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

Full text

(1)

Renal Cell Carcinoma: Advances in

Diagnosis

B. Iványi, MD

Department of Pathology

(2)

ISUP Vancouver Classification of Renal Neoplasia

Am J Surg Pathol 37:1469-1489, 2013

• 13 histologic types of RCC

• Aim: review of the cytomorphologic features and

the immunoprofile of 8 types of RCC and aspects of grading

(3)

Clear cell T1 Papill T2 Papill Chrom Coll duct Muc tub spindle Clear cell papill Xp11 Acquired CD-assoc. Onc CAIX + + + - - + + - No data -CD10 + + + - - + - + + + CK7 - + + focal + + + + - - -AMACR + + + - - + - + + -CD117 - - - + - no data no data no data no data + TFE3 - - - + - -Immunoprofile of RCCs1,2

1Al-Ahmadie et al. Role of immunohistochemistry in the evaluation of needle core biopsies in adult renal cortical tumors. Am J Surg Pathol 35:949-961, 2011

2Tan et al. Renal tumors. Diagnostic and biomarkers. Am J Surg Pathol 37:1518-1531

CAIX: carbonix anhydrase IX

(4)

Clear cell RCC. CAIX: circumferential membranous expression;

CD10: membranous and cytoplasmic expression

(5)

Clear cell T1 Papill T2 Papill Chrom Coll duct Muc tub spindle Clear cell papill Xp11 Acquired CD-assoc. Onc CAIX + + + - - + + - No data -CD10 + + + - - + - + + + CK7 - + + focal + + + + - - -AMACR + + + - - + - + + -CD117 - - - + - no data no data no data no data + TFE3 - - - + -

-Immunoprofile of clear cell RCC

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

(7)

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

(8)

Clear cell tumors with nonconventional features:

• subnuclear clearing

• tubulopapillary structure

• sheetlike growth pattern

(9)
(10)

Basolateral (cup-shaped) CAIX-positivity, diffuse CK7-positivity, and CD10-negativity  clear cell tubulopapillary RCC

(11)

Clear cell T1 Papill T2 Papill Chrom Coll duct Muc tub spindle Clear cell papill Xp11 Acquired CD-assoc. Onc CAIX + + + - - + + - No data -CD10 + + + - - + - + + + CK7 - + + focal + + + + - - -AMACR + + + - - + - + + -CD117 - - - + - no data no data no data no data + TFE3 - - - + -

(12)
(13)
(14)

Papillary architecture and clear cells in a 31-y-o pt

(15)
(16)

Diffuse nuclear TFE3-protein positivity 1st case 4th case 3rd case 2nd case

(17)

Clear cell T1 Papill T2 Papill Chrom Coll duct Muc tub spindle Clear cell papill Xp111 Acquired CD-assoc. Onc CAIX + + + - - + + - No data -CD10 + + + - - + - + + + CK7 - + + focal + + + + - - -AMACR + + + - - + - + + -CD117 - - - + - no data no data no data no data + TFE3 - - - + -

-1Some Xp11 translocation RCCs can express Melan-A, HMB45 and cathepsin-K

(18)

Papillary RCC. Type 1: small cells with scanty cytoplasm;

Type 2: larger cells with eo cytoplasm, higher nuclear grade

(19)
(20)

Type 1 PRCC: positive for CK7 and AMACR

(21)

Clear cell T1 Papill T2 Papill Chrom Coll duct Muc tub spindle Clear cell papill Xp11 Acquired CD-assoc. Onc CAIX + + + - - + + - No data -CD10 + + + - - + - + + + CK7 - + + focal + + + + - - -AMACR + + + - - + - + + -CD117 - - - + - no data no data no data no data + TFE3 - - - + - -Immunoprofile of papillary RCC

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

(23)

Clear cell T1 Papill T2 Papill Chrom Coll duct Muc tub spindle Clear cell papill Xp11 Acquired CD-assoc. Onc CAIX + + + - - + + - No data -CD10 + + + - - + - + + + CK7 - + + focal + + + + - - -AMACR + + + - - + - + + -CD117 - - - + - no data no data no data no data + TFE3 - - - + -

-Immunoprofile of mucinous tubular and spindle cell RCC

(24)

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

(25)
(26)
(27)

Clear cell T1 Papill T2 Papill Chrom Coll duct Muc tub spindle Clear cell papill Xp11 Acquired CD-assoc. Onc CAIX + + + - - + + - No data -CD10 + + + - - + - + + + CK7 - + + focal + + + + - - -AMACR + + + - - + - + + -CD117 - - - + - no data no data no data no data + TFE3 - - - + -

-Immunoprofile of collecting duct RCC

Overlap between CDRCC and urothelial carcinoma:

(28)
(29)

Chromophobe RCC: chromophobe cells are arranged along vascular channels

(30)

Hale’s colloidal iron: diffuse cytoplasmic staining

(31)
(32)

Immunoprofile of chromophobe RCC: CK7+, CD117 +

(33)

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

(34)

Diff. dg.: eosinophilic variant vs oncocytoma

(35)

Immunoprofile of RO: CK7-, 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, c-kit1, vimentin and TFE3

• Reading: no (<10%), focal (<75%) or diffuse

(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

(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;92-109, 2011

(39)

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

(40)

Diffuse, membranosus CAIX and CD10 positivity

(41)
(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;37:1490-1514

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

(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

Figure

Updating...

References

Updating...

Related subjects :