6/5/2010. Renal vein invasion & Capsule Penetration (T3a) Adrenal Gland involvement (T4 vs. M1) Beyond Gerota s Fascia? (?T4).

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1 GU Cancer Staging: Updates and Challenging Areas 13 th Current Issues in Surgical Pathology San Francisco, CA June 5, 2010 Jeffry P. Simko, PhD, MD Associate Professor Departments of Urology and Anatomic Pathology AJCC Cancer Staging manual 7 th Edition Effective 1/1/2010 TNM Helpdesks: Staging Changes: General ptnmrglv ptn (Chapter 1) pmx eliminated, just ptn ( can have pm1) R category (margin status) still present, L,V categories dropped. R0= excised, R1= residual microscopic, R2 = macroscopic Special classifiers are clarified neoadjuvant stage (y) from recurrence stage (r) (m) for multiple primary tumors in same organ Added Prognostic Features (nonanatomic) e.g. Multigene signature for Breast. PSA for prostate Goal: Improve Staging Accuracy Kidney Renal vein invasion & Capsule Penetration (T3a) Adrenal Gland involvement (T4 vs. M1) Beyond Gerota s Fascia? (?T4). Bladder Tumors (renal pelvis, ureter, urethra) Invasion or not? (Tis/Ta vs. T1). Muscle invasion (T1 vs. T2) Beyond the bladder (T2 vs. T3 vs. T4) Prostate Gland Prostate Gland Bladder neck invasion (T3a or T4?). Capsule Penetration (T2 vs. T3a) 1

2 Kidney: Staging Changes T2 split T2a ( 7cm < T <= 10cm) vs. T2b ( > 10 cm) Adrenal gland involvement Direct extension into adrenal = T4 Tumor deposit in adrenal = M1 Renal Vein involvement: Changed from T3b to T3a Node staging simplified (N0 vs. N1) Kidney: Tumor type aids in staging Primary renal tumors are Expansile masses Pushing, compressing & crushing Cortex rather than medulla or pelvis Encapsulated or pseudo-encapsulated! exceptions = collecting duct & medullary CA Urothelial carcinomas are infiltrative (as are collecting duct & medullary CA) Replacing rather than pushing No capsule! Renal Pelvis or Medulla rather than Cortex? In situ vs. invasive tumor 2

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4 Problem area: Gross vessel invasion Tumor in any muscle-walled vessel T3a (Exception: Vena cava T3b or c) Gross Evaluation: Open renal vessels Microscopic confirmation: Trichrome and Elastin stains helpful 4

5 CD 31 Problem areas: Tumor thrombus Surgeon / imaging for staging (pt3a, b or c). Margin status: Tumor infiltrating at margin. (Patients disqualified from clinical trials) Histologic confirmation (thrombus type). Fibrin vs. xanthogranulomatous clot vs. tumor 5

6 Problem area: Capsular Penetration (?pt3a) Problem area: Capsular Penetration 6

7 Capsular Penetration Problem area: Kidney Capsular Penetration Capsular Penetration Capsular Penetration Capsule: LET THE GROSS GUIDE YOU Fat mobile over tumor No fat invasion Fat falls off over tumor No fat invasion Take sections where fat adherent to kidney. Renal sinus involvement: more difficult Fat naturally immobile Take multiple sections Look for benign tubules in capsule wall? More likely vascular invasion? (Trichrome stain) 7

8 Capsular Penetration Capsular Penetration 8

9 Problem area:? pt4 (Gerota s fascia) 9

10 Problem area:? T4? (Through Gerota s fascia?) Gerota s Fascia Often the margin of a nephrectomy specimen Noticeable when removing kidney at autopsy Other organs in specimen? Likely T4. (Liver, spleen, pancreas, bowel, skeletal musc.) Surgeon can tell easier than pathologist! Problem area:? T4? (Adrenal gland invasion) Is it adrenal cortex or a renal tumor? Immunohistochemical stains CA IX in CCRCC; Melan-A, Inhibin in Adrenal PAX-2 and RCC Ag can be + in Adrenal CA! Direct extension pt4 Tumor deposit in Adrenal pm1 10

11 6/5/2010 Adrenal Inhibin IHC Cortical Rests: Melan-A Adrenal Cortical Rests Adrenal Cortical Rests in Kidney RCC Ag IHC 11

12 Renal Pelvis, Ureters, Urethra NO staging changes Problem Area: Kidney / Renal pelvis Kidney involvement by Pelvic Urothelial CA Discriminate in situ (ptis) from invasive tumor (pt3)! 12

13 Kidney involvement by urothelial CA? Is tumor confined to tubules? Tis CIS colonizing tubules / glomeruli Expansion of native structures Adjacent stroma without tumor At most, small masses / apparent small sheets Tubule destruction? T3 Tumor around native structures Desmoplasia Large tumor cell sheets / masses Uninvolved structures surrounded by tumor 13

14 Urinary Bladder: Staging Changes T4a: Directly into prostate from bladder tumor Extra-nodal extension (bladder) 1.0 Disease-specific survival p<0.001 Nodal classification (Node location) N1: A single positive node, primary drainage N2: Two or more positive in primary drainage N3: Common iliac nodes involved M1: Other nodes involved (e.g. para-aortic) Near Future: Extranodal Extension? p<0.001 Without ENE (n=79) Without ENE (n=79) With ENE (n=80) With ENE (n=80) Years (R Seiler, et al., 99 th USCAP Meeting 2010, Wash. D.C., Abstract #975) (R Seiler, et al., 99 th USCAP Meeting 2010, Wash. D.C., Abstract #975) Problem Areas: Invasive vs. in situ (pta / ptis VS. pt1) Problem Area: Is there muscularis propria invasion?? Muscularis Propria Invasion (pt1b vs. T2) BIG differences in Rx for these diagnoses!!! Tis intravesicle Rx, T1 many options, T2 definitive Rx (cystectomy). Difficult and important area Many times cannot be certain Should always report if muscularis propria present or not. Should always report if smooth muscle involved by tumor and indicate type if possible Immunohistochemistry: Actin, smoothelin 14

15 Epstein, et al., Bladder Biopsy Interpretation, LWW 2004 Epstein, et al., Bladder Biopsy Interpretation, LWW 2004 Problem Area: Tumor in pericystic fat? (pt3) Fat can be present in Urinary bladder wall Tumor must be seen beyond muscle bundles to be certain T3a Epstein, et al., Bladder Biopsy Interpretation, LWW

16 Problem Area: Tumor in pericystic fat? (T2b vs. T3)? T3a or T2b with LVI? Problem Area: Tumor in pericystic fat? Image of fat in smooth muscle 16

17 Problem Area: Bladder tumor into prostate (T4a)? In situ vs. invasive tumor? Bladder smooth muscle (T2) vs. directly into prostate / vagina smooth muscle (pt4a) In situ extension into prostate NOT T4!!! Grade bladder and prostate tumors separately Prostate T2 Bladder T2 17

18 Bladder stage T2 Bladder stage T4a Prostate stages Prostate Tis Bladder tumor into prostate gland (T4a vs. other) Direct into prostate stroma T4a Via in situ spread along urethra: Two tumors Via in situ spread along urethra: Two tumors Stage bladder tumor in urinary bladder Stage tumor in prostate separately (prostatic urethral tumor). 18

19 Prostate Gland: Staging Changes Direct extension of tumor into Urinary Bladder has been clarified Microscopic urinary bladder invasion T3a Macroscopic urinary bladder invasion T4 Prostate T3a 19

20 Problem area: EPE (extra-prostatic extension) EPE Rules: NO capsule at apex Skeletal muscle invasion not helpful Just can report margin status Microscopic tumor in bladder musc = T3a Must see tumor in fat!?!?! Fat extremely rare in benign prostate Desmoplastic fibrosis? (subtle)! Trichrome useful! Ohori, et. al, Mod Pathol (2004). Ohori, et. al, Mod Pathol (2004). 20

21 Ohori, et. al, Mod Pathol (2004). Evans, et. al, Am J Srug Pathol 32: (2008). Problem area: EPE Tumor in fat, T3a Tumor expanding the capsule Tumor in desmoplasia T3a? Why can t capsule be stretched and not penetrated? Can use trichrome to discriminate Smooth muscle between fat & Tumor T2 No smooth muscle between T3a Evans, et. al, Am J Srug Pathol 32: (2008). 21

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23 Prostate: Surgical Margins Tumor touching ink margin +? Area of EPE or is it a cut into prostate? Length of positive margin, Gleason grade Tumor not on ink margin clear Report distance for EPE tumor. Do not report distance if T2 (might make comment if just a few fibroblasts from ink). Ohori, et. al, Mod Pathol (2004). Summary General changes (Chapter 1 of manual) TNM helpdesks on the web. Kidney (guidance from the gross) Vein invasion, fat invasion (special stains) Bladder (pelvis, ureters, urethra) unique issues at interface of all stages In situ vs. invasion of prostate (kidney). Prostate Bladder invasion, EPE, and margin status Ohori, et. al, Mod Pathol (2004). 23

24 That s all Folks!!!!! 24