CT and MRI features of the Pathologic Subtypes of Papillary Renal Cell Carcinoma. Melissa Price, MD Aoife Kilcoyne, MD Mukesh G.

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1 CT and MRI features of the Pathologic Subtypes of Papillary Renal Cell Carcinoma Melissa Price, MD Aoife Kilcoyne, MD Mukesh G. Harisinghani, MD

2 Disclosures Neither I nor my immediate family members have a financial rela8onship with a commercial organiza8on that may have a direct or indirect interest in the content.

3 Objec8ves Discuss pathologic and clinical features of papillary renal cell carcinoma (RCC) and the prognos8c importance of making this diagnosis Iden8fy imaging findings which dis8nguish papillary RCC from other RCC subtypes Review CT and MR characteris8cs of type 1 and 2 papillary RCC Highlight imaging mimics of papillary RCC and challenges to prospec8vely iden8fying the pathologic subtype of papillary RCC by imaging

4 Renal Cell Carcinoma Accounts for approximately 2% of cancers in adults Renal cell carcinoma makes up 85% of renal malignancies Pathologic subtypes of RCC: Clear cell (70%) Papillary (10-15%) Chromophobe (4-8%) Renal medullary carcinoma Clear cell tubulopapillary Acquired cys8c disease associated RCC Tubulocys8c MiT family transloca8on RCC Srigley et al. Am J Surg Pathol 2013; Young et al. Radiology 2013

5 Prognos8c Implica8ons of RCC Subtype Overall papillary RCC has a significantly be[er clinical prognosis compared with clear cell RCC 5 year survival rates vary by pathologic subtype of RCC Clear cell: 44-69% Papillary 82-92% Chromophobe 78-87% Vast majority of metasta8c RCC occurs from clear cell tumors Histologic classifica8on of RCC strongly impacts treatment and management based on survival differences Delahunt et al. Hum Pathol 2001; Young et al. Radiology 2013

6 Why Subtype RCC Clear cell vs non clear cell Papillary and chromophobe RCC à slow growing & be[er prognosis In case of recurrence or metastases: Clear cell RCC responds to Tyrosine Kinase Inhibitors mtor inhibitors have shown promise in non clear cell RCC

7 Histologic Subtyping of Papillary RCC Among papillary RCC, type 2 tumors are more aggressive histologically and clinically compared with type 1 Type 1 tumors associated with lower Fuhrman grade Higher tumor associated death and tumor stage with type 2 Méjean et al reported 5 year survival rates of 95% and 66% for pa8ents with type 1 and type 2 papillary RCC respec8vely Méjean et al. Journal of Urology 2003

8 Pathologic and Imaging Features of Papillary RCC Histologically defined by papillary architecture with malignant cells forming tubules with two dis8nct morphotypes Type 1: basophilic tumor cells with minimal cytoplasm arranged in a single layer overlying papillary cores Type 2: Pseudostra8fied nuclei with abundant eosinophilic cytoplasm overlying papillary cores Imaging features of papillary RCC: Rela8vely low enhancement compared with clear cell T2 hypointense par8cularly type 1 variety Rela8vely hyperdense on unenhanced CT Delahunt et al. Hum Pathol 2001; Young et al. Radiology 2013

9 Mul8phasic CT Enhancement Pa[erns Mean enhancement of clear cell RCC is markedly lower than papillary in the cor8comedullary (125 vs. 54 HU) and nephrographic (103 vs 64 HU) phases For papillary RCC, enhancement tends to peak in the nephrographic phase Mul8phasic enhancement thresholds ~ 85% accurate in dis8nguishing clear cell from papillary RCC Young et al. Radiology 2013 Used with permission

10 Papillary RCC CT Enhancement Pa[erns Noncontrast Cor8comedullary Nephrographic 22 HU 45 HU 34 HU Hypoenhancing papillary RCC showing peak enhancement in the cor8comedullary phase Peak enhancement of 45 HU is significantly lower than the expected peak enhancement for a clear cell RCC (>100 HU)

11 Papillary RCC CT Enhancement Pa[erns Noncontrast Post- Contrast (nephrographic phase) 53 HU 57 HU Images of a type 1 papillary RCC stage pt1b and Fuhrman nuclear grade II/IV The tumor demonstrates high a[enua8on on unenhanced CT and no convincing enhancement on CT MRI with post- contrast subtrac8on images can be helpful in these cases to further assess for intra- lesional enhancement

12 Noncontrast CT appearance Papillary RCC typically high a[enua8on on unenhanced CT This type 2 papillary RCC tumor measured ~ 45 HU on unenhanced CT

13 Papillary RCC MR Enhancement Papillary RCC typically hypoenhances rela8ve to renal parenchyma on MR Tumors with equivocal or no enhancement on CT have been shown to enhance on MRI, par8cularly with post- contrast subtrac8on images Degree of enhancement cannot be used to reliably dis8nguish type 1 from 2 subtype papillary RCC Egbert et al. AJR 2012

14 Papillary RCC MR Enhancement T1:Gd T1:Gd (sub) Type 1 papillary RCC showing hypoenhancement on post- contrast T1 coronal image (lel) Subtrac8on image (right) confirms enhancement within the lesion

15 Dis8nguishing the 2 Subtypes of Papillary RCC Type 1 Smaller tumor size at 8me of diagnosis Well- defined mass Homogeneous density on CT T2 hypointense Type 2 Larger tumor size at 8me of diagnosis Infiltra8ve margins suggests type 2 histology May have calcifica8ons Frequently T2 hyperintense Extensive overlap between the 2 subtypes Enhancement pa[erns cannot be used to dis8nguish the subtypes on CT or MRI Type 1 papillary RCC Egbert et al. AJR 2012; Yamada et al. AJR Type 2 papillary RCC

16 Tumor Margins Type 1 Type 2 Type 1 tumors tend to have well- defined margins Rarely involve the renal hilum Renal capsule remains intact More indis8nct margins with growth of tumor toward renal hilum Greater likelihood of disrup8on of the renal capsule by tumor Yamada et al. AJR 2008

17 T2 Signal: Type 1 T2 hypointense type 1 papillary RCC arising adjacent to a simple cyst: Majority of type 1 papillary RCC tumors are T2 hypointense rela8ve to renal cortex Frequently T2 signal is heterogeneous as shown above Egbert et al. AJR 2012

18 Type 2 Papillary RCC: T2 Signal T2 hypointense type 2 papillary RCC arising within atrophic cystic right kidney: T2 axial FSE Coronal SSFE T2 47- year- old woman with acquired cys8c renal disease and T2 hypointense lesion arising from the upper pole of the right kidney Pathology from nephrectomy showed type 2 papillary RCC with 5 perihilar metasta8c lymph nodes

19 Recurrent Type 2 Papillary RCC in Nephrectomy Bed Following nephrectomy the same pa8ent was found to have an enhancing retroperitoneal sol 8ssue mass near the nephrectomy bed Biopsy confirmed recurrent type 2 papillary RCC

20 Atypical Papillary RCC Not all papillary RCC tumors can be classified as type 1 or 2 at pathology atypical histology is not uncommon Pathology of this T2 hyperintense lel renal lesion with enhancement most pronounced along the periphery showed high- grade papillary RCC (not classified as either type 1 or 2) Tumor extended to the perinephric fat Pathologic tumor stage: pt3a Egbert et al. AJR 2012

21 Challenges in Imaging Diagnosis T2 hypointense type 2 papillary RCC: Extensive overlap exists between imaging features of type 1 and 2 papillary RCC This pa8ent has a well- defined, T2 hypointense lel renal mass features commonly associated with type 1 The mass was biopsied - pathology showed type 2 papillary RCC Although sugges8ve in many cases, imaging features are not defini8ve for the subtypes of papillary RCC and biopsy may useful for accurate diagnosis

22 Challenges in Imaging Diagnosis Type 1 papillary RCC with heterogeneous T2 signal: Axial post contrast CT T2 axial FSE Coronal post contrast CT This type 1 tumor demonstrates foci of calcifica8on and some heterogeneous T2 signal, imaging features more commonly associated with type 2 papillary RCC In these cases, biopsy may useful to conclusively obtain a histologic diagnosis given the overlapping imaging features between the 2 subtypes

23 Differen8al considera8ons for T2 hypointense renal lesions

24 Lipid Poor AML vs. Papillary RCC In many cases, lipid poor AMLs and papillary RCC will be indis8nguishable on MRI: both T2 hypointense and enhance post- contrast Biopsy should be considered in these cases

25 Conclusion Papillary RCC has dis8nct imaging features and an improved prognosis compared with clear cell RCC, which makes dis8nguishing these en88es important clinically Type 1 and 2 papillary RCC have mul8ple different CT and MR imaging features, which can be used to suggest the correct pathologic diagnosis, although there is extensive overlap Given the similar enhancement pa[erns on CT and MR, the tumor morphology and MR signal characteris8cs may be most useful in iden8fying the correct subtype The difference in pathologic subtype has a marked impact on clinical disease course given the poorer prognosis associated with type 2 papillary RCC

26 References Delahunt B, Eble JN, McCredie MRE, et al. Morphologic typing of papillary renal cell carcinoma: comparison of growth kine8cs and pa8ent survival in 66 cases. Hum Pathol 2001; 32: Egbert ND, Caoili EM, Cohan RH, et al. Differen8a8on of papillary renal cell carcinoma subtypes on CT and MRI. AJR 2012; 201: Méjean A, Hopirtean V, Bazin JP et al. Prognos8c factors for the survival of pa8ents with papillary renal cell carcinoma: meaning of histological typing and mul8focality. Journal of Urology 2003; 170: Srigley JR, Delahunt B, Eble JN et al. The interna8onal society of urologic pathology (IUSP) Vancouver Classifica8on of renal neoplasia. Am J Surg Path 2013; 37: Yamada T, Endo M, Tsuboi M, et al. Differen8a8on of pathologic subtypes of papillary renal cell carcinoma on CT. AJR 2008; 191: Young JR, Margolis D, Sauk S, et al. Clear cell renal cell carcinoma: discrimina8on from other renal cell carcinoma subtypes and oncocytoma at mul8phasic mul8detector CT. Radiology 2013; 267: Author contact informa8on: Melissa Price, MD: Aoife Kilcoyne, MD: Mukesh Harisinghani, MD:

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