polypectomy and local resections of the colorectum

POLYPECTOMY AND LOCAL RESECTIONS

OF THE COLORECTUM

STRUCTURED REPORTING

PROTOCOL

(2nd Edition 2020)

Incorporating the:

International Collaboration on Cancer Reporting (ICCR)

Colorectal Excisional Biopsy (Polypectomy) Dataset www.ICCR-Cancer.org

http://www.iccr-cancer.org/

2

Polypectomy and Local Resections of the Colorectum Structured Reporting Protocol 2nd

Edition

Core Document versions:

• ICCR dataset: Colorectal Excisional Biopsy (Polypectomy) 1st edition1

• AJCC Cancer Staging Manual 8th edition2

• World Health Organization (2019) Classification of Tumours. Pathology and

Genetics of Tumours of the Digestive System (5th edition).3

3

ISBN: 978-1-76081-426-7

Publications number (SHPN) : (CI) 200283

Online copyright

© RCPA 2020

This work (Protocol) is copyright. You may download, display, print and reproduce the

Protocol for your personal, non-commercial use or use within your organisation subject

to the following terms and conditions:

1. The Protocol may not be copied, reproduced, communicated or displayed, in

whole or in part, for profit or commercial gain.

2. Any copy, reproduction or communication must include this RCPA copyright notice

in full.

3. With the exception of Chapter 6 - the checklist, no changes may be made to the

wording of the Protocol including any Standards, Guidelines, commentary, tables

or diagrams. Excerpts from the Protocol may be used in support of the checklist.

References and acknowledgments must be maintained in any reproduction or

copy in full or part of the Protocol.

4. In regard to Chapter 6 of the Protocol - the checklist:

o The wording of the Standards may not be altered in any way and must be

included as part of the checklist.

o Guidelines are optional and those which are deemed not applicable may be

removed.

o Numbering of Standards and Guidelines must be retained in the checklist, but can

be reduced in size, moved to the end of the checklist item or greyed out or other

means to minimise the visual impact.

o Additional items for local use may be added but must not be numbered as a

Standard or Guideline, in order to avoid confusion with the RCPA checklist items.

o Formatting changes in regard to font, spacing, tabulation and sequencing may be

made.

o Commentary from the Protocol may be added or hyperlinked to the relevant

checklist item.

Apart from any use as permitted under the Copyright Act 1968 or as set out above, all

other rights are reserved. Requests and inquiries concerning reproduction and rights

should be addressed to RCPA, 207 Albion St, Surry Hills, NSW 2010, Australia.

First published: November 2020, 2nd Edition (Version 2.0)

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Disclaimer

The Royal College of Pathologists of Australasia ("College") has developed these

protocols as an educational tool to assist pathologists in reporting of relevant information

for specific cancers. While each protocol includes “standards” and “guidelines” which are

indicators of ‘minimum requirements’ and ‘recommendations’, the protocols are a first

edition and have not been through a full cycle of use, review and refinement. Therefore,

in this edition, the inclusion of “standards” and “guidelines” in each document are

provided as an indication of the opinion of the relevant expert authoring group, but

should not be regarded as definitive or as widely accepted peer professional opinion. The

use of these standards and guidelines is subject to the clinician’s judgement in each

individual case.

The College makes all reasonable efforts to ensure the quality and accuracy of the

protocols and to update the protocols regularly. However subject to any warranties,

terms or conditions which may be implied by law and which cannot be excluded, the

protocols are provided on an "as is" basis. The College does not warrant or represent

that the protocols are complete, accurate, error-free, or up to date. The protocols do not

constitute medical or professional advice. Users should obtain appropriate medical or

professional advice, or where appropriately qualified, exercise their own professional

judgement relevant to their own particular circumstances. Users are responsible for

evaluating the suitability, accuracy, currency, completeness and fitness for purpose of

the protocols.

Except as set out in this paragraph, the College excludes: (i) all warranties, terms and

conditions relating in any way to; and (ii) all liability (including for negligence) in respect

of any loss or damage (including direct, special, indirect or consequential loss or

damage, loss of revenue, loss of expectation, unavailability of systems, loss of data,

personal injury or property damage) arising in any way from or in connection with; the

protocols or any use thereof. Where any statute implies any term, condition or warranty

in connection with the provision or use of the protocols, and that statute prohibits the

exclusion of that term, condition or warranty, then such term, condition or warranty is

not excluded. To the extent permitted by law, the College's liability under or for breach

of any such term, condition or warranty is limited to the resupply or replacement of

services or goods.

5

Contents Scope ................................................................................................................. 6

Abbreviations ..................................................................................................... 7

Definitions .......................................................................................................... 9

Introduction ..................................................................................................... 12

Authority and development .............................................................................. 16

1 Pre-analytical ......................................................................................... 20

2 Specimen handling and macroscopic findings ........................................ 22

3 Microscopic findings ............................................................................... 29

4 Ancillary studies findings ....................................................................... 47

5 Synthesis and overview ......................................................................... 49

6 Structured checklist ............................................................................... 51

7 Formatting of pathology reports ............................................................ 68

Appendix 1 Pathology request information and surgical handling

procedures ......................................................................... 69

Appendix 2 Guidelines for formatting of a pathology report ................. 76

Appendix 3 Examples of a pathology report .......................................... 77

Appendix 4 WHO Classification of tumours of the colon and

rectum 5th edition ............................................................... 81

Appendix 5 Polyp types ........................................................................ 83

Appendix 6 Polyposis syndromes ........................................................ 103

Appendix 7 Colonoscopy surveillance guidelines ................................ 107

Appendix 8 Risk of residual disease following malignancy ................. 110

Appendix 9 Practice audits ................................................................. 112

References ..................................................................................................... 114

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Scope

This protocol contains standards and guidelines for the preparation of structured reports

for local excisions of the colon and rectum. These include polypectomies, endoscopic

mucosal resections (EMR), endoscopic submucosal dissections (ESD), endoscopic full

thickness resections (EFTR), transanal submucosal excisions, transanal minimally

invasive surgery (TAMIS) and transanal endoscopic microsurgery (TEMS) specimens. It

is not intended to apply to tumours of the appendix, small bowel and anus. It does not

cater for full resection specimens including neuroendocrine carcinomas (NECs) and

mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs), as these specimens are

covered by a separate protocol.

Structured reporting aims to improve the completeness and usability of pathology

reports for clinicians and improve decision support for cancer treatment. This protocol

can be used to define and report the minimum dataset, but the structure is scalable and

can equally accommodate a maximum dataset or fully comprehensive report.

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Abbreviations

AJCC American Joint Committee on Cancer

CRC Colorectal cancer

EFTR Endoscopic full thickness resections

EMR Endoscopic mucosal resection

ESD Endoscopic submucosal dissection

FAP Familial adenomatous polyposis

GCHP goblet cell hyperplastic polyp

HGD High grade dysplasia

HP Hyperplastic polyp

IBD Inflammatory bowel disease

ICCR International Collaboration on Cancer Reporting

LIS Laboratory information system

LST Lateral spreading tumours

MAP MUTYH-associated polyposis

MCP Malignant colorectal polyp

MiNEN Mixed neuroendocrine-non-neuroendocrine neoplasm

MMR Mismatch repair

MSI Microsatellite instability

MPHP Mucin-poor hyperplastic polyp

MVHP Microvesicular hyperplastic polyp

NEC Neuroendocrine carcinoma

NET Neuroendocrine tumour

NHMRC National Health and Medical Research Council

NOS Not otherwise stated

PJS Peutz Jegher syndrome

PSC Primary sclerosing cholangitis

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RCPA Royal College of Pathologists of Australasia

SSL Sessile serrated lesion

SSLD Dysplasia in sessile serrated lesion

TAMIS Transanal minimally invasive surgery

TEMS Transanal endoscopic microsurgery

TNM Tumour-node-metastasis

TSA Traditional serrated adenoma

UICC Union for International Cancer Control

WHO World Health Organization

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Definitions

The table below provides definitions for general or technical terms used in this protocol.

Readers should take particular note of the definitions for ‘standard’, ‘guideline’ and

‘commentary’, because these form the basis of the protocol.

Ancillary study An ancillary study is any pathology investigation that may form

part of a cancer pathology report but is not part of routine

histological assessment.

Clinical

information

Patient information required to inform pathological assessment,

usually provided with the specimen request form, also referred to

as ‘pre-test information’.

Commentary Commentary is text, diagrams or photographs that clarify the

standards (see below) and guidelines (see below), provide

examples and help with interpretation, where necessary (not

every standard or guideline has commentary).

Commentary is used to:

• define the way an item should be reported, to foster

reproducibility

• explain why an item is included (e.g. how does the item assist

with clinical management or prognosis of the specific cancer).

• cite published evidence in support of the standard or guideline

• state any exceptions to a standard or guideline.

In this document, commentary is prefixed with ‘CS’ (for

commentary on a standard) or ‘CG’ (for commentary on a

guideline), numbered to be consistent with the relevant standard

or guideline, and with sequential alphabetic lettering within each

set of commentaries (e.g. CS1.01a, CG2.05b).

General

commentary General commentary is text that is not associated with a specific

standard or guideline. It is used:

• to provide a brief introduction to a chapter, if necessary

• for items that are not standards or guidelines but are included

in the protocol as items of potential importance, for which

there is currently insufficient evidence to recommend their

inclusion. (Note: in future reviews of protocols, such items

may be reclassified as either standards or guidelines, in line

with diagnostic and prognostic advances, following evidentiary

review).

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Guideline Guidelines are recommendations; they are not mandatory, as

indicated by the use of the word ‘should’. Guidelines cover items

that are unanimously agreed should be included in the dataset

but are not supported by the National Health and Medical

Research Council (NHMRC) level III-2 evidence.4 These elements

may be clinically important and recommended as good practice

but are not yet validated or regularly used in patient

management.

Guidelines include key information other than that which is

essential for clinical management, staging or prognosis of the

cancer such as macroscopic observations and interpretation,

which are fundamental to the histological diagnosis and

conclusion e.g. macroscopic tumour details, block identification

key, may be included as either required or recommended

elements by consensus of the expert committee. Such findings

are essential from a clinical governance perspective, because they

provide a clear, evidentiary decision-making trail.

Guidelines are not used for research items.

In this document, guidelines are prefixed with ‘G’ and numbered

consecutively within each chapter (e.g. G1.10).

Macroscopic

findings Measurements, or assessment of a biopsy specimen made by the

unaided eye.

Microscopic

findings In this document, the term ‘microscopic findings’ refers to histo-

morphological assessment.

Predictive factor A predictive factor is a measurement that is associated with

response or lack of response to a particular therapy.

Prognostic factor A prognostic factor is a measurement that is associated with

clinical outcome in the absence of therapy or with the application

of a standard therapy. It can be thought of as a measure of the

natural history of the disease.

Standard Standards are mandatory, as indicated by the use of the term

‘must’. Standards are essential for the clinical management,

staging or prognosis of the cancer. These elements will either

have evidentiary support at Level III-2 or above (based on

prognostic factors in the NHMRC levels of evidence4 document).

In rare circumstances, where level III-2 evidence is not available

an element may be made a Standard where there is unanimous

agreement in the expert committee. An appropriate staging

system e.g. Pathological tumour-node-metastasis (TNM) staging

would normally be included as a required element. These

elements must be recorded and at the discretion of the

pathologist included in the pathology report according to the

needs of the recipient of the report.

The summation of all standards represents the minimum dataset

for the cancer.

In this document, standards are prefixed with ‘S’ and numbered

consecutively within each chapter (e.g. S1.02).

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Structured report A report format which utilises standard headings, definitions and

nomenclature with required information.

Synoptic report A structured report in condensed form (as a synopsis or precis).

Synthesis Synthesis is the process in which two or more pre-existing

elements are combined, resulting in the formation of something

new.

The Oxford dictionary defines synthesis as ‘the combination of

components or elements to form a connected whole’.

In the context of structured pathology reporting, synthesis

represents the integration and interpretation of information from

two or more modalities to derive new information.

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Introduction

Colorectal cancer

Colorectal cancer is currently one of the most common cancers diagnosed in Australia

and has the second highest incidence of cancer-related deaths after lung cancer.5 Recent

advances have been made in the biological understanding of this disease, which have

resulted in new surgical, chemotherapeutic and radiotherapeutic strategies.

Colonoscopy is the first-line investigation for assessing the colon and rectum, and has a

sensitivity of 95% for detection of colorectal cancer.6 Colonoscopy allows biopsy and

histologic confirmation of the diagnosis of cancer as well as identification and immediate

removal of synchronous polyps.

Precursor lesions to colorectal carcinoma fall into 2 main types – conventional adenoma

(tubular, tubulovillous and villous) and serrated adenomas (sessile serrated lesion and

traditional serrated adenoma). Conventional adenoma pathway are the precursor to

approximately 70% to 80% of colorectal cancers (CRCs). They are mostly found in the

left colon and rectum and approximately 25% of the population develop at least one by

age 50 years, and half the population have a conventional adenoma by age 70 years.7

Progression to CRC occurs in a limited number of conventional adenomas; one study

estimated a 10% to 15% chance of progression during 10 years for a 10 mm

conventional adenoma,8 while another review puts the risk of developing cancer at 3-

5%.9 If progression of a conventional adenoma to CRC occurs it takes approximately 15

years.10 There is good evidence that the endoscopic removal of conventional adenomas

decreases the incidence of subsequent CRC.11,12 Serrated lesions are the precursors for

approximately 20% to 30% of all CRCs.13-16 Most of these are sessile serrated lesions

(SSLs) and are mainly identified in the right colon. The progression risk of SSL to CRC is

unknown, however, it is unlikely to be higher than for a similar sized conventional

adenoma and the time for progression is approximately 15 years on average.17 The

development of dysplasia within these polyps marks a rapid acceleration point in

carcinogenesis.16,18-20 Colonoscopic screening programs have been less effective at

reducing right-sided CRC, in large part because of the difficulty in appreciating serrated

precursors.21

Benefits of structured reporting

The pathology report lays the foundation for a patient’s cancer journey and conveys

information which:

• Provides the definitive diagnosis

• Includes critical information for Tumour-Node-Metastasis (TNM) staging

• Evaluates the adequacy of the surgical excision

• Provides morphological and biological prognostic markers which determine

personalised cancer therapy

However, the rapid growth in ancillary testing such as immunohistochemistry, flow

cytometry, cytogenetics, and molecular studies, have made the task of keeping abreast

of advances on specific cancer investigations extremely difficult for pathologists. The use

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of structured reporting checklists by pathologists ensures that all key elements are

included in the report specifically those which have clinical management, staging or

prognostic implications. Consequently minimum or comprehensive datasets for the

reporting of cancer have been developed22,23 around the world. Both the United

Kingdom,24 and United States25 have produced standardised cancer reporting protocols

or ‘datasets’ for national use for many years.

The use of cancer reporting checklists improves completeness and quality of cancer

reporting and thereby ensures an improved outcome for cancer patients. This has long

term cost implications for public health by ensuring the most effective and timely

treatment based on accurate and complete information.

The use of a structured reporting format also facilitates easy extraction of the necessary

information by secondary users of the information i.e. cancer registries.

International Collaboration on Cancer Reporting

The International Collaboration on Cancer Reporting (ICCR), founded in 2011 by the

Royal College of Pathologists of Australasia (RCPA), United States College of American

Pathologists (US CAP) and Royal College of Pathologists United Kingdom (RCPath UK)

Colleges of Pathology Canadian Association of Pathology - Association Canadienne des

Pathologistes (CAP-ACP) in association with the Canadian Partnership Against Cancer

(CPAC), was established to explore the possibilities of a collaborative approach to the

development of common, internationally standardised and evidence-based cancer

reporting protocols for surgical pathology specimens.

The ICCR, recognising that standardised cancer datasets have been shown to provide

significant benefits for patients and efficiencies for organisations through the ease and

completeness of data capture26-29 undertook to use the best international approaches

and the knowledge and experience of expert pathologists, and produce cancer datasets

which would ensure that cancer reports across the world will be of the same high quality

– ensuring completeness, consistency, clarity, conciseness and above all, clinical utility.

Representatives from the four countries participating in the initial collaboration

undertook a pilot project in 2011 to develop four cancer datasets - Lung, Melanoma,

Prostate (Radical Prostatectomy), and Endometrium. Following on from the success of

this pilot project, the ICCR was joined by the European Society of Pathology (ESP) in

2013 and in 2014 incorporated a not-for-profit organisation focussed on the

development of internationally agreed evidence-based datasets developed by world

leading experts. The ICCR Datasets are made freely available from its website

www.ICCR-Cancer.org

Design of this protocol

This structured reporting protocol has been developed using the ICCR dataset on

Colorectal excisional biopsy (polypectomy) as the foundation.

This protocol includes all of the ICCR cancer dataset elements as well as additional

information, elements and commentary as agreed by the RCPA expert committee. It

provides a comprehensive framework for the assessment and documentation of

pathological features of Colorectal excisional biopsies (polypectomies).

ICCR dataset elements for colorectal excisional biopsy (polypectomy) specimens are

included verbatim. ICCR Required elements are mandatory and therefore represented as

standards in this document. ICCR Recommended elements, that is, those which are not

mandatory but are recommended, may be included as guidelines or upgraded to a

standard based on the consensus opinion of the local expert committee.


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The ICCR elements are identified in each chapter with the ICCR logo placed before the

Standard or Guideline number or bullet and the ICCR element description and

commentary is boarded by a grey box as shown below:

G3.02 The intraglandular extent should be recorded as a percentage.

Additional commentary by the RCPA expert committee may be added to an ICCR

element but is not included in the grey bordered area nor indicated with an ICCR logo

e.g.

G2.03 If present, the laterality of the lymph nodes submitted may be recorded

as left, right or bilateral.

CS2.03a If present, record site and number. All lymph node tissue

should be submitted for histological examination.

Further information on the ICCR is available at www.iccr-cancer.org

Checklist

Consistency and speed of reporting is improved by the use of discrete data elements

recorded from the checklist. Items suited to tick boxes are distinguished from more

complex elements requiring free text or narrative. A structured or discrete approach to

responses is favoured, however the pathologist is encouraged to include free text or

narrative where necessary to document any other relevant issues, to give reasons for

coming to a particular opinion and to explain any points of uncertainty.

Report format

The structure provided by the following chapters, headings and subheadings describes

the elements of information and their groupings but does not necessarily represent the

format of either a pathology report (Chapter 7) or checklist (Chapter 6). These, and the

structured pathology request form (Appendix 1) are templates that represent

information from this protocol, organised and formatted differently to suit different

purposes.

Key documentation

• Clinical Practice Guidelines for Surveillance Colonoscopy – in adenoma follow-up;

following curative resection of colorectal cancer; and for cancer surveillance in

inflammatory bowel disease, developed by the Colonoscopy Surveillance Working

Party, Cancer Council Australia.30

• Guidelines for Authors of Structured Cancer Pathology Reporting Protocols, Royal

College of Pathologists of Australasia, 200931

• The Pathology Request-Test-Report Cycle — Guidelines for Requesters and

Pathology Provider28

• World Health Organization Classification of Tumours, Digestive System Tumours.

5th Edition, 20193


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• AJCC Cancer Staging Manual 8th edition, American Joint Committee on Cancer,

20162

• ICCR dataset: Colorectal excisional biopsy (Polypectomy) dataset 1st edition v1.0

Changes since last edition

Inclusion of ICCR Core and Non-core elements.

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Authority and development This section provides information about the process undertaken to develop this protocol.

This 2nd edition of the protocol is an amalgam of three separate processes:

1. This protocol is based on the ICCR dataset – Colorectal excisional biopsy

(polypectomy) 1st edition. All ICCR elements from this dataset, both required

(mandatory) and recommended (optional), are included in this protocol,

verbatim. (It should be noted that RCPA feedback from all Anatomical Pathology

fellows and specifically the local expert committee was sought during the

development process of the ICCR dataset). Details of the ICCR development

process and the international expert authoring committee responsible for the

ICCR dataset are available on the ICCR website: iccr-cancer.org.

2. Additional elements, values and commentary have been included as deemed

necessary by the local expert committee. In addition, the standard inclusions of

RCPA protocols e.g. example reports, request information etc., have also been

added.

3. This protocol was developed by an expert committee, with assistance from

relevant stakeholders.

Authorship – 2nd edition (2020)

Dr Ian Brown (Lead author 1st and 2nd editions), Pathologist

Prof Priyanthi Kumarasinghe (Gastrointestinal Series Chair), Pathologist

A/Prof Christophe Rosty, Pathologist

A/Prof David Ellis, Pathologist

A/Prof Andrew Ruszkiewicz, Pathologist

Dr Julie Lokan, Pathologist

Dr Duncan McLeod, Pathologist

Dr Nicole Kramer, Pathologist

Conjoint Prof Stephen Ackland, Medical Oncologist

Dr Spiro Raftopoulos, Gastroenterologist

Authorship – 1st edition

Dr Ian Brown, Pathologist (Chair and lead author), Pathologist

Conjoint Professor Stephen Ackland, Medical Oncologist

Prof Michael Bourke, Gastroenterologist

A/Prof Bastiaan deBoer, Pathologist

Associate Professor Robert Eckstein, Pathologist

Professor Nicholas Hawkins, Pathologist

Dr Andrew Hunter, Colorectal Surgeon

Dr Andrew Kneebone, Radiation Oncologist

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Clinical Prof Priyanthi Kumarasinghe, Pathologist

A/Prof Andrew Ruszkiewicz, Pathologist

Dr Mee Ling Yeong, Pathologist

Editorial manager

Christina Selinger, PhD, Royal College of Pathologists of Australasia

Acknowledgements

The Polypectomy and local colorectal expert committee wish to thank all the pathologists

and clinicians who contributed to the discussion around this document.

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Stakeholders

ACT Cancer Registry

ACT Health

Anatomical Pathology Advisory Committee (APAC)

Australasian Gastro-Intestinal Trials Group (AGITG)

Australian Commission on Safety and Quality in Health Care

Australian Digital Health Agency (ADHA)

Australian Institute of Health and Welfare (AIHW)

Australian Pathology

Cancer Australia

Cancer Council ACT

Cancer Council Australia and Australian Cancer Network (ACN)

Cancer Council NSW

Cancer Council Queensland

Cancer Council SA

Cancer Council Tasmania

Cancer Council Victoria

Cancer Council Western Australia

Cancer Institute NSW

Cancer Services Advisory Committee (CanSAC)

Cancer specific expert groups – engaged in the development of the protocols

Cancer Voices Australia

Cancer Voices NSW

Clinical Oncology Society of Australia (COSA)

Colorectal Surgical Society of Australia and New Zealand (CSSANZ)

Department of Health, Australian Government

Gastroenterological Society of Australia (GESA)

Health Informatics Society of Australia (HISA)

Independent Review Group of Pathologists

Medical Oncology Group of Australia (MOGA)

Medical Software Industry Association (MSIA)

National Pathology Accreditation Advisory Council (NPAAC)

New Zealand Cancer Control Agency

New Zealand Cancer Registry

New Zealand Committee of Pathologists

New Zealand Society of Gastroenterology (NZSG)

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Northern Territory Cancer Registry

Public Pathology Australia

Queensland Cooperative Oncology Group (QCOG)

Representatives from laboratories specialising in anatomical pathology across Australia

Royal Australasian College of Physicians (RACP)

Royal Australasian College of Surgeons (RACS)

Royal Australian and New Zealand College of Radiologists (RANZCR)

Royal Australian College of General Practitioners (RACGP)

Royal College of Pathologists of Australasia (RCPA)

South Australia Cancer Registry

Southern Cancer Network, Christchurch, New Zealand

Standards Australia

Tasmanian Cancer Registry

Victorian Cancer Registry

Western Australia Clinical Oncology Group (WACOG)

Western Australian Cancer Registry

Development process

This protocol has been developed following the seven-step process set out in Guidelines

for Authors of Structured Cancer Pathology Reporting Protocols.31

Where no reference is provided, the authority is the consensus of the local expert group

for local inclusions and the ICCR Dataset Authoring Committee for ICCR components

denoted with the ICCR logo.

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1 Pre-analytical

This chapter relates to information that should be recorded on receipt of the specimen in

the laboratory.

The pathologist is reliant on the quality of information received from the clinicians or

requestor. Some of this information may be received in generic pathology request forms,

however, the additional information required by the pathologist specifically for the

reporting of local resection of the colon is outlined in Appendix 1. Appendix 1 also

includes a standardised request information sheet that may be useful in obtaining all

relevant information from the requestor.

Surgical handling procedures affect the quality of the specimen and recommendations for

appropriate surgical handling are included in Appendix 1.

S1.01 All demographic information provided on the request form and

with the specimen must be recorded.

CS1.01a The Royal College of Pathologists of Australasia (RCPA) The

Pathology Request-Test-Report Cycle — Guidelines for

Requesters and Pathology Providers must be adhered to.32

This document specifies the minimum information to be

provided by the requesting clinician for any pathology test.

CS1.01b Ideally the laboratory information system (LIS) should include

documentation as to whether or not the patient identifies as

Aboriginal and/or Torres Strait Islander in Australia, or Māori

in New Zealand. This is in support of government initiatives to

monitor the health of those who identify as indigenous,

particularly in relation to cancer.

CS1.01c The patient’s health identifiers may include the patient’s

Medical Record Number as well as a national health number

such as a patient’s Medicare number (Australia), Individual

Healthcare Identifier (IHI) (Australia) or the National

Healthcare Index (New Zealand).

S1.02 All clinical information as documented on the request form must

be recorded verbatim.

CS1.02a The request information may be recorded as a single text

(narrative) field or it may be recorded in a structured format.

CS1.02b In most cases all clinical information should be transcribed:

however in a small number of cases the pathologist may

exercise discretion regarding the inclusion of provided clinical

information, for instance, possibly erroneous information or

information that may impact on patient privacy. In such case

reference should be made as to the location of the complete

clinical information e.g. ‘Further clinical information is

available from the scanned request form.’

G1.01 The copy doctors requested on the request form should be recorded.

21

S1.03 The pathology accession number of the specimen must be

recorded.

S1.04 The principal clinician involved in the patient’s care and

responsible for investigating the patient must be recorded.

CS1.04a The principal clinician should provide key information

regarding the clinical presentation of the patient. Follow up

may be required with the principal clinician for a number of

reasons:

• The clinical assessment and staging may be incomplete

at the time of biopsy.

• The pathology request is often authored by the

clinician performing the surgical excision/biopsy rather

than the clinician who is investigating and managing

the patient.

• The identity of this clinician is often not indicated on

the pathology request form

In practice therefore, it is important in such cases that the

reporting pathologist should be able to communicate with the

managing clinician for clarification.

CS1.04b The Australian Healthcare identifiers i.e. Healthcare Provider

Identifier - Individual (HPI-I) and Healthcare Provider

Identifier - Organisation (HPI-O) should be included, where

possible, to identify the principal clinician involved in the

patient's care.

G1.02 Any clinical information received in other communications from the

requestor or other clinician should be recorded together with the source

of that information.

CG1.02a There should be a free text field so that the referring doctor

can add anything that is not addressed by the above points,

such as previous cancers, risk factors, investigations,

treatments and family history.

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2 Specimen handling and macroscopic findings

This chapter relates to the procedures required after the information has been handed

over from the requesting clinician and the specimen has been received in the laboratory.

Tissue banking

➢ Pathologists may be asked to provide tissue samples from fresh specimens

for tissue banking or research purposes. The decision to provide tissue

should only be made if the pathologist is sure that the diagnostic process

will not be compromised. As a safeguard, research use of the tissue

samples may be put on hold until the diagnostic process is complete.

➢ If tissue is sampled for banking or research, then this should be done in

consultation with a pathologist and recorded in the report. It is good

practice to specify a paraffin block that is ideal for future ancillary testing or

research purposes, if possible.

Specimen handling

➢ Detailed fixation and specimen handling instructions are available from the

RCPA online Cut-up Manual:

https://www.rcpa.edu.au/Manuals/Macroscopic-Cut-Up-Manual

➢ The specimen must be handled in a systematic and thorough

fashion to ensure completeness and accuracy of pathological data.

Macroscopic findings

S2.01 Polyp identification label and number per container must be

recorded.

CS2.01a Polyp number is an essential component used in bowel

screening registries and for surveillance guidelines.

Preferably, the endoscopist should submit tissue piece(s) from

each polyp resection in a separate container, so that each

specimen jar will contain only one polyp sample for

histological evaluation.

When multiple polyps or an unknown number of polyps are

received in a specimen container, this may preclude accurate

assessment of i) the number of polyps received; ii) polyp

classification; iii) the number of positive polyps if carcinoma is

present in more than one fragment. As polyps are often

resected in multiple fragments (piecemeal resection), the

number of fragments does not necessarily reflect the number

of polyps removed.

In the event that fragments are received from multiple polyps

in a specimen container from multiple sites, the ability to

https://www.rcpa.edu.au/Manuals/Macroscopic-Cut-Up-Manual

23

accurately record polyp features corresponding to the polyp

site of origin may be compromised. This may have impacts for

bowel screening registry follow up.

CS2.01b The total number of polyps may be unreliable especially if

there are large numbers of polyps submitted and/or

numerous fragmented specimens, however an estimate of the

total number can be used as an indicator of polyposis

syndrome.

CS2.01c The term ‘polyp’ is used throughout this protocol as a generic

designation for all lesions presenting as an elevated mucosal

abnormality. It is recognised that uncommon neoplastic

lesions may be entirely flat or even depressed. Since this

protocol is relevant to the designation and reporting of such

lesions, the term ‘polyp’ is still used as a generalisation.

S2.02 Clinical information must be recorded.

CS2.02a Clinical information can be provided by the clinician on the

endoscopy report or the pathology request form. Pathologists

could search for additional information from possible previous

pathology reports.

The presence of a known polyposis syndrome, Lynch

syndrome, chronic inflammatory bowel disease (IBD) or any

other relevant gastrointestinal disorder should be recorded

and provided to the pathologist as awareness of such

underlying conditions may influence histological

interpretation.

The diagnosis of conventional adenoma or advanced serrated

polyp in a patient with IBD raises the possibility of IBD-

associated dysplasia in the involved segment.

S2.03 The type of endoscopic procedure must be recorded.

CS2.03a The type of endoscopic procedure is important as it may

affect histological analysis, including the evaluation of

resection margins.

Polypectomy removes polyps using a snare without or with

submucosal injection of a solution to lift the lesion (EMR).

Diminutive (1-5 millimetres (mm)) polyps and small (6-9

mm) sessile polyps are usually removed by cold snare or

sometimes hot snare (mechanical transection without or with

electrocautery). Hot snare polypectomy may be used for

larger (10-19 mm) sessile polyps and pedunculated polyps.

Depending on polyp size and configuration, en bloc or

piecemeal removal is performed.33

CS2.03b Cold snare polypectomy is utilised for most sessile polyps,

irrespective of size. However, any lesion <10 mm should

utilise cold snare technique as standard.34

CS2.03c Endoscopic submucosal dissection (ESD) consists of en bloc

resection of superficial lesions of any size after submucosal

injection of a solution, using specialised endoscopic knives. It

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is more commonly used in the upper gastrointestinal tract and

sometimes performed in the large bowel for suspected

superficial invasive carcinomas. One of the main advantages

of ESD compared with EMR is an accurate evaluation of

resection margins.

Transanal endoscopic microsurgery (TEMS) is a minimally

invasive surgical procedure for en bloc removal of large rectal

lesions and early rectal carcinomas not amenable to

colonoscopic resection. For malignant lesions, the muscular

layer of the rectum is removed with the specimen.

Transanal minimally invasive surgery (TAMIS) is a crossover

procedure between laparoscopic surgery and TEMS for

resection of benign and early-stage malignant lesions in the

lower and mid rectum. The TAMIS technique can also be used

for non-curative intent surgery of more advanced lesions in

patients who are not candidates for radical surgery.

Endoscopic full thickness resection (EFTR) is a recent

minimally invasive endoscopic technique that can be

performed in the large bowel resulting in the full transection

of all layers of the bowel. EFTR can be used for the

management of challenging epithelial and subepithelial lesions

that are not amenable to conventional endoscopic resection

methods and previously required a surgical approach.

S2.04 The specimen sites of the polyps submitted must be recorded if

provided by the clinician.

CS2.04a Determination of specimen site is based on clinical

information provided on the container label, the pathology

request form or the endoscopy report. Any discrepancy should

be discussed with the endoscopist.

CS2.04b Ideally, when polyps are resected from different sites, they

should be placed in separate, clearly labelled containers

indicating number of polyps and resection site. If container

contains piecemeal resected polyp, this should be clearly

stated by the clinician.

CS2.04c To facilitate best practice, it is advantageous for the

pathologist to have access to a comprehensive endoscopy

report. This may be available online or alternately should

accompany the pathology request form.

CS2.04d Particular factors apply to the polyps arising in the right colon

versus the left colon, underlying the importance of site of

polyp origin to subsequent colorectal carcinoma risk.

There is an increased risk for both metachronous adenomas

with high grade dysplasia and colorectal cancer if multiple

adenomas are found in the right colon at baseline

colonoscopy.35-38 Increasing age is associated with an increase

in the number of adenomas in the right colon.39 Other factors

that may be responsible for the increased risk of

25

metachronous lesions include of the finding of sessile polyps

(e.g. sessile serrated adenoma/polyps/lesions [SSA/P/L]),

more anatomical ‘blind spots’ and more difficulty achieving

adequate bowel preparation.

S2.05 For specimens other than TEMS, record if polyps are received

intact or fragmented.

CS2.05a Many large sessile polyps are removed by piecemeal EMR.40,41

This can make histological evaluation of the completeness of

excision difficult or impossible.

S2.06 For specimens other than TEMS, record the diameter of each

intact polyp.

CS2.06a Adenomas are classified based on their diameter.30 Refer

CG2.02a for further detail.

CS2.06b The probability of developing future advanced adenomas or

cancers increases with the size of adenoma found at index

examination, and ranges, depending on the study, from 1.5-

7.7% for adenomas less than 5 mm, through 3-15.9% for

adenomas of 5-20 mm, to 7-19.3% for adenomas >20

mm.35,42-47 Size is usually considered a more robust marker of

risk than histological characteristics of advanced polyps such

as higher grades of villosity or dysplasia, with which it is

closely associated.36,42,48

CS2.06c Grossly, measurement of the size can be done from the

formalin-fixed specimen, excluding the stalk, if present.

CS2.06d Note that the macroscopic diameter may not correspond to

the diameter seen at microscopy due to the finding at

microscopy that the lesion represents only a proportion of the

specimen, the remainder being a cuff of normal mucosa. The

microscopic size is more reflective of lesional risk in this

situation.

G2.01 When received in a fragmented fashion or where multiple tissue pieces

are placed in a single specimen jar, the diameter of the largest fragment

should be recorded.

CG2.01a An aggregate measure of the total tissue submitted in 3

dimensions may be useful for the pathologist.

G2.02 A description of each polyp is recommended.

CG2.02a Polyp size is associated with risk of metachronous polyp and

colorectal carcinoma, and is used to determine colonoscopy

surveillance intervals. Conventional adenomas <10 mm are

considered as low-risk lesions while conventional adenomas

≥10 mm are classified as advanced lesions. Polyps <10 mm

in size are further divided into small (6-9 mm) and diminutive

(1-5 mm) lesions. The size of conventional adenoma

correlates with other advanced histologic features (villosity

>25% of the polyp and high- grade dysplasia). Sessile

serrated lesions (formerly known as sessile serrated

adenoma/polyp) and hyperplastic polyps ≥10 mm are

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considered advanced lesions.

Information on endoscopic appearances of polyps should be

recorded for endoscopy/histology correlation. This may be

helpful to pathologists who may request deeper levels in

tissue blocks when the first histologic impression does not

match the endoscopic appearance (optical diagnosis).

Superficial and early neoplasms of the gastrointestinal tract

can be assessed on the basis of their endoscopic appearance.

Various classifications are used.

Using the Paris classification, type 0 neoplastic lesions are

classified as polypoid (Ip and Is), non-polypoid (IIa, IIb and

IIc), and non-polypoid and excavated (III) (Figure 1).49

Lateral spreading tumours (LSTs) are a subgroup of the type

IIa lesions, larger than 10 mm in diameter, and classified into

2 groups: granular and non-granular LSTs.50 Granular LSTs

are subclassified into homogenous and nodular mixed types.

Non-granular LSTs have a higher malignant potential than the

granular LST and are subclassified into flat, elevated and

pseudo-depressed types.

For direct optical diagnosis of colorectal lesions, usually both

high-definition white light as well as image-enhanced

endoscopy, are becoming increasingly used. Various

strategies and classifications exist, including the Narrow-band

imaging (NBI) International Colorectal Endoscopic (NICE), the

Japanese NBI Expert Team (JNET) and the Workgroup

serrAted polypS and Polyposis (WASP) classifications.51-53 The

endoscopist’s optical diagnosis can be reported as a specific

type of the classification used or as histologic category:

serrated lesions/polyps (hyperplastic polyp, sessile serrated

lesion, sessile serrated adenoma with dysplasia), adenoma,

early adenocarcinoma, advanced adenocarcinoma,

submucosal lesion, others.

CG2.02b NICE classification:53

1 – serrated/hyperplastic lesion

2 – conventional adenoma

3 – advanced dysplastic lesion/early cancer

S2.07 For all en bloc resections, the dimensions of the specimen must

be recorded.

CS2.07a The dimensions of large en bloc resection specimens (large

EMR, ESD, TEMS, TAMIS, EFTR) need to be recorded. If

possible, a photograph should be taken and recorded. When

the specimen contains normal tissue and the polyp is

macroscopically clearly visible, the maximum diameter of the

polyp (without the stalk if pedunculated) should be given.

27

For polyps resected in piecemeal fashion, a measurement of

the aggregated tissue fragments with a dimension of the

largest piece of tissue can be given to provide some

information about the amount of tissue submitted.

Resection specimens of sessile polyps usually include various

amounts of normal surrounding colonic mucosa. The

dimension of these specimens does not reflect the actual size

of the polyp. The microscopic size may be more appropriate

for these cases.

Various studies demonstrated some discordance between

polyp sizes determined by endoscopy and pathology, with a

tendency for larger endoscopy than pathology sizing.54 For all

polyps resected in piecemeal fashion, the endoscopic size is

used for determining surveillance intervals. For en bloc

resection specimens, the pathology size may be more

accurate; however, these lesions are often large with little

impact of size differences for determining colonoscopy

surveillance intervals.

G2.03 For all en bloc resections, a detailed description should be recorded.

CG2.03a The description should include:

o Dimensions of the lesion

o Colour

o Surface contour e.g. villiform, nodular, granular

o Presence of ulceration

CG2.03b Ideally the specimen should be photographed.

S2.08 The nature and sites of all blocks must be recorded.

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Figure 1. Schematic representation of the major variants of type 0 neoplastic

lesions of the digestive tract: polypoid (Ip and Is), non-polypoid (IIa, IIb, and

IIc), non-polypoid and excavated (III). Terminology as proposed in a consensus

macroscopic description of superficial neoplastic lesions. Reproduced with permission

from Paris workshop participants (2003). The Paris endoscopic classification of superficial

neoplastic lesions: oesophagus, stomach, and colon: November 30 to December 1, 2002.

Gastrointest Endosc 58(6 Suppl):S3-43.49

29

3 Microscopic findings

Microscopic findings relate to purely histological or morphological assessment.

Information derived from more than one type of investigation (e.g. clinical, macroscopic

and microscopic findings), are described in Chapter 5.

S3.01 The histological type of polyps must be recorded.

CS3.01a Each polyp should be classified according to the World Health

Organization (WHO) Classification of Tumours of the Digestive

System 5th edition, 2019.55

Conventional adenomas are divided based on the proportion

of villous component: tubular adenoma (villous component

<25% of the polyp), villous adenoma (villous component

>75% of the polyp) and tubulovillous adenoma for all other

cases. Conventional adenomas with a significant villous

component (>25%) are advanced lesions. The presence of

high grade dysplasia is reported. Conventional adenomas with

high grade dysplasia are regarded as advanced lesions in

colonoscopy surveillance guidelines. High grade dysplasia is

characterised by marked architectural changes visible at low

magnification (complex crowding, irregularity of glands,

cribriform architecture, intraluminal necrosis), associated with

cytological features (loss of cell polarity, enlarged nuclei with

prominent nucleoli, often with atypical mitotic figures).

Epithelial misplacement of adenomatous glands into the head

or stalk of the polyp can be present in usually large

pedunculated polyps. This should be recorded as a separate

value in addition to the main histological subtype of polyp.

Dysplasia in sessile serrated lesion (SSLD), formerly known as

sessile serrated adenoma/polyp, shows greater morphological

heterogeneity than conventional adenoma. The dysplasia

should not be graded because biologically advanced SSLDs

may show mild morphological changes.56

Traditional serrated adenoma is considered as a low-grade

dysplastic lesion with different morphology than the usual

dysplasia in conventional adenomas. However, superimposed

dysplasia can develop as these lesions progress. Only when

high grade dysplasia is present, this be should recorded as

traditional serrated adenoma (TSA), high grade.

Serrated adenoma unclassified can be used for lesions that

are difficult to classify as either TSA or SSLD, not for SSL

versus hyperplastic polyp.

Some advanced conventional adenomas or serrated

lesions/polyps may demonstrate histological features

suspicious but not definite for the diagnosis of

adenocarcinoma. This can be due to limited amount of tissue,

cautery artefact or cases difficult to distinguish between

epithelial misplacement of adenomatous glands and invasive

adenocarcinoma. Such cases should be recorded as an

additional value ‘Suspicious for adenocarcinoma’. The clinical

behaviour of these lesions is not clear. The pathologist should

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comment in the report when an invasive carcinoma cannot be

excluded but should not complete the elements for

adenocarcinoma if the diagnosis of adenocarcinoma is not

definite.

Neuroendocrine neoplasms are classified into neuroendocrine

tumours (NETs), NECs and MiNENs. NETs are graded 1-3

using the mitotic count and Ki-67 proliferation index (Table

1).55 If the two proliferation indicators suggest different

grades, the higher grade is assigned. Most NETs of the

gastrointestinal tract are grade 1 or 2.

For adenocarcinoma in a polyp, NEC or MiNEN, refer to

additional elements specific to malignant polyps (see S3.01

Histological type).

Other benign polyps (hamartomatous polyps, inflammatory

polyps) do not have dysplasia. If superimposed dysplasia is

identified in a hamartomatous polyp or if a particular subtype

of hamartomatous polyp is identified (e.g., juvenile polyp,

Peutz-Jeghers polyp), it should be recorded as an additional

feature. Dysplasia arising in an inflammatory polyp raises the

possibility of IBD-associated dysplasia.

Various types of mesenchymal polyp can be identified in

polypectomy specimens, including perineurioma, Schwann cell

hamartoma, schwannoma, neurofibroma, ganglioneuroma,

lipoma, granular cell tumour, inflammatory fibroid polyp or

gastrointestinal tumour. This should be recorded under the

‘other’ category.

CS3.01b For each location from which specimens have been received

and recorded in S2.04, record the type of polyp (refer to

Appendix 5) and the number of polyps of that type.

CS3.01c If carcinoma, follow protocol for malignant polyp outlined

below from S3.04-G3.04.

S3.02 If present, the grade of dysplasia must be recorded.

CS3.02a This should be recorded as low or high grade which replaces

previous terms such as mild, moderate and severe. Most

dysplastic lesions will have low grade dysplasia. Features of

high grade dysplasia are listed in Appendix 5. High grade

dysplasia is an indicator of an advanced polyp, and hence a

shorter surveillance interval (Appendix 7). As discussed in

CS3.01a, all dysplasia, even when subtle, developing in a SSL

represents a biologically advanced lesion and hence should not

be graded.

Polypoid dysplastic lesions arising in a setting of inflammatory

bowel disease should also be graded as low or high grade.

31

Figure 2. High grade adenoma example


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S3.03 The presence of a significant component of villous architecture

must be recorded in conventional adenoma.

CS3.03a The significance of villous architecture in other polyp types

e.g. TSA or sessile serrated lesion with dysplasia (SSL/D) is

unknown. The presence of villous architecture in such lesions

may be recorded, but is not a requisite to guide subsequent

follow up.

G3.01 Evidence of polyposis syndrome should be recorded.

CG3.01a The pathologist should be cognisant of the presence of

33

polyposis syndromes (refer to Appendix 6). These include:

• Familial Adenomatous Polyposis (FAP)

• Hyperplastic (serrated ) polyposis syndrome

• MUTYH-associated polyposis (MAP)

• Juvenile polyposis

• Peutz–Jeghers syndrome

• Cowden syndrome (PTEN hamartoma tumour syndrome)

• Hereditary mixed polyposis syndrome

CG3.01b For these syndromes the polyps suggestive of the syndrome

can be and often are cumulative over time. The pathologist

may need to review previous reports of specimens

accessioned from the patient if available.

G3.02 The adequacy of resection of non-malignant polyp should be reported

where the polyp is received intact and where the margin of resection is

unequivocally seen.

CG3.02a This is typically only able to be done in a small percentage of

specimens.

Malignant Polyps

A malignant colorectal polyp (MCP) is a malignant process developing from an adenoma

(conventional or serrated) or less commonly without an identifiable precursor (polypoidal

carcinoma) within which the malignant cells have breached the muscularis mucosa and

invaded the submucosa (stage pT1). This process provides the potential for spread to

regional lymph nodes or distant organs.57 Adenocarcinoma is found in 0.5 to 5.6% of

colorectal adenomas (closer to the lower end of this range in large volume practices).

There is a higher prevalence of adenocarcinoma in adenomas detected as part of a faecal

blood screening program.57-60 MCP’s account for 10% of all the CRC’s detected in these

screening programs61 and approximately half of all stage 1 CRCs.60,62,63 The importance

of this lesion lies in the clinical decision as to whether a patient should precede to

subsequent surgery or whether endoscopic polypectomy alone is sufficient treatment,

given that the vast majority of malignant polyps are not associated with residual disease.

Histological adverse features including large invasive tumour size, high tumour grade,

tumour budding, lymphovascular invasion, greater depth of invasion and resection

margin involvement, are associated with increased risk for residual carcinoma and

regional or distant spread57,64-68 and are generally considered indications for surgery.

While it is generally agreed that in the absence of adverse features, endoscopic resection

alone, with adequate margin clearance, is sufficient for disease control and optimal

overall patient outcome.

S3.04 The specific tumour type must be recorded.

CS3.04a Colorectal cancers should be typed according to the WHO

Classification of Tumours of the Digestive System, 5th edition,

2019.55 This applies only in the setting of a malignant polyp

and not of an endoscopic biopsy specimen. If identified, the

precursor polyp/lesion from which the adenocarcinoma arose

should be recorded. Some endoscopic resection specimens

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following a large biopsy or neoadjuvant therapy may only

show a scar but no residual tumour.

Most colorectal adenocarcinomas are of no specific type (not

otherwise specified (NOS)) but some subtypes of

adenocarcinoma are defined as follows:

Mucinous adenocarcinoma classification requires greater than

50% of the tumour to comprise pools of extracellular mucin

containing malignant glands or individual tumour cells.

Microsatellite instability is present in a higher proportion

compared to adenocarcinoma NOS. Tumours with less than

50% mucinous content are described as having a mucinous

component.

Signet-ring cell adenocarcinoma classification requires greater

than 50% of the tumour to demonstrate single malignant cells

with intracytoplasmic mucin, displacing and typically indenting

the nuclei, imparting signet-ring cell morphology. Signet-ring

cell adenocarcinoma has stage-independent adverse

prognostic significance relative to adenocarcinoma NOS.69

There is a strong association with microsatellite instability and

with Lynch syndrome.70 Tumours with less than 50% signet-

ring cell content are described as having a signet-ring cell

component.

Medullary carcinoma is characterised by sheets of malignant

cells with indistinct cell boundaries, vesicular nuclei,

prominent nucleoli, abundant eosinophilic cytoplasm and

prominent intratumoural lymphocytes and neutrophils. These

tumours almost invariably demonstrate microsatellite

instability and are associated with a good prognosis.71

Serrated adenocarcinoma shares morphological similarities

with precursor serrated polyps, demonstrating glandular

serrations, which are often slit-like, abundant eosinophilic or

clear cytoplasm, minimal necrosis and sometimes areas of

mucinous differentiation.72

Micropapillary adenocarcinoma is characterised by small,

rounded clusters of tumour cells lying within stromal spaces

mimicking vascular channels. At least 5% of the tumour

should demonstrate this feature to classify as micropapillary

adenocarcinoma. This pattern is most frequently encountered

alongside adenocarcinoma NOS. There is a strong association

with adverse pathological features including a high risk of

lymph node metastatic disease.73

Adenoma-like adenocarcinoma is defined as an invasive

adenocarcinoma in which at least 50% of the invasive tumour

has an adenoma-like appearance with villous architecture, low

grade cytology, a pushing growth pattern and minimal

desmoplastic stromal reaction.74 Diagnosis of adenocarcinoma

on endoscopic biopsy is exceedingly difficult. This variant is

associated with a good prognosis.

35

Neuroendocrine carcinomas (NECs) show marked cytological

atypia, brisk mitotic activity, and are subclassified into small

cell and large cell subtypes. NECs are considered high-grade

by definition. A Ki-67 proliferation index <55% is associated

with better overall survival.75 MiNENs are usually composed of

a poorly differentiated NEC component and an

adenocarcinoma component. If a pure or mixed NEC is

suspected on morphology, immunohistochemistry is required

to confirm neuroendocrine differentiation, usually applying

synaptophysin and chromogranin A as a minimum.

Other epithelial tumours rarely encountered include

adenosquamous carcinoma, carcinoma with sarcomatoid

components, undifferentiated carcinoma, squamous cell

carcinoma and non-signet-ring cell poorly cohesive

adenocarcinoma. Many of these are extremely rare.

If multiple primary tumours are present, separate datasets

should be used to record histological tumour type and all

following elements for each primary tumour.

CS3.04b The description must be based on the WHO Histological

Classification of Tumours of the Colon and Rectum (refer to

Appendix 4).55

CS3.04c Virtually all colorectal cancers are adenocarcinomas. The term

‘Adenocarcinoma NOS’ on the reporting checklist is used to

indicate conventional adenocarcinoma without any of the

special features of the tumour types listed below it.

S3.05 The histological tumour grade must be recorded.

CS3.05a Grading applies only to malignant polyps not to endoscopic

biopsy specimens. Despite low level of interobserver

agreement,76 histological grade is associated with nodal

status and is an independent prognostic factor used in risk

assessment models for colorectal carcinoma.77-79

Various grading systems have been used over the years. A

two-tiered grading system is more reproducible and more

prognostically relevant than a four-tiered grading system. For

consistency with the latest WHO classification,55 grading

should be based on gland formation: low grade (formerly well

to moderately differentiated) and high grade (formerly poorly

differentiated). Grading is based on the least differentiated

component of the tumour, although there is no good evidence

to support this stance and a minimum area of high grade

tumour required for this classification has not been defined.

Grading may not be applicable if the adenocarcinoma is very

small.

Tumour buds most commonly seen at the invasive tumour

front, should not be considered in the evaluation of grade.

Refer to ICCR dataset for full commentary.

Emerging data suggests that grading based on poorly

differentiated clusters is superior to conventional grading with

http://www.iccr-cancer.org/getattachment/Datasets/Published-Datasets/Digestive-Tract/Colorectal-Excisional-Biopsy-Polypectomy-TNM8/ICCR-Polypectomy1st-edn-v1-0-bookmark.pdf

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respect to both prognostic value and reproducibility.80,81

Only adenocarcinoma NOS and mucinous adenocarcinoma

should be graded. Grading is not applicable to other subtypes

of adenocarcinoma, as grading by gland formation is difficult

to apply to subtypes and most of these are associated with

their own clinical prognosis e.g., bad for signet-ring cell

adenocarcinoma, micropapillary adenocarcinoma, serrated

adenocarcinoma and good for medullary carcinoma and

adenoma-like adenocarcinoma. Mucinous adenocarcinoma

should be graded on gland formation and epithelial

maturation.55 Tumour mismatch repair (MMR) status is likely

to influence clinical behaviour of some histological tumour

types, including mucinous adenocarcinoma, but some studies

have found morphological grading superior to MMR status for

prognostication of mucinous adenocarcinomas.82,83 A

cribriform pattern of invasive adenocarcinoma is associated

with greater risk of nodal metastasis in malignant polyps.68

CS3.05b Histological grading of invasive colorectal adenocarcinoma is

based on a balance of the different levels of differentiation.

The 8th edition American Joint Committee on Cancer (AJCC)

staging system provides a classification grading scheme (see

Table 2).

Ideally pathologists should designate the differentiation of

adenocarcinoma arising in a polyp by at least one grading

system descriptor. Because most studies on the prognosis of

early carcinomas arising in malignant polyps have used

tumour differentiation rather than tumour grade, it is

advisable for clarity that a designation of high grade is spelt

out as being equivalent to poor differentiation (or rarely,

undifferentiated).

S3.06 The presence of any degree of poor differentiation/

undifferentiated tumour must be recorded.

CS3.06a Several studies have specifically examined the relevance of

poor differentiation of any extent and have identified this as

an adverse prognostic feature associated with an average

approximate 10% risk of lymph node or systemic metastasis.

CS3.06b Poor differentiation is often seen at the advancing edge and

associated with a prominent desmoplastic stromal reaction. It

is identified to variable extent in 6-9% of malignant polyps. In

addition to the conventional grading system, the following

patterns are indicative of poor differentiation.

1. Signet ring cells

2. Small tumour nests with ≥5 cells (termed ‘poorly

differentiated clusters’).84 This pattern forms a

continuum with micropapillary carcinoma.

3. Tight cribriform arrangements characterised by

small closely associated gland lumina and/or fused

37

chain like arrangements. This pattern is often

reminiscent of Gleason pattern 4 prostatic

adenocarcinoma.

Tumour budding (invasive groups of <5 cells) does not

equate with poor differentiation but represents an

independent adverse prognostic feature (see below).

Poor differentiation remains a subjective feature and hence

has less interobserver agreement than other features listed

below.

G3.03 The presence of any amount of tumour budding should be recorded.

CG3.03a Tumour budding is defined as single cells or clusters of up to

4 tumour cells at the invasive front of invasive carcinomas. It

is considered to be the morphological manifestation of

epithelial mesenchymal transition.85 Tumour budding is

different from tumour grade (based on gland formation) and

poorly differentiated clusters (≥5 cells).

There is increasing evidence that tumour budding is an

independent adverse prognostic factor in colorectal

carcinoma. Several studies have shown that pT1 colorectal

carcinomas, including malignant polyps, with tumour budding

score Bd2 and Bd3 (≥5 buds) are associated with an

increased risk of lymph node metastasis.67,86-89 For stage II

colorectal carcinomas, tumour budding score Bd3 is

associated with increased risk of recurrence and mortality.90-92

Tumour budding is reported as the number of buds and

scored using a three-tiered system. According to the

recommendations from a consensus conference on tumour

budding,93 the number of tumour buds is the highest count

after scanning 10 separate fields (20x objective lens) along

the invasive front of the tumour or the entire lesion for

malignant polyps (‘hotspot’ approach). The count of tumour

buds is only performed in non-mucinous, non-signet-ring cell

adenocarcinoma areas. The number of tumour buds is

counted on H&E. If the invasive front of the tumour is

obscured by inflammatory cells, immunohistochemistry using

pan-cytokeratin can be used to help identifying the buds, but

the final count is performed on H&E. Depending on the

eyepiece field number diameter of the microscope, the

number of buds may need to be normalised to represent the

number for a field of 0.785 mm2 (objective lens 20x with

eyepiece diameter of 20 mm).

Tumour budding should only be reported in non-mucinous

and non-signet-ring cell adenocarcinoma areas.94

S3.07 Lymphatic and venous invasion must be reported.

CS3.07a For colorectal cancer, it is important to report the presence or

absence of lymphovascular invasion and to classify this

further according to the type of vessels involved and, for

veins, their intramural or extramural location, as these

features may have different clinical and prognostic

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implications.

Small vessel invasion should be reported separately from

venous (large vessel) invasion. Small vessel invasion is

defined as tumour involvement of thin-walled structures lined

by endothelium, without an identifiable smooth muscle layer

or elastic lamina. Small vessels may represent lymphatics,

capillaries or post-capillary venules. Lymphatics and venules

may be distinguished by D2-40 immuno-histochemistry,

which only stains lymphatic endothelial cells, not venular, but

this is not routinely recommended in reporting polypectomy

specimens. All forms of small vessel invasion are considered

under the ‘L’ classification under Union for International

Cancer Control (UICC)/AJCC TNM 8th editions.2,95 Small vessel

invasion is associated with lymph node metastatic disease and

has been shown to be an independent indicator of adverse

outcome in several studies.96-98 A higher prognostic

significance of extramural small vessel invasion has been

suggested, but the importance of anatomic location in small

vessel invasion is not well established.97 In malignant polyps,

lymphatic invasion is associated with an increased risk of

lymph node metastasis.65,67

Venous invasion is defined as tumour present within an

endothelium-lined space that is either surrounded by a rim of

muscle or contains red blood cells.99 It should be suspected in

the presence of a rounded or elongated deposit of tumour

beside an artery. Interpretation of such features is subjective

and can be improved by the application of

immunohistochemical and histochemical stains, in particular

elastic staining to identify venous elastic lamina.100,101 A

circumscribed tumour nodule surrounded by a smooth muscle

wall or an identifiable elastic lamina, evident on haematoxylin

& eosin (H&E) or elastic stains, is considered sufficient to

classify as venous invasion. Examination of multiple levels in

blocks showing features suspicious of venous invasion can

also be helpful in borderline cases.

Extramural (beyond muscularis propria) venous invasion has

been demonstrated by multivariate analysis in multiple

studies to be a stage independent adverse prognostic factor

for colonic and rectal cancer.97,102 However, it would only be

identified in TAMIS or EFTR specimens. There is also evidence

from several studies that intramural (intramuscular or

submucosal) venous spread is also of prognostic importance

but the evidence is much weaker than for extramural venous

invasion.103

S3.08 Perineural invasion must be reported.

CS3.08a Multiple independent studies and one meta-analysis have

demonstrated the adverse prognostic implication of perineural

invasion in colorectal cancer, particularly in stage II

disease.104,105 One large multicentre study reported adverse

prognostic significance of both intramural and extramural

39

perineural invasion.104 However, the importance of anatomic

location in perineural invasion is not well established.

In malignant polyps, perineural invasion is extremely rare. It

can sometimes be found in endoscopic resection or

TEMS/TAMIS for early rectal carcinomas.

S3.09 The margin status must be recorded.

CS3.09a The margin status is an essential component of the

histological examination. Assessment of margins can only be

done for en bloc polypectomy, ESD, EFTR, TAMIS and TEMS

specimens. Margins cannot be reliably assessed for specimens

resected in piecemeal fashion.

An involved (positive) deep resection margin is a predictor for

adverse outcome.106 However, if no other adverse histological

features are present, an involved deep margin is associated

with a risk of local recurrence but not lymph node or distant

metastasis. Various cut-offs have been used to define an

involved deep margin. Most studies have shown that a

clearance of <1 mm should be regarded as a positive

margin.107,108 Pathologists should report the deep margin as

either involved if carcinoma cells are present directly at the

margin, or record the clearance distance to nearest 0.1 mm

between the deep margin and the closest invasive carcinoma.

If the invasive carcinoma is within a diathermy zone, the

distance between the outer aspect of the diathermy zone and

the closest carcinoma should be reported if possible. In cases

for which extensive diathermy artefacts obscure the presence

of possible carcinoma at the margin, immunohistochemistry

for CDX2 or pancytokeratin may be helpful in this

assessment. If measurement is not possible, the margin

status should be reported as non-assessable.

Lateral margin is less critical for patient management but

needs to be recorded. A positive lateral margin does not

influence local recurrence rate.109 The status of the lateral

margin should be recorded as either involved or by measuring

the distance to nearest 0.1 mm between the closest lateral

margin and the neoplasm (dysplasia or carcinoma). If

possible, the component of the malignant polyp present at the

margin (carcinoma or benign precursor polyp/lesion) should

be specified. However, this distinction is not always possible.

CS3.09b Margins cannot be reliably assessed for specimens resected in

piecemeal fashion, however, it is good practice to comment

on clearance to a deep margin in this situation, particularly if

the invasive carcinoma is present in one or a limited number

of pieces.

It is recommended to record the distance of invasive

carcinoma to the cauterized/deep margin, even in piecemeal

resections.

G3.04 Where possible record whether the malignant polyp had a pedunculated

or sessile morphology. Pedunculated polyps require the presence of a

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Edition

stalk.

CG3.04a This may require correlation with the macroscopic and/or

endoscopic appearance.

CG3.04b This may be difficult in poorly orientated or fragmented

specimens.

CG3.04c In pooled analysis, sessile polyps containing malignancy are

associated with an approximately 10 times increased

mortality risk over pedunculated polyp with malignancy.110

This appears to be largely related to the increased frequency

of a positive polypectomy margin, although increased rate of

vascular invasion and other factors may contribute. Because

positive margin seems to be the most significant feature,

further treatment is not usually warranted in a sessile polyp

with malignancy where there is a clear resection margin at

polypectomy and no other adverse factors.

S3.10 The extent of invasion must be recorded.

CS3.10a The anatomic extent of tumour invasion, based on a

combination of macroscopic and microscopic assessment of

an excision specimen, is the most important prognostic factor

in colorectal cancer. pT classification indicates the extent of

invasion of the primary tumour in the absence of application

of neoadjuvant therapy. Criteria of the UICC95 and AJCC2 8th

editions are applied, with the exception that pT in situ is not

recognised. Rare cases of colorectal neoplasia confined to

invasion of the lamina propria (intramucosal carcinoma) are

acknowledged but, given the negligible metastatic potential of

such neoplasms, including those with a poorly differentiated

morphology,111,112 these should be classified under high grade

dysplasia/non-invasive neoplasia.

Some rare polyps will remain difficult to classify as either

invasive or non-invasive neoplasia, in particular when

epithelial misplacement is present. Some adenomas may

involve submucosal lymphoglandular complexes, mimicking

invasive carcinoma,113 but the distinction with an

adenocarcinoma invading the submucosa can be challenging.

In other cases, signet-ring cells limited to the mucosa may be

identified in an adenoma.114 The clinical behaviour of such

lesions is not clear. The pathologist should comment in the

report when an invasive carcinoma cannot be excluded or for

rare cases with unknown clinical behaviour.

For endoscopic resection of early colorectal carcinoma,

tumours are usually invading no deeper than into the

submucosa (pT1). For rectal carcinoma removed by

TEMS/TAMIS, invasion into the muscularis propria (pT2) or

the perirectal fat tissue (pT3) can be present. Further

consideration of colorectal carcinoma invading beyond the

submucosa is provided in a separate surgical resection

41

dataset.

S3.11 The maximum depth or width of invasive tumour must be

recorded.

CS3.11a Depth of invasion is one of the main histological risk factors

associated with clinical outcome and used for patient

management.115,116 Submucosal invasion ≥1 mm is associated

with an increased risk of lymph node metastasis.67,86,117 Depth

of invasion is the maximum thickness of invasive carcinoma,

measured in mm, from the deepest aspect of the invasive

tumour in the submucosa to either the overlying muscularis

mucosae or from the Haggitt line (Haggitt level 2; the neck of

the polyp) in a pedunculated polyp or the surface of the

polyp, if the carcinoma is ulcerated or has overgrown the

precursor polyp. This requires well-oriented sections

perpendicular to the surface. If the resection is piecemeal, the

maximum depth of invasion in any fragment is used.

The maximum width of invasive carcinoma can also be

recorded. Tumours with an invasive component ≥4 mm are

more likely to be associated with lymph node metastasis.64,68

If the resection is piecemeal, the maximum width of invasion

in any fragment is used.

Refer to ICCR dataset for full commentary.

CS3.11b A semi-quantitative evaluation of the depth of invasion into 3

or 4 levels may still be used in some parts of the world as

follows:

- Haggitt levels 1 (head), 2 (neck), 3 (stalk) and 4 (beyond

stalk) for pedunculated polyps. Level 1,2 and superficial

(≤1mm) level 3 invasion is not associated with any risk

for lymph node metastases unless there is vascular

invasion present. There is a significant increased risk of

lymph metastasis for level 3 with invasion ≥3 mm and for

level 4 polyps.116,118 This requires intact polyp with well-

oriented sections from the head to the base.119,120

- Kikuchi levels sm1 (superficial submucosa), sm2 (mid

submucosa) and sm3 (deep submucosa) for sessile

polyps, with significant increased risk of nodal metastasis

for sm3 polyps.121,122 This requires the presence of the

muscularis propria to define the deep boundary of the

submucosa, which is often absent in endoscopic resection

specimens. The Kikuchi system can be more reliably

applied in TEMS, TAMIS and EFTR specimens.

Refer to Figures 5-8.

S3.12 The presence of other relevant coexistent pathological

abnormalities in the bowel must be recorded.

CS3.12a The presence and type of chronic inflammatory bowel disease

(Crohn disease, ulcerative colitis, primary sclerosing

cholangitis (PSC) related colitis) and any other clinically

relevant pathology is important information that needs to be

http://www.iccr-cancer.org/getattachment/Datasets/Published-Datasets/Digestive-Tract/Colorectal-Excisional-Biopsy-Polypectomy-TNM8/ICCR-Polypectomy1st-edn-v1-0-bookmark.pdf

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Edition

recorded.

CS3.12b In both ulcerative colitis and Crohn disease, patients with

more extensive disease and duration of disease >10 years are

at increased risk of colorectal cancer.123,124 Ulcerative colitis

patients with co-existing primary sclerosing cholangitis are

especially at risk of developing colorectal neoplasia.125

The following text may be added to the report to allow

clarification of colorectal carcinoma risk:

‘Dysplastic lesions arising in an area affected by inflammatory

bowel disease are a heterogeneous group. Many are

adenoma–like and are not progressive. Conservative

management may be warranted if the following conditions are

met: Macroscopically adenoma – like in appearance; excised

with clear margins; no flat dysplasia of surrounding mucosa

and/or polyp stalk. If these criteria are not met, the lesion

should be regarded as having a significant risk for associated

or subsequent colorectal carcinoma.’

G3.05 A comment on the likelihood of residual disease post polypectomy may

be included.

CG3.05a The pathologist can provide clinical guidance based on

published studies and meta-analysis to the likelihood of

residual disease post polypectomy. This can be considered as

low risk or high risk. Appendix 8 provides a summary of

useful prognostic data.

G3.06 Any additional relevant information should be recorded.

CG3.06a There must be a free text field so that the pathologist can add

any essential information that is not addressed by the above

points.

43

Figure 5. Levels of invasion of colorectal adenomas.

Adapted from Haggitt RC, Glotzbach RE, Soffer EE and Wruble LD (1985). Prognostic

factors in colorectal carcinomas arising in adenomas: implications for lesions

removed by endoscopic polypectomy. Gastroenterology 89(2):328–336. Reproduced

with permission.

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Edition

Figure 6. Measurement in a sessile polyp

Figure 7. Measurement in a pedunculated polyp

45

Figure 8. Sessile polyps

sm1: slight submucosal

invasion from the muscularis

mucosae.

sm2: intermediate between

sm1 and sm 3

sm3: carcinoma invasion near

the inner surface of the

muscularis propria

0.2-0.3mm

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Edition

Table 1. Classification and grading for neuroendocrine neoplasms.

Terminology Differentiation Grade Mitotic count

(mitoses/2

mm2)

Ki-67

index

NET, grade 1

Well

differentiated

Low <2 <3%

NET, grade 2 Intermediate 2-20 3-20%

NET, grade 3 High >20 >20%

NEC, small cell

type Poorly

differentiated High

>20 >20%

NEC, large cell

type

>20 >20%

MiNEN Well or poorly

differentiated

Variable Variable Variable

Reproduced with permission from Klimstra DS et al (2019). Classification of

neuroendocrine neoplasms of the digestive system. In: World Health Organization

Classification of Digestive System Tumours. 5th ed. IARC Press, Lyon. © World Health

Organization/International Agency for Research on Cancer126

Table 2. AJCC 8th edition tumour grading system2

47

4 Ancillary studies findings

Ancillary studies are being increasingly used to aid diagnosis as prognostic

biomarkers or to indicate the likelihood of patient response to specific biologic

therapies.

S4.01 Ancillary studies for mismatch repair by immunohistochemistry

must be performed on appropriate specimens.

CS4.01a Testing colorectal carcinoma for MMR protein deficiency is

standard of care for Lynch syndrome screening and provides

therapeutic decision information for patient management.127

MMR deficiency is associated with good prognosis, poor

response to 5-Fluorouracil and predicts response to immune

checkpoint blockage therapy.128,129

CS4.01b Immunohistochemistry for mismatch repair markers (MLH-1,

MSH-2, MSH-6 and PMS-2) can help identify an adenoma as

originating in Lynch syndrome.

CS4.01c Approximately 70% of adenomatous polyps in patients with

Lynch syndrome demonstrate an absence of immunoreaction

for one or four common mismatch repair markers.130

Adenomas in Lynch syndrome are often large, villous, right

sided and demonstrate high grade dysplasia.131,132 Adenomas

with these features are more likely to demonstrate an

immunohistochemical abnormality. The incidental occurrence

of sporadic adenomas in patients with Lynch syndrome

probably accounts for the approximately 30% of adenomas

that exhibit preservation of mismatch repair markers. Hence,

the presence of preserved MMR expression/staining does not

exclude that a patient has Lynch Syndrome, making routine

testing for MMR deficiency in adenomas, of limited clinical

use.

The original Bethesda criteria133 recommended investigation

for Lynch syndrome in ‘Individuals with adenomas diagnosed

at age less than 40’. Currently no universal testing guideline

exists and the use of MMR immunohistochemistry in

adenomas should be restricted to specific clinical situations.

CS4.01d The identification of Lynch syndrome may affect subsequent

treatment decisions.

G4.01 Ancillary studies for microsatellite instability, BRAF (V600E) mutation

testing, MLH1 promoter methylation testing, RAS mutation testing should

be documented.

CG4.01a BRAF mutation testing and MLH1 promoter methylation

analysis are performed to help distinguish sporadic MLH1-

deficient colorectal carcinomas from Lynch syndrome

associated tumours, caused by constitutional MLH1 mutation.

The presence of either BRAF V600E mutation or MLH1

promoter methylation effectively excludes Lynch syndrome.

BRAF mutation status may also have predictive/therapeutic

value.

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Edition

CG4.01b Immunohistochemistry for MLH1 can help confirm the

presence of dysplasia in a SSLD.

Loss of staining in an area with morphological atypia

suggestive of dysplasia confirms SSLD. Loss of expression of

MLH1 is seen in approximately 80% of SSLD. Isolated crypts

in an otherwise morphologically normal SSL may also show

loss of MLH1 expression, however, in the absence of a

morphological abnormality, this does not equate with SSLD.

G4.02 Special stains may aid detection of lymphatic and venous invasion in

malignant polyps

CG4.02a Lymphatic invasion – use of the lymphatic endothelium

marker D2-40 can highlight that a space containing tumour is

lined by lymphatic endothelium

Venous invasion – the use of elastic stains such as VVG and

Orcein can aid identification of veins containing tumour. A

Desmin immunohistochemical stain may highlight smooth

muscle in the wall of a compressed vein.

G4.03 Any additional studies for colorectal carcinoma should be performed.

CG4.03a If a pure or mixed neuroendocrine neoplasm is suspected on

morphology, immunohistochemistry is required to confirm

neuroendocrine differentiation, usually applying

synaptophysin and chromogranin A as a minimum. As with

other gastrointestinal tract and pancreatic neuroendocrine

neoplasms, assessment of proliferation index by Ki-67

immunohistochemistry is fundamental to grading of the

neuroendocrine component. A Ki-67 proliferation index <55%

is associated with better overall survival in NECs.75

49

5 Synthesis and overview

Information that is synthesised from multiple modalities and therefore cannot reside

solely in any one of the preceding chapters is described here. For example, tumour

stage is synthesised from multiple classes of information – clinical, macroscopic and

microscopic. Overarching case comment is synthesis in narrative form. Although it

may not necessarily be required in any given report, the provision of the facility for

overarching commentary in a cancer report is essential.

By definition, synthetic elements are inferential rather than observational, often

representing high-level information that is likely to form part of the ‘Diagnostic

summary’ section in the final formatted report (see G5.01).

G5.01 The ‘Diagnostic summary’ section of the final formatted report should

include:

For carcinoma:

a. Specimen site(s)

b. Polyp type

c. Degree of differentiation

d. Lymphatic and venous invasion

e. Depth of invasion

f. Margin status

For conventional adenoma*:

a. Polyp identification and number

b. Specimen site of polyp

c. Polyp type

d. Diameter

e. Presence or absence of high grade dysplasia

f. Villous component

g. Evidence of polyposis syndrome

h. Adequacy of excision

For sessile serrated lesions/adenoma/polyps:



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Edition

c. Diameter

d. Presence or absence of dysplasia

e. Evidence of polyposis syndrome

f. Adequacy of excision

For hyperplastic polyps:



*A table may be advantageous to report on large numbers of polyps.

S5.01 A field for free text or narrative in which the reporting

pathologist can give overarching case comment must be

provided.

CS5.01a This field may be used, for example, to:

• list any relevant ancillary tests

• document any noteworthy adverse gross and/or

histological features

• express any diagnostic subtlety or nuance that is

beyond synoptic capture

• document further consultation or results still pending.

CS5.01b Use of this field is at the discretion of the reporting

pathologist.

G5.02 The edition/version number of the RCPA protocol on which the report is

based should be included on the final report.

CG5.02a For example, the pathology report may include the following

wording at the end of the report: ‘the data fields within this

formatted report are aligned with the criteria as set out in the

RCPA document ‘ XXXXXXXXXX’ XXXX Edition dated

XXXXXXX’.

51

6 Structured checklist

The following checklist includes the standards and guidelines for this protocol which

must be considered when reporting, in the simplest possible form. The summation of

all ‘standards’ is equivalent to the ‘minimum dataset’ for polypectomies and local

resections of the colorectum. For emphasis, standards (mandatory elements) are

formatted in bold font.

S6.01 The structured checklist provided may be modified as required

but with the following restrictions:

a. All standards and their respective naming conventions,

definitions and value lists must be adhered to.

b. Guidelines are not mandatory but are recommendations

and where used, must follow the naming conventions,

definitions and value lists given in the protocol.

G6.01 The order of information and design of the checklist may be varied

according to the LIS capabilities and as described in Functional

Requirements for Structured Pathology Reporting of Cancer Protocols.134

CG6.01a Where the LIS allows dissociation between data entry and

report format, the structured checklist is usually best

formatted to follow pathologist workflow. In this situation, the

elements of synthesis or conclusions are necessarily at the

end. The report format is then optimised independently by the

LIS.

CG6.01b Where the LIS does not allow dissociation between data entry

and report format, (for example where only a single text field

is provided for the report), pathologists may elect to create a

checklist in the format of the final report. In this situation,

communication with the clinician takes precedence and the

checklist design is according to principles given in Chapter 7.

CG6.01c To aide implementation of Level 6 structured reporting (where

each reporting element is digitally captured using a discrete

data field), some reporting elements may require repeating,

such as in the case of synchronous primary tumours. For this

scenario, the superscript r is indicated next to the element ID

(e.g. S2.05r) to assist with coding of the protocol template.

G6.02 Where the checklist is used as a report template (see G6.01), the

principles in Chapter 7 and Appendix 2 apply.

CG6.02a All extraneous information, tick boxes and unused values

should be deleted.

G6.03 Additional comment may be added to an individual response where

necessary to describe any uncertainty or nuance in the selection of a

prescribed response in the checklist. Additional comment is not required

where the prescribed response is adequate.

52

Polypectomy and Local Resections of the Colorectum Structured Reporting Protocol 2nd Edition

Values in italics are conditional on previous responses.

Values in all caps are headings with sub values.

S/G Item description Response type Conditional

Pre-analytic

S1.01 Demographic information

provided

S1.02 Clinical information provided

on request form

Text

OR

Information not provided

OR

Structured entry as below:

Multi select value list (select all that apply):

• Screening colonoscopy

• Known polyposis syndrome

o Familial adenomatous polyposis (FAP)

o MUTYH-associated polyposis (MAP)

o Serrated polyposis

o Other, specify

• Lynch syndrome

• Chronic inflammatory bowel disease

o Ulcerative colitis

o Crohn disease

• Previous polyp(s)

53


• Previous colorectal cancer

G1.01 Copy To doctors recorded Text

S1.03 Pathology accession number Alpha-numeric

S1.04 Principal clinician Text

G1.02 Other clinical information

received

Text

Macroscopic findings

S2.01r Clinical information Text

S2.02r Endoscopic procedure Single selection value list:

• Not specified

OR

Multi select value list(select all that apply):

• Polypectomy / Endoscopic mucosal resection

(EMR)

o Cautery

▪ Not specified

▪ Used

▪ Not used

o Submucosal injection

▪ Not specified

▪ Used (EMR)

▪ Not used

o Resection type

54



▪ Not specified

▪ En bloc

▪ Piecemeal

• Endoscopic submucosal dissection (ESD)

• Transanal endoscopic microsurgery (TEMS)

• Transanal minimally invasive surgery (TAMIS)

• Endoscopic full thickness resection (EFTR)

• Other, specify

S2.03 Polyp identification Not specified / not assessable

OR

Label

Note: For each specimen submitted record: how

the specimen is labelled, the number of

polyps/tissue pieces, the polyp site location,

polyp conformation and intact polyp diameter.

Record the polyp label, number

of polyps and polyp location for

each container

Number per container:___

S2.04r Specimen sites of polyps • Not specified

• Caecum

• Ileocaecal valve

• Appendiceal orifice

• Ascending colon

• Hepatic flexure

• Transverse colon

If other, specify the site

55


• Splenic flexure

• Descending colon

• Sigmoid colon

• Rectosigmoid junction

• Rectum

• Anorectal junction

• Numeric: __mm from anal verge

• Other, specify

Note: this will be repeated for each specimen

noted in S2.01

For large numbers of polyps a table may assist to

present this in a clearer format.

S2.05r Polyp conformation Single selection value list:

• Intact

• Fragments

Note: this will be repeated for each polyp noted

in S2.02

S2.06 Intact polyp diameter Numeric: ___mm

Note: this will be repeated for each intact polyp

noted in S2.02.

G2.01 Diameter of the largest

fragment

Numeric: ___mm

OR

Numeric: __x__x__mm aggregate tissue

G2.02r Description of polyp (e.g. colour,

shape, contour, ulceration etc.)

Text

56



Note: this will be repeated for each polyp noted

in S2.02

Single selection value list:

• Not specified

• Numeric: ___mm

• Size range: __mm to __mm

• Size category:

o Diminuitive

o Small

o Large

Classification Not given

OR

Paris Classification Text

Lateral spreading tumour

classification

Text

Optical diagnosis Text

S2.07 Specimen dimensions Conditional on a TEM being

submitted.

Maximum dimension of intact

specimen

Numeric: __x__mm

Maximum diameter of intact

polyp

Numeric: __mm

Aggregated dimensions for Numeric: __x__mm

57


fragmented polyps

Maximum dimension of largest

piece for fragmented polyps

Numeric: __mm

G2.03 TEMS SPECIMEN

Lesion dimensions Numeric: __x__x__mm

Colour Text

Surface contour Text

Ulceration Single selection value list:

• Absent

• Present

S2.08 Nature and site of blocks Text

Microscopic findings

S3.01 Polyp type and number Note: For each location from which

specimens have been received and recorded

in S2.02, record the type of polyp from the

list below and the number of polyps/tissue

pieces of that type.

Single select value list if intact polyps

received. Multi select where a location has

polyp fragments:

• No polyp identified (normal mucosa)

• Tubular adenoma

• Tubular adenoma, high grade

• Tubulovillous adenoma

If carcinoma, S3.05 – S3.11

must be recorded, and consider

recording G3.03-4.

58



• Tubulovillous adenoma, high grade

• Villous adenoma

• Villous adenoma, high grade

• Hyperplastic polyp

• Sessile serrated lesion

• Sessile serrated lesion with dysplasia

• Traditional serrated adenoma

• Traditional serrated adenoma, high grade

• Serrated adenoma unclassified

• Suspicious for adenocarcinoma

• Adenocarcinoma*

• Neuroendocrine tumour

o Grade 1

o Grade 2

o Grade 3

• Neuroendocrine carcinoma

o Small cell type

o Large cell type

• Mixed neuroendocrine-non-neuroendocrine

neoplasm (MiNEN)

• Hamartomatous polyp

• Inflammatory polyp

59


• Mucosal prolapse polyp

• Other, specify

Additional features Not applicable For neuroendocrine neoplasms

only

Mitotic count Numeric:___ / 2 mm2

AND/OR

Ki-67 proliferation index Numeric:___ %

S3.02 Dysplasia Single selection value list:

• Cannot be assessed

• Absent

• Present

Note: this should be recorded for each polyp or

fragments per location recorded in S3.01.

If present, record the grade of

dysplasia. Note: If sessile

serrated adenoma with dysplasia

(SSLD) selected in S3.01, S3.02

is not required.

Grade of dysplasia Single selection value list:

• Low grade

• High grade

• Not specified

Note: this should be recorded for each polyp

recorded in S3.01. If fragments received, the

highest grade of dysplasia should be recorded.

Conditional on the presence of

dysplasia

S3.03 Significant villous

architecture


• Absent

• Present

Note: this should be recorded for each

Conditional on conventional

adenoma being selected in S3.01

60



conventional adenoma recorded in S3.01.

G3.01 Evidence of polyposis syndrome Single selection value list:

• Absent

• Present

If present provide details

Details Text

G3.02 Polyp resection (non-malignant) Single selection value list:

• Adequate

• Inadequate

S3.04 Tumour type Single selection value list:

• Not applicable

• No evidence of residual tumour

• Adenocarcinoma not otherwise specified

(NOS)

• Mucinous adenocarcinoma

• Signet ring cell carcinoma

• Medullary carcinoma

• Serrated adenocarcinoma

• Micropapillary adenocarcinoma

• Adenoma-like adenocarcinoma


o Small cell type

o Large cell type

61


• Mixed neuroendocrine-non-neuroendocrine

• Other, specify


classified as malignant in S3.01

Precursor polyp/lesion Single selection value list:

• Absent

• Present, specify type#

Note: Refer to S3.01 Type of polyp.

S3.05 Histological tumour grade Single selection value list:

• Not applicable

• Low grade (formerly well to moderately

differentiated)

• High grade (formerly poorly differentiated)



Only adenocarcinoma NOS and

mucinous adenocarcinoma

should be graded

S3.06 Poor differentiation

(undifferentiated) tumour


• Absent

• Present



G3.03 Tumour budding Cannot be assessed

OR

Number of tumour buds*: ___

*Note: After scanning 10 fields on a 20x

objective lens, the hotspot field normalised to

If present, consider recording

the number of foci

62



represent a field of 0.785 mm2.

Tumour budding score Single selection value list:

• Bd1 – low budding (0-4 buds)

• Bd2 – intermediate budding (5-9 buds)

• Bd3 – high budding (>10 buds)



S3.07 Lymphatic and venous

invasion


• Not identified

• Present

o Small vessel (lymphatic, capillary or

venular)

o Large vessel (venous)

o Intramural

o Extramural



S3.08 Perineural invasion Single selection value list:

• Not identified

• Present



S3.09r Margin status Note: this should be recorded for each polyp If involved, record the involved

63


classified as malignant in S3.01 margin(s)

If not involved, record the

clearance from deep margin and

clearance from nearest

peripheral margin

Deep margin Single selection value list:


• Involved

• Not involved, specify distance to invasive

carcinoma

Distance to invasive

carcinoma

Numeric: ___mm

Lateral margin Single selection value list:


• Involved, specify

• Not involved, specify distance to neoplasia

Involved margin(s) Text

Distance to neoplasia Numeric: ___mm

G3.04 Morphology Single selection value list:

• Pedunculated

• Sessile

• Indeterminate


64




S3.10 Extent of invasion Single selection value list:

• Non-invasive neoplasia/high grade dysplasia

• Invasion into submucosa

• Invasion into muscularis propria

• Invasion through the muscularis propria into

pericolorectal connective tissue

• Invasion into the surface of the visceral

peritoneum

• Invasion into the adjacent

structure(s)/organ(s), specify

S3.11 Invasive carcinoma

dimensions

Cannot be assessed

OR

Maximum depth of invasion: ___ mm

Cannot be assessed

OR

Maximum width of invasion: ___ mm

S3.12r Coexistent abnormalities Multi select value list (select all that apply):

• None noted

• Ulcerative colitis

• Crohn disease

• Primary sclerosing cholangitis (PSC)

• Inflammatory bowel disease, not otherwise

If ‘Other’ is selected, provide

details.

If Ulcerative colitis, Crohn

disease, Primary sclerosing

cholangitis (PSC) or

Inflammatory bowel disease, not

otherwise specified is selected

the following text may be added

65


specified

• Other, specify

to allow clarification of

colorectal carcinoma risk

‘Dysplastic lesions arising in an area

affected by inflammatory bowel

disease are a heterogeneous group.

Many are adenoma – like, and are

not progressive. Conservative

management may be warranted if

the following conditions are met:

Macroscopically adenoma – like in

appearance; excised with clear

margins; no flat dysplasia of

surrounding mucosa and/or polyp

stalk. If these criteria are not met,

the lesion should be regarded as

having a significant risk for

associated or subsequent colorectal

carcinoma.’

G3.05 Comment on risk for residual

disease

Text

G3.06 Additional microscopic comment Text

Ancillary test findings

S4.01 Mismatch repair (MMR)

status by

immunohistochemistry


• Not tested

• Not interpretable

• MMR proficient

• MMR deficient

o MLH1/PMS2 loss

o MSH2/MSH6 loss

66



o MSH6 loss

o PMS2 loss

o Other, specify

Note: Mismatch repair enzyme

immunohistochemistry results may be recorded

for each malignant polyp recorded in S3.01.

Mismatch repair (MMR) status

by microsatellite instability

(MSI) testing


• Not tested

• Test failed

• MSI-high

• MSI-low

• MS-stable

G4.01 Additional ancillary studies

BRAF (V600E) mutation testing Single selection value list:

• Not tested

• Test failed

• Mutated

• Wild type

MLH1 promoter methylation

testing


• Not tested

• Test failed

• Methylated

67


• Not methylated

• Inconclusive

RAS mutation testing Single selection value list:

• Not tested

• Test failed

• Mutated, specify

• Wild type

G4.02 Special stains Text

G4.03 For neuroendocrine neoplasm

neuroendocrine markers


Not applicable

For neuroendocrine neoplasms

only

Neuroendocrine markers Text

Ki-67 proliferation index Numeric: ___ %

Other Text

Synthesis and overview

G5.01 Diagnostic summary Text

S5.01 Overarching comment Text

G5.02 Edition/version number of the

RCPA protocol on which the

report is based

Text


Edition

7 Formatting of pathology reports

Good formatting of the pathology report is essential for optimising communication

with the clinician, and will be an important contributor to the success of cancer

reporting protocols. The report should be formatted to provide information clearly

and unambiguously to the treating doctors, and should be organised with their use of

the report in mind. In this sense, the report differs from the structured checklist,

which is organised with the pathologists’ workflow as a priority.

Uniformity in the format as well as in the data items of cancer reports between

laboratories makes it easier for treating doctors to understand the reports; it is therefore

seen as an important element of the systematic reporting of cancer. For guidance on

formatting pathology reports, please refer to Appendix 2. An example of a pathology

report is shown in Appendix 3.

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Appendix 1 Pathology request information and surgical handling procedures

This appendix describes the information that should be collected before the pathology

test. Some of this information can be provided on generic pathology request forms;

any additional information required specifically for the reporting of local resections of

the colon may be provided by the clinician on a separate request information sheet.

An example request information sheet is included below. Elements which are in bold

text are those which pathologists consider to be required information. Those in non-

bold text are recommended.

Patient information

➢ Adequate demographic and request information must be provided

with the specimen.

• Items relevant to cancer reporting protocols include:

• patient name

• date of birth

• sex

• identification and contact details of requesting doctor

• date of request

• The patient’s ethnicity should be recorded, if known. In

particular whether the patient is of aboriginal or Torres

Strait islander origin. This is in support of a government

initiative to monitor the health of indigenous Australians

particularly in relation to cancer.

➢ The patient’s health identifiers should be provided.

• The patient’s health identifiers may include the patient’s

Medical Record Number as well as a national health

number such as a patient’s Medicare number (Australia),

Individual Healthcare Identifier (IHI) (Australia) or the

National Healthcare Index (New Zealand).

Clinical Information

The presence of a known polyposis syndrome, Lynch syndrome, chronic

inflammatory bowel disease or any other relevant gastrointestinal

disorder should be recorded.

• Clinical information can be provided by the clinician on the

endoscopy report or the pathology request form. Pathologists

could search for additional information from possible previous

Polypectomy and Local Resections of the Colorectum Structured Reporting Protocol

2nd Edition

pathology reports.

• The presence of a known polyposis syndrome, Lynch syndrome,

chronic IBD or any other relevant gastrointestinal disorder should

be recorded and provided to the pathologist as awareness of such

underlying conditions may influence histological interpretation.

• The diagnosis of conventional adenoma or advanced serrated

polyp in a patient with IBD raises the possibility of IBD-associated

dysplasia in the involved segment.

➢ The proceduralist’s identity and contact details should be recorded.

• Name of operating surgeon, contact details, and date of operation.

➢ The number of specimens submitted should be recorded.

The endoscopic tumour morphology should be recorded in accordance

with the Paris Classification of superficial neoplastic lesions.135

This information is attained at time of colonoscopy by the

requesting clinician.

Select all that apply:

• Polypoid

o 0-Ip (protruded, pedunculated)

o 0-Is (protruded, sessile; >2.5 mm above baseline)

• Non-Polypoid

o 0-IIa (superficial, elevated; <2.5 mm above

baseline)

o 0-IIb (flat)

o 0-IIc (superficial shallow, depressed)

o 0-III (excavated/ulcerated)

Refer to Figures 1 and 7.

The Paris classification provides a means of distinguishing sessile

polypoid lesions (Type 0-Is, protruding above 2.5 mm) from the

non-polypoid ones (Type 0-IIa protruding below 2.5 mm), the

distinction being crucial given the highly significant differences in

cancer rates between non-polypoid and sessile polypoid

(adenomatous and serrated) lesions.136

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Figure 9. Neoplastic lesions with ‘superficial’ morphology

Terminology as proposed in a consensus macroscopic description of superficial

neoplastic lesions. Reproduced with permission from Paris workshop participants

(2003). The Paris endoscopic classification of superficial neoplastic lesions:

oesophagus, stomach, and colon: November 30 to December 1, 2002.

Gastrointest Endosc 58(6 Suppl):S3-43.49


2nd Edition

➢ The location in the large bowel from which each specimen has been

taken should be recorded.

• Choose from one of the following:

• Not specified

• Caecum

• Ileocaecal valve

• Appendiceal orifice

• Ascending colon

• Hepatic flexure

• Transverse colon

• Splenic flexure

• Descending colon

• Sigmoid colon

• Rectosigmoid junction

• Rectum

• Anorectal junction

• Numeric: __mm from anal verge

• Other, specify

➢ The diameter of each resected polyp should be recorded.

• The diameter may be measured either in situ or after retrieval.

➢ The presence of multiple unexcised polyps should be recorded.

• In some cases polyps are too numerous to excise all lesions, and

only a sample is taken. The presence of numerous polyps is

considered high risk for future high grade adenomas and may be

indicative of FAP.30

➢ The reason for the procedure should be provided.

• Options include:

• Initial screening colonoscopy (baseline or index procedure)

• Surveillance – no previous history of adenoma or malignancy

• Surveillance – high risk e.g. FAP, other polyposis syndromes,

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Lynch syndrome

• Surveillance – previous adenoma/high grade dysplasia

(HGD)/malignant polyps

• Positive faecal occult blood test (FOBT)

• Other, specify

• If the reason for the procedure is surveillance following previous

findings of adenoma or malignancy, the date and results of that

previous encounter should be provided.

➢ Any relevant patient or family history should be provided.

• Of particular relevance is a family history of colorectal cancer;

FAP or other polyposis syndromes; Lynch syndrome, ulcerative

colitis, inflammatory bowel disease or Crohn disease.

➢ Any previous colorectal surgery should be detailed.

• Details regarding when the previous procedure has occurred and

relevant results will be important.

➢ Any other relevant issues noted during the procedure.

• Information such as the presence of inflammatory conditions;

dysplasia etc. is of importance to the pathologist.


2nd Edition

Example Request Information Sheet

The above Request Information Sheet is also available on the RCPA Cancer Protocols webpage.

https://www.rcpa.edu.au/Library/Practising-Pathology/Structured-Pathology-Reporting-of-Cancer/Cancer-Protocols


75

The above Request Information Sheet is also available on the RCPA Cancer Protocols webpage.




2nd Edition

Appendix 2 Guidelines for formatting of a pathology report

Layout

Headings and spaces should be used to indicate subsections of the report, and

heading hierarchies should be used where the LIS allows it. Heading hierarchies may

be defined by a combination of case, font size, style and, if necessary, indentation.

Grouping like data elements under headings and using ‘white space’ assists in rapid

transfer of information.137

Descriptive titles and headings should be consistent across the protocol, checklist

and report.

When reporting on different tumour types, similar layout of headings and blocks of

data should be used, and this layout should be maintained over time.

Consistent positioning speeds data transfer and, over time, may reduce the need for

field descriptions or headings, thus reducing unnecessary information or ‘clutter’.

Within any given subsection, information density should be optimised to assist in

data assimilation and recall. The following strategies should be used:

• Configure reports in such a way that data elements are ‘chunked’ into a single

unit to help improve recall for the clinician.137

• Reduce ‘clutter’ to a minimum.137 Thus, information that is not part of the

protocol (e.g. billing information or SNOMED codes) should not appear on the

reports or should be minimised.

• Reduce the use of formatting elements (e.g. bold, underlining or use of

footnotes) because these increase clutter and may distract the reader from the

key information.

Where a structured report checklist is used as a template for the actual report, any

values provided in the checklist but not applying to the case in question must be

deleted from the formatted report.

Reports should be formatted with an understanding of the potential for the

information to ‘mutate’ or be degraded as the report is transferred from the LIS to

other health information systems.

As a report is transferred between systems:

• text characteristics such as font type, size, bold, italics and colour are often lost

• tables are likely to be corrupted as vertical alignment of text is lost when fixed

font widths of the LIS are rendered as proportional fonts on screen or in print

• spaces, tabs and blank lines may be stripped from the report, disrupting the

formatting

• supplementary reports may merge into the initial report.

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Appendix 3 Examples of a pathology report

Adenoma polyp – example report


Edition

Malignant polyp – example report

79

Multiple polyp – example report

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Appendix 4 WHO Classification of tumours of the colon and rectum 5th edition

Benign epithelial tumours and precursors

8213/0* Serrated dysplasia, low grade

8213/2* Serrated dysplasia, high grade

Hyperplastic polyp, microvesicular type

Hyperplastic polyp, goblet cell

8210/0* Adenomatous polyp, low-grade dysplasia

8210/2* Adenomatous polyp, high-grade dysplasia

8211/0* Tubular adenoma, low grade

8211/2* Tubular adenoma, high grade

8261/0* Villous adenoma, low grade

8261/2* Villous adenoma, high grade

8263/0* Tubulovillous adenoma, low grade

8263/2* Tubulovillous adenoma, high grade

Advanced adenoma

8148/0 Glandular intraepithelial neoplasia, low grade

8148/2 Glandular intraepithelial neoplasia, high grade

Malignant epithelial tumours

8140/3 Adenocarcinoma NOS

8213/3 Serrated adenocarcinoma

8262/3* Adenoma-like adenocarcinoma

8265/3 Micropapillary adenocarcinoma

8480/3 Mucinous adenocarcinoma

8490/3 Poorly cohesive carcinoma

8490/3 Signet-ring cell carcinoma

8510/3 Medullary adenocarcinoma

8560/3 Adenosquamous carcinoma

8020/3 Carcinoma, undifferentiated, NOS

8033/3* Carcinoma with sarcomatoid component

8240/3 Neuroendocrine tumour NOS

8240/3 Neuroendocrine tumour, grade 1



Edition


8152/3 L-cell tumour

8152/3 Glucagon-like peptide-producing tumour

8152/3 PP/PYY-producing tumour

8241/3 Enterochromaffin-cell carcinoid

8241/3 Serotonin-producing tumour

8246/3 Neuroendocrine carcinoma NOS

8013/3 Large cell neuroendocrine carcinoma

8041/3 Small cell neuroendocrine carcinoma

8154/3 Mixed neuroendocrine–non-neuroendocrine neoplasm (MiNEN)

These morphology codes are from the International Classification of Diseases for

Oncology, third edition, second revision (ICD-O-3.2).138 Behaviour is coded /0 for

benign tumours; /1 for unspecified, borderline, or uncertain behaviour; /2 for

carcinoma in situ and grade III intraepithelial neoplasia; /3 for malignant tumours,

primary site; and /6 for malignant tumours, metastatic site. Behaviour code /6 is not

generally used by cancer registries.

This classification is modified from the previous WHO classification, taking into account

changes in our understanding of these lesions.

* Codes marked with an asterisk were approved by the IARC/WHO Committee for ICD-

O at its meeting in April 2019.

© International Agency for Research on Cancer (IARC). Reproduced with permission.

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Appendix 5 Polyp types

Polyps are classified as:

• No polyp identified (normal mucosa)

• Tubular adenoma

• Tubular adenoma, high grade

• Tubulovillous adenoma

• Tubulovillous adenoma, high grade

• Villous adenoma

• Villous adenoma, high grade

• Hyperplastic polyp

• Sessile serrated lesion

• Sessile serrated lesion with dysplasia

• Traditional serrated adenoma

• Traditional serrated adenoma, high grade

• Serrated adenoma unclassified

• Suspicious for adenocarcinoma

• Adenocarcinoma*

• Neuroendocrine tumour

o Grade 1

o Grade 2

o Grade 3


o Small cell type

o Large cell type

• Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN)

• Hamartomatous polyp

• Inflammatory polyp

• Mucosal prolapse polyp

• Other, specify

CONVENTIONAL ADENOMA

Conventional adenomas are neoplastic lesions characterised by the presence of dysplasia.

Most are polypoid, but they may be flat or even depressed.

Dysplasia is evidenced by nuclear enlargement, hyperchromasia, stratification and loss of

polarity. Increased mitotic activity and apoptosis are easily appreciated. All adenomas are

regarded as having malignant potential. ‘Advanced adenoma’ is a term used for lesions at

much higher risk for malignant progression. Advanced adenoma is characterised by one or


Edition

more of the following: 1) size >10mm, 2) villous architecture and 3) high grade dysplasia.

Increased number of adenomas is also associated with an increased risk for colorectal

adenocarcinoma.

1) Number

The number of individual adenomas identified at the baseline colonoscopy correlates with an

increased likelihood of finding an advanced adenoma at that time or in subsequent

colonoscopies.36,37,139,140 Analysis of pooled data from several prospective studies indicates

that risk for metachronous advanced adenomas increased with the number of adenomas at

base line and was 8.6% (1 adenoma), 12.7% (2 adenomas), 15.2% (3 adenomas), 19.6%

(4 adenomas) and 24.1% (5 adenomas).36 In another study the risk of developing

colorectal cancer/advanced adenoma was double in patients with ≥3 adenomas (0.8-1.1%)

than with ≤3 adenomas (0.5%) at baseline colonoscopy.141

Current NHMRC guidelines (2011) recommend follow up colonoscopy 12 months after the

identification of ≥5 adenomas and sooner in patients with ≥10 adenomas. If the number of

polyps found at baseline colonoscopy is ≥10, then FAP or MAP may be the cause.41,142-144

Pathologists should highlight this in the report (See S3.03).

From the above it can be concluded that two objective criteria namely adenoma size and

adenoma number, are strong predictive factors for a subsequent finding of advanced

adenoma or colorectal carcinoma, and in multivariate analyses are typically more important

than degree of villous architecture or dysplasia.17

Adenoma size ≥20 mm and/or ≥4 adenomas, identified at baseline colonoscopy, are

associated with a 20% risk of finding either advanced adenoma or colorectal carcinoma on

subsequent colonoscopy.

2) Villous architecture

While a strict universal definition of what defines a villous structure is lacking,145 most

studies have identified villosity as a risk factor for metachronous advanced adenoma and

colorectal carcinoma. Villous pattern has been defined as fronds covered by neoplastic cells.

These may appear to be floating free on tangential section or to be connected to the main

body of the polyp by a narrow stalk.146

Some studies have identified villosity as an independent risk factor, while in other studies it

correlates with adenoma size which is easier to measure, and less prone to inter-observer

variation amongst pathologists.35,36,42-48,147-155

Adenomas with a villous component have more malignant potential and are usually larger

than the more common tubular adenomas. The 2019 WHO defines tubular adenomas as

having <25% villous component, tubulovillous as 25-75% and villous as >75% villous

component.55

3) Degree of dysplasia

Dysplasia is an unequivocal neoplastic transformation in the epithelium. In conventional

adenoma it is characterised by evidence of epithelial proliferation - multilayering, variable

gland complexity and increased mitotic and apoptotic activity. Epithelial cells display nuclear

hyperchromasia and nuclear enlargement.

Dysplasia is classified on the basis of its severity. A progression from low grade to high

grade has been demonstrated in some (but not all cases) before malignancy develops.156,136

85

At present, the degree of dysplasia is not reported for serrated pattern lesions as any

degree of unequivocal cytological dysplasia is regarded as evidence of an advanced lesion.

Reparative changes in the superficial aspect of polyps due to trauma or erosion may mimic

HGD and could be over interpreted as such.136 Pathologists should take this into account if

there is evidence of erosion, torsion or other trauma in the adenoma.

Although not verified in all multivariate studies, HGD in adenomas at index colonoscopy

increases the risk for advanced metachronous adenomas.36

High grade dysplasia (HGD) is diagnosed when architectural and/or cytological abnormality

is marked. Only one or two glands with HGD that are identifiable at low power examination

are needed to classify an adenoma as high grade. Significant interobserver variability in the

diagnosis of HGD has been reported.145 Gland architectural abnormality is more easily

identified and has more importance to the diagnosis of HGD. The following are features

diagnostic of HGD:

1. Architecture

Glandular complexity typified by:

o Crowding and irregularity

o Prominent glandular budding

o Cribriform pattern with ‘back to back’ glands

o Prominent intraluminal papillary tufting

2. Cytology

o Loss of cell polarity

o Nuclear stratification - at least 2–5 nuclear rows

o variable number of rows within individual glands

o The nuclei are haphazardly distributed within all three thirds of the height of the

epithelium

o No maturation towards the luminal surface

o Abnormal goblet cell forms (retronuclear/dystrophic goblet cells)

o Nuclei - vesicular , enlarged, irregular thickened nuclear membranes, prominent

nucleolus, loss of polarity, atypical mitotic figures

o Prominent apoptosis

o Focal cell debris and necrosis - ‘dirty necrosis pattern’

Usually more than one of the above features is present in an adenoma with HGD.

3. Size

The probability of developing future advanced adenomas or cancers increases with the size

of adenoma found at index examination, and ranges, depending on the study, from 1.5-

7.7% for adenomas less than 5 mm, 3-15.9% for adenomas of 5-20 mm and 7-19.3% for

adenomas >20 mm.35,36,42-45,48 As an objective feature, size is a more robust marker of risk

than histological characteristics (i.e. higher grades of villosity and dysplasia) which are

subjective.36,42,48


Edition

Neoplastic invasion into the submucosa through the muscularis mucosae into submucosa is

diagnostic of invasive adenocarcinoma (pT1).136

Rarely polyps are encountered that are completely excised and contain invasive

adenocarcinoma in the lamina propria with or without extension into but not completely

through the muscularis mucosae. Some pathologists may prefer the technically correct term

‘intramucosal carcinoma’ for this abnormality. This abnormality may be associated with

submucosal invasion in deeper levels. If submucosal invasion is not identified then this

lesion has negligible risk for metastatic spread (presumably, because of the absence of

communicating lymphatics in the colorectal lamina propria).The term ‘high grade dysplasia’

is therefore adequate and recommended. Caution may be warranted in the setting of

intramucosal carcinoma with poor differentiation since metastatic spread has been

reported.157


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Edition


HYPERPLASTIC POLYP

Hyperplastic polyps (HP) account for 25-30% of resected polyps in most series.158-162 and

have an estimated prevalence of 10-20% in Western populations. These lesions frequently

harbour BRAF or KRAS mutations, supporting a neoplastic nature.

Three HP subtypes are recognised 1) microvesicular hyperplastic polyp (MVHP); 2) goblet

cell hyperplastic polyp (GCHP) and 3) mucin-poor hyperplastic polyp (MPHP). MVHPs and

GCHPs are the most common.163 This subdivision remains only of theoretical interest at this

time and its use in routine reporting is not required.

Microvesicular hyperplastic polyps are characterised by a serrated gland profile and an

ordered ‘test-tube’ arrangement of the crypts which taper toward the muscularis

mucosae.164 Microvesicular mucin droplets impart a faint basophilic quality to the

89

cytoplasm. Superficial goblet cells are usually found.163 The subepithelial basement

membrane and muscularis mucosae are thicker than in the adjacent normal mucosa.163,165

Figure 13. Typical appearance of microvesicular hyperplastic polyp

Goblet cell hyperplastic polyps display crowded crypts163 containing an increased

number of mature goblet cells.163 Serration is often minimal or limited to the upper third of

the crypt, but tufting of the epithelial surface is frequent. Thickening of the basement

membrane and muscularis mucosae is minimal.

Mucin poor hyperplastic polyp is poorly categorised potential sub-group which has been

dropped as a subcategory from the 5th edition of the WHO.

Hyperplastic polyps of all types are currently regarded as innocuous lesions with no

significant malignant potential and therefore no requirement for follow up.

SERRATED ADENOMA/POLYP/LESION

Classification schema for these polyps are still evolving and histological interpretation of

these serrated polyp types differs between pathologists.47,166,167

The 2019 WHO classification scheme divides this group into sessile serrated lesion (SSL)

(also known as sessile serrated adenoma and sessile serrated polyp) and traditional

serrated adenoma (TSA).

The majority of studies suggest that both TSA and SSL have malignant potential and are

associated with subsequent development of metachronous neoplasia.152-155,166,168 There is

variability and uncertainty as to the extent of the risk.169-172 It has been estimated that 1 in

25 SSLs progress to malignancy,40 a rate approximately equivalent to that of a conventional

adenoma.


Edition

A retrospective follow-up study of patients with SSLs found all but one patient had further

polyps/tumours (including one CRC). This supports surveillance colonoscopies in patients

with SSL.173

1) SSL

The emergence of SSL as an entity distinct from HP is based on 1) epidemiologic evidence

of CRC risk and 2) morphologic and 3) biological differences.174,175 When examined

carefully, SSL has a prevalence of 9% of resected polyps. 75% occur on the right colon and

polyp size is variable - 36% ≤5mm, 47% 6-10 mm and 17% ≥11 mm.

The lesions are sessile and often coated by thick mucus making them difficult to appreciate

at colonoscopy.

At low power the typical features of SSL reflect asymmetric proliferation. Most characteristic

are the dilated crypts as well as crypts with basal horizontal growth of crypts in L or

inverted T shapes along the muscularis mucosae.165,176 The 2019 WHO recommends one

such crypt is adequate for diagnosis.177 Crypts are irregularly spaced and may display

branching.163,165,178 Crypt serration extends into the crypt base. Increased intraluminal

mucin is common and displaced crypts can be seen herniating into the submucosa.179 At

higher power, disturbance to proliferation and maturation is evident,163,165 with asymmetric

proliferative zones178 and maturation towards both the luminal and basal aspects of the

crypts. This means that mature goblet cells extend toward both the luminal and basal

aspects of the crypt.179 Dystrophic goblet cells may be prominent. A minor degree of

nuclear atypia characterised by nuclear enlargement (with small nucleoli) is allowable,

particularly in the crypt bases.163 SSL’s (and also HPs) may be associated with a perineural

proliferation in the stroma (previously known as ‘fibroblastic polyp’). SSLs may also be

associated with a submucosal lipomatous proliferation and with inversion into the

submucosa that should not be mistaken for invasion.

Figure 14. Typical appearance of sessile serrated lesion

91

Figure 15. SSL with associated perineural cell proliferation

Figure 16. SSL with subjacent lipomatous proliferation


Edition

The natural history of SSLs remains to be defined.180 A 2017 study has found a lead time of

approximately 15 years based on differenced in the median age of patients with SSL and

MLH-1 deficient CRC.17

2) Traditional serrated adenoma

Named by Torlakovic et al in 2003163, TSAs account for around 1% of colorectal polyps

(range 0.6-1.9%).160,162,181 They occur throughout the large bowel but have a predilection

for the distal colon and rectum. Right sided lesions may arise from a sessile serrated lesion

and have BRAF mutation. Left sided lesions have a KRAS mutation and are occasionally

seen to arise in continuity with a goblet cell rich hyperplastic polyp.

The histopathological features of TSAs are characteristic resulting in high diagnostic

reproducibility.178 They usually display tubulovillous architecture, eosinophilic tall columnar

epithelium with prominent serration and ectopic crypt foci. The epithelial cells are most

characteristic with abundant pink cytoplasm and centrally located palisaded, pencillate

nuclei with dispersed chromatin.178,181 TSA may present as a flat lesion, especially in the

distal rectum. True dysplasia is characterised by similar features to those described for high

grade dysplasia in a conventional adenoma. Development of dysplasia in a TSA represents

an advanced neoplastic progression. Dysplasia arising in a TSA is characterised by loss of

cytoplasmic eosinophilia and nuclear and architectural changes that are equivalent to high

grade dysplasia in conventional adenomas. This should be separated from lesions that show

combination features of low grade conventional adenoma and TSA. These lesions should be

considered as conventional adenoma if ≤50% of the lesion is of conventional pattern and

TSA if >50% of the lesion has a TSA pattern. The follow up implications are usually the

same regardless. These combined lesions are sometimes identified in the distal rectum and

appear to have a higher recurrence risk because the margins are often ill defined.

Figure 17. Typical appearance of traditional serrated adenoma

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Figure 18. Traditional serrated adenoma arising from a background of hyperplastic

polyp.

Filiform serrated adenoma182,183 reportedly accounts for 4% of TSAs, occurs distally and is

characterised by very long (filiform) villi and marked lamina propria oedema.


Edition

Figure 19. Filiform traditional serrated adenoma

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Figure 20. Traditional serrated adenoma with high grade dysplasia

Figure 21. Traditional serrated adenoma with high grade dysplasia


Edition

Figure 22. Traditional serrated adenoma with high grade dysplasia – cytological

atypia

3) Sessile serrated lesion with dysplasia (SSLD)

Dysplastic sessile serrated adenoma represents most of what in past was termed ‘mixed

hyperplastic polyp/adenomatous polyps’. The development of dysplasia in SSL is believed to

herald a more aggressive lesion with possible risk of rapid progression to CRC. This is

suggested by the similar median age of patients with SSLD and MLH-1 deficient CRC.17

In a large population based study, 13.2% of SSLs showed dysplasia, accounting for 0.17%

of all colorectal polyps.184

Two types of dysplasia are described in the 5th edition WHO:185,186

1) ‘conventional adenomatous dysplasia’ - similar to that of conventional adenomatous

polyps with increased nuclear hyperchromasia, stratification and variable loss of

polarity, increased mitoses and basophilic cytoplasm. The changes extend to the

polyp surface; Caution is warranted in poorly oriented sections where there is risk of

over-interpretation of the proliferative zone as dysplastic. This pattern can rarely be

mimicked by a collision lesion comprising a SSL and a conventional adenoma.187 This

should always be considered if MLH1 staining is retained in the dysplastic area.

97

Figure 23. Sessile serrated lesion with dysplasia – conventional

adenomatous pattern.

2) ‘serrated dysplasia’ in which the glands frequently retain serration, the cells have

ample eosinophilic cytoplasm and the nuclei are vesicular and basally located.

Figure 24. Sessile serrated lesion with development of serrated pattern

dysplasia.

Sometimes dysplasia arising in a SSL may be subtle, with only mild cytoarchitectural

change. The term ‘minimal deviation’ has been applied to this pattern.56 Loss of

expression of MLH1 in the abnormal area confirms the diagnosis.


Edition

Figure 25. MLH1 loss in SSL with dysplasia. The lower lesion displays a

minimal deviation pattern in the left hand side of the lesion.

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Development of dysplasia in a SSL is a marker of particularly high risk for invasive

carcinoma and pathologists should indicate this in their reports. While the mean age of

patients with SSL is approximately 20 years younger than the mean age of patients with

sporadic MLH1 deficient colorectal carcinoma, the means age of SSLD is identical, indicating

that a rapid pathway to colorectal carcinogenesis may proceed once dysplasia develops.17

MLH-1 is lost in dysplastic foci of SSLD in approximately 80% of cases and can be a useful

adjunct investigation to confirm this high grade lesion.

A local study of SSLD identified four major morphological patterns of dysplasia; minimal

deviation (19%), serrated (12%), adenomatous (8%) and not otherwise specified (79%)

respectively. Minimal deviation dysplasia has only minor architectural and cytological

changes that usually requires loss of MLH1 immunohistochemical expression to support the

diagnosis. Serrated dysplasia and adenomatous dysplasia have distinctive histological

features and are less frequently associated with loss of MLH1 expression (13% and 5%,

respectively). Dysplasia not otherwise specified encompasses most cases and shows a

diverse range of morphological changes that do not fall into the other subgroups and are

frequently associated with loss of MLH1 expression (83%).56

MALIGNANT POLYP (see Appendix 8)

EPITHELIAL MISPLACEMENT (PSEUDOINVASION)

Epithelial misplacement is seen in 2-10% of pedunculated polyps. There is predilection for

the left colon (sigmoid), presumably due to increased intraluminal forces leading to polyp

torsion. As dysplastic epithelium is displaced into the submucosa, the pattern may be

misinterpreted as invasive carcinoma. It is important to be aware that invasive carcinoma

may coexist with pseudoinvasion.

Distinction from invasive carcinoma relies on assessment of:

1. Architecture

o Narrow gap in muscularis mucosae188

o Rounded appearance to focus

o Rounded appearance of glands within focus

2. Stromal change

o Lamina propria surrounds glands

o Dense fibrosis (not desmoplasia)

o Smooth muscle hypertrophy (and ‘fibromuscular’)

o Haemosiderin

o Chronic inflammation


Edition

o Extravasated mucin

o Either no epithelium or epithelium at periphery of the mucin. Epithelium floating

within mucin pools is indicative of adenocarcinoma.

3. Cytology

This is the same as the overlying epithelium and may incorporate some non dysplastic

epithelium. High grade nuclear abnormality should raise concern that the abnormality may

represent invasive adenocarcinoma.

Figure 26. Example of pseudoinvasion with herniation of the mucosa through

narrow gaps in the muscularis mucosae.

NEUROENDOCRINE TUMOURS

Neuroendocrine tumours are occasionally removed as polypoid lesions. Most are low grade

lesions (previously referred to as carcinoid tumour). There is an increasing recognition of

tumours with mixed adenoma/neuroendocrine features.189,190

WHO Classification:

• Neuroendocrine tumour NOS (‘carcinoid tumours’)

o EC cell ‘carcinoid’ tumours – right colon; like ileal tumours

o L cell ‘carcinoid’ tumour – rectum

o (Microcarcinoid in colorectal adenoma)

• Neuroendocrine carcinoma NOS (poorly differentiated)

101

o Seldom presents as a polyp amenable to local resection. May be small cell or

large cell type.

• Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN)

o Need 2 distinct recognisable malignant components (>30% glandular)191

o Seldom presents as a polyp amenable to local resection.

• Other specified malignant neoplasms of colon

POLYPOID LESIONS IN THE SETTING OF INFLAMMATORY BOWEL DISEASE189,192-195

Polyps arising in the setting of IBD may be inflammatory (‘inflammatory pseudopolyp’) or

neoplastic in nature. The neoplastic lesions may be any from the list provided above.

There is a predilection for hyperplastic polyp like lesions to develop in the setting of

longstanding IBD. The significance of this is unknown but is likely to be limited.196 The term

‘serrated epithelial change’ is widely used for this process. Broad serrated lesions (with or

without dysplasia) may also occur and have not been specifically studied but possibly

portend a significant risk for CRC.

Sporadic adenomas may arise in patients with IBD either in areas never involved by disease

or in the setting of active or quiescent disease.

Most attention has focused on polypoid dysplastic lesions in areas involved by colitis

(current or past). For polyps harbouring dysplasia, knowledge of the endoscopic polyp

appearance and most importantly, the adequacy of endoscopic resection is required.

Biopsies from the mucosa surrounding the polyp and/or the polyp stalk must also be

examined. These features are required to determine appropriate follow up as discussed

below.

Polypoid lesions are of 2 types: endoscopically resectable (adenoma like lesion) and non-

endoscopically resectable (non adenoma like lesion).The latter are usually non resectable

because of a variable combination of large size, margin irregularity, sessile areas and

ulceration. Endoscopically resectable polyps can be followed up as per sporadic adenoma

(which most in fact are) as long as no dysplasia is found in the surrounding mucosa,

elsewhere in the colon or in the polyp stalk (in the case of a pedunculated lesion).

Nonresectable polypoid dysplastic lesions are associated with high risk (>40%) of

identifying invasive adenocarcinoma in a subsequent resection specimen and hence a

colectomy is typically performed.195,197

Because the reporting pathologist may not be made aware of the appearance and resection

status of a dysplastic lesion in a setting of inflammatory bowel disease, the following

comment should be applied to such lesions:

‘Dysplastic lesions arising in an area affected by inflammatory bowel disease are a

heterogeneous group. Many are adenoma – like, and are not progressive. Conservative

management may be warranted if the following conditions are met: Macroscopically

adenoma – like in appearance; excised with clear margins; no flat dysplasia of surrounding

mucosa and/or polyp stalk. If these criteria are not met, the lesion should be regarded as

having a significant risk for associated or subsequent colorectal carcinoma.’


Edition

While many polypoidal dysplastic lesion arising in chronic inflammatory bowel disease have

features similar to conventional adenoma, non conventional patterns are increasingly being

recognised. In a recent study six morphologic patterns were recognized. Hypermucinous

dysplasia (n = 15; 42%) presented as either a 'pure type' (n = 5; 14%) or a 'mixed type'

with either conventional or another nonconventional subtype (n = 10; 28%). Serrated

lesions, as a group, were equally common (n = 15; 42%) and included three variants:

traditional serrated adenoma-like (n = 10; 28%), sessile serrated lesion-like (n = 1; 3%),

and serrated lesion, not otherwise specified (n = 4; 11%). Dysplastic lesions with increased

Paneth cell differentiation (n = 4; 11%) and goblet cell deficient dysplasia (n = 2; 6%)

were rare.198 It remains to be determined to what extent these morphological patterns

affect the prognosis of the lesion.

103

Appendix 6 Polyposis syndromes

A number of inherited genetic defects can give rise to syndromes characterised, at least in

part, by the formation of multiple polyps within the large bowel. Increasingly, these

syndromes are becoming defined by the inherited genetic defect, and there is often

considerable overlap in phenotypic expression between syndromes, making morphological

distinctions challenging. The notes below provide accepted phenotypic definitions, though

these may change as the underlying genetics become better understood.

Pathologists should make mention of the possibility of an underlying genetic syndrome

whenever multiple polyps are encountered. Often the nature of the polyps indicates the

most likely syndrome, however, definitive diagnosis requires formal genetic screening which

is accomplished by next generation sequencing panels. Pathologists should include a

comment in reports to the effect of - ‘the number and/or combination of polyp types

encountered in this patient raise the possibility of an underlying genetic syndrome. Referral

to a genetics service should be considered’.

In all polyposis syndromes, the polyp count is cumulative over time and the

pathologist should also refer to previous patient specimens reported in their

laboratory.

Hyperplastic (serrated) polyposis syndrome

While it remains a poorly understood syndrome with no known biological basis, the WHO

has revised the previous diagnostic criteria for hyperplastic (serrated) polyposis syndrome

and simplified these into either of two diagnostic requirements:

1) five or more serrated polyps proximal to the rectum with two or more being

larger than 10 mm in diameter and all being at least 5 mm in size;

2) more than 20 serrated polyps of any size distributed throughout the large bowel,

with at least five being proximal to the rectum.

Familial adenomatous polyposis (FAP)

Affected individuals usually develop hundreds to thousands of adenomatous polyps of the

colon and rectum, a small proportion of which will progress to colorectal carcinoma if not

surgically treated. Gardner syndrome is a variant of FAP in which desmoid tumours,

osteomas, and other neoplasms occur together with multiple adenomas of the colon and

rectum. See http://omim.org/entry/175100.

Peutz Jegher syndrome (PJS)199

One of the following:

• Two or more PJS polyps of the small intestine.

• One hamartomatous polyp in a patient who has a characteristic pigmentation of

the mouth, lips, nose, eyes, genitalia, or fingers.

• One hamartomatous polyp in a patient who has a family history of PJS

http://omim.org/entry/175100


Edition

See http://omim.org/entry/175200

Juvenile polyposis syndrome199

One of the following:

• At least three–five juvenile polyps of the colon.

• Multiple juvenile polyps found throughout the gastrointestinal tract.

• Any number of juvenile polyps in an individual with a family history of JPS.


Cowden syndrome (PTEN hamartoma tumour syndrome)199 International consortium

criteria have been established and are weighted heavily to the presence of the characteristic

mucocutaneous lesions.

Gastrointestinal tract (GIT) manifestations occur in 60% of Cowden Syndrome patients and

comprise the following lesions:

i. Hamartomatous polyps

• <10-20 mm

• lamina propria fibrosis

• gland/crypt elongation and dilatation

• found throughout GIT

ii. Nodular lymphoid hyperplasia

iii. Adipose tissue in the lamina propria/true lipomas

iv. Ganglioneuromas (ganglioneuromatous hamartoma)

v. Glycogenic acanthosis in the oesophagus

vi. Probably colorectal carcinoma (not universally accepted)


MUTYH-associated polyposis (MAP)

A cumulative lifetime count of >15 adenomatous polyps (or 10 adenomatous polyps before

age 50 years) has been suggested a threshold for genetic testing200: Serrated polyps may

co-exist with adenomatous polyps in MAP. Extra intestinal manifestations identical to those

of familial adenomatous polyposis can occur.




105


Hereditary Mixed Polyposis syndrome (HMPS)201,202

An autosomal dominant condition characterised by presence of mixed hyperplastic-

adenomatous polyps as well as conventional adenomatous polyps (up to 100) throughout

the colon and rectum.


Many polyposis syndromes have a genetic basis. The table below highlights the features of

familial syndromes associated with colorectal polyps.

Table 3. Familial syndromes associated with increased risk of colorectal cancer203

Syndrome Gene responsible Inheritance Typical phenotype Extracolonic

manifestations

Lynch syndrome*

EPCAM deletion leading to epigenetic silencing of MSH2 , MLH1, MSH6 or PMS2

Autosomal dominant

Early onset colorectal cancer, particularly in the proximal colon The incidence of adenomas is not high but those that do arise have a high risk of rapidly progressing to malignancy; Cancers display microsatellite instability

Endometrial, ovarian, gastric, pancreatic, urothelial, renal pelvic, small intestine, biliary tract, brain, sebaceous gland adenomas and keratoacanthomas

Familial adenomatous polyposis (FAP)*

APC Autosomal dominant

> 100 adenomas Duodenal, gastric, desmoid, brain, thyroid, hepatoblastoma

Attenuated FAP (AFAP)

APC Autosomal dominant

> 10 adenomas before age 30 years or 20–100 adenomas

Duodenal, gastric

MUTYH-associated polyposis

MUTYH Autosomal recessive

Usually 20–100 adenomas but may have > 100

Duodenal, gastric

Polymerase proofreading-associated polyposis (PPAP)

POLD1 or POLE Autosomal dominant

10–100 adenomas and variable number of serrated polyps

Endometrial

NTHL1-associated polyposis (NAP)

NTHL1 Autosomal recessive

8–50 adenomatous polyps

Endometrial

Peutz-Jeghers syndrome

STK11 Autosomal dominant

Histologically characteristic hamartomatous

Upper gastrointestinal and small intestine, breast, gynaecological,




Edition

polyps throughout gastrointestinal tract and mucocutaneous pigmentation

pancreas

Juvenile polyposis syndrome

SMAD4 or BMPR1A Autosomal dominant

Histologically characteristic hamartomatous polyps throughout gastrointestinal tract; polyps of mixed histology may also be present

Upper gastrointestinal and small intestine but no evidence of excess risk for extra-gastrointestinal cancers

Serrated polyposis syndrome

Unknown Unclear and low penetrance

At least 5 serrated polyps proximal to the sigmoid with ≥ 2 of these > 10 mm or > 20 serrated polyps of any size but distributed throughout the colon#

Nil known

Cowden syndrome

PTEN Autosomal dominant

Some patients develop adenomas and hyperplastic polyps in addition to colonic hamartomas. There is no evidence that all families with PTEN are at high risk of bowel cancer. Families with a history of colorectal cancer should follow screening guidelines based on their family history.

Breast, endometrial, thyroid, renal, skin lesions (trichilemmoma, papilloma). Cowden Syndrome is often associated with macrocephaly.

*Note on nomenclature Historically, eponymous names were used to refer to specific clinical phenotypes in an individual patient, but now that the genetic basis of FAP and LS is known they should be avoided.

• Gardner Syndrome refers to classic FAP where intestinal polyposis is associated with extra-intestinal manifestations including osteomas (typically of the skull), fibromas, epidermoid cysts and desmoid tumours.

• Muir-Torre syndrome refers to Lynch syndrome associated with sebaceous gland tumours such as sebaceous epitheliomas, sebaceous adenomas, sebaceous carcinomas and keratoacanthomas.

• Turcot syndrome (brain tumour – polyposis syndrome) refers to the occurrence of multiple colorectal adenomas and a primary brain tumour. It can also be associated with cafe-au-lait spots. Turcot syndrome is associated with at least 2 distinct types of germline defects:

o Type I is associated with a mutation in one of the mismatch repair genes and gliomas (predominantly astrocytomas) and accounts for about one third of cases.

o Type 2, which accounts for two thirds of cases, is associated with a mutation in the APC gene (FAP variant) and medulloblastoma is the most common type of brain tumour.

# any number of serrated polyps proximal to the sigmoid colon in an individual who has a first-degree relative with serrated

polyposis syndrome

Reproduced with permission from Leggett B, Poplawski N, Pachter NP, Rosty C, Norton I, Wright C, Win AK, Macrae F, Cancer Council Australia Colorectal Cancer Guidelines Working Party. [Version URL: https://wiki.cancer.org.au/australiawiki/index.php?oldid=173052, cited 2020 Apr 26]. Available from https://wiki.cancer.org.au/australia/Guidelines:Colorectal_cancer/High-risk_familial_syndromes.203

107

Appendix 7 Colonoscopy surveillance guidelines

The general principles of surveillance are to ensure that the risk for CRC is matched by

the pathology findings. The new NHMRC guidelines30 provide for considerable detail to

allow appropriated risk stratification of patients. The role of the pathologist is more

considerable than at any previous time.

The basic features are combinations of

1) Polyp type

2) Presence of high grade dysplasia (conventional adenoma) and

any dysplasia (serrated lesions)

3) Number of polyps

4) Size of adenoma (10 mm being the cut off)

5) Age of patient

6) Number of the colonoscopy

Table 4. Summary of recommendations for first surveillance intervals

following removal of conventional adenomas only

Surveillance recommendations should be made after the colon has been cleared of all significant neoplasia, once histology is known and in the context of individualised assessment of benefit to the patient. Villosity is defined in the First surveillance intervals following removal of high-risk conventional adenoma section.

Polyp/adenoma size as per the endoscopist documentation should be used for determining surveillance intervals.

a Consider colonoscopy at an interval of 5 years (Y) in low risk individuals with clinical evidence of the metabolic syndrome b If a significant family history of CRC is present, use screening recommendation if the interval is shorter than 10Y (see the Clinical practice guidelines for the prevention, early detection and management of colorectal cancer) c Return to the NBCSP with FOBT after 4 years is also an appropriate option and should be discussed with the patient d Complete excision of lesions is required before surveillance intervals can be recommended

https://wiki.cancer.org.au/australia/Clinical_question:What_should_be_the_surveillance_colonoscopy_for_patients_at_high_risk%3F

https://wiki.cancer.org.au/australia/Clinical_question:What_should_be_the_surveillance_colonoscopy_for_patients_at_high_risk%3F

https://wiki.cancer.org.au/australia/Guidelines:Colorectal_cancer/Risk_and_screening_based_on_family_history

https://wiki.cancer.org.au/australia/Guidelines:Colorectal_cancer/Risk_and_screening_based_on_family_history


Edition

e Adenomas ≥20 mm are more likely to be excised piecemeal and should be considered under the large and laterally spreading adenomas section (see section on Large and laterally spreading adenomas)

Reproduced with permission from Cancer Council Australia Surveillance

Colonoscopy Guidelines Working Party. Clinical practice guidelines for surveillance

colonoscopy. Sydney: Cancer Council Australia. [Version URL:

https://wiki.cancer.org.au/australiawiki/index.php?oldid=208067, cited 2020 Jul 6].

Available from:

https://wiki.cancer.org.au/australia/Guidelines:Colorectal_cancer/Colonoscopy_sur

veillance.

https://wiki.cancer.org.au/australia/Clinical_question:What_should_be_the_surveillance_colonoscopy_following_sessile_and_laterally_spreading_adenomas%3F

https://wiki.cancer.org.au/australia/Clinical_question:What_should_be_the_surveillance_colonoscopy_following_sessile_and_laterally_spreading_adenomas%3F

109

Table 5. Summary of recommendations for first surveillance intervals

following removal of clinically significant serrated polyps (± conventional

adenomas)

Polyp/adenoma size as per the endoscopist documentation should be used for determining surveillance intervals. Clinically significant serrated polyp: sessile serrated adenoma, traditional serrated adenoma, large (≥10mm) hyperplastic polyp. Low-risk conventional adenoma: small (<10 mm) tubular adenoma without high-grade dysplasia. High-risk conventional adenoma: size ≥10 mm, high-grade dysplasia or villosity.

TSA: traditional serrated adenoma; Y: years.

Reproduced with permission from Cancer Council Australia Surveillance

Colonoscopy Guidelines Working Party. Clinical practice guidelines for surveillance

colonoscopy. Sydney: Cancer Council Australia. [Version URL:

https://wiki.cancer.org.au/australiawiki/index.php?oldid=208067, cited 2020 Jul 6].

Available from:

https://wiki.cancer.org.au/australia/Guidelines:Colorectal_cancer/Colonoscopy_sur

veillance.


Edition

Appendix 8 Risk of residual disease following malignancy

Endoscopically removed malignant polyps may be of two types:

1) Invasive carcinoma arising from a pre-existing adenoma or

2) Polypoid carcinoma without a pre-existing adenoma evident.

Features determining risk for locally recurrent or metastatic disease are the same in

both situations. These factors can be considered as either qualitative (poor

differentiation, vascular invasion, tumour budding) or quantitative (Haggitt level, depth

of invasion, width of invasive tumour). The number of qualitative prognostic factors

present in a malignant polyp appears to be synergistic for the risk of adverse outcome.

In the Ueno paper (ref 33) the risk for lymph node metastases was 0.7% if none were

present, 20.7% if one adverse factor was present and 36.4% if ≥2 factors were

present.

Several studies have identified the rectum (particularly the distal one third) as a site of

increased adverse behaviour with increased lymph node metastatic rate (one third) and

increased risk of recurrent or residual disease (5-28%).118,204-206 The reason for this

increased adverse behaviour is unclear.

A more aggressive treatment approach has been advocated for a distal rectal site.205

The following 3 tables have been developed as a result of meta-analyses of the

published data and provide a useful clinical guidance that can be added as a comment

to the histopathological report. The ultimate decision for further surgery is based on a

weighted assessment of clinical and pathological aspects of the individual case.

Table 6. Scoring the risk of residual disease following resection of a malignant

polyp.

Criteria Degree of Risk

Resection margin <1 mm* ++++

Resection margin 1-2 mm* +

Pedunculated polyp with invasion ≥3 mm below the Haggitt line

+++

Sessile invasion ≥2mm ++

Poor differentiation +++

Tumour budding +

Lymphovascular invasion +++

Combination of ≥2 of the above +++ to ++++

111

* Risk for residual carcinoma at the polypectomy site

Table 7. Risk stratification based on sum of risk factors

Criteria are based on histological description of endoscopically resected malignant polyp

weighted for prognostic significance of each risk factor. Where more than one risk

factor is present, the degree of risk is added together to give a total risk score.207

Table 8. Risk features in endoscopically resected malignant polyps

Feature Prevalence of

feature

Rate of lymph

node

metastasis*

Sessile polyp depth

≥2mm

~60% ~5%

Pedunculated polyp

with stalk invasion

≥3mm

<10% ~10%

Vascular invasion ~20% ~10%

Poor differentiation ~10% ~10%

Tumour budding

(BD2/3)

~10-20% ~5%

Resection margin

involvement+

~30% ~5%

• *Overall rate observed in studies with this feature reported. Does not account

for the concurrent presence of other risk factors

• + Margin directly involved or undefined

Total score Grade of Risk

Current estimate of potential % risk of

residual cancer

Recommended course of action to be discussed with patient

0 Very low <3% Routine follow up

+ Low <5% Assess other factors - Careful follow up

++ Medium 5-10% Discussion of risks/benefit of surgery or follow up with patient

+++ High 8-15% Discuss risks with patient – recommend surgery

++++ (or more) Very high >20% Recommend surgery unless patient unfit


Edition

Appendix 9 Practice audits

Structured reporting for polypectomies and local resections of the colorectum present

an ideal opportunity to perform practice audits. This is because structured pathology

reports are more likely to produce consistent data on the expected range of positive

findings. High frequency polypectomies are ideal for performing practice audits.

In some jurisdictions58,208 the following parameters have been helpful for practice audit

and cross practice correlation:

Table 9. Incidence of polyps in a study population using WHO diagnostic

criteria

Polyp type Incidence in patients with

at least 1 polyp

identified*

Tubular adenoma with low grade dysplasia 55%

Tubular adenoma with high grade dysplasia 1%

Tubulovillous adenoma with low grade dysplasia 10%

Tubulovillous adenoma with high grade dysplasia 1.5%

Villous adenoma with low grade dysplasia 0.1%

Villous adenoma with high grade dysplasia 0.1%

Hyperplastic polyp 40%

Sessile serrated lesion 20%

Sessile serrated lesion with dysplasia 1%

Traditional serrated adenoma 1%

Adenocarcinoma arising in a polyp 0.5%

Audit data from Envoi pathology. Different patient populations may yield different data.

113

Table 10. Number, size and distribution of polyps208

Reproduced with permission from Bettington M, Walker N, Rahman T, Vandeleur A,

Whitehall V, Leggett B and Croese J (2017). High prevalence of sessile serrated

adenomas in contemporary outpatient colonoscopy practice. Intern Med J 47(3):318-

323.208


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