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)
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
Images hosted on other servers:
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
Cytology description
- Foamy macrophages and intracytoplasmic hemosiderin (Cancer 1998;84:303)
Cytology images
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