Papillary Renal Cell Carcinoma



Papillary Renal Cell Carcinoma


Satish K. Tickoo, MD

Victor E. Reuter, MD





Key Facts


Terminology



  • Papillary renal cell carcinoma (PRCC)


  • 2nd most common subtype of renal cell carcinoma, usually showing predominant or exclusive papillary architecture, frequently with well-formed tumor capsule


Etiology/Pathogenesis



  • Majority of sporadic PRCCs are characterized by trisomy of chromosomes 7 and 17, as well as loss of chromosome Y


Clinical Issues



  • Although majority of patients with unilateral tumors, PRCC is more often bilateral and multifocal compared to other common renal cell tumors


Macroscopic Features



  • Often surrounded by fibrous pseudocapsule on gross evaluation


  • Most exhibit variegated cut surface


Microscopic Pathology



  • Majority of PRCCs exhibit broad morphologic spectrum, including papillary, tubular, and solid patterns


  • Areas containing papillary architecture seen in most cases


  • Cores of papillae are mostly loose and fibrovascular, often containing variable amount of foamy macrophages


  • WHO divides papillary RCC into type 1 and type 2







Gross photograph of a papillary RCC shows an encapsulated mass with a necrotic and hemorrhagic cut surface. Among the common renal cell tumors, papillary RCC is the most likely to have a capsule.






This photomicrograph shows the typical features of a papillary RCC, with prominent papillae and abundant foamy macrophages in the papillary cores. The lining cells are amphophilic and cuboidal.


TERMINOLOGY


Abbreviations



  • Papillary renal cell carcinoma (PRCC)


Synonyms



  • Chromophilic renal cell carcinoma


Definitions



  • 2nd most common subtype of renal cell carcinoma, usually showing predominant or exclusive papillary architecture, frequently with well-formed tumor capsule


ETIOLOGY/PATHOGENESIS


Molecular Characteristics



  • Majority of sporadic PRCCs are characterized by trisomy of chromosomes 7 and 17, as well as loss of chromosome Y


  • Trisomies of chromosomes 12, 16, and 20 and loss of heterozygosity at 9p13 are observed in some cases



    • Some investigators suggest that tumors with trisomy 7/17 alone are likely to have benign behavior



      • Whereas those with additional genetic abnormalities behave aggressively


  • More gains of 7p and 17p by CGH reported by some in type 1, compared to type 2 tumors


  • Activating mutations of MET oncogene, located at 7q31, present in all cases of hereditary papillary renal carcinoma syndrome



    • Similar mutations observed in approximately 13% sporadic papillary RCCs


CLINICAL ISSUES


Epidemiology



  • Incidence



    • Comprise 11-15% of renal cell neoplasms


  • Age



    • Ranges from 3rd to 8th decades of life with peak incidence in 6th and 7th decades


    • Similar to other renal cell tumors


  • Gender



    • Reported M:F = 1.8:1-4:1


Presentation



  • > 50% of cases present as incidental masses, detected on radiologic investigation for unrelated conditions


  • Reported size ranges from 1-18 cm (median: 6.4 cm)



    • However, downward size migration seen in modern times due to incidental discovery on imaging


  • Although majority of patients have unilateral tumors, PRCC is more often bilateral and multifocal compared to other common renal cell tumors


Treatment



  • Surgical approaches



    • Partial nephrectomy is preferred option



      • Total or radical nephrectomy rarely performed now at some institutions even for tumors > 4 cm in size


  • Drugs



    • Resistance to systemic therapy characterizes patients with metastatic papillary RCC


    • Targeted therapies against VEGF tyrosine kinases (e.g., sunitinib) in metastatic PRCC with clinical responses in occasional case



      • Similar targeted therapies are focus of attention in multiple ongoing clinical trials


    • Targeting MET signaling pathway is another therapeutic approach under active investigation


Prognosis



  • Overall, 5- and 10-year survivals better than clear cell RCC, and possibly worse than chromophobe RCC



    • However, some studies show no significant prognostic differences between PRCC and chromophobe RCC



MACROSCOPIC FEATURES


General Features



  • Well-circumscribed mass


  • Often surrounded by fibrous pseudocapsule on gross evaluation



    • Of all common renal cell tumor types, papillary renal cell carcinoma is most likely to be surrounded by fibrous pseudocapsule


  • Most exhibit variegated cut surface



    • Color is related to microscopic findings



      • Tumors with abundant foamy macrophages, tan to yellow


      • Tumors with intratumoral hemorrhage, dark tan to brown


  • Grossly visible areas of necrosis, hemorrhage, and cystic change very common, present in 32-70% of tumors



    • Some tumors almost entirely necrotic


  • Multifocality is present in > 45% of cases



    • In some, this is reported to be only a microscopic finding



      • Many such microscopic tumors may be considered papillary adenomas now


MICROSCOPIC PATHOLOGY


Histologic Features



  • Majority of PRCCs exhibit broad morphologic spectrum, including papillary, tubular, and solid patterns



    • Papillary patterns include



      • Classic papillary with discrete papillary fronds lined by neoplastic cells with central fibrovascular core


      • Papillary-trabecular with delicate, elongated papillations arranged in parallel fashion


      • Papillary-solid with closely packed papillae, sometimes masking their true growth pattern


    • Areas containing papillary architecture seen in most cases


    • However, > 50% show variable proportion of “solid,” tubular, &/or glomeruloid growth patterns



      • Glomeruloid growth pattern composed of tubular structures with intraluminal tufting of tumor cells


      • Cells lining tubules are cuboidal with scant to moderate amphophilic cytoplasm


      • Cells tufting into lumen with abundant eosinophilic cytoplasm and usually higher-grade nuclei


    • Rarely, sarcomatoid growth may be seen and is sign of aggressive disease


  • Cores of papillae are mostly loose and fibrovascular, often containing variable number of foamy macrophages



    • However, variations in morphology of cores are not uncommon, and may include



      • Cores with no macrophages


      • Cores with branching papillae


      • Some papillae with no distinct cores, as in tumors with micropapillary features


      • Marked hyalinization of cores


      • Variable degree of edema, sometimes leading to fluid-filled, grape-like polypoid structures


  • WHO divides papillary RCC into 2 types



    • Type 1 with papillae covered by smaller cells with scant, amphophilic cytoplasm


    • Type 2 with larger tumor cells, often with higher nuclear grade, eosinophilic cytoplasm, and nuclear pseudostratification


    • Type 1 tumors more often positive for CK7 than type 2 PRCC


    • Reportedly worse prognosis in type 2 compared to type 1 tumors


    • Trisomies 7 and 17 more often reported in type 1 than type 2 PRCC


    • MET gene mutations only present in type 1 PRCC


    • Many tumors that are not PRCC and have prominent papillary architecture are more often mistakenly regarded as type 2 PRCC


  • Psammoma bodies, hemosiderin-laden macrophages, hemosiderin deposition within tumor cells are often seen in PRCC



  • WHO classification system does not address issue of PRCC with mixture of type 1 and type 2 morphologic features



    • Combination of features of both types not uncommon



      • In older literature, such tumors designated as “duophilic”


    • Recently, tumors with oncocytic cytoplasm with low-grade nonoverlapping nuclei described as “oncocytic” PRCC



      • Immunohistochemically CK7 positive


      • Show trisomies 7 and 17


      • Show biologic behavior similar to type 1 PRCC


      • Features suggest that eosinophilic PRCC with low-grade nuclei are molecularly and biologically similar to type 1 tumors


    • Molecular evaluation also suggests modified classification of PRCC



      • Type 1: Similar to type 1 of WHO


      • Type 2A: Tumors with eosinophilic cytoplasm but low-grade nuclei


      • Type 2B: Tumors with mixture of type 1 and type 2A features


      • Type 2C: Tumors with high-grade nuclei; tumors often with topoisomerase II-α overexpression


    • Nuclear grading



      • Many believe Fuhrman grading system is well suited for PRCC


      • Others disagree and do not use Fuhrman grading scheme in PRCC


      • Others recently proposed only assessment of nucleolar prominence in most pleomorphic foci rather than Fuhrman grade


Predominant Pattern/Injury Type



  • Neoplastic


Predominant Cell/Compartment Type



  • Epithelial


ANCILLARY TESTS


Immunohistochemistry



  • Diffuse positivity for CK7 very frequent



    • More often in type 1 than type 2 tumors


  • AMACR diffusely positive, with cytoplasmic granular staining


  • CD10 often positive, usually with luminal membranous staining


  • CA9 either negative or focally positive



    • Positivity usually limited to papillary tips or perinecrotic areas


  • RCC and pax-2 positive


DIFFERENTIAL DIAGNOSIS


Clear Cell RCC Exhibiting Papillary or Pseudopapillary Growth



  • Focal papillary architecture may be seen in clear cell RCC



    • Usually result of cell drop-off in areas away from feeding vessels



      • This usually creates pseudopapillary appearance


      • Adequate sampling and presence of typical cytoarchitectural features of clear cell RCC in other areas should clarify issue


    • Prominent psammoma bodies and hemosiderin deposition within tumor cells are not present in clear cell RCC


    • Any fibrovascular cores would be unusual in clear cell RCC and, if present, would be focal


    • Clear cells in clear cell RCC usually have optically transparent, completely clear cytoplasm



      • In papillary RCC, clear-appearing cells usually with variable granularity and often fine hemosiderin


    • CK7 and AMACR immunoreactivity usually (-) or very focal in clear cell RCC


    • CA9 shows diffuse membranous reactivity in majority of clear cell RCCs


Collecting Duct Carcinoma (CDC)



  • Has variable amount of papillary growth pattern


  • Is centered in medulla


  • Invariably widely infiltrative and pseudocapsule, if present, is focal


  • Virtually always high grade


  • Associated with pronounced desmoplastic stroma


  • Shows prominent multinodular growth pattern and glandular and sheet-like architecture


  • Intracytoplasmic and luminal mucin, often focal, common feature


  • Often reactive for CEA, PNA, soybean agglutin, ULEX-1, Ulex europaeus, and HMCK(34βE12)



    • CK7 may be expressed in both tumors


  • Cytogenetic studies may be needed to solve difficult diagnostic problems


MiTF/TFE Family Translocation-associated Renal Carcinomas (TFE Carcinoma)



  • More common in young patients


  • Rarely multifocal


  • Admixture of solid, nested, and papillary growth


  • Usually with high nuclear grade and often with cells showing voluminous cytoplasm



    • Cytoplasm varies from clear to eosinophilic


  • (-) or only focally (+) for cytokeratins and EMA/MUC1



    • Characteristically exhibit nuclear immunoreactivity for TFE3 or TFEB, depending on the translocation


Hereditary Leiomyomatosis RCC (HLRCC)-Related Renal Carcinoma



  • Tumors show variable, but often prominent, papillary architecture



    • Considered to be type 2 PRCCs in the past


  • Other architectural patterns, including glandular, alveolar, and solid are often present


  • Usually CK7 negative


  • History of leiomyomas, both uterine and others, is common


  • Most characteristic morphologic feature is very prominent nucleoli with perinucleolar halos



  • Molecular evidence of fumarate hydratase (FH) gene alterations

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Jul 7, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Papillary Renal Cell Carcinoma

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