Kidney tumor
Adult renal cell carcinoma - common
Papillary
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Last author update: 1 March 2018
Last staff update: 26 May 2023 (update in progress)
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PubMed Search: "Papillary type" renal cell carcinoma kidney
See Also: Type 1, Type 2, Solid pattern
Table of Contents
Definition / general | Essential features | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Frozen section images | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Cytology images | Positive stains | Negative stains | IHC panels | Electron microscopy description | Molecular / cytogenetics description | Differential diagnosis | Board review style question #1 | Board review style answer #1Cite this page: Andeen NK, Tretiakova M. Papillary. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneytumormalignantrccpap.html. Accessed June 9th, 2023.
Definition / general
- Malignant neoplasm derived from renal tubular epithelium with predominantly papillary or tubulopapillary architecture (Moch: WHO Classification of Tumours of the Urinary System and Male Genital Organs, 4th Edition, 2016); often well circumscribed and encapsulated
- Second most commonly encountered renal cell carcinoma (RCC), comprising approximately 18.5% of RCCs (Moch: WHO Classification of Tumours of the Urinary System and Male Genital Organs, 4th Edition, 2016)
- Type 1 vs. type 2 described in 1997 by Delahunt and Elbe (Mod Pathol 1997;10:537)
Essential features
- Papillary renal cell carcinoma (PRCC) comprises more than one entity which may have morphologic overlap but have distinct molecular pathways and clinical behavior, currently grouped at least into type 1 and type 2 PRCC
- Subclassification (type 1 or 2) and exclusion of other renal cell carcinomas with papillary architecture is important
- Type 1 PRCC:
- Papillae are lined by a single layer of cells with scanty basophilic cytoplasm and low nuclear grade
- Have +7, +17 and other trisomies, MET mutations, better prognosis
- Type 2 PRCC:
- Papillae are lined by pseudostratified layers of cells with more abundant eosinophilic cytoplasm and higher nucleolar grade
- Multiple genetic changes described, likely represents more than one entity, worse prognosis
- Type 1 PRCC:
Epidemiology
- Mean age (59 - 63 years) is similar to clear cell renal cell carcinoma (Moch: WHO Classification of Tumours of the Urinary System and Male Genital Organs, 4th Edition, 2016)
- M:F = 1.5:1
Sites
- Kidney
Pathophysiology
- Depends on subtype
Etiology
- Most are sporadic but may be seen in familial papillary renal cell carcinoma syndrome (type 1 PRCC) and in Birt-Hogg-Dubé syndrome (Moch: WHO Classification of Tumours of the Urinary System and Male Genital Organs, 4th Edition, 2016)
Clinical features
- Presents similarly to other renal cell carcinomas; typical triad of mass, flank pain and hematuria is uncommon, found in only 5 - 10% of cases (Moch: WHO Classification of Tumours of the Urinary System and Male Genital Organs, 4th Edition, 2016)
- Tends to present at early stage (> 50% as incidental masses)
- 5 year survival is 82 - 90%; may be better than clear cell carcinoma (Am J Surg Pathol 2002;26:281)
- Although majority are unilateral, papillary renal cell carcinoma is more often bilateral and multifocal compared to other common renal cell carcinomas
Diagnosis
- In one series of papillary renal cell carcinomas, roughly 25% had classical type 1 features, 25% were type 2 and 50% had some degree of overlapping features (Am J Surg Pathol 2014;38:887)
Radiology description
- May appear hypovascular due to spontaneous tumor necrosis (Moch: WHO Classification of Tumours of the Urinary System and Male Genital Organs, 4th Edition, 2016)
- Up to 30% may have foci of calcifications (Moch: WHO Classification of Tumours of the Urinary System and Male Genital Organs, 4th Edition, 2016)
- Radiology techniques may detect differences between clear cell renal cell carcinoma (Moch: WHO Classification of Tumours of the Urinary System and Male Genital Organs, 4th Edition, 2016) as well as between type 1 and type 2 papillary renal cell carcinoma (Abdom Radiol (NY) 2017;42:1911)
Radiology images
Images hosted on other servers:
CT scan upper pole tumor
Prognostic factors
- Need to distinguish between type 1 and type 2 papillary renal cell carcinoma for accurate prognosis
Case reports
- 56 year old man with ipsilateral synchronous clear cell renal cell carcinoma (Urol Case Rep 2017;16:110)
- 70 year old man with osteosarcomatous differentiation (Int J Surg Pathol 2017;25:745)
- 78 year old man with collision tumor with oncocytoma (Am J Clin Pathol 2015;144:811)
- 83 year old man with ipsilateral synchronous urothelial carcinoma of renal pelvis (Urol Case Rep 2015;3:93)
Treatment
- Resection
- Tyrosine kinase inhibitors, including sunitinib (Ann Oncol 2015;26:1123)
- 80% of type 1 papillary renal cell carcinomas have an alteration in MET genetic sequence or copy number and may be susceptible to inhibitors of MET pathway (NIH: Papillary Kidney Carcinoma [Accessed 27 March 2018])
- Systemic therapy varies (NCCN: NCCN Guidelines [Accessed 27 March 2018])
Gross description
- Often circumscribed with prominent pseudocapsule
- Occurs in renal cortex, may be multifocal
- Tan-yellow to red-brown
- Friable tumor may "pour out" of kidney
- Larger tumors may contain cystic degeneration, fibrosis, hemorrhage and necrosis (Moch: WHO Classification of Tumours of the Urinary System and Male Genital Organs, 4th Edition, 2016)
- Looks necrotic but microscopically less necrosis than expected
Gross images
Contributed by Nicole K. Andeen, M.D. and Maria Tretiakova, M.D., Ph.D.
PRCC
Images hosted on other servers:
Tan pink mass with satellite nodules
Renal vein extension
Large cystic tumor infiltrates perirenal fat
Hemorrhagic and partially necrotic tumor
Multiple tumor nodules, one is hemorrhagic cystic
Capsular invasion
Frozen section images
Contributed by Debra L. Zynger, M.D.
Delicate papillary cores
Microscopic (histologic) description
- Often circumscribed with prominent pseudocapsule
- Papillae or tubulopapillary architecture with fibrovascular cores which may contain foamy macrophages, psammoma bodies and hemosiderin
- Approximately 5% have sarcomatoid change (Moch: WHO Classification of Tumours of the Urinary System and Male Genital Organs, 4th Edition, 2016)
- Fibrovascular cores may be edematous, cystic, long or solidly packed
- Focal clear cell-like areas may be present (J Urol 2011;185:30, Am J Surg Pathol 2008;32:1780)
- Assess nucleolar prominence based upon high power field with greatest nuclear pleomorphism (Am J Surg Pathol 2006;30:1091)
- Grade according to International Society of Urological Pathology (ISUP) nucleolar grade (Pathologe 2015;36:310)
Microscopic (histologic) images
Contributed by Nicole K. Andeen, M.D., Maria Tretiakova, M.D., Ph.D., Semir Vranić, M.D., Ph.D. and @SueEPig on Twitter
Type 1
Type 2
Mixed type 1 and type 2
Type 1 PRCC
Type 2 PRCC with focal CK7 expression and diffuse AMACR expression (red)
Oncocytic variant of papillary renal cell carcinoma
Papillary renal cell carcinoma
Cytology description
- Foamy macrophages and intracytoplasmic hemosiderin (Cancer 1998;84:303)
Cytology images
Contributed by Debra L. Zynger, M.D.
Papillary structures and foamy histiocytes
Images hosted on other servers:
Foamy macrophages
Positive stains
- CK7 (83% type 1, 20% type 2) (Am J Surg Pathol 2004;28:69)
- AMACR diffuse (Am J Surg Pathol 2004;28:69, Am J Surg Pathol 2008;32:1780, Hum Pathol 2006;37:698)
- AE1 / AE3, low molecular weight cytokeratin, EMA / MUC1 (membranous), RCC Ma, CD10 (often apical staining), CK8 / CK18, CK19, vimentin (Am J Surg Pathol 2005;29:747)
- CD117 / c-kit (cytoplasmic, Mod Pathol 2004;17:611)
- Variable vimentin, variable glycogen
- PAX8, PAX2
Negative stains
- 34betaE12 (high molecular weight cytokeratin), Ulex europaeus, parvalbumin, WT1, TFE3, CAIX (variable), p63
IHC panels
| Hale | KIT | CK7 | S100A1 | VIM | CAIX | AMACR | SDH | TFE3 | |
| Chromophobe RCC | +++ | +++ | +++ | - | - | - | - | +++ | - |
| Clear cell RCC | - | - | - | - | +++ | +++ | - | +++ | - |
| Oncocytoma | - | +++ | rare | +++ | - | - | - | +++ | - |
| Papillary RCC | - | - | +++ | - | +++ | - | +++ | +++ | - |
| Translocation RCC | - | - | - | - | - | - | ++ | +++ | +++ |
| SDH deficient RCC | - | - | - | - | - | - | - | - | - |
References: Pathol Res Pract 2015;211:303, Ann Diagn Pathol 2020;44:151448, Am J Surg Pathol 2014;38:e6, Arch Pathol Lab Med 2019;143:1455, Transl Androl Urol 2019;8:S123, Hum Pathol 2020 Jul 13 [Epub ahead of print]
Electron microscopy description
- Variably sized microvilli, small amounts of cytoplasmic lipid, no glycogen
Molecular / cytogenetics description
- Molecular signatures are different between papillary renal cell carcinoma (PRCC) type 1 and 2 (Cancer Res 2005;65:5628) and potentially a third type of PRCC (Am J Surg Pathol 2017;41:1618)
- 80% of type 1 PRCCs have an alteration in MET genetic sequence or copy number (NIH: Papillary Kidney Carcinoma [Accessed 28 March 2018])
- Type 1: +7 (75%), +17 (80%), +12, +16, +20, +3q, -Y, -X (p or q for all chromosomes)
- Type 2: cytogenetically heterogenous; poorer prognosis in those with CpG island methylation or loss of CDKN2A tumor suppressor gene (NIH: Papillary Kidney Carcinoma [Accessed 28 March 2018])
- Not usually associated with p53 mutations or 3p-
Differential diagnosis
- Acquired cystic disease associated renal cell carcinoma (ACD-RCC):
- Occurs in setting of end stage renal disease, often has sieve-like architecture and abundant calcium oxalate crystals
- Clear cell renal cell carcinoma (RCC) with papillary architecture or cytoplasmic eosinophilia:
- Clear cell RCC may have papillary component but is CAIX+ and AMACR- and CK7-
- Clear cell RCC also has 3p alteration, not trisomy 7 / 17 (Am J Surg Pathol 2008;32:1780)
- Clear cell papillary RCC:
- Collecting duct carcinoma:
- High grade, infiltrative with a desmoplastic response
- Expresses high molecular weight cytokeratins, Ulex europaeus, CK7 and is negative for AMACR and CD10
- Hereditary leiomyomatosis and renal cell cancer associated RCC (HLRCC):
- May have many similar features but some cells have distinct, prominent eosinophilic nucleolus with clear halo (CMV-like) and biallelic inactivation of fumarate hydratase (FH- / 2SC nuclear and cytoplasmic expression)
- CK7 usually negative
- Metanephric adenoma:
- MiT family RCC:
- Is also papillary with eosinophilic and clear cells
- MiT family associated RCCs express cathepsin K, TFE3 / TFEB and some express HMB45 or MelanA, with limited keratin reactivity
- FISH for TFE3 tends to be technically superior to immunohistochemistry
- Mucinous tubular and spindle cell carcinoma (MTSCC):
- Type 1 papillary renal cell carcinoma (PRCC) may be predominantly solid with spindle cell areas but has papillary areas, lacks mucinous areas and FISH for trisomy 7 or 17 would be positive, unlike MTSCC
- Papillary adenoma:
- Similar morphology to type 1 PRCC (usually without fibrous capsule) but size 15 mm or less by WHO criteria
- Papillary urothelial carcinoma of pelvicalyceal system:
- Papillae lined by urothelium
- Positive for CK7 / CK20, GATA3, high molecular weight cytokeratin and p63
- Type 1 vs. type 2 papillary renal cell carcinoma (PRCC):
- Type 2 PRCC has more cytologic pleomorphism, pseudostratification and cells are more eosinophilic; foamy macrophages and psammoma bodies are less common
- Type 2 PRCC has patchy weak or negative CK7 and EMA and higher expression of Ki67 and p53 than type 1 PRCC (Am J Surg Pathol 2014;38:887)
Board review style question #1
Given the sometimes broad differential, what is generally the most useful group of stains for evaluating a renal cell carcinoma with papillary architecture?
- CAIX, CK7, AMACR, TFE3
- p53, p63, CD10
- PAX8, RCC, Hale colloidal iron
- Vimentin, RCC, CD10
Board review style answer #1
