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Update in TNM Staging and Handling of Kidney Cancer
Kiril Trpkov, MD FRCPC Department of Pathology and Laboratory Medicine
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Disclosure of Relevant Financial Relationships
Dr. Kiril Trpkov declares no conflicts of interest
to disclose.
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Update in TNM Staging and Handling of
Kidney Cancer - Objectives Understand rationale for proper handling and staging of renal specimens Identify differences in TNM staging compared to 7th AJCC edition Understand prognostic rationale for changes of staging system for renal cancers
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Prognostic factors in RCC
1. Pathologic stage
2. Tumor WHO/ISUP grade
3. Morphologic type
4. Sarcomatoid-rhabdoid differentiation
5. Tumor necrosis
(Microvascular invasion)
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ISUP Consensus Meeting on Adult Renal Tumors Vancouver, March, 2012
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Trpkov K et al. Am J Surg Pathol 2013; 37:1505-17
ISUP Consensus Meeting on Adult Renal Tumors
Vancouver, March, 2012
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Bonert M, Kuo-Cheng H, Trpkov K. Diagnostic Histopathology 2016;22(2):57-67
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#1 Best Seller in Oncology
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Stage pT3a pT3 Tumor extends into major veins or perinephric tissues, but not into the ipsilateral adrenal gland and not beyond Gerota’s fascia pT3a Tumor extends into the renal vein or its segmental branches, or invades the pelvicalyceal system, or invades perirenal and/or renal sinus fat but not beyond Gerota’s fascia
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Renal tumor stage summary of changes AJCC/TNM 8th edition
Definition of Primary Tumor (pT): T3a disease
Word “grossly” was eliminated from the description of renal vein involvement
“Muscle containing” was changed into “segmental veins”
Invasion of the pelvicalyceal system was added
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Key prognostic parameter Used in prognostic nomograms 7th edition (2009) 8th edition (2017)
Renal tumor stage
Robson CJ et al. J Urol 1969; 101:297–301
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Handling of renal tumors
Pathologist Pathologist
Goals: Thorough gross examination Adequate sampling Reporting of stage and other important prognostic parameters
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Specimen received in the lab
Identify and sample: Adrenal gland Vascular margins Ureter
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Ureteral stump opened and examined
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Ureteral invasion
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Initial section of specimen along long axis (lateral or medial)
Probes in collecting system or in largest hilar veins
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Initial section of specimen along long axis (lateral or medial)
Consider additional parallel sections through venous system
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Radical and partial nephrectomies should be inked
Complete Localized Selective (resection margin)
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Renal tumor measurement (greatest dimension)
Measure any tumor invading into extracapsular tissue
Do not measure tumor invading into renal/caval vein
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Stage T1 and T2 Tumor limited to kidney!
TNM 2009 (7th edition) same in AJCC/TNM 2017 (8th edition)
T2a (>7 cm but ≤10 cm) T2b (>10 cm)
≤ 4cm
> 4 but ≤ 7cm
> 7cm
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How many blocks should you submit for examination?
Important to assess tumor relationship with: Renal capsule (perirenal fat) Renal sinus Adrenal gland Renal pelvis
Areas of different appearance or consistency! Sarcomatoid differentiation, necrosis etc.
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Sarcomatoid carcinoma (dedifferentiation)
In any histologic type – poor prognosis! (report %)
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One block per cm,
minimum of 3 blocks
(subject to modification)
Sampling of renal tumor for examination
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Multiple renal tumors Hereditary:
Von Hippel Lindau disease Birt-Hogg Dubbé Sy Hereditary papillary carcinoma Tuberous sclerosis Oncocytosis
Sporadic:
Bratslavsky, G. & Linehan, W. M. Nat. Rev. Urol. 2010; 7: 267–275
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Multiple renal tumors Papillary RCC and bilateral more common Index and satellite tumors mostly identical Discordant TU 17-26% (clear cell + papillary) Likely local recurrence if nephron-sparing surgery
Prognosis (with radical surgery)
Richstone L et al J Urol 2004; 171, 615–620
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Measure and report tumor
dimensions for all tumors,
up to a maximum of 5
Measurement of multiple tumors
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Minimum of 5 largest tumors (if smaller look similar)
If uncertain about histologic type or adverse findings in remaining tumors, do additional sampling
Largest T used – label with (m) mpT
Different subtype – separate stage
Sampling and staging of multiple tumors
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Stage pT3a pT3 Tumor extends into major veins or perinephric tissues, but not into the ipsilateral adrenal gland and not beyond Gerota’s fascia pT3a Tumor extends into the renal vein or its segmental branches, or invades the pelvicalyceal system, or invades perirenal and/or renal sinus fat but not beyond Gerota’s fascia
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Assesment of perinephric fat invasion (pT3a)
Pushing border, even if beyond normal kidney, NOT diagnostic of fat invasion
Invasion: lost smooth interface, or irregular nodules protruding into fat
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Assesment of perinephric fat invasion (pT3a)
Multiple perpendicular sections of tumor fat interface
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Assesment of perinephric fat invasion (pT3a) - micro
Tumor touching fat Tumor extending as irregular tongues into fat (with or without desmoplasia)
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Problematic perinephric fat invasion (pT3a)
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Problematic perinephric fat invasion (pT3a)
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Renal sinus
Central perinephric fat compartment Between pelvicalyceal system and renal parenchyma Main lymphovascular supply of kidney
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Principal route for extrarenal extension: Clear cell RCC, but also other types >90% of clear cell RCCs ≥7 cm invaded renal sinus
Renal sinus invasion (pT3a)
Bonsib SM. J Urol. 2005;174:1199-1202.
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Invasion into sinus - worse prognosis than perinephric fat invasion Recognition of renal sinus invasion in the last 10-15 years prompted practice changes Targeted sampling of renal sinus in nephrectomies – routine practice!
Brödel M. Johns Hopkins Hospital Bulletin 1901;118:10–13.
Renal sinus invasion (pT3a)
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Renal sinus invasion - sampling
If sinus invasion grossly evident, or obviously absent, (e.g. small peripheral tumor): Sample only 1 block to confirm sinus invasion present or absent
When uncertain if sinus invasion present:
Sample at least 3 blocks of tumor – sinus interface
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Renal sinus invasion present on micro if tumor seen in:
Direct contact with sinus fat In loose connective tissue beyond renal parenchyma
Any endothelial lined space within sinus, regardless of size
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Renal vein invasion – AJCC 8th edition
Renal vein invasion (pT3a):
“tumor (grossly) extends into
renal vein or segmental
branches”
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Tumor attached to the
vessel wall or
Tumor fills and distends
vessel lumen
Renal vein invasion
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Vein invasion in the renal sinus (segmental)
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Renal vein and margin sampling
Submit actual margin
+
Additional sections of tumor
thrombus, if grossly suspected
to be adherent to vein wall Renal margin negative –
retraction of vein after fixation
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Renal vein margin positivity
Renal margin positive only if tumor adherent at actual margin, confirmed microscopically
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Invasion into pelvicalyceal system = pT3a (new in AJCC 8th edition)
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Vena cava invasion
Tumor into vena cava below or above diaphragm
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Vena cava invasion – pT3c
Tumor grossly extends into vena cava above diaphragm or invades wall of vena cava
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Specimen submitted as “caval thrombus”
Tumor invades the wall of vena cava (pT3c)
Include 2 or more
sections to search for
adherent caval wall
tissue and possible
invasion
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Adrenal gland involvement
Contiguous spread (pT4)
Metastasis (pM1)
Prognostic significance!
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Direct adrenal gland involvement - pT4
Direct invasion into adrenal – pT4 disease Associated with significantly worse prognosis than perinephric fat invasion! Matches pT4 tumors (invasion into adjacent organs)
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Metastatic adrenal gland involvement – M1
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Assesment of hilar lymph nodes
Restrict evaluation to palpation and dissection of hilar fat only Nodes found in less than 10% of cases Nodes rarely identifiable!
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Assesment of hilar lymph nodes Grossly visible hilar nodes positive in 80% of cases Microscopic nodes found in only 25% of cases = all benign! Searching for occult nodes not practical!
Mehta V et al. Arch Pathol Lab Med 2013; 137:1584-90.
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Regional lymph nodes – N1 Single or multiple regional nodes involved
Examine all submitted separately
Renal hilar
Caval (pre-, para-, retro)
Aortic (pre-, para-, retro-, interaortocaval)
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Sampling uninvolved renal parenchyma
Adjacent to tumor, as well as
distant from tumor
Routine assessment for
concurrent glomerular,
tubulointerstital and vascular
kidney disease
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Non-neoplastic kidney pathology
Diabetic nephropathy (KW nodules) Hypertensive vascular disease
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Eur Urol 2010; 58: 588-95
It is expected that AJCC
8th edition staging for
renal cancer will perform
(at least) as well as the
7th AJCC/TNM edition
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Take home messages
Proper staging depends on adequate sampling of renal specimens Stage is key to prognostication of renal cancer patients AJCC 8th edition introduces some (minor) staging changes and refines some definitions, but retains most of the 7th edition parameters
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