Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we...
Transcript of Renal tumour immunohistochemistry - Jon Oxley · Renal tumour immunohistochemistry •When do we...
The value of immunohistochemistry in Renal tumours
Jon Oxley
Bristol
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
RCC DIAGNOSTIC PROCESS
• MORPHOLOGY
80%
• IMMUNOCYTOCHEMISTRY
10-15%
• MOLECULAR GENETICS
5%
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
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.
What’s new?
• PAX 2 and 8
• Carbonic anhydrase IX
• RCC marker
• Cathepsin K
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.
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.
Carbonic anhydrase IX (CA IX)
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
PAX 8 – Normal kidney
PAX8 - Oncocytoma
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.
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
Panels
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)
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
TFE 3 – nuclear staining
DISTINCT IMMUNOPHENOTYPE
EMA CAM 5.2
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*
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
CHROMOPHOBE vs ONCOCYTOMA
MORPHOLOGY
PERINUCLEAR HALO
BINUCLATE CELLS
RAISINOID NUCLEI
MITOSES
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%
CK 7 in CHROMOPHOBE CARCINOMA vs ONCOCYTOMA
CK7
CHROMOPHOBE ONCOCYTOMA
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
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.
Metastatic tumours
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
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.
ISUP conclusion
• ISUP concluded that PAX8 is most useful marker
Examples in action.....
Case 1 • Looks like a clear cell carcinoma but sharp
borders – could it be chromophobe?
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.
E cadherin, CK7 both negative => CC RCC
CA IX positive in
ccRCC but not
chromophobe
Case 2
• Core biopsies reveal papillary lesion - ?TCC or Papillary RCC
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.
CK 7 +ve, p63 –ve Papillary RCC
GATA3 positive in
Urothelial ca but
not papillary RCC
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.
Case 3 • CC RCC but slightly different area
?Solid papillary RCC
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.
CK 7 +ve
What now?
• Morphology is key
Case 4
• Spindle cell tumour ?AML or Leiomyoma
Melan A
HMB45
AML
• Can sometimes be very weak staining for HMB45
• Melan A maybe useful
Case 5
• Chromophobe or Oncocytoma
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%
CK7
CD15 and Racemase -ve
=> Chromophobe
Case 6
• Partial nephrectomy with cystic areas ?benign cortical cyst or multilocular cystic RCC
CK 7
CD10
EMA
Vimentin
Case 6 specimen B
CK 7
CD10
EMA
Vimentin
Summary
Cortical cyst Multilocular Cystic Renal neoplasm of low malignant potential
CD10 negative positive
CK7 positive positive
Vimentin positive positive
EMA negative positive
Comments
• CK 7 can be expressed by clear cell RCC and is expressed by MLC RCC
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
PAX 8
Immunoprofile
• S100, melan A, - negative
• Vimentin, EMA, CD10, MNF116, PAX8 positive
Metastatic Clear cell
renal cell carcinoma
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.
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