Disclosure. Relevant Financial Relationship(s) None. Off Label Usage None MFMER slide-1

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1 Disclosure Relevant Financial Relationship(s) None Off Label Usage None 2013 MFMER slide-1

2 Case Presentation A 43 year old male, with partial nephrectomy for a right kidney mass 2013 MFMER slide-2

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6 Morphologic diagnosis: A. Clear cell renal cell carcinoma B. Papillary carcinoma C. Mixed epithelial stromal tumor D. Clear cell tubulopapillary renal cell carcinoma E. Tubulocystic renal cell carcinoma 2013 MFMER slide-6

7 Immunohistochemistry CK7 CK903 RCMS 2013 MFMER slide-7

8 DIAGNOSIS Clear cell (tubulo)papillary renal cell carcinoma 2013 MFMER slide-8

9 New (and refined) entities in the ISUP Vancouver and WHO 2016 Classification of Renal Neoplasia Rafael E. Jiménez 2013 MFMER slide-9

10 2013 MFMER slide-10

11 New Renal Epithelial Tumor Categories Tubulocystic renal cell carcinoma Acquired cystic disease-associated renal cell carcinoma Clear cell (tubulo)papillary renal cell carcinoma MiT family translocation carcinomas Xp11 tranlocation RCC (*) t(6;11) RCC Hereditary leiomyomatosis-rcc syndromeassociated RCC Succinate dehydrogenase-deficient RCC (*) already included in 2004 WHO classif 2013 MFMER slide-11

12 Tubulocystic carcinoma Previously considered as a low grade variant of collecting duct carcinoma. >70 cases reported Usually present in low stages (pt1-pt2). Well circumscribed, encapsulated, bubble wrap cut surface 2013 MFMER slide-12

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15 Appl Immunohistochem Mol Morphol Aug;24(7): TC-RCC demonstrates variable status of chromosomes 7, 17, and Y even in cases with typical/uniform morphology. The biological nature of Papillary RCC or High-grade NOS RCClike areas within TC-RCC remains unclear. Heterogeneous TC-RCCs may be associated with an adverse clinical outcome. HG TC-RCC indistinguishable from HLRCC 2013 MFMER slide-15

16 Tubulocystic RCC Dx should be restricted to pure cases >90% indolent behavior Distant metastasis and death described in 4 cases MFMER slide-16

17 Clear cell tubulopapillary RCC Initially reported in end stage kidneys, however majority are sporadic. Variable papillary, tubular/acinar, cystic architecture. May contain dense muscular stroma (RAT). Linear arrangement of low grade nuclei away from base MFMER slide-17

18 2013 MFMER slide-18

19 Clear cell tubulopapillary RCC 2013 MFMER slide-19

20 Clear cell tubulopapillary RCC IHC Profile Diffuse CK7 CD10 negative Diffuse CA-IX (cup shaped distribution) Negative racemase Patchy to diffuse 34BE12 Prognosis Indolent clinical behavior No metastases reported in pure tumors One case with sarcomatoid change, metastases, and DOD recently reported 2013 MFMER slide-20

21 CCTP-RCC CC-RCC 2013 MFMER slide-21

22 Am J Surg Pathol 2015;39: cases with morphologic overlap with CC TubPap-RCC Atypical features, including labeling for CD10 and AMACR, higher nuclear grade and tumor stage, and tumor necrosis. The majority of such tumors demonstrated abnormalities of chromosome 3p by FISH or karyotyping, arguing that they are best regarded as a manifestation of clear cell renal cell carcinoma MFMER slide-22

23 Translocation-associated carcinomas Translocations involving Xp11.2 (TFE3). ASPL-TFE3 PRCC-TLFE3 Translocation involving TFEB [t(6;11)] TFE3 and TFEB part of the MiT subfamily of transcription factors 50% of RCC of pediatric age. <5% of adult RCC 2013 MFMER slide-23

24 Translocation Xp11 RCC ASPL-TFE3 PRCC-TFE MFMER slide-24

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26 Translocation Xp11RCC IHC Profile Focal or negative expression of keratins and EMA RCC, CD10, PAX2 positive Strong nuclear TFE3 immunoreactivity Keratin - Negative TFE MFMER slide-26

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28 Translocation Xp11 RCC Prognosis Usually present with high stage Children good prognosis despite high stage Not enough long term survival data Adults 1-2 years survival Late recurrences (20-30 years) 2013 MFMER slide-28

29 t(6;11) RCC Mean age 28.5 years Alpha-TFEB gene fusion. Biphasic morphology: large and small cells Basement membrane material Express melanocytic markers Negative for cytokeratins 10% metastatic and death rate in reported cases Image from: Magers et al, Arch Pathol Lab Med. 2015;139: MFMER slide-29

30 Acquired Cystic Disease-Associated RCC Most common neoplasm in the end-stage kidney setting Arise from cyst wall or adjacent parenchyma Multifocality and bilaterality IHC Profile Diffusely for racemase Negative CK7 Relatively good prognosis, although sarcomatoid and rhabdoid change may occur Sieve-like appearance 2013 MFMER slide-30

31 Acquired Cystic Disease-Associated RCC Calcium oxalate crystals 2013 MFMER slide-31

32 Precursor multicystic lesions End-stage kidney background 2013 MFMER slide-32

33 Hereditary Leiomyomatosis-related RCC Autosomal dominant mutations in the fumarate hydratase gene Smooth muscle and renal neoplasms Highly aggressive renal neoplasms High-grade with inclusionlike nucleoli surrounded by halo 2013 MFMER slide-33

34 Papillae (previously papillary RCC or CDC) Tubulocystic 2013 MFMER slide-34

35 Succinate-dehydrogenase-deficient RCC Part of spectrum of tumors developed by patients with germline mutations of SDH, which also include paragangliomas and GISTS. Oncocytic tumor with characteristic cytoplasmic vacuolization Other SDH-deficient histologies being identified, but rare MFMER slide-35

36 SDH-deficient RCC Typical vacuolated cytoplasm with floculent inclusions Absent staining in tumor cells with SDHB At least one case with widespread metastasis and DOD reported, although majority low grade, indolen 2013 MFMER slide-36

37 2013 MFMER slide-37

38 Refinement of concepts on old entities Clear cell renal cell carcinoma: Multilocular cystic renal cell neoplasm of low malignant potential Chromophobe renal cell carcinoma: Hybrid oncocytic tumors 2013 MFMER slide-38

39 Multilocular cystic renal cell neoplasm of low malignant potential Numerous cysts, the septa of which contain small groups of clear cells grade I Cysts lined by clear cells. No solid areas with expansive nodules Excellent prognosis >200 patients with f/u >5 years 2013 MFMER slide-39

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43 Oncocytosis Oncocytic tumors and other oncocytic changes in the renal parenchyma: Oncocytomas Chromophobe carcinomas Hybrid tumors Oncocytic change in medullary tubules 2013 MFMER slide-43

44 Hybrid oncocytic tumors Oncocytomas with focal atypia Well-defined nests, but cellular atypia. Classic cytologic features of oncocytoma, but loss of the nested architecture. Others exhibit well-defined areas of chromophobe carcinoma, coexisting with classic areas of oncocytoma MFMER slide-44

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49 Summary The Vancouver ISUP classification of renal neoplasia and the 2016 WHO classification define new entities readily identifiable on morphologic basis. Selected concepts on well-established diagnostic categories continue further refinement. Unresolved issues on kidney tumor categories guarantees further updates and revisions of renal neoplasia classification 2013 MFMER slide-49

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