Papillary Renal Cell Carcinoma

Epidemiology and Etiology:

• Middle age mostly
• M:F 2:1
• 6-18% of RCC

Common sites:

Gross features:

• Well circumscribed
• Thick capsule often
• frequently multifocal (unlike clear cell and chromophobe RCC)
• calcification in 30% of cases on imaging)
• minimum 0.5cm (by definition), median 6.5cm
• variegated appearance
• friable
• hemorrhagic
• typically hemorrhagic and cystic

Histologic features:

• cuboidal or low columnar cells arranged in papillary or tubulopapillary formations
• may be tightly packed resulting in an apparent solid growth
• interstitial foam cells in papillary cores is common
• scanty but highly vascularized stroma
• thick fibrous pseudocapsule is common
• necrosis common
• psammoma bodies commonly present within fibrovascular stalk
• variable nuclear features
• oncocytic maybe (not given its own subtype)
• type 1:
• single layer of cells covering papillae
• scant, pale to amphophilic cytoplasm
• nuclei small and hyperchromatic
• most Fuhrman grade 1 to 2
• psammoma bodies
• aggregates of foamy macrophages
• type 2:
• pseudostratification
• more abundant intensely eosinophilic cytoplasm
• nuclei more open
• nucleoli often prominent
• many are Fuhrman grade 3, maybe 4

Immunophenotype:

Marker:	Sensitivity:	Specificity:
LMWK
CK7	Type 1 more frequently
Vimentin	Type 1 more frequently
CD10
Hale’s colloidal iron (neg)
CK20	Type 2 more frequently
MUC1	Type 2 more frequently

Molecular features:

• sporadic (both type I and type II):
• trisomy / tetrasomy 7
• also seen in papillary adenoma
• note trisomy 7 is nonspecific
• may be seen in non-neoplastic kidney and other neoplasms
• trisomy 17
• trisomy 16
• trisomy 12
• trisomy 20
• loss of Y in males
• also seen in papillary adenoma
• some trisomy 3, 8, 12, 16, 20
• associated with aggressive behavior
• LOH at VHL
• LOH at FHIT
• NOT loss of 3p typically
• But not absolute
• Type 1:
• Gains 7p, 17p
• type II show additional abnormalities:
• allelic imbalance of one or more of chromosomes 1p, 3p, 5, 6, 8, 9p, 10, 11, 15, 18, and 22
• loss of 8p, 9p, 11, 18
• gain 1q
• loss of 8p, 9q, and 11q are associated with advanced stage
• MET activating mutations (subset)
• MiTF/TFE renal translocation carcinomas
• Hereditary papillary renal cell carcinoma (HPRCC):
• MET activating mutations (7q22)
• tyrosine kinase receptor for hepatocyte growth factor
• trisomy 7
• may harbor duplicated MET mutations
• Hereditary leiomyomatosis and renal cell carcinoma (HLRCC):
• Uterine and cutaneous leiomyomas and papillary RCC
• Fumarate hydratase (FH) mutations
• single renal tumours in 30%

Other features:

•  Better prognosis than clear cell type
• Type 2 may have worse prognosis
• Prognostic and predictive impact of translocation is not established due to rarity and conflicting results
• Spontaneous hemorrhage is a presenting feature in 8 % of cases (unlike clear cell RCC)

References:

•  Kumar V, Fausto N, Abbas A. Robbins & Cotran Pathologic Basis of Disease, Seventh Edition. 7th ed. Saunders; 2004.
• Silverberg SG, DeLellis RA, Frable WJ, LiVolsi VA, Wick MR. Silverberg's Principles and Practice of Surgical Pathology and Cytopathology: 2-Volume Set. 4th ed. Churchill Livingstone; 2005.
• Zhou AG, Owens CL, Cosar EF, Jiang Z. Clinical implications of current developments in genitourinary pathology. Arch Pathol Lab Med 2013;137:887-893.
• Srigley JR et al. (The ISUP Renal Tumor Panel) The International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia. Am J Surg Pathol 2013;37:1469-1489.