Renal Cell Carcinoma: Advances in Diagnosis B. Iványi, MD

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1 Renal Cell Carcinoma: Advances in Diagnosis B. Iványi, MD Department of Pathology University of Szeged, Hungary

2 ISUP Vancouver Classification of Renal Neoplasia Am J Surg Pathol 37: , histologic types of RCC Aim: review of the cytomorphologic features and the immunoprofile of 8 types of RCC and aspects of grading

3 Immunoprofile of RCCs1,2 Onc Clear cell T1 Papill T2 Papill Chrom Coll duct Muc tub spindle Clear cell papill Xp11 Acquired CDassoc. CAIX No data CD10 CK7 focal AMACR CD117 no data TFE3 CAIX: carbonix anhydrase IX AMACR: αmethylacyl Coenzyme A Racemase 1AlAhmadie et al. Role of immunohistochemistry in the evaluation of needle core biopsies in adult renal cortical tumors. Am J Surg Pathol 35:949961, Tan et al. Renal tumors. Diagnostic and biomarkers. Am J Surg Pathol 37:

4 Clear cell RCC. CAIX: circumferential membranous expression; CD10: membranous and cytoplasmic expression CAIX CD10

5 Immunoprofile of clear cell RCC Onc Clear cell T1 Papill T2 Papill Chrom Coll duct Muc tub spindle Clear cell papill Xp11 Acquired CDassoc. CAIX No data CD10 CK7 focal AMACR CD117 no data TFE3 We routinely evaluate CAIX and CK7 stainings in high grade tumors and in clear cell tumors with nonconventional features

6 High grade tumor cells with eosinophilic cytoplasm. Positive for CAIX and negative for CK7 clear cell RCC CAIX

7 If tumor giant cells display circumferential membrane staining with CAIX and are negative for CK7 clear cell RCC CAIX

8 Clear cell tumors with nonconventional features: subnuclear clearing tubulopapillary structure sheetlike growth pattern require immunostainings

9 Evaluation of a case with subnuclear clearing

10 Basolateral (cupshaped) CAIXpositivity, diffuse CK7positivity, and CD10negativity clear cell tubulopapillary RCC CK7 CAIX

11 Immunoprofile of clear cell (tubulo)papillary RCC Onc Clear cell T1 Papill T2 Papill Chrom Coll duct Muc tub spindle Clear cell papill Xp11 Acquired CDassoc. CAIX No data CD10 CK7 focal AMACR CD117 no data TFE3

12 Tubulopapillary growth pattern in a 72yold patient

13 RCC with clear cells and papillary growth pattern in a 39yold pt

14 Papillary architecture and clear cells in a 31yo pt Consultation case; courtesy of G. Cserni, Kecskemét, Hungary

15 40yold pt. Sheetlike growth pattern and clear cells

16 Diffuse nuclear TFE3protein positivity 3rd case 1st case 2nd case 4th case

17 Immunoprofile of TFE3 (Xp11) translocation RCC Clear cell T1 Papill T2 Papill Chrom Coll duct Muc tub spindle Clear cell papill Xp111 Acquired CDassoc. CAIX No data CD10 CK7 focal AMACR CD117 no data TFE3 1Some Xp11 translocation RCCs can express MelanA, HMB45 and cathepsink Onc

18 Papillary RCC. Type 1: small cells with scanty cytoplasm; Type 2: larger cells with eo cytoplasm, higher nuclear grade Type 1 Type 2

19 Variant of T1 PRCC: solid nests or tubuloglomeruloid structures

20 Type 1 PRCC: positive for CK7 and AMACR AMACR CK7

21 Immunoprofile of papillary RCC Onc Clear cell T1 Papill T2 Papill Chrom Coll duct Muc tub spindle Clear cell papill Xp11 Acquired CDassoc. CAIX No data CD10 CK7 focal AMACR CD117 no data TFE3 Type 2 PRCC has variable staining patterns because this is likely a heterogeneous category rather than a distinct entity

22 Mucinous tubular and spindle cell RCC: tubules lined by bland cuboidal cells together with spindle cells and intercellular mucin Consultation case; courtesy of I. Pálka, Kiskunhalas, Hungary

23 Immunoprofile of mucinous tubular and spindle cell RCC Onc Clear cell T1 Papill T2 Papill Chrom Coll duct Muc tub spindle Clear cell papill Xp11 Acquired CDassoc. CAIX No data CD10 CK7 focal AMACR CD117 no data TFE3 Some cases cannot be distinguished from type 1 papillary RCC

24 Collecting duct RCC: 1) high grade tumor; 2) tubular or tubulopapillary growth; 3) desmoplasia; 4) medullary location

25 Diff. dg.: CDRCC can resemble to type 2 papillary RCC

26 Diff. dg.: urothelial carcinoma invading the kidney

27 Immunoprofile of collecting duct RCC Onc Clear cell T1 Papill T2 Papill Chrom Coll duct Muc tub spindle Clear cell papill Xp11 Acquired CDassoc. CAIX No data CD10 CK7 focal AMACR CD117 no data TFE3 Overlap between CDRCC and urothelial carcinoma: PAX 8 can be positive in UCC, and p63 can be positive in CDRCC

28 CDRCC vs UCC: several cuts from the renal pelvis

29 Chromophobe RCC: chromophobe cells are arranged along vascular channels

30 Hale s colloidal iron: diffuse cytoplasmic staining (eosinophilic variant can be negative)

31 Ultrastructure: microvesicles in the cytoplasm

32 Immunoprofile of chromophobe RCC: CK7, CD117 CK7 CD117

33 Immunoprofile of chromophobe RCC Onc Clear cell T1 Papill T2 Papill Chrom Coll duct Muc tub spindle Clear cell papill Xp11 Acquired CDassoc. CAIX No data CD10 CK7 focal AMACR CD117 no data TFE3

34 Diff. dg.: eosinophilic variant vs oncocytoma RO RO

35 Immunoprofile of RO: CK7, CD117 RO, CK7 RO, CD117

36 Incidences of RCC types in Szeged (Investigators: B. Ivanyi, L. Kuthi, A. Jenei) The key histologic features were sought in HE sections of 612 consecutive RCCs Tissue microarray blocks from 96 cases were analyzed with an antibody panel of CAIX, CD10, CK7, AMACR, ckit1, vimentin and TFE3 Reading: no (<10%), focal (<75%) or diffuse staining

37 Results 85% clear cell 6.8% papillary 4.7% chromophobe 1.8% unclassified 0.3% Xp11 0.3% clear cell (tubulo)papillary 0.3% collecting duct 0.16% hybrid oncocytic/chromophobe tumor

38 Diagnosis of metastasis of renal origin The application of CK7, CD10, CAIX1, vimentin, Pax 2/Pax 8 in various combinations is usually conclusive 1CAIX can be expressed by carcinomas of endometrium, stomach, cervix, breast, lung, and liver tumors, neuroendocrine tumors, and mesotheliomas. Truong LD, Shen SS. Immunohistochemical diagnosis of renal neoplasms. Arch Pathol Lab Med 135;92109, 2011

39 Bx from the pancreas: high grade carcinoma; Negative for CK20, CK7, MUC5AC

40 Diffuse, membranosus CAIX and CD10 positivity CAIX CD10

41 CK7 Vimentin

42 Diagnosis: invasion of pancreas by high grade clear cell RCC Search for clinical data: nephrectomy performed not in Szeged because of high grade RCC 2 years earlier

43 The ISUP Grading System for Renal Cell Carcinoma and Other Prognostic Parameters Am J Surg Pathol 2013;37: The main morphotypes of RCC have prognostic significance Excellent prognosis Multilocular cystic RCC (multilocular cystic renal neoplasm of low malignant potential) Good prognosis Extensively cystic CCRCC Clear cell (tubulopapillary) RCC, MTSRCC Bad prognosis CDRCC

44 Sarcomatoid component, rhabdoid differentiation, tumor necrosis have prognostic impact. Reporting is recommended

45 ISUP grading system for clear cell and papillary RCC Grade I inconspicous or absent nucleoli at 400x Grade II distinctly visible nucleoli at 400x Grade III distinctly visible nucleoli at 100x Gr IV tumors with sarcomatoid or rhabdoid differentiation or with extreme nuclear pleiomorphism or with tumor giant cells

46 Take home message Utilizing immunostains improves classification of renal tumors Both extent and patterns must be considered for a definitive diagnosis Clear cell carcinomas with subnuclear clearing or tubulopapillary architecture should raise the possibility of clear cell (tubulo)papillary RCC or translocation RCC

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