Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we...

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The value of immunohistochemistry in Renal tumours Jon Oxley Bristol

Transcript of Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we...

Page 1: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

The value of immunohistochemistry in Renal tumours

Jon Oxley

Bristol

Page 2: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

Renal tumour immunohistochemistry

• When do we need it?

• What’s new?

• Useful panels

• Examples

Page 3: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

When do we need it?

• Nephrectomy specimens

– Rarely

• Needle core biopsies

– Fashion towards biopsy

• Metastatic deposits

– Commonest role

Page 4: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

RCC DIAGNOSTIC PROCESS

• MORPHOLOGY

80%

• IMMUNOCYTOCHEMISTRY

10-15%

• MOLECULAR GENETICS

5%

Page 5: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

Needle core biopsies

• Al-Ahmadie et al Am J Surg Path 35(7) July 2011. p949

• Took core biopsies from nephrectomies.

• 123 cases where adequate material obtained

• 83% just H&E, increasing to 90% for commonest 4 tumours.

• Adding immuno improved to 99% for commonest 4 tumours

• Panel: CAIX, AMACR, CD117, CK7, CD10

Page 6: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

IMMUNOPROFILES OF THE MAJOR RENAL NEOPLASMS (%staining)

Stain Clear Cell RCC Papillary

RCC

Chromophobe

RCC Collecting

Duct

Carcinoma

Sarcomatoid

RCC

Xp11

Translocatio

n RCC

MTSCC Tubulocystic

RCC Urothelial

Carcinoma

Oncocytoma

CK7 ± (0-37) + (80-87) + (73-86) + (83) N/A + (17) + (79-100) + (62-91) + (92) ± (0-10)

CK8 + (40) + (87) + (53) + (83) N/A N/A - + (100) + (100) + (100)

CK18 + (100) + (100) + (100) + (100) N/A N/A + (100) + (100) + (83) + (100)

CK20 - - - - N/A N/A - - + (25-68) -

HMW CKs ± (0-13) + (33) - + (29-67) N/A N/A + (15-33) ± (0-67) + (100) + (10)

CK5/6 - - - + (17) N/A - - + (75) -

AE1/AE3 CKs + (35) + (82) + (16) N/A N/A + (0-25) + (83) N/A + (100) + (16)

Vimentin + (87) + (100) - + (100) N/A + (65-70) + (55-100) + (55) + (33) -

AMACR + (4-68) + (80-100) ± (0-29) ± (0-18) N/A + (100) + (92-100) + (77-100) + (20) + (2-25)

Carbonic anhydrase

IX

+ (100) + (57) - + (40-100) N/A + (40) - + (42) + (100) -

PAX2 + (92) + (87) ± (0-83) ± (0-100) - ± (0-100) + (75-100) + (37-42) - + (88-100)

PAX8 + (98) + (87) + (83) + (100) + (28) + (100) + (100) + (100) ± (0-8) + (87-95)

RCC marker + (72-85) + (87-95) + (0-91) - + (0-22) + (100) + (7-92) + (100) - -

CD10 +(94-100) + (67-93) ± (0-72) + (25) N/A + (100) + (9-50) + (33-100) + (50) + (12-58)

E-cadherin ± (0-14) + (13-31) + (100) + (75) N/A + (66) + (93) N/A + (76-100) + (47-100)

Kidney-specific

cadherin

± (0-30) ± (0-29) + (86-100) - N/A + (66) - + (71) - + (75-95)

Parvalbumin ± (0-8) ± (0-31) + (80-100) N/A N/A N/A N/A N/A N/A + (47-100)

Claudin-7 - + (28-35) + (67-95) N/A N/A N/A N/A N/A N/A + (23-73)

Claudin-8 N/A N/A + (27) N/A N/A N/A N/A N/A N/A + (88)

S100A1 + (57-73) + (62-94) ± (0-26) N/A N/A N/A N/A N/A N/A + (93)

CD82 ± (2-23) - + (78-87) N/A N/A N/A N/A N/A N/A ± (0-7)

CD117 ± (0-5) ± (0-13) + (82-100) ± (0-53) ± (4-95) N/A N//A N/A + (4-30) + (58-100)

TFE3 - - - - - + (87) - - - -

Thrombomodulin - N/A N/A N/A - N/A N/A N/A + (49-100) N/A

Uroplakin III 0/32 RCCs - - N/A N/A N/A N/A N/A + (33-100) N/A

p63 - - - + (0-14) - N/A N/A N/A + (81-100) N/A

S100P - - - - - N/A N/A N/A + (71-96) N/A

HMB-45 N/A N/A N/A N/A N/A + (46) N/A N/A N/A N/A

Melan-A N/A N/A N/A N/A N/A + (89) N/A N/A N/A N/A

Reference: Truong LD, Shen SS. Immunohistochemical diagnosis of renal neoplasms. Arch Pathol Lab Med. 2011 Jan;135(1):92-109.

Page 7: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

What’s new?

• PAX 2 and 8

• Carbonic anhydrase IX

• RCC marker

• Cathepsin K

Page 8: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

IMMUNOPROFILES OF THE MAJOR RENAL NEOPLASMS (%staining) CA IX, PAX2, PAX8 and RCC marker

Stain Clear Cell RCC

Papillary RCC

Chromophobe RCC

Collecting

Duct Carcinoma

Sarcomatoid RCC

Xp11 Translocation RCC

MTSCC Tubulocystic RCC

Urothelial

Carcinoma

Oncocytoma

Carbonic anhydrase IX

+ (100) + (57) - + (40-100)

N/A + (40) - + (42) + (100) -

PAX2 + (92) + (87) ± (0-83)

± (0-100)

- ± (0-100)

+ (75-100)

+ (37-42)

- + (88-100)

PAX8 + (98) + (87) + (83) + (100) + (28) + (100)

+ (100) + (100) ± (0-8) + (87-95)

RCC marker + (72-85)

+ (87-95)

+ (0-91)

- + (0-22) + (100)

+ (7-92)

+ (100) - -

Reference: Truong LD, Shen SS. Immunohistochemical diagnosis of renal neoplasms. Arch Pathol Lab Med.

2011 Jan;135(1):92-109.

Page 9: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

Carbonic anhydrase IX (CA IX)

– Transmembrane enzyme that regulates cell proliferation, adhesion and invasion.

– Expressed by wide variety of tissues but not normal kidney

– Expressed in most clear cell carcinomas and proportion of papillary carcinomas

– High expression frequency in other primary carcinomas including endometrium, stomach, cervix, breast, lung, liver, brain tumours neuroendocrine tumours and mesotheliomas.

Page 10: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

Carbonic anhydrase IX (CA IX)

Page 11: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

PAX2 and PAX8

• Pax 2 and 8 are transcription factors – PAX8 - a paired-box gene important in

embryogenesis of the thyroid, Müllerian, and renal/upper urinary tracts, and expression of PAX8 has been described in carcinomas from each of these sites

– Thyroid transcription factor-1, RCC, and Wilms tumor-1 are needed to split the primary tumour sites.

– PAX2 and 8 also expressed by nephrogenic metaplasia

Page 12: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

PAX 8 – Normal kidney

Page 13: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

PAX8 - Oncocytoma

Page 14: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

RCC marker • The RCC a monoclonal antibody directed against a

glycoprotein identified in the brush border of healthy renal proximal tubular cells

• Positive: almost all papillary, clear cell RCCs

• Negative: collecting duct RCC, oncocytoma

• For other renal neoplasms widely variable

• Expression reported in a small percentage of other neoplasms, including breast carcinoma, testicular embryonal carcinoma, and parathyroid tumours.

• More recent studies suggest a much wider expression (17%–100%) in tumours from the adrenal cortex, colon, breast, prostate, ovary, melanoma, lung, and parathyroid,and in malignant mesothelioma.

Page 15: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

Cathepsin K

• Cathepsin K is a protease, which is defined by its high specificity for kinins, that is involved in bone resorption and expressed by osteoclasts

• Studies in osteoclasts have shown a consistent ability of MiTF to modulate the cathepsin-K promoter

• Target DNA sequences of MiTF overlap with those of TFE3 and TFEB

• Overexpressed TFE3 fusion proteins or native TFEB promote cathepsin-K

Page 16: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

Panels

Page 17: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

Tumours comprised predominantly of “Clear” Cells

Tumour type CA IX CK7 CD117 Cathepsin-K* HMB 45

Clear cell RCC Positive

(diffuse

membranous)

Negative Negative Negative Negative

Clear cell

PRCC

Positive (cup

like)

Positive Negative Negative Negative

Chromophobe

RCC

Negative Positive

(cytoplasmic)

Positive

(membranous

)

Negative Negative

Epithelioid

AML

Negative Negative Negative Positive

(cytoplasmic)

Positive

(cytoplasmic)

MiTF-TFE

tumours

Xp11 family Variable but

focal

Negative Variable Positive 50%

(cytoplasmic)

Negative

t(6;11) Variable but

focal

Negative Negative Positive

(cytoplasmic)

Positive

(always focal)

Page 18: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

Xp11 translocation RCC

• RCC with various TFE3 gene fusions

• Underexpress epithelial markers such as EMA and cytokeratin relative to usual RCC

• Express Cathepsin K and TFE3

Page 19: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

TFE 3 – nuclear staining

Page 20: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

DISTINCT IMMUNOPHENOTYPE

EMA CAM 5.2

Page 21: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

Tumours with a significant papillary component

Tumour

type

CA IX CK7 AMACR Cathepsin-K 34E12 TFE3/TFEB

ccRCC with

papillary

growth

Positive

(membranous)

Negative Negative Negative Negative Negative

PRCC

“type 1”

Negative Positive Positive Negative Negative Negative

PRCC

“type 2”

Negative +/-

Positive

Positive Negative Negative Negative

Clear cell

PRCC

Positive (cup-

shaped)

Positive

(diffuse)

Negative Negative Negative Negative

MiTF-TFE

tumours

Variable but

focal

Negative Positive Positive

(50%)

Negative Positive*

Page 22: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

Tumours with Oncocytic features

Tumour type CD117 CK7 Ksp-

cadherin

HMB-45 Cathepsin-K

Oncocytoma Positive

(membran

ous)

Negative Positive Negative Negative

Chromophobe

RCC

eosinophilic

Positive

(membran

ous)

Positive

(but

variable)

+/- Positive Negative Negative

Oncocytic

PRCC

Negative Positive

(but focal)

Not known Negative Not known

Oncocytic

AML

Negative Negative Negative Positive

(focal)

Negative

Page 23: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

CHROMOPHOBE vs ONCOCYTOMA

MORPHOLOGY

PERINUCLEAR HALO

BINUCLATE CELLS

RAISINOID NUCLEI

MITOSES

Page 24: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

CHROMOPHOBE V ONCOCYTOMA IMMUNOPHENOTYPE

ANTIBODY CHROMOPHOBE ONCOCYTOMA

DIFFUSE CK7 65% RARE

FOCAL CK7 35% 79%

CD15 NEG 63%

CK20 NEG 53%

CD117 MOST MOST

RCC 45% <5%

CD82 78% RARE

AMACR 36% >90%

PAX 2 6% >90%

Page 25: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

CK 7 in CHROMOPHOBE CARCINOMA vs ONCOCYTOMA

CK7

CHROMOPHOBE ONCOCYTOMA

Page 26: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

Tumours with a predominant sarcomatoid pattern of growth1

Tumour type Vimentin2 CA IX 3 PAX 8 CK7 34E12 GATA3 p63

ccRCC Positive Positive

(membranous)

Positive Negative Negative Negative Negative

PRCC Positive Negative Positive Focal or

Negative

Negative Negative Negative

Chromophobe

RCC

Positive Negative Positive Positive Negative Negative Negative

MTSC Positive Negative Positive Positive Variable Negative Negative

Urothelial Ca Positive +/- Negative Negative4 Positive Positive Positive Positive

Sarcoma Positive Negative Negative Negative Negative Negative Negative

Page 27: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

Immunoprofiles of "Small Round Cell Tumour" of the Kidney

CK LCA S100 WT1 Vim Des CD99 CD56 Chro Synp Nephroblastoma (Wilms tumour)

+ - - + + + - + - -

Ewing sarcoma/PNET Variable

- - - + - + - - -

Synovial sarcoma, poorly Differentiated

Variable

- Usually -

- + - + + - -

Lymphoma - + - - + - - - - - Small cell carcinoma + - - - - - - + Variabl

e Variabl

e Metanephric tumour + - - + + - - - - - Congenital mesoblastic nephroma, cellular

- - - - + Variable

- - - -

Rhabdoid tumour Variable

- - - + - - - - -

Clear cell sarcoma - - - - + - - - - -

REFERENCE: Truong LD, Shen SS. Immunohistochemical diagnosis of renal neoplasms. Arch Pathol Lab Med. 2011 Jan;135(1):92-109.

Page 28: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

Metastatic tumours

Page 29: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

Metastatic tumours

• Sangoi et al, Adv Anat Pathol 17(6) Nov2010, p377-393 - review

• Describe specific panels for specific biopsy sites.

• Combining PAX8, PAX2, hKIM-1, RCCma and CD10

• Clear cell meningioma – can be EMA and CD10 positive – advise RCCma

Page 30: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

Comparison of Metastatic and Primary Renal Cell Carcinomas (RCC)

Metastasis Primary

Stain Positive cases% Staining Extent Positive cases % Staining extent

PAX2 74 61% of tumour cells (mean) 85 50% of tumour cells (mean)

RCC marker 35-46 46% of tumour cells (mean) >50% of tumour cells stained in 17% of cases

85 >50% of tumour cells stained in 72% of cases

Kidney-specific cadherin

2a Rare cells 34b >50% of tumour cells stained in 64% of cases

PAX8 Similar to PAX2 Similar to PAX2 Similar to PAX2 Similar to PAX2

CD10 100c >50% tumour cells stained in 86% of cases

86 >50% of tumour cells stained in 73% of cases

Parvalbumin 10d Most cells 27e 60%-100% of tumour cells

AMACR 82f >50% of tumour cells stained in 60% of cases

70 Diffuse staining in most cases

AMACR 100g Most cells 35h >90% of cells

a These were metastatic clear cell RCCs; metastatic chromophobe RCC was not present b Most of these cases are chromophobe RCC c Only clear cell RCCs were included d Of 10 metastatic RCCs, 1 was positive (10%) and it was a metastatic chromophobe RCC e Most positive cases were chromophobe RCC f Of 28 metastatic RCCs, 23 were positive (82%), and all 28 cases (100%) were clear cell RCCs g Of 6 cases, all 6 (100%) were papillary metastatic RCC h There were 35 primary papillary RCCs included, and all of them (100%) were positive. REF: Truong LD, Shen SS. Immunohistochemical diagnosis of renal neoplasms. Arch Pathol Lab Med. 2011 Jan;135(1):92-109.

Page 31: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

ISUP conclusion

• ISUP concluded that PAX8 is most useful marker

Page 32: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

Examples in action.....

Page 33: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

Case 1 • Looks like a clear cell carcinoma but sharp

borders – could it be chromophobe?

Page 34: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples
Page 35: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

IMMUNOPROFILES OF THE MAJOR RENAL NEOPLASMS (%staining)

Stain Clear Cell RCC Papillary

RCC

Chromophobe

RCC Collecting

Duct

Carcinoma

Sarcomatoid

RCC

Xp11

Translocatio

n RCC

MTSCC Tubulocystic

RCC Urothelial

Carcinoma

Oncocytoma

CK7 ± (0-37) + (80-87) + (73-86) + (83) N/A + (17) + (79-100) + (62-91) + (92) ± (0-10)

CK8 + (40) + (87) + (53) + (83) N/A N/A - + (100) + (100) + (100)

CK18 + (100) + (100) + (100) + (100) N/A N/A + (100) + (100) + (83) + (100)

CK20 - - - - N/A N/A - - + (25-68) -

HMW CKs ± (0-13) + (33) - + (29-67) N/A N/A + (15-33) ± (0-67) + (100) + (10)

CK5/6 - - - + (17) N/A - - + (75) -

AE1/AE3 CKs + (35) + (82) + (16) N/A N/A + (0-25) + (83) N/A + (100) + (16)

Vimentin + (87) + (100) - + (100) N/A + (65-70) + (55-100) + (55) + (33) -

AMACR + (4-68) + (80-100) ± (0-29) ± (0-18) N/A + (100) + (92-100) + (77-100) + (20) + (2-25)

Carbonic anhydrase

IX

+ (100) + (57) - + (40-100) N/A + (40) - + (42) + (100) -

PAX2 + (92) + (87) ± (0-83) ± (0-100) - ± (0-100) + (75-100) + (37-42) - + (88-100)

PAX8 + (98) + (87) + (83) + (100) + (28) + (100) + (100) + (100) ± (0-8) + (87-95)

RCC marker + (72-85) + (87-95) + (0-91) - + (0-22) + (100) + (7-92) + (100) - -

CD10 +(94-100) + (67-93) ± (0-72) + (25) N/A + (100) + (9-50) + (33-100) + (50) + (12-58)

E-cadherin ± (0-14) + (13-31) + (100) + (75) N/A + (66) + (93) N/A + (76-100) + (47-100)

Kidney-specific

cadherin

± (0-30) ± (0-29) + (86-100) - N/A + (66) - + (71) - + (75-95)

Parvalbumin ± (0-8) ± (0-31) + (80-100) N/A N/A N/A N/A N/A N/A + (47-100)

Claudin-7 - + (28-35) + (67-95) N/A N/A N/A N/A N/A N/A + (23-73)

Claudin-8 N/A N/A + (27) N/A N/A N/A N/A N/A N/A + (88)

S100A1 + (57-73) + (62-94) ± (0-26) N/A N/A N/A N/A N/A N/A + (93)

CD82 ± (2-23) - + (78-87) N/A N/A N/A N/A N/A N/A ± (0-7)

CD117 ± (0-5) ± (0-13) + (82-100) ± (0-53) ± (4-95) N/A N//A N/A + (4-30) + (58-100)

TFE3 - - - - - + (87) - - - -

Thrombomodulin - N/A N/A N/A - N/A N/A N/A + (49-100) N/A

Uroplakin III 0/32 RCCs - - N/A N/A N/A N/A N/A + (33-100) N/A

p63 - - - + (0-14) - N/A N/A N/A + (81-100) N/A

S100P - - - - - N/A N/A N/A + (71-96) N/A

HMB-45 N/A N/A N/A N/A N/A + (46) N/A N/A N/A N/A

Melan-A N/A N/A N/A N/A N/A + (89) N/A N/A N/A N/A

Reference: Truong LD, Shen SS. Immunohistochemical diagnosis of renal neoplasms. Arch Pathol Lab Med. 2011 Jan;135(1):92-109.

Page 36: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

E cadherin, CK7 both negative => CC RCC

CA IX positive in

ccRCC but not

chromophobe

Page 37: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

Case 2

• Core biopsies reveal papillary lesion - ?TCC or Papillary RCC

Page 38: Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we need it? •What’s new? •Useful panels •Examples

IMMUNOPROFILES OF THE MAJOR RENAL NEOPLASMS (%staining)

Stain Clear Cell RCC Papillary

RCC

Chromophobe

RCC Collecting

Duct

Carcinoma

Sarcomatoid

RCC

Xp11

Translocatio

n RCC

MTSCC Tubulocystic

RCC Urothelial

Carcinoma

Oncocytoma

CK7 ± (0-37) + (80-87) + (73-86) + (83) N/A + (17) + (79-100) + (62-91) + (92) ± (0-10)

CK8 + (40) + (87) + (53) + (83) N/A N/A - + (100) + (100) + (100)

CK18 + (100) + (100) + (100) + (100) N/A N/A + (100) + (100) + (83) + (100)

CK20 - - - - N/A N/A - - + (25-68) -

HMW CKs ± (0-13) + (33) - + (29-67) N/A N/A + (15-33) ± (0-67) + (100) + (10)

CK5/6 - - - + (17) N/A - - + (75) -

AE1/AE3 CKs + (35) + (82) + (16) N/A N/A + (0-25) + (83) N/A + (100) + (16)

Vimentin + (87) + (100) - + (100) N/A + (65-70) + (55-100) + (55) + (33) -

AMACR + (4-68) + (80-100) ± (0-29) ± (0-18) N/A + (100) + (92-100) + (77-100) + (20) + (2-25)

Carbonic anhydrase

IX

+ (100) + (57) - + (40-100) N/A + (40) - + (42) + (100) -

PAX2 + (92) + (87) ± (0-83) ± (0-100) - ± (0-100) + (75-100) + (37-42) - + (88-100)

PAX8 + (98) + (87) + (83) + (100) + (28) + (100) + (100) + (100) ± (0-8) + (87-95)

RCC marker + (72-85) + (87-95) + (0-91) - + (0-22) + (100) + (7-92) + (100) - -

CD10 +(94-100) + (67-93) ± (0-72) + (25) N/A + (100) + (9-50) + (33-100) + (50) + (12-58)

E-cadherin ± (0-14) + (13-31) + (100) + (75) N/A + (66) + (93) N/A + (76-100) + (47-100)

Kidney-specific

cadherin

± (0-30) ± (0-29) + (86-100) - N/A + (66) - + (71) - + (75-95)

Parvalbumin ± (0-8) ± (0-31) + (80-100) N/A N/A N/A N/A N/A N/A + (47-100)

Claudin-7 - + (28-35) + (67-95) N/A N/A N/A N/A N/A N/A + (23-73)

Claudin-8 N/A N/A + (27) N/A N/A N/A N/A N/A N/A + (88)

S100A1 + (57-73) + (62-94) ± (0-26) N/A N/A N/A N/A N/A N/A + (93)

CD82 ± (2-23) - + (78-87) N/A N/A N/A N/A N/A N/A ± (0-7)

CD117 ± (0-5) ± (0-13) + (82-100) ± (0-53) ± (4-95) N/A N//A N/A + (4-30) + (58-100)

TFE3 - - - - - + (87) - - - -

Thrombomodulin - N/A N/A N/A - N/A N/A N/A + (49-100) N/A

Uroplakin III 0/32 RCCs - - N/A N/A N/A N/A N/A + (33-100) N/A

p63 - - - + (0-14) - N/A N/A N/A + (81-100) N/A

S100P - - - - - N/A N/A N/A + (71-96) N/A

HMB-45 N/A N/A N/A N/A N/A + (46) N/A N/A N/A N/A

Melan-A N/A N/A N/A N/A N/A + (89) N/A N/A N/A N/A

Reference: Truong LD, Shen SS. Immunohistochemical diagnosis of renal neoplasms. Arch Pathol Lab Med. 2011 Jan;135(1):92-109.

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CK 7 +ve, p63 –ve Papillary RCC

GATA3 positive in

Urothelial ca but

not papillary RCC

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GATA3 specific for UC vs RCC

• Gonzalez-Roibon N, Faraj SF, Munari E, Bezerra SM, Albadine R, Sharma R, Argani P, Allaf ME, Netto GJ. Comprehensive profile of GATA binding protein 3 immunohistochemical expression in primary and metastatic renal neoplasms. Hum Pathol. 2014 Feb;45(2):244-8.

• Exceptions were some oncocytomas, Xp11.2-RCC, and CDC.

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Case 3 • CC RCC but slightly different area

?Solid papillary RCC

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IMMUNOPROFILES OF THE MAJOR RENAL NEOPLASMS (%staining)

Stain Clear Cell RCC Papillary

RCC

Chromophobe

RCC Collecting

Duct

Carcinoma

Sarcomatoid

RCC

Xp11

Translocatio

n RCC

MTSCC Tubulocystic

RCC Urothelial

Carcinoma

Oncocytoma

CK7 ± (0-37) + (80-87) + (73-86) + (83) N/A + (17) + (79-100) + (62-91) + (92) ± (0-10)

CK8 + (40) + (87) + (53) + (83) N/A N/A - + (100) + (100) + (100)

CK18 + (100) + (100) + (100) + (100) N/A N/A + (100) + (100) + (83) + (100)

CK20 - - - - N/A N/A - - + (25-68) -

HMW CKs ± (0-13) + (33) - + (29-67) N/A N/A + (15-33) ± (0-67) + (100) + (10)

CK5/6 - - - + (17) N/A - - + (75) -

AE1/AE3 CKs + (35) + (82) + (16) N/A N/A + (0-25) + (83) N/A + (100) + (16)

Vimentin + (87) + (100) - + (100) N/A + (65-70) + (55-100) + (55) + (33) -

AMACR + (4-68) + (80-100) ± (0-29) ± (0-18) N/A + (100) + (92-100) + (77-100) + (20) + (2-25)

Carbonic anhydrase

IX

+ (100) + (57) - + (40-100) N/A + (40) - + (42) + (100) -

PAX2 + (92) + (87) ± (0-83) ± (0-100) - ± (0-100) + (75-100) + (37-42) - + (88-100)

PAX8 + (98) + (87) + (83) + (100) + (28) + (100) + (100) + (100) ± (0-8) + (87-95)

RCC marker + (72-85) + (87-95) + (0-91) - + (0-22) + (100) + (7-92) + (100) - -

CD10 +(94-100) + (67-93) ± (0-72) + (25) N/A + (100) + (9-50) + (33-100) + (50) + (12-58)

E-cadherin ± (0-14) + (13-31) + (100) + (75) N/A + (66) + (93) N/A + (76-100) + (47-100)

Kidney-specific

cadherin

± (0-30) ± (0-29) + (86-100) - N/A + (66) - + (71) - + (75-95)

Parvalbumin ± (0-8) ± (0-31) + (80-100) N/A N/A N/A N/A N/A N/A + (47-100)

Claudin-7 - + (28-35) + (67-95) N/A N/A N/A N/A N/A N/A + (23-73)

Claudin-8 N/A N/A + (27) N/A N/A N/A N/A N/A N/A + (88)

S100A1 + (57-73) + (62-94) ± (0-26) N/A N/A N/A N/A N/A N/A + (93)

CD82 ± (2-23) - + (78-87) N/A N/A N/A N/A N/A N/A ± (0-7)

CD117 ± (0-5) ± (0-13) + (82-100) ± (0-53) ± (4-95) N/A N//A N/A + (4-30) + (58-100)

TFE3 - - - - - + (87) - - - -

Thrombomodulin - N/A N/A N/A - N/A N/A N/A + (49-100) N/A

Uroplakin III 0/32 RCCs - - N/A N/A N/A N/A N/A + (33-100) N/A

p63 - - - + (0-14) - N/A N/A N/A + (81-100) N/A

S100P - - - - - N/A N/A N/A + (71-96) N/A

HMB-45 N/A N/A N/A N/A N/A + (46) N/A N/A N/A N/A

Melan-A N/A N/A N/A N/A N/A + (89) N/A N/A N/A N/A

Reference: Truong LD, Shen SS. Immunohistochemical diagnosis of renal neoplasms. Arch Pathol Lab Med. 2011 Jan;135(1):92-109.

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CK 7 +ve

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What now?

• Morphology is key

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Case 4

• Spindle cell tumour ?AML or Leiomyoma

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Melan A

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HMB45

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AML

• Can sometimes be very weak staining for HMB45

• Melan A maybe useful

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Case 5

• Chromophobe or Oncocytoma

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CHROMOPHOBE V ONCOCYTOMA IMMUNOPHENOTYPE

ANTIBODY CHROMOPHOBE ONCOCYTOMA

DIFFUSE CK7 65% RARE

FOCAL CK7 35% 79%

CD15 NEG 63%

CK20 NEG 53%

CD117 MOST MOST

RCC 45% <5%

CD82 78% RARE

AMACR 36% >90%

PAX 2 6% >90%

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CK7

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CD15 and Racemase -ve

=> Chromophobe

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Case 6

• Partial nephrectomy with cystic areas ?benign cortical cyst or multilocular cystic RCC

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CK 7

CD10

EMA

Vimentin

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Case 6 specimen B

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CK 7

CD10

EMA

Vimentin

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Summary

Cortical cyst Multilocular Cystic Renal neoplasm of low malignant potential

CD10 negative positive

CK7 positive positive

Vimentin positive positive

EMA negative positive

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Comments

• CK 7 can be expressed by clear cell RCC and is expressed by MLC RCC

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Case 7

• 46yr male Rapidly growing lesion on shoulder

• ?melanoma ?merkel

• H&E – vascular lesion with spindle cells and focal clear cells.

• ?KS/melanoma/met

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PAX 8

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Immunoprofile

• S100, melan A, - negative

• Vimentin, EMA, CD10, MNF116, PAX8 positive

Metastatic Clear cell

renal cell carcinoma

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Conclusion

• Immunohistochemistry is rarely required in renal tumours

• More recent markers may not be specific enough to be useful

• Will always be a small group of tumours that have unusual morphology/IHC that require molecular studies.

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Thanks and Links • Diagnostic Pathology: Genitourinary: Mahul Amin, ISBN-10:1931884285

• WHO Classification of Tumours of the Urinary System and Male Genital Organs WHO/IARC Classification of Tumours, 4th Edition, Volume 8 Edited by Moch H, Humphrey PA, Ulbright TM, Reuter VE

• The ISUP Vancouver Classification of Renal Neoplasia J.R. Srigley, Am J Surg Pathol 2013 37(10)

• Best practices recommendations in the application of immuno-histochemistry in the kidney tumors: report from the ISUP consensus conference. Reuter VE Am J Surg Pathol. 2014 Aug;38(8):e35-49.

• Recent advances of immunohistochemistry for diagnosis of renal tumors Naoto Kuroda. Pathology International 2013: 63(8), 381–90

• Thanks to Prof Fleming, Dr Jonathan Shanks, Dr Nick Mayer, and Catherine Neal for typing immuno table

• Uropathology EQA at www.histopathologyeqa.org

• This and other lectures/cut up protocols:

www.jonoxley.com