirmed after surgical resection and microscopic examination
Radiology description
  • Generally 2 categories of findings: solid and cystic, with Bosniak III or IV features (Urology 2017;103:136, AJR Am J Roentgenol 2020;214:579)
    • Solid: mass with relatively low level enhancement, with well defined margins
    • Cystic: heterogeneous regions of hyper enhancement and predominantly unilocular
    • These findings are shared with both clear cell and papillary renal cell carcinoma enhancement patterns
Prognostic factors
  • Unknown at this time
Case reports
Treatment
  • Radical nephrectomy or nephron sparing surgery, including partial nephrectomy or cryoablation therapy
Gross description
  • Mean size: 2.0 cm (0.2 - 7.5 cm)
  • Solid or cystic, occasionally with flattened peripheral cysts (Int J Mol Sci 2021;23:151)
  • Relatively small and well encapsulated within a fibrous capsule
  • Solid tumor component cut surface appears tan-white, pink-tan, yellow or red-brown in color
  • Necrosis is not observed; focal areas of hemorrhage may occasionally be present
Gross images

Contributed by Gregory MacLennan, M.D.
Partial nephrectomy specimen Partial nephrectomy specimen

Partial nephrectomy specimens

Acquired cystic kidney disease

Acquired cystic kidney disease

Microscopic (histologic) description
  • Various proportions of 2 broad patterns:
    1. Focally branched papillary architecture with hypocellular fibrovascular cores lined by cuboidal to flat cells with clear cytoplasm projecting into cystic spaces; extensively branched papillae are uncommon
    2. Areas of dense, compact arrangement of tubular structures lined by clear cells with characteristic luminal polarization of nuclei
  • Nuclear and nucleolar size, almost always histologic grade 1 or 2
  • Extrarenal extension including vascular invasion is not seen
  • Stroma may be fibromyomatous but unusual or conspicuous amounts of fibromyomatous stroma should raise concern for a different entity, a distinct renal epithelial neoplasm harboring mutations in TSC1, TSC2, MTOR and ELOC / TCEB1 (see Differential diagnosis)
  • Eosinophilic secretions may be seen
  • Reference: Epstein: Differential Diagnoses in Surgical Pathology - Genitourinary System, 2nd Edition, 2022
Microscopic (histologic) images

Contributed by Gregory MacLennan, M.D.
Overall architecture Overall architecture

Overall architecture

Papillary architecture

Papillary architecture

Tubular architecture

Tubular architecture

Low grade nuclear features Low grade nuclear features

Low grade nuclear features


CAIX IHC

CAIX

CK7 IHC

CK7

CD10 IHC

CD10

AMACR IHC

AMACR

Virtual slides

Images hosted on other servers:

CCPRCT

Cytology description
  • Tumor cells arranged in small nests, clusters, arrays or as single cells (Cancer Cytopathol 2017;125:48)
  • Columnar tumor cells with eccentric, small, round to oval nuclei with evenly distributed, finely granular chromatin and regular nuclear membrane contour
  • Clear cytoplasm containing small vacuoles, with ill defined cytoplasmic borders
  • Chief value may be to provide a differential diagnosis that includes clear cell papillary renal cell tumor (Cancer Cytopathol 2021;129:190)
Positive stains
Negative stains
Molecular / cytogenetics description
  • Not well understood
  • Various chromosomal aberrations identified: monosomy of chromosomes 16, 17, 20; trisomy of chromosomes 10, 12 (Int J Mol Sci 2021;23:151)
    • Lower frequency of chromosome 7 and 17 trisomy than PRCC (Int J Mol Sci 2021;23:151)
    • Small proportion of patients with von Hippel-Lindau (VHL) disease develop tumor with morphology and immunohistochemical expression consistent with CCPRCT; however, such tumors appear to be genomically related to CCRCC and distinct from CCPRCT (Hum Pathol 2014;45:1966Am J Surg Pathol 2013;37:1131)
    • Absence of VHL gene modifications are observed in cases with immunohistochemical coexpression of CAIX, HIF1 and GLUT1, suggesting VHL mutation independent mechanism of HIF pathway activation
    • Hypothesized sorbitol accumulation as a method of HIF1 pathway activation (Int J Clin Exp Pathol 2014;7:7312)
  • Mitochondrial DNA:
  • Noncoding RNA:
    • Overexpression of miR-200a, miR-200b, miR-200c, miR-141 and miR-429, suggesting enhanced E-cadherin mediated suppression of tumor progression (J Pathol 2014;232:32)
    • Upregulation of miR-210 is associated with VHL independent manner of HIF1 pathway activation (J Vet Sci 2013;14:69)
Sample pathology report
  • Right kidney, partial nephrectomy:
    • Clear cell papillary renal cell tumor, 2.5 cm
    • Surgical margins, negative for tumor
    • Comment: Immunostaining demonstrate diffuse positivity for CAIX and CK7 and negative staining for CD10 and AMACR.
Differential diagnosis
  • Clear cell renal cell carcinoma:
    • Papillary architecture absent or very limited
    • Nuclei are not aligned (does not have piano key appearance)
    • May present with higher grade nuclear features, necrosis and hemorrhage
    • Also has diffuse CAIX but is positive for CD10 and negative or focal for CK7
    • Loss of chromosome 3p commonly seen
  • Papillary renal cell carcinoma:
    • Clear glycogenated cytoplasm is rare
    • Foamy macrophages and psammoma bodies are common
    • Also usually positive for CK7 but negative or only focal CAIX and often has apical CD10 expression
    • Some have +7 / +17 chromosomes
  • Xp11 translocation carcinoma:
  • Renal angiomyoadenomatous tumor (RAT):
    • Shares similarities in the absence of VHL gene mutations / modifications and chromosome 3p loss
    • Biphasic tumor with collapsed acinar architecture and angioleiomyoma-like fibrous / smooth muscle stroma
    • Tumors with the appearance of clear cell papillary renal cell tumor but with conspicuous fibromyomatous stroma, may represent a distinct renal epithelial neoplasm harboring mutations in TSC1, TSC2, MTOR and ELOC / TCEB1 (Am J Surg Pathol 2015;39:889, Am J Surg Pathol 2019;43:1135, Am J Surg Pathol 2020;44:571)
Board review style question #1

Which of the following is most strongly associated with this kidney lesion?

  1. Absence of metastasis
  2. Female predilection
  3. Pyelonephritis
  4. Smoking history
  5. Von Hippel-Lindau disease
Board review style answer #1
A. Absence of metastasis

Comment Here

Reference: Clear cell papillary renal cell tumor
Board review style question #2
Clear cell papillary renal cell tumors are indolent tumors with distinct histologic findings. Which of the following immunohistochemical profiles would best support this diagnosis?

  1. CD10+, CAIX+, CK7+, AMACR-
  2. CD10-, CAIX-, CK7+, AMACR-
  3. CD10-, CAIX+, CK7+, AMACR-
  4. CD10+, CAIX+, CK7-, AMACR+
  5. CD10+, CAIX+, CK7- AMACR-
Board review style answer #2
C. CD10-, CAIX+, CK7+, AMACR-

Comment Here

Reference: Clear cell papillary renal cell tumor
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