the pathology of common renal tumors victor e. reuter, … the patholo… · 1976: papillary renal...
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THE PATHOLOGY OF
COMMON RENAL TUMORS
Victor E. Reuter, M.D
Memorial Sloan Kettering Cancer Center
Disclosures: none
A Practical Approach to Genitourinary Pathology
Firenze, Italy
May, 2016
RENAL NEOPLASIA
Landmarks in the pathological classification
over the past 4+ decades
1970 WHO classification:
Clear cell, Papillary, Granular, Sarcomatoid
1976: Oncocytoma (Klein and Valensi)
Cancer 1976;38:906
1976: Papillary Renal cell carcinoma (Mancilla-Jimenez et al)
Cancer 1976: 38:2469
1985: Chromophobe RCC (Thoenes and Storkel)
Virchow’s Arch 1985;48:207 and J Pathol 1988;155:277
1986: Classification of RCC (Thoenes and Storkel)
Pathol Res Pract 1986;181:125
1997: The Heidelberg classification
2004: WHO classification
2013: ISUP-Vancouver classification
Am J Surg Pathol 2013;37:1469
2016 WHO classification
2011-2014: IGC, TCGA et al ;
genomic classification of RCC
CLASSIFICATION OF RENAL EPITHELIAL TUMORS*
Clear cell carcinoma
Papillary carcinoma
Chromophobe carcinoma
Oncocytoma
Multilocular cystic renal cell neoplasm
Renal cell carcinoma with fibromuscular stroma
Collecting duct carcinoma
Medullary carcinoma
Mucinous Tubular and Spindle Cell carcinoma
MiTF-family translocation associated carcinoma
BHD-associated renal tumor
Tubulocystic carcinoma
Clear cell papillary
Hereditary leiomyomatosis renal cell carcinoma
SDH related carcinoma
TSC related carcinoma
Circa 1985:
Clear cell
Papillary
Granular cell
Sarcomatoid
Heidelberg, 1995
Comprehensive molecular characterization of clear cell renal cell
carcinoma: The Cancer Genome Atlas Network
Nature. 2013 Jul 4;499:43-9
Oostewijk et al Eur Urol, 2011;60:620
CLEAR CELL RENAL CELL CARCINONA
• 60% - 65% of renal epithelial neoplasms
• mean age at presentation: 6th to 7th decade
- younger in hereditary cases
• M:F 1.7- 2.0:1
• Most are asymptomatic at presentation
- triad (hematuria/ pain/ mass) in < 10%
• 10% multifocal, 3% bilateral
•VHL is a tumor suppressor gene at 3p25.3
•Well established role in CCRCC tumorigenesis
• Silencing via multiple mechanisms
• PBRM1 mutations (41%) SWI/SNF
• Inactivation of histone modifying genes
VHL
CLEAR CELL RENAL CELL CARCINONA
Microscopic features:
• variable growth pattern, loosely related to grade
- solid/acinar, delicate fibrovascular septa
- sheet-like, pseudopapillary, rhabdoid, sarcomatoid
• fibrosis and hyalinization are common
• geographic necrosis and hemorrhage are common
• cell shape is variable, loosely related to grade
• cytoplasm is variable, loosely related to grade
The many cytomorphologies of clear cell RCC
Feature Score
T stage:
pT1 0
pT2 1
pT3 2
pT4 2
N stage:
pNx or pN0 0
pN1 or pN2 2
M stage:
pM0 0
pM1 4
Tumor size (cm):
<5 0
≥5 2
Nuclear grade:
1 0
2 0
3 1
4 3
Necrosis:
Absent 0
Present 2
The SSIGN scoring algorithm
The scores from each category in this table are added together
and the total is used to determine survival
Frank et al. J. Urol. 2005;.173: 48–51)
SSIGN score % Estimated cancer specific survival
1-year 3-year 5-year 7-year 10-year
0–1 100 99.7 99.4 98.7 97.1
2 99.1 95.9 94.8 90.3 85.3
3 97.4 90.3 87.8 81.8 77.9
4 95.4 87.1 79.1 70.8 66.2
5 91.1 71.3 65.4 57.1 50.0
6 87.0 69.8 54.0 46.4 38.8
7 80.3 52.4 41.0 34.0 28.1
8 65.1 38.9 23.6 12.7 12.7
9 60.5 26.8 19.6 18.1 14.8
≥10 36.2 11.9 7.4 4.6 4.6
International Journal of Urology 2010;18:20
Kapur P et al, Lancet Oncol. 2013;14:159
Hakimi AA et al Eur Urol. 2012
Renal-call carcinoma: a step closer to a new classification
Choueri et al, Lancet Oncol.2013;14:105
49% 29% 8% 8% 6%
WILL THE FURHMAN NUCLEAR GRADING SYSTEM SURVIVE?
• Virtually nobody applies strict size criteria
• Follow-up data does not support 4 risk groups
• Four tiered grading schemes suffer from
reproducibility issues
Furhman Nuclear Diameter Nuclear Shape Nucleoli
G1 10 μm Round, uniform Absent
G2 15 μm Subtle irregularities Visible at 400X
G3 20 μm Obvious irregularities Visible at 100X
G4 20 μm, bizarre, spindle
WILL THE FURHMAN NUCLEAR GRADING SYSTEM SURVIVE?
Delahunt et al, AJSP, 2011;35:1134
• Nucleolar grade is superior to nuclear grade in clear cell RCC
• Difference between nucleolar grade 2 & 3 is magnification-dependent
Delahunt et al, AJSP, 2013;37:311
• Novel grading system for clear cell carcinoma incorporating necrosis
• Nucleolar (ISUP) grade
• Coagulative necrosis
• Sarcomatoid or rhabdoid morphology
NUCLEOLAR GRADE
100X magnification
Grade 1 Grade 2 Grade 3
Grade 4:
Rhabdoid,
Sarcomatoid
THE IMPORTANCE OF THE RENAL
SINUS AND ITS VESSELS IN
PREDICTING TUMOR PROGRESSION
Bonsib SM et al Am J Surg Pathol, 2000;24:451
Leibovich BC et al, J Urol, 2005;73:716
Bonsib SM, Am J Surg Pathol, 2004;28:1594
Thompson RH et al Am J Surg Pathol, 2007;31:1089
Bonsib SM, Mod Pathol, 2007;20:44
The end result is modification of the AJCC/UICC staging classification
(2010, 7th ed) where Renal Vein Invasion below the diaphragm
and Invasion of Muscular Branches of the Renal Vein are both pT3a
ANATOMY OF THE KIDNEY
CLEAR CELL CARCINOMA
Feifer A, et al. J Urol. 2011;185:35-42
CLEAR CELL RENAL CELL CARCINONA
Differential diagnosis:
• Papillary RCC
• Chromophobe RCC
• Epithelioid AML
• RCC with fibromuscular stroma
• Translocation-associated
RCC
• Adrenal cortical
carcinoma
• Metastatic disease
TUMORS COMPOSED PREDOMINANTLY OF “CLEAR” CELLS
Tumor type CA IX CK7 CD 117 Cathepsin-K HMB45
Clear cell RCC Positive, diffuse membranous
Negative Negative Negative Negative
Clear cell papillary RCC
Positive, cup-like
Positive Negative Negative Negative
Chromophobe RCC, classic
Negative Positive, cytoplasmic
Positive, membranous
Negative Negative
Epithelioid AML
Negative Negative Negative Positive, cytoplasmic
Positive, cytoplasmic
MiTF-TFE tumors
Xp11 family Variable but focal
Negative Negative Positive (50%), cytoplasmic
Negative *
t (6;11) Variable but focal
Negative Negative Positive, cytoplasmic
Positive (always focal)
Immunohistochemistry for classification
General comments (isuporg.org)
• Over a dozen entities to deal with
• Dozens of antibodies have been evaluated in at least one publication
• Nothing better than level II or Level III evidence (no validation studies)
• Inter-laboratory variability
• clone, methodology
• Most studies do not focus on “hard to classify” tumors but rather classic cases
• Best applied as Ab panels, taking into consideration a differential diagnosis
• tumors with clear cell cytology
• tumors with a predominant papillary pattern of growth
• high grade tumors with pleomorphic features
Clear cell RCC
Vimentin
CA IX EMA
PAPILLARY RENAL CELL CARCINOMA
• 13% to 18% of renal epithelial neoplasms
• M:F 2.1-3.9:1
• mean age at presentation in the 6th-7th decade
- earlier in hereditary cases
•most cases are asymptomatic
Met receptor
HGF
Activating mutation
Therapeutic approach to selected “type 1” papillary RCC
Tyrosine kinase inhibition
PAPILLARY RENAL CELL CARCINOMA
Microscopic features:
• broad morphologic spectrum
- papillary, papillary/tubular, papillary/solid
• classic features
-discrete papillary fronds with central fibrovascular core
- cuboidal, columnar or polygonal cells
- cytoplasmic basophilia, amphophilia or eosinophilia
- psammoma bodies, foamy macrophages
- geographic necrosis
PAPILLARY RENAL CELL CARCINOMA
PAPILLARY RENAL CELL CARCINOMA
GROWTH PATTERN
Pure papillary 27 (32.5%)
> 50% papillary* 36 (43.4%)
< 50% papillary* 20 (24.1%)
* also tubular, solid, spindled,
glomeruloid
CYTOPLASMIC FEATURES
Eosinophilic 10 (12.0%)
Amphophilic 13 (15.7%)
Basophilic 4 ( 4.8%)
Mixed 56 (67.5%)
Amin et al. Am J Surg
Pathol. 21:621,1997.
Type 1 PRCC Type 2 PRCC
Delahunt et al. Hum Pathol. 32:590,2001
Delahunt et al. AJSP 37:311;2013
- ISUP nucleolar grade but not necrosis
Sukov et al. J Urol 187:54;2012
- Furhman grade superior to tumor type
PAPILLARY RENAL CELL CARCINOMA
HISTOLOGIC SUBCLASSIFICATION
Type Cell size Cytoplasm Grade Molecular
classification
1 small pale 1-2 1
1 and 2A small and
large
pale and
eosinophilic
1-2 1
2A large eosinophilic 1-2 1
2B large eosinophilic 3-4 2
Yang, X. J. et al. Cancer Res 2005;65:5628-5637
Type “1” Type “2a’ Type “2b”
Current state of papillary renal neoplasia
• It’s a mess
• Type 2 papillary RCC is not an entity
• How many morphologic, clinical and molecular entities are included is yet to be defined
• Type 1 papillary RCC is better defined but needs fine tuning
• Some papillary RCC have morphologic features of both type 1 and type 2 tumors
• Morphologic
continuum?
• Grade related?
Papillary Renal Cell Carcinoma
MSKCC study on Type 1 Papillary RCC
•We investigated the clinicopathological features, including cancer specific (CSS) and progression free survival (PFS), of PRCC with any type 1 component, based on the premise that the presence of even focal typical type 1 morphology would define the tumor classification
•199 cases of PRCC with the WHO-defined type 1 features, diagnosed at our institution from 1995 to 2008.
•Tumors with type 2 features were included if any identifiable type 1 areas were present. The type 2 areas were quantified in tumors with mixed histology. Various pathological features were evaluated.
•Clinical features and follow up information were obtained from an IRB-approved annotated clinical database.
Murugan P et al, USCAP 2015
0%
2%
4%
6%
8%
10
%12
%
Pro
bability o
f R
ecurr
ence
0 3 6 9 12 15
Years since Nephrectomy
199 169 130 67 24 5 Number at risk
Figure 1: Probability of a recurrence
0%
2%
4%
6%
8%
10
%12
%
Pro
bability o
f C
ancer-
Spe
cific
Mort
ality
0 3 6 9 12 15
Years since Nephrectomy
199 175 133 68 24 5 Number at risk
Figure 2: Probability of cancer-specific mortality
• There were 10 patients who died of disease and 12
who recurred.
• The median follow-up time among those who did not
die of disease was 7.8 years (IQR: 5.7, 10.0).
The Kaplan Meier estimated probability of recurrence at 15 years of follow-up
was 7% (95% CI 4%, 11%) and for cancer-specific death was 6% (95% CI 3%, 10%).
Type 1 Papillary RCC Study
Murugan P et al, USCAP 2015
MSKCC phase 1 study on Type 1 Papillary RCC
• 95 tumors (48%) contained some type 2 component; the median
amount of type 2 morphology was 25% (IQR: 10%, 70%).
• PFS and CSS showed no significant association with the
presence of type 2 morphology in the tumor (p=0.2 and 0.2,
respectively) or its percentage (p=0.052 and 0.13, respectively).
• Associations with cancer specific survival (CSS) rates:
Tumor size (p=0.003)
Mitotic rate (<0.0001)
Circumscription (0.0002)
Lymphovascular invasion (LVI) (<0.0001) (6/6 pts DOD)
Sarcomatoid and solid architectures (<0.0001, and 0.014)
Murugan P et al, USCAP 2015
MSKCC phase 1 study on Type 1 Papillary RCC
conclusions
• PRCC with any component of type 1 morphology, regardless of
presence or amount of type 2 features, have excellent long-term
outcome.
• Both predominant Fuhrman and ISUP nucleolar grades are
significantly associated with clinical outcome, but focal high
grade nuclear or nucleolar features are not.
• Tumor size, mitotic rate, tumor circumscription, lymphovascular
invasion, sarcomatoid and solid architectures are significantly
associated with outcome in type 1 papillary RCC.
Murugan P et al, USCAP 2015
PAPILLARY RENAL CELL CARCINOMA
Differential diagnosis:
• Clear cell RCC with pseudopapillary areas
• Clear cell papillary RCC
• Metanephric adenoma
• Translocation-associated RCC
• Metastatic carcinoma
• ACDK-associated RCC
• Hereditary leiomyomatosis PRCC syndrome
TUMORS WITH A SIGNIFICANT PAPILLARY COMPONENT
CAIX CK7 AMACR Cathepsin-K 4A4 TFE3/TFEB
Clear cell RCC with papillary growth
Positive, membranous
Negative Negative Negative Negative Negative
Papillary RCC “type I”
Negative Positive Positive Negative Negative Negative
Papillary RCC “type II”
Negative +/- positive Positive Negative Negative Negative
Clear cell papillary RCC
Positive, cup-like
Positive, diffuse
Negative Negative Negative Negative
MiTF-TFE trans-assoc
Variable but focal
Negative Positive Positive (50%)
Negative Positive*
Collecting duct Ca
Negative Positive +/- positive
Negative Positive Negative
Papillary RCC
CK7
AMACR Vimentin CAIX
WT-1 +
CD57 +
BRAF +
CK7 +
AMACR + WT-1 +
Metanephris adenoma Type 1 PRCC (solid) Wilms tumor
Papillary adenoma
Definition (WHO 2016)
Size: 15 mm or less
Papillary, tubulo-papillary or
solid
Fuhrman grade 1-2
Nucleolar grade 1-2
No peritumoral pseudocapsule
CHROMOPHOBE RENAL CELL
CARCINOMA
• 6% to 11% of renal epithelial neoplasms
• M:F 1.5-2.0:1
• mean age at presentation in the 6th-7th decade
• 10% multifocal, 3% bilateral
• asymptomatic in 58%
• hematuria in 19%, palpable mass in 30%
MICROSATELLITE ANALYSIS IN
CHROMOPHOBE CELL RENAL CARCINOMA
CASE: 1 2 3 6 10 13 17 21
17
18
19
20
21
22
= LOH = No LOH NI= Not informative
Bugert et al. Lab Invest 76:203-208,1997.
CHROMOPHOBE
RENAL CELL CARCINOMA
Microscopic features:
• dominated by large round-to-polygonal cells with well defined cell borders and amphophilic to basophilic reticulated cytoplasm
• smaller number of polygonal cells with eosinophilic cytoplasm
• larger cells with abundant foamy cytoplasm
• hyperchromatic nuclei with irregular membranes
• binucleate cells are common
• bizarre nuclei (degenerative atypia) in up to 50%
CHROMOPHOBE RENAL CELL CARCINOMA
CHROMOPHOBE RENAL CELL CARCINOMA
May be confused with clear cell RCC.
Alternatively some clear cell RCC may
have chromophobe-like areas
Kidney TCGA
Unsupervised
clustering of DNA
copy number
profiles
KICH TCGA
early data
Clear cell RCC - TCGA
Case Outliers*
Pathology review**
Category Number
Clear cell/likely clear cell 18
Clear cell papillary 4
Chromophobe/likely chromophobe 15
Oncocytoma/likely oncocytoma 2
Not clear cell or chromophobe 6
Not reviewed 16
Total 61
*Outliers:
Chomo-like genotype
wtVHL
No 3p loss
** Pathologists
Satish Tickoo (MSKCC)
Pheroze Tamboli (MDACC)
Maria Merino (NCI)
Sabina Signoretti (DFCC)
Victor Reuter (MSKCC)
CHROMOPHOBE CARCINOMA
Predictors of Aggressive Behavior
on multivariate analysis
Predictor Relative Hazard
ratio (p)
95% CI
Sarcomatoid change 4.7 (0.013) 1.4, 16.0
Microscopic necrosis 3.5 (0.020) 1.2, 10.0
pT stage (3,4 vs 1,2) 3.4 (0.025) 1.1, 9.7
Tumor size (>7.5cm) 1.0 (0.75) 0.9, 2.2
Amin et al. Am J Surg Pathol. 2008
Table 2. Cox regression to evaluate predictors of disease-free survival following
nephrectomy for chromophobe renal cell carcinoma, adjusted for age at surgery
Characteristic Hazard Ratio 95% CI P Value adjusted for age
Gender (Female vs Male) 2.00 1.10, 3.67 0.02
Tumor size (cm) 1.08 1.01, 1.15 0.03
T stage, 2010 AJCC classification
T2a/b vs T1a/b 1.32 0.63, 2.76
T3a/b, T4 vs T1a/b 1.42 0.69, 2.93 0.6
Nodal status at presentation
NX vs N0 1.30 0.70, 2.40
N1 vs N0 7.75 1.72, 34.90 0.03
Microscopic necrosis (yes vs no) 2.69 1.37, 5.27 0.004
Gross necrosis (yes vs no) 0.72 0.28, 1.84 0.5
Sarcomatoid differentiation (yes vs no) 6.80 2.04, 22.60 0.002
Mitotic count (> 1/10 HPF vs ≤ 1/10 HPF) * * *
Vascular invasion (yes vs no) 1.95 0.92, 4.13 0.08
Capsular invasion (yes vs no) 1.38 0.66, 2.89 0.4
Renal sinus invasion
Yes vs No 1.05 0.35, 3.13
Not interpretable vs No 0.84 0.45, 1.58 0.8
Renal sinus vessel invasion
Yes vs No 1.35 0.31, 5.78
Not interpretable vs No 0.94 0.51, 1.75 0.9
Przybycin Am J Surg Pathol 2011;35:962
203 cases
Median f/u: 6.1 yr
Mets at presentation: 5
Progression after surgery: 8
MIB-1
CHROMOPHOBE
RENAL CELL CARCINOMA
Differential diagnosis:
• Clear cell RCC
• Oncocytoma
• Epithelioid (pleomorphic) AML
•“Hybrid” oncocytic tumors (HOCT)
•Oncocytosis/Birt-Hogg-Dubé
•Tuberous sclerosis complex (TSC)-associated
• Succinate Dehydrogenase (SDH)-associated
RENAL ONCOCYTOMA
• Peak incidence in 6th to 7th decade
• 5%-10% or renal epithelial tumors
• M : F = 2:1
• Most are asymptomatic
• No consistent genetic abnormalities
- loss of chromosomes 1and Y
- rare translocations (chr 11)
- mitochondrial DNA defects
• Well circumscribed, mahogany brown
• Central scar in 30%
• No necrosis
• Hemorrhage (20%)
RENAL ONCOCYTOMA
Microscopic features:
• compact nests, acini, tubules or microcysts
• hyalinized hypocellular stroma
• round to polygonal epithelial cells densely
eosinophilic cytoplasm
• round, regular nuclei with dispersed
chromatin and central nucleoli
RENAL ONCOCYTOMA
Acceptable findings:
• degenerative cytologic atypia
• peri-renal or sinus fat invasion
• vascular invasion
Non-acceptable findings:
• more than an isolated mitotic figure
• tumor necrosis
• overt papillary architecture
• true cytologic atypia
Our contemporary study on renal oncocytoma Renal oncocytoma: a clinicopathologic study of 70 cases.
Perez-Ordonez B, Am J Surg Pathol 1997;21:871-883
• Benign
• Considerable controversy regarding the definition of renal
oncocytoma
•RCC unclassified (oncocytic, at worst low grade malignant)
•Renal oncocytic neoplasm
•Hybrid oncocytic tumor
•Renal cell carcinoma with oncocytic features
• In general, because we aim to keep this a benign entity the
morphologic criteria applied by most pathologists are extremely
rigorous
• However, even within our own institution, thresholds vary….
• VER and SKT agree it is oncocytoma
• VER and SKT agree it is NOT oncocytoma
• VER and SKT disagree whether it is oncocytoma or not
Agree yes
Agree no Agree no
Disagree
Our contemporary study on renal oncocytoma
• 183 patients with oncocytic neoplasms resected at our institution from 2000-
2010
• All non-oncocytoma (like) tumors were excluded from the study
• Cases put into one of three groups
1. definite oncocytoma [102 (53%)]
2. disagreement between pathologists whether oncocytoma or not [56 (29%)]
3. definite not oncocytoma [35 (18%)]
• Morphologic features described within each group
• Clinical follow-up information was interrogated
• Median f/u of 60 months (5 d-166 mo)
• No metastases of tumor-related deaths in any of the 3 groups
Conclusions:
1. Renal oncocytoma or oncocytoma-like tumors all have excellent long-term
prognosis
2. “Atypical” morphologic features are likely unduly overemphasized in
excluding the diagnosis of renal oncocytoma
ONCOCYTOMA
Differential diagnosis:
• Eosinophilic variant of Chromophobe RCC
• Epithelioid (oncocytic) AML
• “Hybrid” oncocytic tumor (HOCT)
•Oncocytosis/Birt-Hogg-Dubé
•Tuberous sclerosis complex (TSC)-associated
• Succinate Dehydrogenase (SDH)-associated
TUMORS WITH ONCOCYTIC FEATURES
CD117 CK7 Ksp-cadherin HMB-45 Parvalbumin
Oncocytoma Positive, membranous
Negative Positive Negative Positive
Chromophobe RCC, eosinophilic
Positive, membranous
Positive but variable
+/- positive Negative Positive
Oncocytic papillary RCC
Negative Positive but focal
Not known Negative Unknown
Oncocytic AML
Negative Negative Negative Positive, focal
Negative
Other Abs said to differentially expressed on oncocytomas and chromophobe RCC
Positive in Oncocytoma, negative in Chromophobe EABA, S100A1
Negative in Oncocytoma, positive in Chromophobe MOC31, EpCam, Caveolin-1, CD82
Renal Cortical Tumors
MSKCC
Median Tumor Size
Incidental detection
Lee et al. Urol Oncol 2002;7:135–40
MSKCCMSKCC
0.00
1.00
2.00
3.00
4.00
5.00
6.00
7.00
8.00
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
Nephrectomy Year
Tu
mo
r S
ize (
cm
)
0.0%
10.0%
20.0%
30.0%
40.0%
50.0%
60.0%
70.0%
80.0%
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
Case Year
HISTOLOGICAL SUBTYPE IN 2,675 PATIENTS
TREATED SURGICALLY FOR A RENAL MASS
Tumors Number of tumors (%)
Benign 311 (11.6)
Oncocytoma 232 (74.5)
Angiomyolipoma 35 (11.2)
Metanephric adenoma 8 ( 2.6)
Other 36 (11.6)
Malignant 2,675 (88.4)
Clear cell 1,679 (71.0)
Papillary 341 (14.4)
Chromophobe 239 (10.1)
Collecting duct 7 ( 0.3)
RCC unclassified 98 (4.1)
Thompson RH, et al J Urol 2009;181:2033-2036 MSKCCMSKCC
BENIGN TUMORS vs RCC ACCORDING TO SIZE IN PATIENTS
TREATED SURGICALLY FOR A RENAL MASS
Size (cm) No. Benign (%) No. RCC (%)
Less than 1 6 (37.5) 10 (62.5)
1 to less than 2 56 (19.2) 236 (80.8)
2 to less than 3 77 (16.5) 391 (83.5)
3 to less than 4 58 (13.0) 390 (87.0)
4 to less than 5 30 (8.7) 315 (91.3)
5 to less than 6 23 (10.0) 206 (90.0)
6 to less than 7 13 (6.6) 183 (93.4)
7 or greater 48 (7.1) 633 (92.9)
Thompson RH, et al J Urol 2009;181:2033-2036
16.1
%
20.2
%
MSKCCMSKCC
CHROMOPHOBE RENAL CELL CARCINOMA
4 cm or less
Cases: 74
Follow-up (mos): 73.5 (median)
Outcome:
NED: 73
AWD: 1 (1.4%)
DOD: 0
Przybycin Am J Surg Pathol 2011;35:962 MSKCCMSKCC
TREATMENT OF “SMALL RENAL MASSES”
• Treating blindly
- Surgery
- Ablation
• Active surveillance
- Life expectancy
- Co-morbidities
- Tumor biology
• Cost
Cases (N) Adequate
material (%)
Correct Diagnosis
on H&E alone
Correct Diagnosis
with IHC
Clear Cell (84) 75 (89) 64 (85) 68 (91)
Papillary (18) 18 (100) 17 (94) 18 (100)
Chromophobe (14) 13 (93) 8 (62) 12 (92)
Oncocytoma (11) 6 (55) 4 (67) 6 (100)
Total (127) 112 (88) 93 (83) 104 (93)
Al-Ahmadie et al, Am J Surg Pathol 2011;35:949
Tumor type Total Ablation Nephrectomy Chemotherapy Active
Surveillance
Clear cell RCC 80 12 24 31 13 (16%)
Papillary RCC 7 3 0 2 2 (29%)
LG
oncocytic
neoplasm
Chromophobe 9 2 2 1 4 (44%)
oncocytoma 9 1 2 0 6 (67%)
NOS 9 0 0 0 9 (100%)
Clear cell papillary RCC 4 1 0 0 3 (75%)
Angiomyolipoma 5 0 0 0 5 (100%)
Misc* 5 0 2 3 0 (0%)
Total 128 19 30 37 42 (33%)
Gel
lert
et
al,
US
CA
P 2
01
2
63%
SUMMARY
• Renal tumors are not a single histologic, clinical or
molecular entity
• Proper molecular and morphological classification
of tumors is of clinical importance for risk
stratification
• Further molecular and morphologic dissection of
renal neoplasms will lead to more appropriate
therapies of both primary and metastatic disease
• In vivo classification of tumors is desirable and
possible in the majority of cases
• Judicious use of antibody panels can be useful to
arrive at a proper diagnosis MSKCCMSKCC