Nodal staging of colorectal cancer, TNM and practical issues Gábor Cserni 1. Bács-Kiskun County Teaching Hospital, Kecskemét 2. University of Szeged, Szeged
Different staging systems: A,B,C,(D) Same letters – sometimes different meaning Cserni G. J Clin Pathol 2003;56:327
Primary tumor: (c)T& pT(TNM7, 2010-) • T & pT – TX: Not assessable (to be minimized) – T0: No tumor – Tis: carcinoma in situ: intraepithelial tumor or involving the lamina propria (intramucosal) – T1: Tumor invading into submucosa. – T2: Tumor invading into muscularis propria. – T3: Tumor invading through the muscularis propria into pericolorectal tissues. – T4a: Tumor penetrating through visceral peritoneum.* – T4b: Tumor invading into adjacent organs or structures* (through the peritoneum or over the m. propria for retro- or infraperitoneal localizations) (opposite meanings in TNM5) * Still reverted in RCPath reporting proforma using TNM5, accessed 1 May 2017
Implementation delayed • In order to ensure that the cancer care community has the necessary infrastructure in place for documenting 8th Edition stage, the AJCC Executive Committee, in dialogue with the National Cancer Institute (NCI-SEER), Centers for Disease Control and Prevention (CDC), the College of American Pathologists (CAP), the National Comprehensive Cancer Network (NCCN, the National Cancer Data Base (NCDB), and the Commission on Cancer (CoC), made the decision to delay the implementation of the 8th Edition Cancer Staging System to January 1, 2018. https://cancerstaging.org/About/news/Pages/Implementation-of-AJCC-8th-Edition- Cancer-Staging-System.aspx
Primary tumor: (c)T&pT (TNM8, 2018-) • T & pT – TX: Not assessable (to be minimized) – T0: No tumor – Tis: carcinoma in situ tumor involving the lamina propria (intramucosal carcinoma) only. (Intraepithelial carcinoma = HG dysplasia ≠ pTis) – T1: Tumor invading into submucosa. – T2: Tumor invading into muscularis propria. – T3: Tumor invading through the muscularis propria. – T4a: Tumor demonstrating serosal involvement. – T4b: Tumor invading into adjacent organs or structures (through the peritoneum or over the m. propria for retro- or infraperitoneal localizations)
pT3: pT3a ( ≤ 5 mm from the muscularis propria) & pT3b (> 5 mm from the muscularis propria) Bori R et al. Pathol Oncol Res 2009;15:527-32. pT3a tumors have a better prognostic profile than pT3b. These are not TNM categories recognized in the AJCC staging books, but are mentioned in the TNM Supplement (since 1993). Merkel S et al. Int J Colorectal Dis 2001;16:298–304.
pT4a – peritoneal involvement (TNM8) • Direct tumor extension • With perforation in which the tumor cells are continuous with the serosal surface through inflammation • No pT4a category for non peritonealized areas (e.g. posterior ascending colon) • <1mm from serosal surface and accompanied by serosal reaction; if multiple levels exclude serosal surface involvement → pT3
pT4a – peritoneal involvement Shepherd N et al. Gastroenterology 1997 (Gloucester) 1. Lack of peritoneal involvement 2. Fibrin and inflammatory exsudate on the peritoneum with tumor cells beneath the peritoneum, but not on it (TNM: pT3) 3. Tumor propagation on the peritoneal surface 4. Ulceration and apparently free tumor cells floating on the peritoneal surface (especially in crevices)
Category 3 & 4 had worse survival Shepherd N et al. Gastroenterology 1997
Assessment of peritoneal involvement Higher pT4 ratio as a result of more precise pathological work-up Percentage of pT1-4 categories 0,9 0,8 n = 0,7 77 0,6 111 0,5 1997 2006 159 0,4 2016 0,3 0,2 0,1 0 (y)pT1 (y)pT2 (y)pT3 pT4
Lymph nodes: pN (TNM7) • pNX: Not assessable (eg: removed earlier / not removed / no LNs identified) • pN0: No regional LN metastasis (including isolated tumor cell clusters) • pN1: Metastasis to 1-3 regional LNs pN1mi Micrometastasis (>0.2 mm and/or >200 cells, but none > 2.0 mm) pN1a Metastasis to 1 LN (>2 mm) pN1b Metastasis to 2-3 LN (at least one metastasis >2 mm) pN1c Tumor deposit(s) (TD) in the subserosa, mesocolon, pericolic, perirectal tissues, without LN structure, if there is no LN metastasis • pN2: Metastasis to 4 or more regional LNs pN2a Metastasis to 4-6 LNs (at least one metastasis >2 mm) pN2b Metastasis to 7 or more LNs (at least one metastasis >2 mm)
LNs (TNM8) • At least 12 • Number of nodes correlates with survival • Micrometastasis (may be designated as pN1mi, but it is better to consider them standard positive nodes) • pN0(i+) (<0.2 mm) worse prognosis than pN0
Theory and practice https://www.slideshare.net/optimaltransformation/a-collection-of-quotes-from-albert-einstein
Is this a lymph node? (1) (x10-x20)
Is this a lymph node? (2) (x10-x20)
Is this a lymph node metastasis? (1) x 2
Is this a lymph node metastasis? (1) x 2
Is this a lymph node metastasis? (1) x 35
Is this a lymph node metastasis? (2) x 2.5
Is this a lymph node metastasis? (2) x 10 (central part)
Is this a lymph node metastasis? (2) x 1.5
Is this a lymph node metastasis? (2) x 25 Smooth muscle, elastic fibers
Is this a lymph node? (3) (x 3)
Is this a lymph node? (3) (x 10)
Is this a lymph node? (4) (x 5)
Is this a lymph node? (4) (x 4.5) (Orcein-H)
Is this a lymph node? (4) (x 4 – x 4.5) (SMA - H-caldesmon)
Is this a lymph node? (5) (x 10)
Is this a lymph node? (5) (x 10 – x 40) Orcein
X4 x20 X40 x20 Is this a LN metastasis? (3)
Primary vs Metastasis Rectosigmoid colon pT1 here, but pT2 elsewhere pN1b (2/10)
Primary vs Metastasis Rectosigmoid colon pT1 here, but pT2 elsewhere pN1b (?) CDX2
Primary vs Metastasis Rectosigmoid colon pT1 here, but pT2 elsewhere pN1 (?) – NO pT2 pN0 & Occult prostatic cancer M1 PSAP CDX2
Is this a LN metastasis? (4)
Is this a LN metastasis? (4)
No cells, just mucin (negative) – ypN0
Halving / Slicing larger LNs
LNs vs TDs (tumor deposits) • Lymph nodes have the following features: – capsule, – subcapsular sinus, – lymphoid tissue, often with follicles, – sometimes perinodal lymphoid tissue as well; – they may have smooth muscle in their capsule – very rarely, it seems, they may have even elastic fibres in the capsule
Tumor deposits • Of 400 pts with pT3 N+M0 colon ca 18% had tumor deposits (TD)(TNM5, 1998) • TD: adenocarcinoma within adipose or fibrous tissue but not associated with a LN • Grossly palpated lesions, generally Goldstein NS, Turner JR. Cancer 2000 submitted as LN
Tumor deposits • Independent factors associated with shorter DFS: – Any TDs (independent of size) – Increasing number of TDs – Increasing number of involved LNs – Grade • TDs proved to be perivascular (large vessels), intravascular and/or perineural tumor foci Goldstein NS, Turner JR. Cancer 2000
Lymph node metastasis vs TD • Tumor nodule lacking elements of a LN • TNM5 – >3 mm: LN metastasis → pN – ≤ 3 mm: discontinuous tumor spread → pT • TNM6 – Regular outline: LN metastasis → pN – irregular outline: venous invasion: → V1
Lymph node metastasis vs TD V1 – orcein stain V1
Lymph node metastasis vs TD • Tumor nodule lacking elements of a LN • TNM7 – Can be: discontinuous tumor spread, completely destroyed LN (N1/2), venous invasion (V1/2), – If destroyed LN: → pN category – Discontinuous spread, venous invasion (V1/2) → TD (pN1c, if no LN metastasis, for T1-2 tumors) • TD and V1 on the basis of the orcein (elastica) stain
TD (TNM8) • No elements of a LN • Not venous invasion (V1, V2), not lymphovascular (small vessel) involvement (L1), not perineural involvement (Pn1) • If there is no LN metastasis: pN1c • If there is a LN metastasis: this should not be added to the number of metastatic nodes
The suggested number of LNs to be assessed for a reliable pN0 • 6 Hernanz F et al. Dis Colon Rectum 1994;37:373-6. • 7 Caplin S et al. Cancer 1998;83:666-72. - Mainprize KS et al. J Clin Pathol 1998;51:165-6. - Cserni G. J Clin Pathol 2002;55:386-90. • 8 Maurel J et al. Cancer 1998;82:1482-6. • 9 Cianchi F et al. World J Surg 2002;26:384-9. • 12 TNM Supplement 3rd Ed • 13 Scott KWM et al. Br J Surg 1989;76:1165-7. • 14 Wong JH et al. J Clin Oncol 1999;17:2896-900. - Tepper JE et al. J Clin Oncol 2001;19:157-63. • 16 Cserni G et al. Pathol Oncol Res 1999;5:291-6. • 17 Goldstein NS. Am J Surg Pathol 2002;26:179-89. • 20 Greco P et al. Virchows Arch 2006;449:647-651.
How many LNs? As many as possible! 8574 T3N0M0 CRC from the SEER database 1.0 5-year OS 0.9 0.8 a survival estimate 0.7 0.6 c b 0.5 0.4 10-year OS 0.3 0.2 0.1 0.0 0 10 20 30 40 number of nodes examined Cserni G, et al. Is there a minimum number of lymph nodes that should be histologically assessed for a reliable nodal staging of T3N0M0 colorectal carcinomas? J Surg Oncol 2002; 81:63-69.
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