Renal Cell Carcinoma: Advances in Diagnosis B. Iványi, MD Department of Pathology University of Szeged, Hungary
ISUP Vancouver Classification of Renal Neoplasia Am J Surg Pathol 37:14691489, 2013 13 histologic types of RCC Aim: review of the cytomorphologic features and the immunoprofile of 8 types of RCC and aspects of grading
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, 2011 2Tan et al. Renal tumors. Diagnostic and biomarkers. Am J Surg Pathol 37:15181531
Clear cell RCC. CAIX: circumferential membranous expression; CD10: membranous and cytoplasmic expression CAIX CD10
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
High grade tumor cells with eosinophilic cytoplasm. Positive for CAIX and negative for CK7 clear cell RCC CAIX
If tumor giant cells display circumferential membrane staining with CAIX and are negative for CK7 clear cell RCC CAIX
Clear cell tumors with nonconventional features: subnuclear clearing tubulopapillary structure sheetlike growth pattern require immunostainings
Evaluation of a case with subnuclear clearing
Basolateral (cupshaped) CAIXpositivity, diffuse CK7positivity, and CD10negativity clear cell tubulopapillary RCC CK7 CAIX
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
Tubulopapillary growth pattern in a 72yold patient
RCC with clear cells and papillary growth pattern in a 39yold pt
Papillary architecture and clear cells in a 31yo pt Consultation case; courtesy of G. Cserni, Kecskemét, Hungary
40yold pt. Sheetlike growth pattern and clear cells
Diffuse nuclear TFE3protein positivity 3rd case 1st case 2nd case 4th case
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
Papillary RCC. Type 1: small cells with scanty cytoplasm; Type 2: larger cells with eo cytoplasm, higher nuclear grade Type 1 Type 2
Variant of T1 PRCC: solid nests or tubuloglomeruloid structures
Type 1 PRCC: positive for CK7 and AMACR AMACR CK7
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
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
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
Collecting duct RCC: 1) high grade tumor; 2) tubular or tubulopapillary growth; 3) desmoplasia; 4) medullary location
Diff. dg.: CDRCC can resemble to type 2 papillary RCC
Diff. dg.: urothelial carcinoma invading the kidney
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
CDRCC vs UCC: several cuts from the renal pelvis
Chromophobe RCC: chromophobe cells are arranged along vascular channels
Hale s colloidal iron: diffuse cytoplasmic staining (eosinophilic variant can be negative)
Ultrastructure: microvesicles in the cytoplasm
Immunoprofile of chromophobe RCC: CK7, CD117 CK7 CD117
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
Diff. dg.: eosinophilic variant vs oncocytoma RO RO
Immunoprofile of RO: CK7, CD117 RO, CK7 RO, CD117
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
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
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
Bx from the pancreas: high grade carcinoma; Negative for CK20, CK7, MUC5AC
Diffuse, membranosus CAIX and CD10 positivity CAIX CD10
CK7 Vimentin
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
The ISUP Grading System for Renal Cell Carcinoma and Other Prognostic Parameters Am J Surg Pathol 2013;37:14901514 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
Sarcomatoid component, rhabdoid differentiation, tumor necrosis have prognostic impact. Reporting is recommended
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
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