Kidney tumor

Adult renal cell carcinoma - common

Papillary



Last author update: 1 November 2023
Last staff update: 1 November 2023

Copyright: 2003-2024, PathologyOutlines.com, Inc.

PubMed Search: Papillary renal cell carcinoma

See Also: Type 1, Type 2, Solid pattern

Vincent Francis Castillo, M.D.
Rola Saleeb, M.D., Ph.D.
Page views in 2023: 54,538
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Cite this page: Castillo VF, Saleeb R. Papillary. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneytumormalignantrccpap.html. Accessed February 23rd, 2024.
Definition / general
  • Usually circumscribed malignant neoplasm characterized by predominantly papillary or tubulopapillary architecture
Essential features
  • Predominantly papillary or tubulopapillary pattern lined by small, basophilic cells or large, eosinophilic cells
  • Size cut off > 15 mm; often contain foamy histiocytes and psammoma bodies
  • Must exclude other renal cell carcinomas (RCCs) with papillary architecture
  • Alpha methyacyl CoA racemase (AMACR) positivity is a desirable feature
  • Histologic subclassification to type 1 and type 2 is no longer recommended
    • Due to poor interobserver reproducibility, the presence of overlapping features in a significant proportion of cases, the lack of prognostic significance and the historical inclusion of outliers (newly recognized entities) in the old type 2 category (Mod Pathol 2021;34:1392)
Terminology
  • Not recommended: tubulopapillary renal cell carcinoma, renal papillary adenocarcinoma, chromophil renal cell carcinoma
ICD coding
  • ICD-O: 8260/3 - papillary renal cell carcinoma
  • ICD-11: 2C90.0 & XH1D07 - renal cell carcinoma of kidney, except renal pelvis & papillary renal cell carcinoma
Epidemiology
Sites
  • Renal cortex
Pathophysiology
  • MET alterations are found mainly in low grade tumors
  • CDKN2A, MYC pathway and NRF2-ARE pathway aberrations are observed in high grade tumors
  • Other pathways or complexes implicated in papillary renal cell carcinoma (PRCC) are the Hippo signaling pathway, SWI / SNF complex and chromatin modifier pathways (N Engl J Med 2016;374:135)
Etiology
Diagrams / tables

Contributed by Rola Saleeb, M.D., Ph.D.
DDx for low grade PRCC

DDx for low grade PRCC

DDx for high grade PRCC

DDx for high grade PRCC

Clinical features
  • Usually asymptomatic; incidental finding on imaging
  • Maybe multifocal or bilateral in chronic kidney disease and hereditary PRCC (germline MET mutation)
Diagnosis
  • Based on the assessment of both the morphology and immunohistochemical profile
  • Essential to exclude outliers particularly in high grade lesions
Radiology description
  • No specific radiologic findings
  • Homogenous, solid mass with relative hypovascularity compared to nonpapillary RCC; may have cystic change and calcifications (Urol Oncol 2021;39:327)
Radiology images

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Hypoenhacing lesion on CT

Hypoenhacing lesion on CT

CT scan upper pole tumor

Prognostic factors
Case reports
Treatment
  • Resection or ablation for localized disease
  • Selective MET kinase inhibitor, MET / VEGF inhibitor, multitargeted tyrosine kinase inhibitors (TKIs) and PD-1 / PDL1 inhibitors for advanced or metastatic disease (Curr Opin Urol 2022;32:344)
  • For advanced metastatic PRCC cabozantinib shows higher efficacy over sunitinib and other MET kinase inhibitors (Lancet 2021;397:695)
Gross description
  • Most tumors are circumscribed, surrounded by a pseudocapsule (Adv Anat Pathol 2019;26:124)
  • Yellow-tan, red-brown or variegated cut surfaces
  • Granular or friable in appearance consistent with the papillary morphology
  • Variable areas of necrosis and cystic degeneration (Cancer 1976;38:2469)
Gross images

Contributed by Nicole K. Andeen, M.D. and Maria Tretiakova, M.D., Ph.D.
Granular cut surface

Granular cut surface



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Circumscribed tumor with extensive hemorrhage

Circumscribed tumor with extensive hemorrhage 

Encapsulated tumor with hemorrhage and necrosis

Encapsulated tumor with hemorrhage and necrosis 

Tumor with capsular invasion

Tumor with capsular invasion 

Tan-pink mass with satellite nodules

Renal vein extension

Frozen section images

Contributed by Debra L. Zynger, M.D.

Delicate papillary cores

Microscopic (histologic) description
  • Predominantly papillary or tubulopapillary architecture (Mod Pathol 2021;34:1392)
  • Lined by cells with variation of morphologies, ranging from small, basophilic cuboidal cells with inconspicuous nucleoli to large, eosinophilic cells with prominent nucleoli; may have clear cytoplasm, known pitfall to have clearing in PRCC
  • Cells can be arranged in linear or a pseudostratified pattern
  • Heterogeneity and mixed morphology are very common (47 - 48% of cases), hence this is one of the reasons why typing is no longer favored (Mod Pathol 2021;34:1392, Am J Surg Pathol 2014;38:887, Am J Surg Pathol 2017;41:1618)
  • Often infiltrated by foamy macrophages
  • Psammoma bodies and hemosiderin pigments can be present
  • Reported patterns (Mod Pathol 2021;34:1392)
    • Biphasic (alveolar / squamoid) PRCC
      • Dual cell populations, nests of larger (squamoid) eosinophilic cells surrounded by smaller amphophilic cells forming an alveolar pattern
      • Evidence of aggressive behavior has been documented in up to 15% of the cases (Histopathology 2018;72:777)
    • Warthin-like PRCC
      • Eosinophilic papillae with dense lymphocytic infiltrates resembling Warthin tumor of the salivary gland
      • Usually high grade tumors that can exhibit aggressive clinical behavior (Ann Diagn Pathol 2017;27:48)
    • Solid (pseudosolid) PRCC
      • Solid architecture due to compressed tubular and papillary structures, lined by small cells with low grade nuclei
      • Reported to have an indolent clinical behavior (Ann Diagn Pathol 2016;23:51)
  • Histologic patterns associated with worse prognosis: solid, micropapillary, hobnailing, microcystic architecture (Am J Surg Pathol 2020;44:582, Am J Surg Pathol 2022;46:392)
  • WHO / ISUP grading system has been validated as a prognostic parameter for PRCC
Microscopic (histologic) images

Contributed by Rola Saleeb, M.D., Ph.D., Vincent Francis Castillo, M.D., Nicole K. Andeen, M.D.,
Maria Tretiakova, M.D., Ph.D., Semir Vranić, M.D., Ph.D. and @SueEPig on Twitter

Circumscribed mass

Circumscribed mass

Papillary architecture

Papillary architecture

Low grade PRCC

Low grade PRCC

PRCC with foamy histiocytes and hemosiderin

PRCC with foamy histiocytes and hemosiderin

Foamy macrophages

Foamy macrophages

PRCC with clear cytoplasm

PRCC with clear cytoplasm


High grade PRCC

High grade PRCC

High grade eosinophilic cells

High grade eosinophilic cells

Pseudosolid pattern

Pseudosolid pattern

Psammoma bodies

Psammoma bodies

Tubulopapillary architecture

Tubulopapillary architecture

PRCC with low grade morphology

PRCC with low grade morphology


PRCC with high grade morphology

PRCC with high grade morphology

Papillary renal cell carcinoma Papillary renal cell carcinoma

Papillary renal cell carcinoma

AMACR positive

AMACR positive

CK7 focally positive

CK7 focally positive

Retained FH expression

Retained FH expression

Virtual slides

Images hosted on other servers:
Papillary renal cell carcinoma

Papillary renal cell carcinoma

Cytology description
  • Papillary fragments with fibrovascular cores
  • Cohesive clusters of small cells with bland nuclei in low grade tumors
  • Intracellular hemosiderin, foamy macrophages (Cancer 1998;84:303)
Cytology images

Contributed by Debra L. Zynger, M.D.

Papillary structures and foamy histiocytes



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Foamy macrophages

Foamy macrophages

Papillary tissue fragment

Papillary tissue fragment

Positive stains
Negative stains

Renal tumors AMACR CK7 Vimentin CAIX CD117 TFE3 FH SDH
Papillary RCC + Variable + - - - + (retained) + (retained)
Clear cell RCC -/+ - + + - - + (retained) + (retained)
Chromophobe RCC - + - - + - + (retained) + (retained)
Oncocytoma - - - - + - + (retained) + (retained)
TFE3 rearranged RCC + - - - - + + (retained) + (retained)
FH deficient RCC Variable - Variable - - - - (loss) + (retained)
SDH deficient RCC - - - - - - + (retained) - (loss)

Molecular / cytogenetics description
  • No molecular markers specific for the diagnosis of PRCC
  • Chromosome 7 and 17 gains and loss of Y chromosome in low grade tumors (N Engl J Med 2016;374:135)
  • MET mutations seen in former type 1 and low grade PRCC; CDKN2A mutation or promoter methylation in aggressive PRCC (N Engl J Med 2016;374:135)
  • Exclude FH gene mutation and TFE3 rearrangements for high grade PRCC
Sample pathology report
  • Right kidney (mass), biopsy:
    • Papillary renal cell carcinoma
    • WHO / ISUP grade 3 in this limited specimen

  • Right kidney (mass), partial nephrectomy:
    • Papillary renal cell carcinoma, pT1a (see synoptic report)
    • WHO / ISUP grade 2
    • Tumor size: 2.5 cm
    • Tumor is limited to kidney
    • Negative for sarcomatoid / rhabdoid features and necrosis
    • Negative for vascular and lymphovascular invasion
    • All margins are negative for tumor
Differential diagnosis
Board review style question #1

A 65 year old man presented with an 8 cm kidney tumor located in the right lower pole extending to the renal sinus. Cut sections showed an encapsulated mass with brown-red surface and necrotic areas. Microscopic examination showed almost exclusively tubulopapillary architecture, which is lined by cells with voluminous, eosinophilic cytoplasm and nuclei with very prominent nucleoli. Calcifications were also noted. Which of the following IHC results are expected in PRCC?

  1. CAIX negative, CD117 negative, AMACR positive, CK7 negative, FH loss, TFE3 negative
  2. CAIX negative, CD117 negative, AMACR positive, CK7 negative, FH retained, TFE3 positive
  3. CAIX negative, CD117 negative, AMACR positive, CK7 patchy, FH retained, TFE3 negative
  4. CAIX negative, CD117 positive, AMACR negative, CK7 positive, FH retained, TFE3 negative
  5. CAIX positive, CD117 negative, AMACR negative, CK7 negative, FH retained, TFE3 negative
Board review style answer #1
C. PRCC is CAIX negative, CD117 negative, AMACR positive, CK7 patchy, FH retained, TFE3 negative. While CK7 is usually positive in PRCC, it may be negative or focal in high grade PRCC. Answer E is incorrect because clear cell RCC is CAIX positive, CD117 negative, AMACR negative, CK7 negative, FH retained, TFE3 negative. Answer A is incorrect because FH deficient RCC is CAIX negative, CD117 negative, AMACR positive, CK7 negative, FH loss, TFE3 negative. Answer D is incorrect because chromophobe RCC is CAIX negative, CD117 positive, AMACR negative, CK7 positive, FH retained, TFE3 negative. Answer B is incorrect because TFE3 rearranged RCC is CAIX negative, CD117 negative, AMACR positive, CK7 negative, FH retained, TFE3 positive.

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Reference: Papillary renal cell carcinoma
Board review style question #2
Regarding papillary renal cell carcinoma, which of the following statements is true?

  1. CK7 is always positive in PRCC
  2. MET mutations are usually seen in aggressive PRCC
  3. Tumors with tubulopapillary, solid and cystic architecture lined by eosinophilic, high grade nuclei is diagnostic of PRCC and does not warrant further IHC studies
  4. WHO / ISUP nucleolar grading has prognostic significance in PRCC and should be reported
Board review style answer #2
D. WHO / ISUP nucleolar grading is accepted as a prognostic histopathologic marker for PRCC and is recommended to be included in surgical pathology report. Answer B is incorrect because MET mutations are mostly observed in low grade PRCC. Answer C is incorrect because tumors composed of histologic patterns other than papillary or tubulopapillary like solid and cystic architecture should raise suspicion for potential mimickers of high grade PRCC. Therefore, IHC studies are recommended. Answer A is incorrect because CK7 can be negative or focal in PRCC with high grade features.

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Reference: Papillary renal cell carcinoma
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