EARLY COLORECTAL CANCER Early colorectal cancer ¢â‚¬â€œendoscopic resection In (suspected) early lesions

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  • EARLY COLORECTAL CANCER The point of view of the pathologist

    Name

    Cord Langner, MD

    Diagnostic & Research Institute of Pathology, Medical University, Graz, Austria

  • DISCLOSURE OF INTEREST

    No conflict of interest

  • AGENDA

     Early colorectal cancer: pathology report of endoscopic resections  Locally advanced colorectal cancer: pathology report of surgical

    resections

  • „MALIGNANT POLYP“

    Langner & Vieth in: Multidisciplinary Treatment of Colorectal Cancer, Springer 2015

  • „MALIGNANT POLYP“

    Langner & Vieth in: Multidisciplinary Treatment of Colorectal Cancer, Springer 2015

    >2000µm

    D2-40

  • RISK ASSESSMENT

    Resch & Langner, Cesk Patol 2015

    0-3% N positive 8-10% N positive 20-25% N positive

    N positive

    Level 1/2 (head / neck invasion) 0

    Level 3 (stalk invasion) 6%

    Level 4 (invasion beyond the stalk) 20-25%

  • RISK ASSESSMENT

    Resch & Langner, Cesk Patol 2015

    Kikuchi level sm1 / Haggitt levels 1- 3 / SM-invasion 1000µm

    or Poor differentiation (G3)

    or Presence of lymphatic invasion (L0)

    or High grade tumour budding

    or Positive resection margin (R0)

  • RECENT DEVELOPMENTS

    Debove et al. Colorectal Dis 2016

  • RECENT DEVELOPMENTS

    Yasue et al. J Gastroenterol 2019

  • THE GOOD PATHOLOGY REPORT Early colorectal cancer – endoscopic resection

     In (suspected) early lesions it is not sufficient just to state the presence of colorectal cancer  All features relevant for risk assessment and clinical decision making need to be considered

     Depth of invasion  Tumour grade  Vascular invasion (L1, V1 – theoretically also perineural invasion)  Tumour budding  Margin status (measure distance to resection margin)

     Pathological risk assessment (low risk versus high risk) has to be made (with or without a comment regarding the appropriate treatment strategy)

  • ASSESSMENT OF THE SURGICAL SPECIMEN

    Distance to proximal, distal and circumferential margins should be documented (in millimetres, separately for primary tumour and involved lymph nodes), which is particularly important for rectum cancer specimens

  • ASSESSMENT OF THE SURGICAL SPECIMEN

  • LYMPH NODE STAGING (N CATEGORY)

    Resch & Langner. World J Gastroenterol 2013

    TNM 8 (2017) Tumour deposits (satellites) are discrete macroscopic or microscopic nodules of cancer in the pericolorectal adipose tissue‘s lymph drainage area of a primary carcinoma that are discontinuous from the primary and without histological evidence of residual lymph node or identifiable vascular or neural structures. If a vessel wall is identifiable (…) it should be classified as venous invasion (V1/V2) or lymphatic invasion (L1). Similarly, if neural structures are identifiable, the lesion should be classified as perineural invasion (Pn1). The presence of tumour deposits does not change the primary tumour T category, but changes the node status (N) to N1c if all nodes are negative on pathological examination.

  • LYMPH NODE STAGING (N CATEGORY)

    Resch & Langner. World J Gastroenterol 2013

     Minimum number of 12 lymph nodes  Thoroughness of the pathologist in dissecting the resection

    specimen  ≥ 95% of specimens without neoadjuvant therapy (DKG)  Technical methods to increase lymph node yield: methylene blue

    injection, fat clearing, acetone (with or without compression)  Absolute number of retrieved lymph nodes  Absolute number of positive lymph nodes  Lymph node ratio  Presence of extracapsular invasion  Technical issues (number of histological sections and/or use of

    immunohistochemistry to identify micrometastasis and/or isolated tumour cells)

  • LYMPH NODE STAGING (N CATEGORY)

    Rössler, Langner et al. Mod Pathol 2017

    Lymph node size is related to presence of lymph node metastasis. A, mean size of positive nodes is 5.6 ± 1.9 mm, compared to 3.6 ± 0.8 mm in

    negative nodes (P

  • LYMPH NODE STAGING (N CATEGORY)

    Rössler, Langner et al. Mod Pathol 2017

    Lymph node size is related to presence of lymph node metastasis. A, mean size of positive nodes is 5.6 ± 1.9 mm, compared to 3.6 ± 0.8 mm in

    negative nodes (P

  • LYMPH NODE STAGING (N CATEGORY)

    Nagtegaal et al. J Clin Oncol 2017

  • HISTOLOGICAL TYPING

    Langner et al. Histopathology 2012; Hugen et al. Ann Oncol 2014

    0

    0.1

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    1

    0 20 40 60 80 100 120 Time (months)

    D is

    ea se

    -fr ee

    s ur

    vi va

    l p ro

    ba bi

    lit y

    Conventional adenocarcinoma

    Adenocarcinoma with mucinous component

    Mucinous adenocarcinoma

    0

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    0.5

    0.6

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    0 20 40 60 80 100 120

    Time (months)

    C an

    ce r-

    sp ec

    ifi c

    su rv

    iv al

    p ro

    ba bi

    lit y

    Conventional adenocarcinoma

    Adenocarcinoma with mucinous component

    Mucinous adenocarcinoma

  • HISTOLOGICAL GRADING

    Langner et al. Histopathology 2012; Nagtegaal et al. WHO Classification 5th Edition 2019

    “Grading of CRC is based on gland formation: low-grade (formerly well to moderately differentiated differentiated) and high-grade (formerly poorly differentiated) tumours. Grading is based on the

    least differentiated component. The invasion front, where formation of tumour budding and poorly differentiated clusters occurs as a sign of epithelial-mesenchymal transition, should not be taken

    into account when grading the tumour, but should be reported separately.”

    Low- grade

    High- grade

    “Grading in mucinous adenocarcinoma should be based upon glandular

    formation and epithelial maturation.”

  • HISTOLOGICAL GRADING

    Resch, Langner et al. Int J Colorectal Dis 2017

  • HISTOLOGICAL GRADING

    Resch, Langner et al. J Clin Pathol 2015

  • MOLECULAR GRADING

    Neumann & Kirchner. Pathologe 2014

    Morphological Grading

    G2 G3 G4

    >95% glands

    50-95% glands

    >0-49% glands

    0% glands

    Adenocarcinoma (NOS)

    Undifferentiated Carcinoma

    G1

    Low Grade High Grade

    Molecular Grading (MSI-Status)

    Adenocarcinoma G3, undifferentiated carcinoma

    and MSI-associated variants (mucinous, signet-ring cell,

    medullary, serrated)

    Low Grade High Grade

    Immunohistochemistry for hMLH1/hMSH2

    negative positive

  • LYMPHOVASCULAR INVASION

    Betge, Langner et al. Cancer 2012

  • LYMPHOVASCULAR INVASION

    Betge, Langner et al. Cancer 2012; Hwang et al. Cancer Res Treat 2016

    Protruding nose sign

    http://www.clydefitchreport.com/wp-content/uploads/2018/04/Trump-Pinoccio-nose-e1525375877287.jpg

  • LYMPHOVASCULAR INVASION

    Betge, Langner et al. Cancer 2012; Dawson et al. Front Oncol 2015

  • LYMPHOVASCULAR INVASION

    Betge, Langner et al. Cancer 2012; Knijn et al. Histopathology 2018

  • PERINEURAL INVASION

    Pöschl, Langner et al. J Clin Oncol 2010

  • PERINEURAL INVASION

    Knijn et al. Am J Surg Pathol 2016

    n % range

    Colorectal Cancer 11321 2 0.6-41.9%

    Colon Cancer 4637 6 2.1-39.3%

    Rectal Cancer 6942 10 6.3-35.4%

  • TUMOUR BUDDING

    Betge, Langner et al. Ann Surg Oncol 2012; Max, Langner et al. Br J Cancer 2016; Rogers et al. Br J Cancer 2016; Lugli et al. Mod Pathol 2017

    Tumour budding is defined as the presence of isolated single cells

    or small clusters of cells (1-4 cells) at the invasive tumour margin

  • TUMOUR BUDDING

    Betge, Langner et al. Ann Surg Oncol 2012; Max, Langner et al. Br J Cancer 2016; Rogers et al. Br J Cancer 2016; Lugli et al. Mod Pathol 2017

    Assessment of tumour budding should be performed on H&E stained slides according to the ITBCC consensus

    recommendation (Bd1-Bd3; Lugli et al.)

  • TUMOUR-ASSOCIATED INFLAMMATION

    Klintrup, Mäkinen et al. Eur J Cancer 2005; Harbaum, Langner et al. Mod Pathol 2015; Max, Langner et al. Br J Cancer 2016

  • TUMOUR-ASSOCIATED INFLAMMATION

    Pagès et al. Lancet 2018

    “An international consortium of 14 centres in 13 countries, led by the Society for Immunotherapy of Cancer, assessed the Immunoscore Assay in patients with TNM stage I–III colon cancer. Patients were randomly assigned to a training set, an internal validation set, or an external validation set. Paraffin sections of the colon tumour and invasive margin from each patient were processed by immunohistochemistry, and the densities of CD3+ and cytotoxic CD8+ T cells in the tumour and in the invasive margin were quantified by digital pathology.”

  • TUMOUR-ASSOCIATED INFLAMMATION

    Pagès et