Coloretal - Iccr

COLORECTAL CANCER
STRUCTURED REPORTING
PROTOCOL
(4th Edition 2020)
Incorporating the:
International Collaboration on Cancer Reporting (ICCR)
Colorectal cancer Dataset
www.ICCR-Cancer.org
Core Document versions:
• AJCC Cancer Staging Manual 8th edition, American Joint Committee on Cancer,
20161
• World Health Organization Classification of Tumours, Digestive System Tumours.
5th Edition, 20192
• ICCR dataset: Colorectal cancer 1st edition v1.0
2 Colorectal Cancer Structured Reporting Protocol 4th edition

ISBN: 978-1-76081-424-3
Publications number (SHPN): (CI) 200281
Online copyright
© RCPA 2020
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wording of the Protocol including any Standards, Guidelines, commentary, tables
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References and acknowledgments must be maintained in any reproduction or copy
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o The wording of the Standards may not be altered in any way and must be
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o Guidelines are optional and those which are deemed not applicable may be
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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, 4th Edition (Version 4.0)

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. Each protocol includes “standards” and “guidelines” which are
indicators of ‘minimum requirements’ and ‘recommendations’, which reflect the opinion
of the relevant expert authoring groups. 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
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Contents
Scope ................................................................................................................. 6
Abbreviations ..................................................................................................... 7
Definitions.......................................................................................................... 8
Introduction ..................................................................................................... 11
Authority and development .............................................................................. 14
1 Pre-analytical ......................................................................................... 18
2 Specimen handling and macroscopic findings ........................................ 20
3 Microscopic findings ............................................................................... 33
4 Ancillary findings ................................................................................... 52
5 Synthesis and overview ......................................................................... 61
6 Structured checklist ............................................................................... 64
7 Formatting of pathology reports ............................................................ 82
Appendix 1 Pathology request information and surgical handling

procedures ............................................................................................. 83
Appendix 2 Guidelines for formatting of a pathology report ......................... 89
Appendix 3 Example of a pathology report ................................................... 90
Appendix 4 WHO Classificationa of tumours of the colon and rectum 5th

edition ................................................................................................... 92
Appendix 5 Histological tumour types – example representative

images ................................................................................................... 94
Appendix 6 Regression grading systems ...................................................... 99
Appendix 6 Practice audits ......................................................................... 100
References ..................................................................................................... 101

Scope
This protocol contains standards and guidelines for the preparation of structured reports
for surgical resection specimens from patients with primary carcinomas of the colon and
rectum, including neuroendocrine carcinomas (NECs) and mixed neuroendocrine-non-
neuroendocrine neoplasms (MiNENs). It is not intended to apply to tumours of the
appendix, small bowel and anus. Local excisions of colorectal carcinomas
(polypectomies) are dealt with in a separate protocol. Neuroendocrine tumours are to be
included in a separate protocol.
Synchronous primary tumours should have separate protocols recorded for each tumour.
Structured reporting aims to improve the completeness and usability of pathology

reports for clinicians and improve decision support for cancer treatment. The protocol
provides the framework for the reporting of any colorectal cancer, whether as a
minimum data set or fully comprehensive report.
Abbreviations
AGPS Australasian Gastrointestinal Pathology Society
AJCC American Joint Committee on Cancer
CRC Colorectal cancer
CRM Circumferential resection margin
HNPCC Hereditary nonpolyposis colorectal cancer
ICCR International Collaboration on Cancer Reporting
LIS Laboratory information system
LN Lymph node
MiNEN Mixed neuroendocrine-non-neuroendocrine neoplasm
MMR Mismatch repair
MMRD Mismatch repair deficient
MRI Magnetic resonance imaging
MSI Microsatellite instability
NCCN National Comprehensive Cancer Network
NEC Neuroendocrine carcinoma
NET Neuroendocrine tumour
NHMRC National Health and Medical Research Council
PBS Pharmaceutical Benefits Scheme
R Residual tumour status
RCPA Royal College of Pathologists of Australasia
TME Total mesorectal excision
TNM Tumour-node-metastasis
UICC Union for International Cancer Control
WHO World Health Organization

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 Patient information required to inform pathological assessment,

information usually provided with the specimen request form. Also referred to
as ‘pretest 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
• clearly 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 General commentary is text that is not associated with a specific

commentary 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).

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.3 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 Measurements, or assessment of a biopsy specimen made by the

findings unaided eye.
Microscopic In this document, the term ‘microscopic findings’ refers to histo-

findings 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 evidence3 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).

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 preexisting

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.

Introduction
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.4 Recent
advances have been made in the biological understanding of this disease, which have
resulted in new surgical, chemotherapeutic and radiotherapeutic strategies.
Pathological reporting
Pathological reporting of resection specimens for colorectal cancer provides important
information both for the clinical management of the affected patient and for the
evaluation of health care systems as a whole. For the patient, it confirms the diagnosis
and describes the variables that will affect prognosis, which will inform future clinical
management. For health care evaluation, pathology reports provide information for
cancer registries and clinical audit, for ensuring comparability of patient groups in clinical
trials, and for assessing the accuracy of new diagnostic tests and preoperative staging
techniques. In order to fulfil all of these functions, the information contained within the
pathology report must be accurate and complete.
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 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
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 developed5,6 around the world. Both the United Kingdom,7
and United States8 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
Australasian (RCPA), United States College of American Pathologists (US CAP) and Royal
College of Pathologists United Kingdom (RCPath UK) and the 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 capture9-12 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 cancer 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 cancers.
ICCR dataset elements for colorectal cancer 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.
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 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
• Guidelines for Authors of Structured Cancer Pathology Reporting Protocols, Royal
College of Pathologists of Australasia, 200913
• The Pathology Request-Test-Report Cycle — Guidelines for Requesters and Pathology
Provider28
• World Health Organization Classification of Tumours, Digestive System Tumours. 5th
Edition, 20192
• AJCC Cancer Staging Manual 8th edition, American Joint Committee on Cancer, 20161
• ICCR dataset: Colorectal cancer 1st edition v1.0
Changes since last edition

Inclusion of ICCR Core and Non-core elements.
V4.2 - S3.04 Lymphovascular invasion was made multi select.

Authority and development
This section provides information about the process undertaken to develop this
protocol.
This 4th edition of the protocol is an amalgam of three separate processes:
1. This protocol is based on the ICCR dataset – Colorectal cancer 1st

edition v1.0. All ICCR elements from this dataset, both core
(mandatory) and non-core (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 – 4th edition (2020)
Dr Ian Brown (Lead author 2nd, 3rd and 4th editions), Pathologist
Prof Priyanthi Kumarasinghe (GI 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-3rd editions
Dr Ian Brown (Chair and lead author 2nd, 3rd and 4th editions), Pathologist
A/Prof Robert Eckstein (Chair and lead author 1st edition), Pathologist
Conjoint Prof Stephen Ackland, Medical Oncologist
A/Prof David Ellis, Pathologist
14 Colorectal Cancer Structured Reporting Protocol 4th Edition

Prof Nicholas Hawkins, Pathologist
Dr Sian Hicks, Medical Scientist
Dr Andrew Hunter, Colorectal Surgeon
Dr Andrew Kneebone, Radiation Oncologist
Dr Andrew Ruszkiewicz, Pathologist
Dr Mee Ling Yeong, Pathologist
Editorial manager
Christina Selinger, PhD, Royal College of Pathologists of Australasia
Acknowledgements
The Colorectal expert committee wish to thank all the pathologists and clinicians
who contributed to the discussion around this document.

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 Gastrointestinal Pathology Society (AGPS)
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)

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 process set out in Guidelines for
Authors of Structured Cancer Pathology Reporting Protocols.13
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.

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 colorectal cancer 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.14 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 Individual Healthcare Identifier (IHI)
(Australia) or the National Health 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.
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.

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 imaging
 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
 Images of the gross specimen showing the overall conformation of the tumour
and, especially in the case of rectal resections, images showing the relation of
the tumour to the resection margins, are desirable, and useful for
multidisciplinary meetings.
Specimen handling
 The specimen must be handled in a systematic and thorough fashion to
ensure completeness and accuracy of pathological data.
• Specimen reception: Specimen fixation, macroscopic assessment and

sampling for histology are crucial. The aim is to make a diagnosis, assess
resection status and glean all other prognostic information.
The opened, cleaned specimen should be fixed, at least overnight, in an
adequate volume of formalin.
Despite the pressure by clinicians on the pathologist for rapid turnaround,
adequate fixation and processing of colorectal specimens is highly
important. Full fixation facilitates obtaining thin transverse slices through
the tumour and it has also been shown to increase lymph node yield.
Slices can be made into mesocolic adipose tissue to aid fixation.
In addition, the experience of the person cutting up and reporting the
specimen, is probably an important determinant of quality pathology,
however further studies in this area are warranted.

• Specimen inspection: The specimen needs to be thoroughly examined
before opening. Areas of possible serosal involvement - often located at
the junction of the mesenteric reflection on the antimesenteric portion of
the bowel - possible distant tumour and lymph node deposits should be
identified. Serosal nodules away from the primary tumour are regarded
as distant metastases in the TNM classification. Assessment of tumour
perforation is best made in the freshly received and unopened specimen.
• Tumour inspection: There are two recommended methods of opening a

colon resection specimen.
The first method involves opening the specimen with scissors anteriorly
up and down to the level of the tumour, which is left unopened. A wick of
formalin soaked paper or gauze is then inserted into the unopened lumen
to aid exposure of the tumour to the fixative. The entire specimen is then
placed in formalin for complete fixation.
The second method involves opening the specimen along its length. If the
tumour is not circumferential, then the specimen should be opened
through an area not involved by tumour. If the tumour is circumferential
then it will have to be cut through at some point, but this should avoid
areas of possible serosal or nonperitonealised resection margin
involvement. Again, the entire specimen should then be placed in an
adequate amount of formalin for complete fixation.
For rectal tumours, leaving the tumour intact and bread-slicing it when
fixed is recommended. This method facilitates assessment of the very
important nonperitonealised resection margin. The relationship of the
tumour, nodes, or extramural tumour deposits to the nonperitonealised
resection margin must be assessed and measured (see S2.04 below).
This facilitates correlation with preoperative imaging and subsequent
microscopic examination.
• Marking of resection margins: The nonperitonealised resection margin

of the rectum or colon needs to be inked. Other cut surgical resection
margins can be inked if the tumour is nearby.
The serosal surface is not a resection margin and is therefore not inked.
Inking of the serosa may result in misinterpretation of serosal surface
involvement as representing margin involvement. It can also mask the
presence of tumour cells on the serosal surface.
• Block selection: The tumour needs to be sliced transversely at 3–4 mm

intervals and the tumour slices laid out sequentially. Block selection must
target the prognostic questions that need to be answered. It is not
possible to give an absolute number. Sufficient blocks (generally at least
4) should be taken to enable the pathologist to fully assess all the
necessary parameters for staging and prognosis. The likelihood of
identifying prognostically useful features, such as extramural venous
invasion and serosal penetration, increases with the number of blocks
taken.
Select blocks that show the greatest depth of tumour invasion. Select
blocks that show tumour close to or at a serosal surface. Serosal
involvement is especially prone to occur at or adjacent to peritoneal
reflections, especially in the clefts adjacent to the bowel wall, and should
be suspected in any areas of serosa that appear granular, dull or
haemorrhagic.

Rectal tumours previously treated with neoadjuvant therapy show
varying degrees of regression, altering their appearance, and tumour
may be difficult to recognise grossly. Blocking of the whole area of
abnormality may be required to confirm the presence of tumour, and to
evaluate tumour regression grade.
Tumour at a longitudinal margin occurs only very rarely and several
studies have questioned the necessity of sampling the cut end margins. If
the tumour is >30 mm from the cut end it is not always necessary to
examine the margin microscopically (see below S2.07). However, it is
often useful to have normal tissue for control purposes and uninvolved
margins can provide this. It is also useful to examine for potential
background disease, such as inflammatory bowel disease, or unrelated
disease processes, such as lymphocytic or collagenous colitis.
The relationship of rectal tumours to the circumferential margin must be
assessed with appropriate blocks (see S2.05). Most of the colon has a
long mesentery, so the assessment of this resection margin is rarely an
issue. However, the cut margin of the mesentery is a surgical margin and
if the tumour is advanced, it may potentially be involved, either by direct
spread, or by involved nodes, at its apex. The caecum and the proximal
ascending colon do not have a mesentery and posteriorly have a
nonperitonealised bare area of variable size which is potentially an area
of surgical margin involvement, especially in tumours arising from the
posterior wall or in circumferential tumours. Involvement of the
nonperitonealised resection margin in tumours at these sites should be
sought and recorded when present.
Lymph node sampling is described below (see below).
Sampling should be performed on any background abnormalities, and in
particular polyps or inflammatory bowel disease.
If there is tumour perforation, then a block should be taken for
histological record.

All regional lymph nodes must be harvested from the specimen and
examined histologically.
• The finding of positive lymph nodes is a major determinant of whether a

patient receives adjuvant therapy. The probability of finding a positive
lymph node increases with the number of nodes found, although this
probability curve flattens out after finding 12–15 nodes. The number of
nodes present depends on a number of factors, including the size of the
specimen, the amount of mesenteric tissue present and whether the
patient has received neo-adjuvant therapy. Whilst for purposes of audit
an average of 12 lymph nodes should be found, lesser numbers of nodes
are present in individual cases.
Pending further evidence, it is prudent to approach lymph node retrieval
as follows
- all identifiable lymph nodes should be retrieved and examined
- if twelve or fewer lymph nodes are found then the specimen
should be re-examined for lymph nodes as a longer period of
fixation in formalin can improve lymph node detection; this is
particularly important in stage II (pN0) tumours
- alternative fixatives and fat clearance methods can be used to
increase lymph node yield but the evidence is most robust in

studies where the yield was low to begin with15
- the greatest yield for positive lymph nodes in a second search is
the region of the tumour bed16
- if 12 or fewer lymph nodes are retrieved a note should be made in
the pathology report, describing how this has been addressed
- assessment of a laboratories average lymph node yield can be
used as a quality indicator but may reflect a particular surgical or
patient cohort, rather than a particular laboratories practice
• Lymph nodes are difficult to find in a poorly fixed specimen. The lymph
node bearing tissue needs to be methodically palpated and sliced at small
intervals. All macroscopically uninvolved nodes need to be embedded
completely. Macroscopically involved nodes require only 1 block for
confirmation. To aid in accurate microscopic examination, strip the lymph
nodes of fat; nodes of dissimilar size should not be embedded in the
same block.
In the case of extended or total colectomy specimens, it may not be
necessary to examine all non regional lymph nodes. All lymph nodes
received in the form of separately identified specimens must be examined
microscopically.
• Any lymph nodes lying close to the nonperitonealised resection margin

need to be sampled in continuity with that margin. If there is tumour in
any of the lymph nodes then it is the measurement from the involved
lymph node to the nonperitonealised resection margin, if it is closer,
rather than from the primary tumour, that is important. This is also true
for any isolated tumour deposit in the perirectal or pericolic fat.
• It is good practice that the apical lymph node should be identified as it is

commonly used in clinical staging.
• In the case of two synchronous primary carcinomas, where appropriate,

lymph nodes need to be assigned and assessed for each cancer
separately.
 A block containing tumour should be nominated for further ancillary studies.
Macroscopic findings
S2.01 The labelling of the specimen(s) must be clearly recorded.
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 or any other
relevant gastrointestinal disorder should be recorded and
provided to the pathologist, as awareness of such underlying
conditions may influence both specimen sampling and

histological interpretation.
CS2.02b Given implications for staging and interpretation of

morphological features related to the primary tumour, it is
important that clinical information is provided to the
pathologist regarding the application of any neoadjuvant
therapy, and details of such therapy, for example
radiotherapy and/or chemotherapy, duration and timing in
relation to surgery.
S2.03 The operative procedure must be recorded.
CS2.03a Information regarding the nature of the operative procedure

should be provided, with any refinements as necessary, for
example the attempted dissection plane in an
abdominoperineal resection. Should the operative specimen
include any tissue or organ not typically submitted within
that specimen type, for example en bloc resection of a
segment of intestine or abdominal wall connective tissue,
this should be clearly indicated. Inclusion of the peritoneal
reflection within an anterior resection specimen distinguishes
a low anterior resection from a high anterior resection.
S2.04 The specimen length must be recorded.
CS2.04a This and all other measurements in this protocol should be

made in millimetres unless otherwise stated.
S2.05 The site of the tumour must be recorded.
CS2.05a If multiple primary tumours are present, separate protocols

should be used to record tumour site and all following
elements for each primary tumour. Determination of tumour
site is based on clinical information provided on the
pathology request form combined with specimen assessment
by the pathologist. Any significant discrepancy should be
discussed with the clinical team and the tumour site clearly
documented by specimen photography. Recording the
anatomical site of tumour allows correlation with prior
endoscopic and radiological investigations, indicates whether
or not a nonperitonealised margin is likely to be present and
defines the presence of regional versus non-regional lymph
nodes. In particular, distinction of colonic from rectal origin
is of importance, given different biologies, clinical features
and management. Every effort should be made, therefore, to
accurately classify a tumour as colonic or rectal in origin.
If a tumour straddles two sites, the site with the greatest
tumour bulk should be recorded. The three taeniae coli of
the sigmoid colon fuse to form the circumferential
longitudinal muscle of the rectal wall, marking the
rectosigmoid boundary. If distinction between the sigmoid
colon and rectum is not possible by pathological assessment,
for example owing to advanced tumour stage obliterating
anatomical landmarks, the tumour site can be recorded
based on clinical information available.

Classification as rectosigmoid should be reserved for cases in
which an accurate determination between rectum and
sigmoid cannot be made by pathological assessment and
clinical information regarding site is not available.
CS2.05b The determination of the site is based on the assessment by

the pathologist and the information provided by the surgeon
on the request form. The anatomical site of the tumour is
relevant for the following reasons:
• It provides correlation with previous investigations.
• It indicates whether a nonperitonealised (circumferential)
margin is likely to be present.
• The natural history and treatment of rectal cancer differs
significantly from colonic cancer.
• It defines the presence of regional lymph nodes versus
non-regional lymph nodes.
CS2.05c Strictly the rectum is that part of the large bowel distal to
the sigmoid colon and its upper limit is indicated by the end
of the sigmoid mesocolon. Standard anatomical texts put
this at the level of the 3rd sacral vertebra17 but it is
generally agreed by surgeons that the rectum starts at the
sacral promontory.18 It was agreed by an international
expert advisory committee13 that any tumour whose distal
margin is seen at 15 cm or less from the anal verge using a
rigid sigmoidoscope should be classified as rectal. The
pathologist can identify the upper end of the rectum as the
point where the colonic taeniae coli merge to form a single
external muscle layer.
S2.06 The maximum tumour diameter must be recorded.
CS2.06a No prognostic significance has been attached to tumour size

for colorectal cancer and size does not directly influence
tumour staging. Recording of size, based on a combination
of macroscopic and microscopic assessment, allows
correlation with preoperative imaging, endoscopic and
surgical assessments. Assessment of tumour dimensions
should, if possible, exclude any inflammatory component or
preinvasive lesion, a separate measurement of which may be
provided.
S2.07 The distance of the tumour to the nearer proximal or distal ‘cut
end’ margin must be recorded.
CS2.07a This is the measurement from the nearer cut end of the
specimen and not the nonperitonealised (circumferential,
radial) margin.
CS2.07b Tumour at a longitudinal margin has always been considered

a poor prognostic feature but it occurs very rarely.19,20 The
necessity of sampling this margin has therefore been
questioned.21-23 It is essential to sample this margin and
examine it histologically if the tumour is close to the margin
(within 30 mm), or if the tumour is found by histology to

have an exceptionally infiltrative growth pattern, to show
extensive blood vascular or lymphatic permeation, or to be a
signet-ring, small cell or undifferentiated carcinoma.23
CS2.07c If included, doughnuts must be embedded for histological

examination.
CS2.07d The difficulty presented by staples is recognised. In this

situation, it is important for blocks taken immediately
adjacent to the line of staples along the plane of the staple
line to be examined.
S2.08 The distance of the tumour to the circumferential margin must

be recorded.
CS2.08a This is the measurement to the nonperitonealised (i.e. the

circumferential or radial) margin.
CS2.08b This measurement is useful for comparison with and

validation of the microscopic measurement.
CS2.08c It is not only the continuous spread of the primary tumour

that is important for this measurement, but also
discontinuous spread in the form of lymph node metastases,
extramural deposits, and tumour in vessels and lymphatics.
Even if the main tumour appears ‘well clear’ of this margin,
it is important to block the tissue between the nearest
tumour edge and the nonperitonealised resection margin to
ensure picking up any discontinuous areas of spread. It may
be that the tissue has to be embedded in two or more
sequential blocks but this margin must be well sampled.
CS2.08d This combined with the clinical and microscopic findings is

used to define the R code status (see Chapter 5).
S2.09 The presence or absence of tumour perforation must be

recorded.
CS2.09a Perforation through the tumour into the peritoneal cavity is a

well-established adverse prognostic factor in colonic24 and
rectal25 cancer and should be recorded. Tumour perforation
is defined as a macroscopically visible full thickness defect
through the tumour, such that the bowel lumen within the
segment involved by tumour is in communication with the
external surface of the resection specimen or with the lumen
of another organ. Such cases are regarded as pT4a in the
Union for International Cancer Control (UICC)/American
Joint Committee on Cancer (AJCC) 8th edition Staging
Systems.1,26 The term perforation should be reserved for the
biological setting and, for clarity, different descriptive
terminology applied should a full thickness defect in the
specimen arise intra-operatively. Such clinical information
should be conveyed to the reporting pathologist to assist
pathological interpretation. If an iatrogenic full thickness
defect in the tumour occurs whilst the specimen is in situ
within the abdominal cavity, this is best regarded as pT4a
disease, given the risk of tumour seeding the peritoneal

cavity. This interpretation is however offered without good
evidence. If such an iatrogenic defect occurs once the
specimen is outside the abdominal cavity, the defect should
not influence pT classification. An explanatory note regarding
interpretation should be provided in the pathology report.
Peritumoural abscess cavity, for example within the
mesentery, that is contained and does not demonstrate
breach of the serosal surface, should not be considered
perforation and is considered pT3 rather than pT4a.
Perforation of the colon as a result of a more distal
obstructing tumour is distinct from tumour perforation and
does not indicate pT4 disease, but nevertheless should be
recorded as it is associated with high mortality risk.
CS2.09b Perforation of the proximal bowel as a result of a distal

obstructing tumour must not be recorded as tumour
perforation, but should be noted (see below).
CS2.09c It is important to distinguish, where possible, between

perforation occurring at the time of surgery and perforation
before surgery.
S2.10 For rectal tumours, the relationship of the tumour to the

anterior peritoneal reflection must be recorded (refer to Figure
1).
CS2.10a For rectal tumours only, the relationship of the tumour to the
anterior peritoneal reflection must be recorded, as this
predicts the risk of local recurrence in addition to peritoneal
recurrence (Figure 1).27 The anterior aspect of the rectum is
covered by peritoneum down to level of the peritoneal
reflection. Posteriorly, the nonperitonealised margin extends
upwards as a triangular shaped bare area containing the
rectal arteries. Superiorly this area is continuous with the
sigmoid mesocolon.
CS2.10b Rectal tumours are classified according to whether they are:

• entirely above the level of the peritoneal reflection
anteriorly
• astride (or at) the level of the peritoneal reflection
anteriorly
• entirely below the level of the peritoneal reflection
anteriorly.

Figure 1. Site of tumour in relation to the anterior level of the peritoneal
reflection
CS2.10c The anterior aspect of the rectum is covered by peritoneum down

to the peritoneal reflection. On the posterior aspect the
nonperitonealised margin extends upwards as a triangular shaped
bare area containing the rectal arteries, which then continues up
to the start of the sigmoid mesocolon (see Figure 2).
CS2.10d The nonperitonealised margin is also known as the radial or

circumferential resection margin. It consists of a ‘bare’ area of
connective tissue at the surgical plane of excision that is not
covered by serosa (see Figure 5). Low rectal tumours will be
completely surrounded by a nonperitonealised margin (the
circumferential margin), while upper rectal tumours have a
nonperitonealised margin posterolaterally and a peritonealised
(serosal) surface anteriorly. Tumours below the peritoneal
reflection have the highest rates of local recurrence.28-31

Figure 2. Site of nonperitonealised margin (bare area of mesorectum)
in relation to the peritoneal reflection
S2.11 For rectal cancer, the plane of mesorectal excision must be recorded.
CS2.11a The quality of surgical technique has been shown by prospective

randomised controlled trials to predict outcome following surgical
treatment for rectal cancer. Total mesorectal excision (TME)
surgery improves local recurrence rates and the corresponding
survival by up to 20%.32,33 Macroscopic evaluation of the
completeness of the mesorectum, by objective assessment of the
surgical plane of excision, predicts margin involvement, local
recurrence and survival.27,34,35 Excision in the mesorectal plane
(complete TME) has the best outcome while excision extending
onto the muscularis propria (incomplete TME) has the worst.
Assessment requires examination of the intact specimen and
overall assessment is based on the worst area, as described
below:
Mesorectal fascia (complete)
• Intact bulky mesorectum with a smooth surface
• Only minor irregularities of the mesorectal surface
• No surface defects greater than 5 mm in depth
• No coning towards the distal margin of the specimen
Intramesorectal (near complete)
• Moderate bulk to the mesorectum
• Irregularity of the mesorectal surface with defects greater

than 5 mm, but none extending to the muscularis propria
• Moderate coning may be evident distally
• No areas of visibility of the muscularis propria except at the
insertion site of the levator ani muscles
Muscularis propria (incomplete)
• Little bulk to the mesorectum
• Defects in the mesorectum down to the muscularis propria
• After transverse sectioning, the circumferential margin
appears very irregular and is formed by muscularis propria
in areas.
CS2.11b The intactness of the specimen may be graded as follows:

– Incomplete (grade 1)
– Nearly complete (grade 2)
– Complete (grade 3)
G2.01 For abdominoperineal excision specimens, the plane of sphincter excision

should be recorded.
G2.01a Abdominoperineal excision for low rectal cancer has been

associated with poorer outcomes compared to anterior resection
for higher tumours due to increased rates of circumferential
resection margin (CRM) involvement and intraoperative full
thickness defects (“perforations”).36 Extralevator abdominoperineal
excision has been shown in meta-analyses to reduce CRM
involvement and intraoperative full thickness defects leading to
better long term outcomes.37 This is due to the removal of more
tissue around the tumour.38 Radiologists are able to predict the
optimal dissection plane in abdominoperineal excision from the
staging magnetic resonance imaging (MRI).39 This should be
correlated with the plane of dissection achieved on the resection
specimen around the sphincters (below the mesorectum). The
plane of surgery in the mesorectum should be assessed
separately.
below:25,40
Extralevator plane
• Dissection plane lies external to the external sphincter and
levator ani muscles, which are removed en bloc with the
mesorectum and anal canal
• Cylindrical-shaped specimen with the levators forming an
extra protective layer above the sphincters
• No significant defects into the sphincter muscles or levators
Sphincteric plane
• Dissection plane lies on the surface of the sphincter
muscles
• No levator ani muscle attached or only a very small cuff

leading to coning or surgical waisting at the level of
puborectalis
• No significant defects into the sphincter muscles
Intrasphincteric plane
• Dissection plane lies within the sphincter muscles or even
deeper into the submucosa
• Full thickness iatrogenic defect of the specimen at any
point below the peritoneal refection
G2.02 For colon cancer specimens, the plane of mesocolic excision should be
recorded.
G2.02a The quality of surgical technique in the mesocolon has been

shown, in retrospective observational studies and one randomised
clinical trial, to predict outcome following surgical treatment for
colon cancer in a similar way to that seen in rectal cancer.41-43
Surgery in the mesocolic plane is associated with a lower rate of
local recurrence and better survival when compared to surgery in
the muscularis propria plane. Complete mesocolic excision, where
surgery occurs in the mesocolic plane with a high vascular ligation,
is associated with better plane of surgery and more lymph nodes,
although the effect of the high ligation on long term outcomes
remains debated.44 The height of the vascular ligation is not taken
into consideration during the plane of mesocolic excision
assessment.
below:
Mesocolic plane
• Smooth surface to the mesocolon (mesocolic fascia and
peritoneum)
• Only minor irregularities
• No surface defects greater than 5 mm in depth
Intramesocolic plane
• Irregularity of the mesocolic surface with defects greater
than 5 mm, but none extending to the muscularis propria
Muscularis propria plane
• Defects in the mesocolon down to the muscularis propria
• After transverse sectioning, the mesocolic margin is
irregular and formed by muscularis propria in areas
G2.03 Any involvement of the peritoneum should be recorded.
CG2.03a This should be recorded as one of the following :

• Tumour invades to the peritoneal surface
• Tumour has formed nodule(s) discrete from the tumour mass
along the serosal surface

CG2.03b Tumour involvement of the serosa discontinuous from the site of
the main tumour is to be recorded as a metastasis.
G2.04 A descriptive or narrative field should be provided to record any macroscopic

information that is not recorded in the above standards and guidelines, and
that would normally form part of the macroscopic description.
CG2.04a Examples include the presence of tissues and organs adherent to

the colon, the presence of tumours other than primary
adenocarcinoma, and coexistent chronic inflammatory bowel
disease.
CG2.04b Other information related to the primary tumour may also be

recorded here such as gross configuration of the tumour and
lymph nodes, appearance of the serosa over the tumour, etc.
CG2.04c The traditional macroscopic narrative recorded at the time of

specimen dissection is often reported separately from the cancer
protocol. Although this remains an option, it is recommended that
macroscopic information be recorded within the overall structure of
this protocol.
CG2.04d Some of these elements are formally recorded in the ‘Microscopic

findings’ (see Chapter 3).
CG2.04e Much of the information recorded in a traditional macroscopic

narrative is covered in the standards and guidelines above and in
many cases, no further description is required.

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 tumour type must be recorded.
CS3.01a Colorectal cancers should be typed according to the World

Health Organization (WHO) Classification of Tumours of the
Digestive System, 5th edition, 2019.45 Almost all are
adenocarcinomas. 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 carcinoma has stage-independent adverse prognostic
significance relative to conventional adenocarcinoma.46 There
is a strong association with microsatellite instability and with
Lynch syndrome.47 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.48
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.49
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.50
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.51 Diagnosis of adenocarcinoma
on endoscopic biopsy is exceedingly difficult. This variant is
associated with a good prognosis.
Neuroendocrine neoplasms are classified into NETs, NECs and
MiNENs.45 NETs are graded 1-3 using the mitotic count and Ki-
67 proliferation index. Pure NETs are not considered within the
scope of this protocol. 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.52 MiNENs are usually composed of a
poorly differentiated NEC component and an adenocarcinoma
component.
While it is convention to only include those tumours with at
least 30% or more of each component in the MiNEN group, any
component of small cell neuroendocrine carcinoma, even if
<30% of the tumour, should be reported in the diagnosis
because of the significant clinical implication, even if the
tumour is not designated to be a MiNEN.
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.
Refer to ICCR dataset for full commentary.
CS3.01b It is important to note, that a small component of

neuroendocrine cells interspersed within a glandular tumour
does not fall into the category of MiNEN.53 This category should
be reserved for tumours displaying two distinct morphologic
and immunohistochemically identifiable areas. Because the
category of ‘MiNEN’ reflects a range of combinations of
tumours, ideally the specific category for the site should be
used e.g. mixed adenocarcinoma-NEC or mixed
adenocarcinoma-NET.54
CS3.01c Serrated adenocarcinoma typically arises from a precursor

serrated polyp (sessile serrated lesion or traditional serrated
adenoma), which may be evident at the edge of the invasive
carcinoma in some cases. They are characterised by mutations
in the MAPK signalling pathway (i.e. BRAF or KRAS).
Micropapillary adenocarcinoma represents an evolving subtype.
In these lesions, epithelial membrane antigen EMA (MUC1)
immunohistochemistry demonstrates an ‘inside-out’ pattern of
staining with expression on the external aspect of the epithelial
nests rather than the luminal aspect.
While the WHO states that rounded clusters of tumour cells
lying within stromal spaces mimicking vascular channels should
represent at least 5% of the tumour to classify as a
micropapillary lesion, it more likely represents a component of
conventional adenocarcinoma. Nonetheless, these features

should be reported.
It is the opinion of the RCPA colorectal cancer (CRC) expert
panel that serrated and micropapillary adenocarcinomas are
relatively uncommon, and current guidelines are not yet
sufficient to adequately describe these lesions.
See Appendix 5 for example representative images of
histological tumour types.
CS3.01d Additional histological tumour types not included in the WHO

Histological Classification of Tumours of the Colon and Rectum
(refer to Appendix 4) include choriocarcinoma, clear cell
carcinoma, microglandular goblet cell carcinoma, carcinomas
with melanin production.
CS3.01e The description should be based on the WHO Histological

Classification of Tumours of the Colon and Rectum (refer to
Appendix 4).55 This publication, as well as a current version of
the AJCC Cancer Staging Manual56 should be readily accessible
to the reporting pathologist.
CS3.01f For most tumours, histological type is not prognostically

significant. Exceptions include tumour types that are, by
definition, high grade (i.e. signet-ring cell carcinoma); and the
medullary subtype, which is invariably associated with
mismatch repair gene deficiency and has a favourable
prognosis when compared to other poorly differentiated and
undifferentiated colorectal carcinomas.55 Note that well
differentiated neuroendocrine (carcinoid) tumours are listed
separately to carcinoma in the WHO histological classification
and are staged and graded differently.55
S3.02 The histological grading of the tumour must be recorded.
CS3.02a Despite low level of interobserver agreement,57 histological

grade is an independent prognostic factor used in risk
assessment models for colorectal carcinoma.58-60 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,45 grading should be 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. Tumour buds or poorly
differentiated clusters, most commonly seen at the invasive
tumour front, should not be considered in the evaluation of
grade. However, emerging data suggests that grading based
on poorly differentiated clusters is superior to conventional
grading with respect to both prognostic value and
reproducibility.61,62
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 and good for adenoma-like adenocarcinoma.
Mucinous adenocarcinoma should be graded on glandular
formation and epithelial maturation.45 Tumour mismatch repair
status is likely to influence clinical behaviour of some
histological tumour types, including mucinous adenocarcinoma,
but some studies have found morphological grading superior to
mismatch repair status for prognostication of mucinous
adenocarcinomas.63,64
CS3.02b Whether grading should be based on the predominant pattern

of differentiation or the area of worst differentiation is
controversial.65,66 In this protocol, it is recommended that,
‘when a carcinoma has heterogeneity in differentiation, grading
should be based on the least differentiated component, not
including the leading front of invasion’, as stated in the WHO
classification.67
Small foci of apparent poor differentiation may be seen at the
advancing edge of tumours but these should not be used to
classify the tumour as poorly differentiated (see also ‘tumour
budding’ below).
CS3.02c A two tiered grading system is recommended, based on the

WHO classification:
• low grade — well differentiated and moderately
differentiated
• high grade — poorly differentiated and undifferentiated
The two tiered grading system is much more reproducible and
more prognostically representative.
S3.03 The maximum degree of local invasion must be recorded.
CS3.03a 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 UICC and AJCC 8th
editions1,26 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 invasive neoplasia
or intramucosal carcinoma) are acknowledged but, given the
negligible metastatic potential of such neoplasms,68 these
should be classified under the same category with high grade
dysplasia/high grade non-invasive neoplasia.
pT1 indicates tumour extension beyond muscularis mucosae
into submucosa, but without involvement of muscularis
propria. Further consideration of pT1 colorectal carcinoma is
provided in a separate local excision protocol.
pT2 indicates extension into muscularis propria but not
beyond. In the low rectum, the internal sphincter represents a
continuation of the muscularis propria and invasion of this also
constitutes pT2. Note that skeletal muscle fibres can cross over
from external to internal sphincter and invasion of skeletal
muscle fibres of the internal sphincter is also classified as pT2.

Such complexities of sphincter anatomy make accurate
assessment of level of invasion in this region challenging.
pT3 indicates tumour spread beyond muscularis propria in
continuity with the primary tumour and excluding tumour
confined to the lumen of veins or lymphatic channels.
Distinction from pT2 may be difficult if tumour extends to the
outer edge of the muscularis propria. If no muscle separates
tumour cells from mesenteric connective tissue, the tumour
should be classified as pT3.69 Invasion beyond internal
sphincter into the intrasphincteric plane, but not involving the
external sphincter, is considered pT3.
pT4 encompasses either tumour infiltration of the peritoneal
surface (pT4a) or tumour involvement of an adjacent organ
(pT4b). Peritoneal involvement has been demonstrated by
multivariate analysis to have a negative impact on
prognosis.70,71 Although some small studies have suggested
that peritoneal involvement was associated with worse
outcome than invasion of adjacent organs, data from a large
cohort of more than 100,000 colon cancer cases indicate that
penetration of the visceral peritoneum carries a 10-20% better
5-year survival than locally invasive carcinomas for each pN
category.72
Involvement of the peritoneal surface (pT4a) is defined as
tumour breaching the serosa with tumour cells visible either on
the peritoneal surface, free in the peritoneal cavity or
separated from the peritoneal surface by inflammatory cells
only.24 Should tumour pass close to the serosal surface and
elicit a mesothelial reaction but no clear invasion, additional
sections and/or multiple levels should be examined. If tumour
does not demonstrate serosal involvement after additional
evaluation, it should be categorised as pT3. Assessment of this
scenario remains prone to interobserver variation.73 Several
studies advocate the application of elastic stains to evaluate
peritoneal elastic lamina invasion, as a staging or prognostic
tool, but others have not found this useful.74-77 Cases with
perforation through tumour should also be classified as pT4a,
even in the absence of microscopic documentation of tumour
cells on the peritoneal surface. This does not apply to colonic
or rectal perforation distant from the tumour, for example
secondary to distal obstruction.
Note, pT4a implies peritoneal involvement through direct
continuity with the primary tumour whereas peritoneal
deposition of tumour discontinuous from the primary tumour is
regarded as distant metastatic disease (pM1c). It is also
important to carefully distinguish involvement of a peritoneal
surface from involvement of a nonperitonealised surgical
resection margin, which is recorded separately. The first is a
risk factor for intraperitoneal metastatic disease while the
latter is a risk factor for local recurrence.
Tumour involvement of an adjacent organ (pT4b) may follow
peritoneal invasion or represent direct extraperitoneal invasion,
for example in low rectal tumours. Tumours adherent to other
organs must be demonstrated microscopically to show invasion
into the adjacent organ, rather than inflammatory adherence,

to be classified as pT4b. Intramural (longitudinal) tumour
extension into an adjacent part of the intestine does not
influence pT classification, for example intramural extension of
a caecal tumour into the terminal ileum or of a rectal tumour
into the anal canal. Tumour involvement of greater omentum is
considered pT4b if it follows transperitoneal invasion. Rarely, a
transverse colonic tumour can invade greater omentum
directly without breaching the serosa, meriting classification as
pT3 rather than pT4b. For rectal tumours, invasion of skeletal
muscle of the external sphincter and/or levator ani is classified
as pT4b.
CS3.03b In the rare situation where discontinuous tumour deposits in

the omentum arise from a directly invading transverse colon
cancer, gross appearance and macroscopic assessment is
important. Recording how the omentum was adherent, and the
location of the mesentry, can be helpful. If the transverse
colon is attached and appears to be involved, then the gross
appearance may be very important in staging.
G3.01 The measurement of invasion beyond muscularis propria should be

recorded.
CG3.01a Tumours classified as pT3 can be prognostically stratified

accordingly to their extent of invasion beyond muscularis
propria, with 5 mm an important cut-off in some studies.78,79
This distance should be measured to the nearest millimetre
from the outer margin of the muscularis propria,
reconstructing this margin if necessary in the event of
destruction by tumour. Note this measurement applies only to
the primary tumour and any discontinuous tumour foci, of any
form, should be discounted in this assessment.
G3.02 The inflammatory cell infiltrate may be assessed.
CG3.02a Inflammatory and immune reactions to CRC are generally

associated with improved outcome.80-82 They are classified as
follows:
Lymphocytic immune reactions. These have several patterns:
tumour-infiltrating lymphocytes, peritumoural lymphocyte
infiltration, and peritumoural lymphoid aggregates
Tumour-infiltrating lymphocytes are associated with mismatch
repair-deficient (MMRD) CRCs.83
There is an evolving role in predicting for a good response to
immunotherapy treatment.84,85
Tumour-infiltrating lymphocytes are an independent predictor
of improved prognosis. They are associated with less
aggressive features including a decreased likelihood of venous
invasion.86-88 The improved outcomes seen in MMRD cancers
are likely the result of the tumour-infiltrating lymphocytic
response seen in these tumours.
Other inflammatory cell reactions that have been shown to
have prognostic relevance include prominent neutrophil and
eosinophil infiltration.89-92

S3.04 The presence of lymphovascular invasion must be recorded.
CS3.04a 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 implications. Extramural
(beyond muscularis propria) venous invasion has been
demonstrated on multivariate analysis by multiple studies to
be a stage independent adverse prognostic factor for colonic
and rectal cancer.93 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.24,94,95
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.96 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.95,97-101 A
circumscribed tumour nodule surrounded by a smooth muscle
wall or an identifiable elastic lamina, evident on hematoxylin
and eosin 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.
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 immunohistochemistry, which
only stains lymphatic endothelial cells, not venular, but this is
not routinely recommended in reporting surgical resection
specimens. All forms of small vessel invasion are considered
under the ‘L’ classification under UICC/AJCC TNM 8th
editions.1,26 Small vessel invasion is associated with lymph
node metastatic disease and has been shown to be an
independent indicator of adverse outcome in some but not all
studies.94,102-104 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.94
CS3.04b Venous invasion by tumour has been repeatedly shown by

multivariate28,105,106 and univariate analyses to be a stage
independent adverse prognostic factor. However some studies
identifying venous invasion as an adverse factor on univariate
analysis have failed to confirm its independent impact on
prognosis on multivariate breakdown.106-108 Similar disparate
results have also been reported for lymphatic invasion.108 In
other reports, vascular invasion as a general feature was

prognostically significant, but no distinction between lymphatic
and venous vessels was made. In a few studies the location as
well as the type of the involved vessels (e.g. extramural veins)
were both considered strong determinants of prognostic
impact.109,110 Data from the many studies are difficult to
amalgamate but nevertheless, the importance of venous and
small vessel (lymphovascular) invasion by tumour is generally
accepted, and it is considered that venous and small vessel
invasion must be sought and separately recorded.
CS3.04c Some groups have recommended that only extramural venous

invasion be recorded,23 while others have recommended that
the site of any venous invasion should be recorded, along with
its location, intra or extramural.109 In one study, intramural
and extramural vascular invasion were shown to have similar
prognostic value.111 It is recommended that extramural and
intramural venous invasion be recorded separately.
CS3.04d There should be a high index of suspicion of involvement of a

vein if an isolated elongated deposit of tumour is seen
alongside an artery. Examination of multiple levels in blocks
showing features suspicious of vascular invasion can be helpful
and there may be a role for the use of immunohistochemical
stains for endothelium and smooth muscle. An elastic tissue
stain such as an orcein histochemical stain is also useful to aid
detection of venous invasion.112 Assessment should be
concentrated at the invasive edge of the tumour. It is an
observation of the Royal College of Pathologists colorectal
reporting protocol that intramural and/or extramural venous
invasion should be detected in at least 30% of colectomy
specimens.113
CS3.04e The prognostic importance of involvement of small (thin-

walled, presumably lymphatic) vessels in the submucosa has
been well documented with respect to polypectomies of
malignant polyps. Such involvement has been shown to be
associated with an increased risk of regional lymph node
metastasis.114
S3.05 The presence of perineural invasion must be recorded.
CS3.05a Multiple independent studies and one meta-analysis have

demonstrated the adverse prognostic implication of perineural
invasion in colorectal cancer, particularly in stage II
disease.102,115-118 One large multicentre study reported adverse
prognostic significance of both intramural and extramural
perineural invasion.115 However the importance of anatomic
location in perineural invasion is not well established.
CS3.05b There is some evidence that perineural infiltration by tumour is

an important indicator of spread, particularly in rectal tumours
where it may involve the sacral plexus and this may be an
indication for radiotherapy.119
S3.06 Results of lymph node histopathology must be recorded.

CS3.06a The regional lymph node status is a major determinant of
whether or not a patient receives adjuvant chemotherapy.
Non-regional lymph node involvement by tumour, within large
resection specimens, should be recorded separately, as this
indicates distant metastatic (pM1) disease. In the case of two
synchronous primary tumours in distinct anatomic regions,
lymph nodes need to be assigned by regional status and
assessed for each cancer separately.
The number of nodes present depends on the length of the
resection specimen, the amount of attached mesenteric tissue,
the age of the patient and whether or not the patient has
received neoadjuvant therapy.120 Diligent pathology dissection
is crucial as many positive lymph nodes are less than 5 mm in
size. Some cases contain only a small number of nodes, but
dissectors and departments should aim for a median lymph
node yield of at least twelve per case. In stage II disease, low
lymph node harvest is an adverse prognostic factor.121
With respect to small nodal tumour deposits, a systematic
review and meta-analysis found higher risk of disease
recurrence in stage I/II colorectal cancer cases in the presence
of only micrometastatic disease in lymph nodes (one or more
deposit ≥0.2 mm and <2 mm) compared to those with
tumour-negative nodes, but no increased risk of disease
recurrence in cases in the presence of only ‘isolated tumour
cells’ in lymph nodes (single tumour cells or groups <0.2 mm
in maximum dimension) compared to those with tumour-
negative nodes.122 Therefore, cases in which isolated tumour
cells, identified on haematoxylin and eosin or
immunohistochemical staining, represent the only form of
nodal involvement should be classified as pN0, with a comment
on the presence of the isolated tumour cells and optional
designation as pN0 (i+). Any lymph node containing tumour
measuring ≥0.2 mm in diameter is counted as a positive node.
If neoadjuvant therapy has been received, designation as
nodal involvement (ypN1/2) is based only on the presence of
viable tumour. Assessment of lymph nodes in this setting
should ideally include a descriptive comment on the presence
or absence of signs of regression (fibrosis, necrosis or mucin)
within nodal tissue, to allow correlation with initial staging MRI.
CS3.06b Although it is now accepted terminology to describe cases as

pN0 - in which isolated tumour cells represent the only form of
nodal involvement, in practice many pathologists and clinicians
often view these nodes as positive.123
CS3.06c Accurate identification of positive lymph nodes is key to

accurate staging and a major determinant of whether a patient
receives adjuvant therapy. The probability of finding a positive
node increases with the number of nodes found and increased
lymph node retrieval is also independently associated with
improved survival.121,124-128
Early studies suggested the likelihood of detecting a positive
lymph node flattened out after finding 12–15 nodes,125 leading
to many guidelines recommending a minimum of 12 lymph

nodes be retrieved. However, there is a lack of consensus on
what a minimum retrieval number should be and the reason is
likely to be that lymph node yield is multifactorial. Lymph node
retrieval is affected by a number of factors which can be
categorised into surgical (length of specimen, type of
procedure), patient (location, size) and laboratory (experience,
caseload) factors.129 Some factors are modifiable, such as
pathologist or surgical experience, while others are not and in
the future it may be that the cut-off is adjusted by patient or
tumour-specific factors.127
Pending further evidence, it is prudent to approach lymph node
retrieval as follows
- all identifiable lymph nodes should be retrieved and
examined
- if twelve or fewer lymph nodes are found then the
specimen should be re-examined for lymph nodes as a
longer period of fixation in formalin can improve lymph
node detection; this is particularly important in stage II
(pN0) tumours
- alternative fixatives and fat clearance methods can be
used to increase lymph node yield but the evidence is
most robust in studies where the yield was low to begin
with15
- the greatest yield for positive lymph nodes in a second
search is the region of the tumour bed16
- if 12 or fewer lymph nodes are retrieved a note should
be made in the pathology report, describing how this
has been addressed
- assessment of a laboratories average lymph node yield
can be used as a quality indicator but may reflect a
particular surgical or patient cohort, rather than a
particular laboratories practice
CS3.06d Direct extension of a colorectal tumour into a lymph node is

considered nodal metastasis. Metastasis in any lymph nodes
other than regional nodes is classified as distant metastasis.130
CS3.06e There is no consensus that occult metastatic disease detected

by immunohistochemistry or other methods discriminates
between high- and low-risk groups of patients. Data are thus
insufficient to recommend routine use of tissue levels or
ancillary special techniques.65,109
CS3.06f Recording small tumour deposits in lymph nodes needs to take

account of the following issues:
• Isolated tumour cells are defined as ‘single malignant cells
or a few tumour cells in microclusters’, not more than
0.2 mm in diameter, present within a lymph node. They
may be single or multiple. They may be visible in H&E
stained sections or detected by immunohistochemistry. The
literature suggests that the finding of such cells is not a
marker of an adverse prognosis for the patient.131-133

• The AJCC TNM 8th edition recommends that cases in which
isolated tumour cells are the only form of nodal
involvement should be classified as pN0, although the
presence of the isolated tumour cells should be noted.56
Optional designation as pN0(i+) may be used in this
situation,134 although a free-text description might provide
clearer communication.
• It has been argued that very small nodal deposits that
show evidence of growth, for example glandular
differentiation, distension of the sinus or a stromal
reaction, should be regarded as metastases irrespective of
size.65
CS3.06g The assessment of isolated deposits of tumour within the

mesocolic and mesorectal fat, in particular whether they
represent nodal metastases, can be difficult.
Isolated tumour deposits may derive from nodes, vascular
invasion, perineural invasion or a combination of these within a
single case. Such deposits are conveniently described as
discontinuous extramural tumour deposits or satellite nodules.
Most examples occur in situations where there are
unequivocally involved nodes anyway (in a literature review of
1520 patients, only 8% of cases were not associated with
lymph node deposits). However even where present without
definite nodal metastasis, they are associated with an adverse
prognosis.135
This difficulty has been neatly addressed in the AJCC TNM 7th
edition by the placing of cases with extramural tumour
deposits within the N category. In the absence of co-existent
definite lymph node metastases (defined in the 7th edition as
having identifiable residual lymph node tissue), these cases are
categorised as N1c.56
G3.03 Involvement of the apical lymph node should be recorded, if required,

where staging systems additional to TNM staging are in use.
CG3.03a Both the Australian Clinicopathological Staging System and the

Dukes staging system are in use in some institutions in
Australasia. These require the status of the apical lymph node
to be recorded.136
G3.04 The ratio of involved lymph nodes to the total number of nodes (‘lymph
node ratio’) should be recorded.
CG3.04a The ratio of involved nodes to the total number of nodes has
emerged as a potential prognostic factor. Lymph node ratio is
defined as the ratio of the number of positive nodes to the
total number of harvested nodes. It is a significant prognostic
feature in stage III colorectal carcinoma where a high ratio
predicts both poor overall survival and disease-free survival.
The predictive value of this factor appears to be higher than
the nodal stage alone.137
S3.07 The presence of tumour deposits must be recorded.

CS3.07a Under the UICC/AJCC TNM 8th editions definition, tumour
deposits (satellites) are discrete macroscopic or microscopic
nodules of cancer in the pericolorectal adipose tissue’s lymph
drainage area of a primary carcinoma that are discontinuous
from the primary and without histological evidence of residual
lymph node or identifiable vascular or neural structures.1,26 The
definition does not specify any minimum size of deposit or
minimum distance of separation from the primary tumour. If a
vessel wall is identifiable on H&E, elastic or other stains, it
should be classified as venous invasion or lymphatic invasion.
Similarly, if neural structures are identifiable, the lesion should
be classified as perineural invasion. Identification of venous,
lymphatic or perineural invasion does not change the T
category. The presence of tumour deposits, as defined, also
does not change the primary tumour T category, but changes
the node status (N) to pN1c if all regional lymph nodes are
negative on pathological examination. Therefore, pN1c is only
applied in the setting of node-negative disease and, if any
nodes contain metastatic tumour, the number of tumour
deposits is not added to the involved node count in
determining final pN category. However, as there is evidence
from meta-analysis of the adverse prognostic significance of
tumour deposits, albeit based on a previous definition, the
presence and number of identified tumour deposits should be
recorded regardless of pN status.138
A mesenteric focus of tumour, without evidence of origin,
which is discontinuous from the primary tumour, located within
its lymphatic drainage area and predominantly subserosal in
location but which penetrates the serosal surface of the
mesentery, should be classified as a tumour deposit rather
than distant metastatic (pM1c) disease. This finding does not
influence the pT category, which should be based on extent of
invasion of the primary tumour only, but a comment may be
added that, given serosal involvement by the tumour deposit,
behaviour may equate to pT4a disease. Guidance on this
interpretation is offered without good evidence. pM1c disease
should be reserved for tumour which appears to have arisen
from metastatic spread via the peritoneal cavity.
Assessment of discontinuous tumour foci is difficult following
administration of neoadjuvant therapy and evident tumour
regression. This setting requires consideration of tissue
separating the primary tumour site from the discontinuous
tumour foci. Designation of such foci as tumour deposits
should require the presence of intervening normal tissue, not
just fibrosis.
G3.05 Tumour budding should be recorded.
CG3.05a Tumour budding is defined as single cells or clusters of up to

four tumour cells at the invasive front of carcinomas. It is
considered to be the morphological manifestation of epithelial
mesenchymal transition.139 Tumour budding is different from
tumour grade (based on gland formation away from the
invasive front) 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 stage pT1 colorectal
carcinomas with tumour budding score Bd2 and Bd3 (≥5 buds)
are associated with an increased risk of lymph node
metastasis.140-144 For stage II colorectal carcinomas, tumour
budding score Bd3 is associated with increased risk of
recurrence and mortality.145-147
Tumour budding is reported as the number of buds and scored
using a three-tier system. According to the recommendations
from a consensus conference on tumour budding,148 the
number of tumour buds is the highest count after scanning ten
separate fields (at 20x objective lens) along the invasive front
of the tumour or the entire lesion for malignant polyps
(‘hotspot’ approach). 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 identify the buds, but the final
count is performed on H&E. Depending on the eyepiece field
diameter of the microscope used, 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). Refer to ICCR dataset for full commentary.
Tumour budding should only be reported in non-mucinous and
non-signet-ring cell adenocarcinoma areas. Furthermore, for
colonic or rectal adenocarcinomas resected after neoadjuvant
therapy, tumour budding should not be reported.
CG3.05b See Table 1 for International Tumour Budding Consensus

Conference (ITBCC) 2016148 conversion table and Figure 3 for
the procedure proposed by the ITBCC 2016 for reporting
tumour budding in colorectal cancer in daily diagnostic
practice.
S3.08 Response to neoadjuvant therapy must be recorded.
CS3.08a Patients with completely excised rectal carcinomas, who have

received preoperative chemoradiotherapy that has resulted in
complete or marked regression of tumour and replacement by
fibrosis, necrosis or acellular mucin, have a better prognosis
than those without significant regression.149-153 A four tier
system of grading regression is recommended, based on a
modification of that described by Ryan et al (2005).154 This
should be applied when any form of neoadjuvant therapy is
administered, to rectal or colonic tumours. Tumour regression
assessment is based on evaluation of the primary tumour site,
but a descriptive comment should be added if any such
features are evident in regional lymph nodes, or at any distant
metastatic sites. Designation as complete pathological
response implies the absence of viable tumour locally (ypT0)
and in lymph nodes (ypN0) and requires processing of the
entire tumour bed for histological examination.
CS3.08b See Appendix 6 Table 6 for a comparison of regression grading

systems.

CS3.08c Chemotherapy and/or radiotherapy before resection is
associated with significant downstaging, and improved
prognosis. These specimens require close gross examination
and additional blocking to demonstrate tumour. The degree of
tumour regression has been shown to correlate with prognosis.
The classification of the AJCC, based on that of Ryan et al, is
recommended:155
• Grade 0: (complete response): No viable cancer cells
• Grade 1: (moderate response): Single cells or small
groups of cancer cells.
• Grade 2: (minimal response): Residual cancer outgrown
by fibrosis
• Grade 3: (poor response): Minimal or no tumour kill;
extensive residual cancer
CS3.08d Note that acellular mucin pools seen in patients after therapy
are regarded as indicators of complete regression. They do not
contribute to T staging, and when seen in lymph nodes do not
count as positive nodes. It is advisable to comment upon their
presence in a free text comment for the purpose of correlation
with pre-operative imaging.
CS3.08e If neoadjuvant chemotherapy or radiotherapy has been given,

the prefix ‘yp’ should be used to indicate that the original p
stage may have been modified by therapy. Tumour remaining
in a resection specimen following neoadjuvant therapy should
always be classified by ypTNM to distinguish it from untreated
tumour.134
S3.09 The margin status must be recorded.
CS3.09a Assessments of longitudinal and circumferential resection

margins may require macroscopic or microscopic
measurement, depending on proximity of tumour to margins.
Separately submitted anastomotic rings (‘doughnuts’) should
be taken into consideration for longitudinal margin
assessment. Unless a tumour has particularly aggressive
morphological features, for example signet-ring cell carcinoma,
it is generally only necessary to histologically examine
longitudinal margins if the tumour extends macroscopically to
within 30 mm.156 For tumours further than this, it can be
assumed that the longitudinal margins are not involved.
The circumferential (radial or nonperitonealised) margin
represents the adventitial soft tissue margin closest to the
deepest penetration of tumour and is created surgically by
blunt or sharp dissection of the retroperitoneal or subperitoneal
aspect, depending on the nature of the surgical resection. This
margin must be assessed for any tumour either unencased or
incompletely encased by peritoneum. Rectal tumours below the
peritoneal reflection will be completely encased by a
circumferential, nonperitonealised margin, while upper rectal
tumours, and often proximal colonic tumours, have a
nonperitonealised margin posteriorly and a peritonealised
surface anteriorly (Figure 4). Transverse and sigmoid colonic

tumours generally only have a narrow, readily identifiable,
nonperitonealised margin, representing the level of surgical
dissection of the mesentery. The term circumferential margin
is favoured, even though the nonperitonealised margin is not
always circumferential.
Circumferential margin involvement, typically defined as
tumour ≤1 mm from the margin, is predictive of local
recurrence and poor survival in rectal tumours,157-161 The
importance of circumferential margin involvement in proximal
colonic tumours has been recognised but less evidence is
available.162,163 Any circumferential margin ≤1 mm from
tumour should be recorded as involved, but the precise
distance recorded, to the nearest 0.1 mm must be included. If
the tumour is clear by <10 mm, the specific distance of
clearance should also be recorded, to the nearest 1 mm.
There is limited outcome data with respect to mode of
circumferential margin involvement by tumour, but this limited
data suggest that cases with margin involvement by
discontinuous or intravascular (blood vessel or lymphatic
vessel) tumour behave similarly to those with margin
involvement by direct tumour spread with respect to local
recurrence.157,158 However, margin involvement by tumour
confined to a lymph node was not associated with a significant
risk of local recurrence in one study.158 Therefore, assuming
the involved lymph node has an intact capsule and has not
been transected at surgery, identification of an involved node
at the circumferential margin should not be interpreted as
margin involvement. An explanatory comment should be added
to the pathology report to this effect. If a margin is designated
as involved by tumour other than the primary mass, this
should be clearly described and a separate measurement
provided with respect to clearance from the margin of the
primary tumour.
CS3.09b Rectal tumours frequently (5–36%) involve the nonperitonealised

surgical CRM and this is associated with significantly higher rates
of local recurrence and cancer-related death.164-171
CS3.09c The frequency of involvement of the CRM depends on the quality

of surgery, advancing TNM stage and whether the patient has
undergone preoperative neoadjuvant therapy. The closer the
tumour is to the CRM, the worse the prognosis.172 The vast
majority of studies, including clinical trials and population studies,
have used a cutoff of 1 mm or less to define margin involvement.
CS3.09d CRM involvement may be through direct continuity with the main
tumour, by tumour deposits discontinuous from the main tumour,
or by tumour in veins, lymphatics or lymph nodes (Figure
4).165,168,173 Some surgeons like to know whether the tumour is
contained within the lymph node or invades beyond the lymph
node, as the latter is associated with a worse prognosis.
S3.10 The presence of histologically confirmed distant metastases and

their site must be recorded.
CS3.10a Tumour classifiable as distant metastatic disease may

sometimes be present within the primary tumour resection
specimen, for example a peritoneal or omental deposit that is
discontinuous from the primary mass. Metastatic deposits in
‘non-regional’ lymph nodes distant from those surrounding the
main tumour will usually be submitted separately by the
surgeon but may be present within an extended colectomy
specimen.
Given different prognostication associated with the pattern of
organ involvement by distant metastatic disease, UICC/AJCC
8th edition Staging Manuals have subclassified pM1 into pM1a
indicating metastatic disease in one distant organ (excluding
metastatic peritoneal disease), pM1b indicating metastatic
disease in two or more distant organs and pM1c indicating
metastatic peritoneal disease (regardless of other organ
involvement).1,26 Note, pathologists can only base assessment
of distant metastatic disease on submitted specimens and
therefore should not use the terms ‘pM0’ or ‘pMX’. cM1 and
cM0 are used when clinical, usually radiological, evidence
suggests the presence or absence respectively of distant
metastatic disease.
G3.06 The presence of any relevant coexistent pathological abnormalities in the

bowel should be recorded.
CG3.06a The presence of any pathological abnormalities in the

background colon or rectum should be recorded. These include
polyps (type, number and whether meeting criteria for any
polyposis syndrome), chronic inflammatory bowel disease
(distribution and specify with or without dysplasia), effects of
any neoadjuvant therapy on non-neoplastic tissue, diverticular
disease and/or changes related to obstruction. Synchronous
carcinomas should have individual protocols completed for all
appropriate elements.
S3.11 The microscopic residual tumour status must be recorded (i.e. the
completeness of resection).
CS3.11a As the assessment of residual tumour status requires the input of

the surgeon, as well as macroscopic and microscopic assessment;
it is further dealt with in Chapter 5 (Synthesis and overview).
G3.07 Any additional relevant information should be recorded.
CG3.07a There must be a free text field so that the pathologist can add any
essential information that is not addressed by the above points.

Table 1. International Tumour Budding Consensus Conference (ITBCC) 2016
conversion table to adjust and standardise the tumour bud count for different
microscope types
Objective magnification: 20
Eyepiece FN Specimen Area Normalisation Factor
Diameter (mm) (mm2)
18 0.636 0.810
19 0.709 0.903
20 0.785 1.000
21 0.866 1.103
22 0.950 1.210
23 1.039 1.323
24 1.131 1.440
25 1.227 1.563
26 1.327 1.690
Reproduced with permission from Lugli et al Recommendations for reporting tumour
budding in colorectal cancer based on the International Tumour Budding Consensus
Conference (ITBCC) 2016. Mod Pathol 30, 1299–1311 (2017).148
https://doi.org/10.1038/modpathol.2017.46

Figure 3. Procedure proposed by the International Tumour Budding Consensus
Conference (ITBCC) 2016 for reporting tumour budding in colorectal cancer in
daily diagnostic practice.
Reproduced with permission from Lugli et al Recommendations for reporting tumour

budding in colorectal cancer based on the International Tumour Budding Consensus
Conference (ITBCC) 2016. Mod Pathol 30, 1299–1311 (2017).148
https://doi.org/10.1038/modpathol.2017.46

x = minimum clearance in mm of primary tumour, extramural or nodal deposit
or tumour in vessel etc, whichever is the closest.
Figure 4. Measurement of the distance of tumour to the circumferential

resection margin

4 Ancillary findings
Ancillary studies of colorectal carcinoma are being increasingly used as prognostic
biomarkers, to aid detection of an underlying genetic basis and to indicate the likelihood
of patient response to specific biologic therapies.
G4.01 Screening for Lynch syndrome should be performed.
CG4.01a Lynch syndrome is the most common inherited cause of

colorectal carcinoma and is defined by an inherited loss of
mismatch repair (MMR) gene function.174,175 Mismatch repair
enzymes are important proteins that fix small errors in the
gene code following DNA synthesis. The four most common
enzymes are MLH1, MSH2, PMS2, MSH6. Defects in the genes
coding for these enzymes can result in loss of the protein, as
well as loss of this important function. Tumours showing this
loss are said to be MMR deficient. MMRD cancers occur either
sporadically (~15-20% of all colorectal cancers, usually as a
result of methylation of the MLH1 gene), or less commonly
(~3%) associated with Lynch syndrome (formerly called
hereditary nonpolyposis colorectal cancer or HNPCC
syndrome) because of changes in the DNA sequence of the
genes (Table 2). The IHC stains can be performed on
diagnostic biopsy material or on the resection specimen.
In a small number of cases, MMR gene function is silenced by
a mutation in an adjacent gene e.g. EPCAM gene which is
immediately upstream of the MSH2 gene and prevents
transcription of the MSH2 gene and LRRFIP2 gene which is
adjacent to MLH1.
Not all MMR genes portend the same risk for CRC.174,175 Table
3 presents current data on the cumulative lifetime risk of CRC
and all cancers in patients with Lynch syndrome. Table 4
outlines a suggested multigene panel for assessment of CRC
with high genetic/familial risk.176
Screening for MMRD serves 2 useful clinical purposes: 1)
detection of Lynch syndrome and 2) Identification of
microsatellite instability in the colorectal carcinoma.
CG4.01b If stains have been done on the preoperative biopsy, these

results should be copied into the structured report, with
acknowledgement that they were performed on the biopsy
material.
CG4.01c Lynch-like syndrome refers to cases clinically suspected to

represent Lynch syndrome on the basis of MSI and deficiency
of immunohistochemical staining for a MMR protein, however
a germline mutation is not able to be identified (Figure 5).
Potential causes include biallelic somatic inactivation of
mismatch repair function or an as yet undetectable germline
abnormality. The latter is believed to be most common.
Currently, follow up is the same as if the patient had
confirmed Lynch syndrome.

CG4.01d In surgical resections there may be zones of poor fixation or
tumour hypoxia, so it is allowable to have up to 10% of the
tumour cells exhibiting equivocal or weak expression for
mismatch repair markers, so long as other areas of the
tumour show uniform strong expression.
See Table 2 for patterns of MMR expression and their clinical
significance.
G4.02 BRAF testing and/or MLH1 methylation testing should be performed where
appropriate.
CG4.02a 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.
G4.03 Screening for mismatch repair deficiency as a marker of microsatellite

instability should be performed.
CG4.03a Testing colorectal carcinoma for MMR protein deficiency is

used for Lynch syndrome screening and provides therapeutic
decision information for patient management. MMR deficiency
is associated with good prognosis, poor response to 5-
fluorouracil-based chemotherapy and predicts response to
immune checkpoint blockade therapy.177,178
G4.04 The result of extended RAS mutation testing should be recorded.
CG4.04a Testing for the presence of mutations in the RAS gene family
is typically requested by the clinician when metastatic disease
is present. Therefore, such testing will most often be
performed after the colorectal resection. In this situation, the
result should be appended to the initial pathology report.
CG4.04b Some studies suggest that individuals with RAS mutant

colorectal cancers have a reduced progression-free survival
and overall survival. More recently RAS mutation status has
been shown to predict response to drugs that specifically
target the epidermal growth factor receptor (EGFR).179-181
Tumours that harbour mutations in RAS are resistant to the
effects of these medications. Thus, testing for RAS mutations
will become increasingly important as the activity of anti EGFR
compounds is confined to only those patients with wild type
RAS mutations. Anti-EGFR treatments are often used in
individuals with metastatic disease, but the status of RAS
family genes in the primary tumour is usually the same as
that of metastases, and thus the findings from the primary
tumour block can be used to predict treatment response in
metastatic settings.
CG4.04c RAS mutation status is currently determined by a variety of

genetic methods that are not routine in most diagnostic

laboratory settings. The majority of these tests can be
performed on formalin fixed paraffin embedded tissue and
requests for blocks containing tumour for extended RAS panel
testing may be received many years after the primary cancer
has been resected. For this reason, for possible subsequent
mutation testing, it is desirable to designate a block from all
colorectal cancer resections that contains a high proportion
(preferably over 70%) of cancer. Ideally, the best block for
molecular testing and the percentage of viable tumour should
be documented in the histopathology report.
G4.05 Any additional studies for colorectal carcinoma should be performed.
CG4.05a 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.45 A Ki-67 proliferation index
<55% is associated with better overall survival in NECs.52
CG4.05b IHC can be performed to exclude metastatic carcinoma. The

classical immunophenotype of colorectal carcinoma is CK7
negative, CK20 positive CDX2 positive and SATB2 positive.
However, it is important to be aware that Cytokeratin 20 and
CDX-2 reactivity may be absent while conversely CK7
expression may be seen in microsatellite unstable colorectal
carcinomas.
CG4.05c Approximately 5% of all colorectal carcinomas arise as a

result of an inherited syndrome, with this prevalence being
10-15% in patients less than 50 years of age.
The detection of an inherited colorectal cancer syndrome
requires a high index of suspicion and knowledge of the
manifestations and inheritance of the common syndromes.
Table 4 is a summary of the more common syndromes.
Syndromes can be divided into those associated with
polyposis (serrated or adenomatous) and those not associated
with significant numbers of polyps (non polyposis) (Table 5).
The most common example of a non polyposis syndrome is
Lynch syndrome, which fortunately can be identified in most
cases via MMRD immunohistochemistry performed on the
colorectal carcinoma. The polyposis syndromes are evidenced
by large numbers of polyps typically developing at a younger
age (<50 years). As a general guidance the NHMRC minimum
requirements for referral to a genetic counselling service are
those provided for MUTYH syndrome and listed in Table 5.
Importantly, the polyp count is cumulative, so referral to
previous pathology findings is useful.
Referral to a genetics service for germline genetic testing for
mutations in MUTYH is indicated for persons with a cumulative
count of ≥20 colorectal adenomas at any age.
Testing may also be considered in patients with ≥10

adenomas and any of the following:182,183
• age under 50
• synchronous colorectal cancer
• both adenomatous and serrated polyps where the
adenomatous polyps dominate
• family history suggestive of recessive inheritance
(e.g. consanguinity in parents or siblings with
documented adenomatous polyposis or colorectal
cancer).
Genetic testing is now performed via a multigene panel. Table
5 lists the National Comprehensive Cancer Network (NCCN)
suggested panel for colorectal cancer.
Figure 5. Lynch-like syndrome
Adapted from Yozu M et al. Australasian Gastrointestinal Pathology Society (AGPS)

consensus guidelines for universal defective mismatch repair testing in colorectal
carcinoma. Pathology. 2019 Apr;51(3):233-239184

Table 2 Patterns of expression of mismatch repair immunohistochemistry and
their clinical significance184,185
Pattern of IHC expression Probability of Lynch Significance / further

MLH1 MSH2 MSH6 PMS2 Syndrome testing
+ + + + Very unlikely Normal pattern. No further
testing unless a strong clinical
suspicion of Lynch syndrome
exists
- + + - Sporadic microsatellite BRAF mutation testing (PCR or
instability high immunohistochemistry) or
Or MLH1 methylation
Lynch syndrome If BRAF mutation or MLH1
methylation is present –
sporadic CRC
If mutation/MLH1 methylation
is absent: investigate for
Lynch syndrome by MLH1,
followed by PMS2 germline
testing
+ - - + Likely MSH2, followed by MSH6
germline testing required
+ + -$ + Likely, unless MSH6, followed by MSH2
chemotherapy/radiotherapy germline testing required.
has been given No testing required if post
chemoradiotherapy
+ + + - Likely PMS2, followed by MLH1
germline testing.
This could also represent
MLH1 mutation producing
protein that is immunoreactive
to the MLH1
immunohistochemical stains
but is non-
- + -* - Unlikely MLH1 promoter
hypermethylation with a
secondary acquired mutation
in a mononucleotide
microsatellite of MSH6 gene
- - - - Possible Germline loss of MSH2 and
hypermethylation of MLH1
or hypermethylation silencing
of both MLH1 and MSH2
+# + + - Unlikely MLH1 promoter
hypermethylation
$ can have a nucleolar pattern of staining in post chemotherapy/radiotherapy setting

*(partial or complete)
# punctate pattern of staining (false positive)
Adapted from Yozu M et al. Australasian Gastrointestinal Pathology Society (AGPS)

consensus guidelines for universal defective mismatch repair testing in colorectal
carcinoma. Pathology. 2019 Apr;51(3):233-239184 and Pai RK & Pai RK. A Practical
Approach to the Evaluation of Gastrointestinal Tract Carcinomas for Lynch Syndrome.
Am J Surg Pathol. 2016 Apr;40(4):e17-34.185

Table 3. Cumulative lifetime risk of colorectal cancer and all cancers to age 75
years in patients with Lynch syndrome174,175
Mismatch Sex Cumulative Cumulative

repair risk of all risk of
gene cancers colorectal
(%) carcinoma
(%)
MLH1 Male 71.4 57.1
Female 81.0 48.3
MSH2 Male 75.2 51.4
Female 84.3 46.6
MSH6 Male 41.7 18.2
Female 61.8 20.3
PMS2 Male/Female 34.1 10.4
Modified from Moller et al (2018) Cancer risk and survival in path_MMR carriers by gene
and gender up to 75 years of age: a report from the Prospective Lynch Syndrome
Database. Gut 67(7):1306-1316 and Dominguez-Valentin et al (2020) Cancer risks by
gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings
from the Prospective Lynch Syndrome Database. Genet Med 22(1):15-25.174,175

Table 4. NCCN suggested multigene panel for assessment of colorectal
carcinoma with high genetic/familial risk176
Gene Risk level Disease Association

APC High FAP and attenuated FAP
ATM Unclear Increased risk for breast and colorectal cancer
AXIN2 Unclear - Polyposis and colorectal carcinoma, dental
possibly high- abnormalities
risk
BLM Unclear - low Colorectal carcinoma
heterozygotes risk at most
BMPR1A High Juvenile polyposis syndrome
CHEK2 Moderate Increased risk for breast and colorectal carcinoma
EPCAM High Lynch syndrome
GALNT12 Unclear - Colorectal carcinoma
probably low
risk
GREM1 Unclear - Hereditary mixed polyposis syndrome
possibly high-
risk
MLH1 High Lynch syndrome
MSH2 High Lynch syndrome
MSH6 High Lynch syndrome
MSH3 Unclear - Polyposis and colorectal carcinoma
possibly high-
risk
MUTYH High (biallelic Polyposis and colorectal carcinoma
mutations)
NTHL1 Unclear - Polyposis in colorectal carcinoma
possibly high-
risk
POLD1 Unclear - Polymerase proofreading associated polyposis
possibly high-
risk
POLE Unclear - Polymerase proofreading associated polyposis
possibly high-
risk
PMS2 high Lynch syndrome
PTEN Moderate to Cowden syndrome/PTEN hamartoma syndrome
high
SMAD4 High Juvenile polyposis syndrome
STK11 High Peutz-Jeghers syndrome
TP53 High Li Fraumeni syndrome
Adapted from Gupta et al NCCN Guidelines Insights: Genetic/Familial High-Risk

Assessment: Colorectal, Version 3.2017. J Natl Compr Canc Netw 15(12):1465-1475.176

Table 5. Familial syndromes associated with increased risk of colorectal cancer186
Syndrome Gene responsible Inheritance Typical phenotype Extracolonic manifestations
Early onset colorectal cancer, particularly in the

proximal colon
Endometrial, ovarian, gastric, pancreatic,
EPCAM deletion leading to
Autosomal urothelial, renal pelvic, small intestine,
Lynch syndrome* epigenetic silencing of MSH2 , The incidence of adenomas is not high but
dominant biliary tract, brain, sebaceous gland
MLH1, MSH6 or PMS2 those that do arise have a high risk of rapidly
adenomas and keratoacanthomas
progressing to malignancy; Cancers display
microsatellite instability
Familial
Autosomal Duodenal, gastric, desmoid, brain, thyroid,
adenomatous APC > 100 adenomas
dominant hepatoblastoma
polyposis (FAP)*
Attenuated FAP Autosomal > 10 adenomas before age 30 years or 20–100
APC Duodenal, gastric
(AFAP) dominant adenomas
MUTYH-associated Autosomal
MUTYH Usually 20–100 adenomas but may have > 100 Duodenal, gastric
polyposis recessive
Polymerase
proofreading- Autosomal 10–100 adenomas and variable number of
POLD1 or POLE Endometrial
associated polyposis dominant serrated polyps
(PPAP)
NTHL1-associated Autosomal
NTHL1 8–50 adenomatous polyps Endometrial
polyposis (NAP) recessive
Histologically characteristic hamartomatous
Peutz-Jeghers Autosomal Upper gastrointestinal and small intestine,
STK11 polyps throughout gastrointestinal tract and
syndrome dominant breast, gynaecological, pancreas
mucocutaneous pigmentation
Histologically characteristic hamartomatous Upper gastrointestinal and small intestine
Juvenile polyposis Autosomal
SMAD4 or BMPR1A polyps throughout gastrointestinal tract; polyps but no evidence of excess risk for extra-
syndrome dominant
of mixed histology may also be present gastrointestinal cancers
At least 5 serrated polyps proximal to the
Unclear and
Serrated polyposis sigmoid with ≥ 2 of these > 10 mm or > 20
Unknown low Nil known
syndrome serrated polyps of any size but distributed
penetrance
throughout the colon

Some patients develop adenomas and
hyperplastic polyps in addition to colonic
hamartomas.
Breast, endometrial, thyroid, renal, skin
Autosomal lesions (trichilemmoma, papilloma).
Cowden syndrome PTEN There is no evidence that all families with
dominant Cowden Syndrome is often associated
PTEN are at high risk of bowel cancer. Families
with macrocephaly.
with a history of colorectal cancer should follow
screening guidelines based on their family
history.
*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.
In: Cancer Council Australia Colorectal Cancer Guidelines Working Party. Clinical practice guidelines for the prevention, early detection
and management of colorectal cancer. Sydney: Cancer Council Australia. Available from:
https://wiki.cancer.org.au/australia/Guidelines:Colorectal_cancer.186

5 Synthesis and overview
Information that is synthesized from multiple modalities and therefore cannot reside
solely in any one of the preceding chapters is described here. For example, tumour stage
is synthesized 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).
S5.01 The tumour stage and stage grouping must be recorded,

incorporating clinical and pathological data, based on the TNM
staging system of the AJCC Cancer Staging Manual (8th Edition).56
CS5.01a TNM staging should be assessed according to the agreed

criteria of the UICC and AJCC 8th editions.1,26 The only
exception is that pT in situ is not recognised for colorectal
cancer in this protocol. Rare cases of colorectal neoplasia
confined to invasion of the lamina propria (intramucosal
invasive neoplasia or intramucosal carcinoma) are
acknowledged but, given the negligible metastatic potential of
such neoplasms,68 these should be classified under the same
category with high grade dysplasia/high grade non-invasive
neoplasia.
Note in the setting of completion surgery following a diagnosis
of carcinoma in a local excision specimen, an overall tumour
stage should be provided based on the pathological findings
within both specimens, usually taking into consideration
extent of local invasion in the local excision specimen and any
residual local or nodal metastatic tumour in the subsequent
surgical resection specimen.
Regarding synchronous carcinomas, whilst individual protocols
should be completed for each tumour, a single overarching
stage should be provided, following the conventions of TNM
and applying the ‘m’ suffix.
CS5.01b The allocation of the TNM stage relies upon synthesis of

information provided in the clinical request form and following
macroscopic and microscopic examination.
CS5.01c The y prefix must be used if there has been prior

chemotherapy or radiotherapy.
CS5.01d The terminology pM1 (distant metastases present) should only

be used by pathologists on the basis of pathological
assessment of a relevant tissue sample. However, pathologists
are strongly encouraged to use clinical terminology (cM0,
cM1) in their final report on the basis of information provided
to them on the surgical request form. It may advisable to
make this clear in a comment (i.e. cM1 – based on clinical

evidence of liver metastases). Under this scenario, the
hierarchy of M stage reports available to the pathologist would
be as follows:
• pM1 in the presence of pathologically proven metastatic
disease
• cM1 where clinical information stated metastases were
present but where there was no pathological evidence of
this
• cM0 where there was a clinical statement of no metastases
and no pathological evidence of metastases.
S5.02 The residual tumour status must be recorded according to the

AJCC Cancer Staging Manual (8th Edition)56
CS5.02a The R codes are as follows. (Used with the permission of the
American Joint Committee on Cancer (AJCC), Chicago, Illinois.
The original source for this material is the AJCC Cancer
Staging Manual, 8th Edition (2017) published by Springer
Science and Business Media LLC, www.springerlink.com.)
• RX: Presence of residual tumour cannot be assessed
• R0: No residual tumour
• R1: Microscopic residual tumour
• R2: Macroscopic residual tumour at the primary cancer site
or regional notal sites (This designation is not used to
indicate metastatic disease identified but not resected at
surgical exploration.)
CS5.02b Residual tumour classification (R status) is not incorporated

into TNM8 staging.1 However, the absence or presence of
residual tumour and status of the margins may provide
important information that affects subsequent treatment and
prognosis and may be recorded in the medical record and
cancer registry.1
CS5.02c The resection status rule also applies to lymph nodes. If a

positive lymph node is left behind it is classified as R2.
CS5.02d Tumour cells that are confined to the lumen of blood vessels
or lymphatics at the resection margin are classified as R0.187
CS5.02e Peritoneal involvement alone is not a reason to categorise the

tumour as incompletely excised.
S5.03 The year of publication and/or edition of the cancer staging

system used in S5.01 must be included in the report.
G5.01 The ‘Diagnostic summary’ section of the final formatted report should
include:
a. specimen label
b. tumour site
c. histological tumour type

d. margin status
e. tumour stage
S5.04 A field for free text or narrative in which the reporting pathologist
can give overarching case comment must be provided.
CS5.04a 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.
CS5.04b 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’.

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 colorectal cancer. 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.188
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.

Item descriptions in italics are conditional on previous responses.
Values in all caps are headings with sub values.
S/G Item description Response type Conditional

Pre-analytical
S1.01 Demographic information
provided
S1.02 Clinical information provided Text
on request form
OR
Information not provided
OR
Structured entry as below:
Known polyposis syndrome Multi selection value list (select all that
apply):
• Familial adenomatous polyposis (FAP)
• MUTYH-associated polyposis (MAP)
• Serrated polyposis
• Other, specify
Lynch syndrome Text
Chronic inflammatory bowel Multi selection value list (select all that
disease apply):
• Ulcerative colitis
• Crohn disease
Previous polyp(s) Text
Previous colorectal cancer Text
Other Text

Neoadjuvant therapy Single selection value list: Describe neoadjuvant therapy, if
known
• Information not provided
• Not administered
• Administered, describe
G1.01 Copy To doctors recorded Text
S1.03 Pathology accession number Alpha-numeric
S1.04 Principal clinician Text
G1.02 Other clinical information Text
received
Macroscopic findings
S2.01 Specimen labelled as Text
S2.02 Clinical information Text
S2.03 Operative procedure Not specified
OR
Single select value list:
• Total colectomy
• Proctocolectomy
• Right hemicolectomy
• Extended right hemicolectomy
• Transverse colectomy
• Left hemicolectomy
• Sigmoid colectomy
• Anterior resection (specify if possible)
o High

o Low/ultralow
• Abdominoperineal resection
• Other, specify
S2.04 Specimen length Numeric:___mm
S2.05r Tumour site Single selection value list: If multiple tumours are present,
separate protocols should be
• Not specified
used to record this and all
• Caecum following elements for each
tumour.
• Ascending colon
• Hepatic flexure
• Transverse colon
• Splenic flexure
• Descending colon
• Sigmoid colon
• Rectosigmoid*
• Rectum
• Other, specify
*Note: Reserved for cases in which an accurate
determination between rectum and sigmoid
cannot be made by pathological assessment and
clinical information regarding site is not available.
S2.06r Tumour dimensions Single selection value list:
• Cannot be assessed, specify
OR
Text: Tumour identification
AND

Numeric: ___mm maximum dimension (largest
tumour)
Notes:
Repeat tumour identification and maximum
dimension for each tumour identified.
Additional dimensions (largest Numeric: ____mm x ____mm
tumour)
S2.07r Distance of tumour to the Single selection value list:
nearer proximal or distal ‘cut
• Cannot be assessed
end’
OR
Numeric: ___mm
S2.08r Distance of tumour to the Single selection value list:
nonperitonealised
circumferential margin
OR
Numeric: ___mm
S2.09r Tumour perforation (defined Single selection value list:
as a macroscopically visible
• Not identified
full thickness defect in the
wall) • Present
o Through tumour (tumour
perforation)
o Not involving tumour
S2.10r Relation of tumour to Single selection value list: Applicable to any specimen
anterior peritoneal reflection containing a rectal cancer e.g.
• Not applicable
(rectal cancer specimens anterior resection,
only) • Entirely above abdominoperineal resection,
proctocolectomy
• Entirely below

• Astride
S2.11r Plane of mesorectal excision Single selection value list: Applicable to any specimen
(rectal cancer specimens containing a rectal cancer e.g.
• Not applicable
only) anterior resection,
• Mesorectal fascia (complete) abdominoperineal resection,
proctocolectomy
• Intramesorectal (near complete)
• Muscularis propria (incomplete)
G2.01r Plane of sphincter excision Single selection value list: Applicable to abdominoperineal
(abdominoperineal excision excision specimens only and
• Extralevator plane
specimens only) should be reported in addition to
• Sphincter plane the mesorectal plane
• Intrasphincter plane
G2.02r Plane of mesocolic excision Single selection value list: Applicable to any specimen
(colon cancer specimens only) containing a colon cancer
• Mesocolic plane
• Intramesocolic plane
• Muscularis propria plane
G2.03r Peritoneum Single selection value list:
• Tumour invades to the peritoneal surface
• Tumour has formed nodule(s) discrete
from the tumour mass along the serosal
surface
G2.04 Other macroscopic comments Text
Microscopic findings
S3.01r Histological tumour type Single selection value list from WHO
Classification of Tumours of the
Gastrointestinal Tract (2019).
Single selection value list:

• Adenocarcinoma, not otherwise specified
(NOS)
• Mucinous adenocarcinoma
• Signet-ring cell adenocarcinoma
• Medullary carcinoma
• Serrated adenocarcinoma
• Micropapillary adenocarcinoma
• Adenoma-like adenocarcinoma
• Other, specify
S3.02r Histological tumour grade Single selection value list: Only adenocarcinoma, NOS, and
mucinous adenocarcinoma
• Not applicable
should be graded
• Low grade >50% (formerly well to
moderately differentiated)
• High grade <50% (formerly poorly
differentiated and undifferentiated)
S3.03r Extent of invasion Single selection value list:
• No evidence of primary tumour
OR
Multi selection value list (select all that
apply):
• High grade dysplasia/non-invasive
neoplasia
• Invasion into submucosa
• Invasion into muscularis propria
• Invasion into subserosa or into pericolic or

perirectal tissues
• Invasion onto the surface of the visceral
peritoneum
• Invasion directly into other
structures/organs, specify
G3.01r Measurement of invasion beyond Single selection value list:
muscularis propria (for pT3
tumours)
OR
Distance beyond muscularis Numeric: __mm
propria
G3.02 Inflammatory cell infiltrate Text Record the scoring system used
S3.04 Lymphatic and venous Single selection value list:
invasion
• Not identified
• Present, specify
Multi selection value list (select all
that apply):
o Small vessel (lymphatic, capillary
or venular)
o Large vessel (venous)
 Intramural
 Extramural
• Indeterminate, specify
S3.05 Perineural invasion Single selection value list:
• Not identified
• Present
S3.06 LYMPH NODE STATUS No nodes submitted or found

OR
Number of lymph Number cannot be assessed
nodes examined
OR
Numeric: ___
Single selection value list: Record the number of lymph
nodes (LN) examined.
• Not involved
If involved, specify the number
• Involved
of positive LN
Number of positive Numeric: ___ Not required if number cannot
lymph nodes be determined is entered above.
G3.03 Apical node involvement Single selection value list:
• Not applicable
• Absent
• Present
G3.04 Ratio of involved/total lymph Involved lymph nodes __ / total lymph
nodes nodes __
S3.07 Tumour deposits Single selection value list: If tumour deposits are present,
specify number of deposits
• Not identified
• Present, specify type
o Vascular
o Other
Number of tumour deposits Numeric: ___
G3.05r Tumour budding Cannot be assessed Should only be reported in non-
mucinous and non-signet-ring
OR
cell adenocarcinoma areas

Number of tumour buds Numeric: ___
Note: After scanning 10 fields on a 20x objective
lens, the hotspot field normalised to 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)
S3.08 Response to neoadjuvant Single selection value list:
therapy
• No neoadjuvant treatment
• Complete response - No viable cancer
cells (score 0)
• Near complete response - Single cells or
rare small groups of cancer cells (score 1)
• Partial response - Residual cancer with
evident tumour regression, but more than
single cells or rare small groups of cancer
cells (score 2)
• Poor or no response - Extensive residual
cancer with no evident tumour regression
(score 3)
• Cannot be assessed, specify
S3.09r MARGIN STATUS
Longitudinal margin status Single selection value list: If not involved by invasive
carcinoma, estimate distance to
closer margin
• Not involved
If involved by invasive
• Involved carcinoma, specify proximal or

Note: Includes assessment of any separately distal margin
submitted anastomotic ring(s).
Distance to closer margin Numeric: __mm
Proximal or distal margin Numeric: __mm
Circumferential margin Single selection value list: If not involved by invasive

status carcinoma record the distance to
nearest 1 mm or >10 mm
• Not involved
If involved by invasive
• Involved carcinoma specify 0 mm or
distance to nearest 0.1 mm
Not involved - Distance to Numeric: __mm
nearest 1 mm or >10 mm
OR
>10 mm
Involved (<1 mm) – specify 0 Numeric: __mm
mm or distance to nearest 0.1
OR
mm
• By primary tumour
• By other, specify
S3.10 Distant metastases Single selection value list:
• Not identified
• Present, specify site(s)
G3.06 Coexistent pathological None identified
abnormalities
OR
Multi select value list:

• Polyp(s), specify
• Synchronous carcinoma(s), specify
• Other, specify
S3.11 Microscopic residual tumour Text
status (completeness of
resection)
G3.07 Additional microscopic comment Text

Ancillary findings
G4.01r Ancillary studies
Mismatch repair (MMR) Not tested
immunohistochemistry
OR
Not interpretable
OR
• MMR proficient
• MMR deficient
o MLH1/PMS2 loss
o MSH2/MSH6 loss
o MSH6 loss
o PMS2 loss
o Other, specify
G4.02 BRAF (V600E) mutation testing Not tested
OR

• Test failed
• Mutated
• Wild type
MLH1 promoter methylation Not tested
testing
OR
• Test failed
• Methylated
• Not methylated
• Inconclusive
G4.03 MMR status by microsatellite Not tested
instability (MSI) testing
OR
Multi select value list:
• Test failed
• MSI-high
• MSI-low
• MSI-stable
G4.04r RAS gene mutation testing Single selection value list: If mutated or wild type, record
(KRAS exons 2, 3 or 4, NRAS laboratory performing test and
• Mutated
exons 2, 3 or 4 or RAS report number
mutation) • Wild type
• Not tested
Comments Text
Laboratory performing test and Text

report number
G4.05 Neuroendocrine neoplasm Text For neuroendocrine neoplasms

neuroendocrine markers only
Ki-67 (labelling index) Numeric: ___ %
Other Text
Synthesis and overview

S5.01 PATHOLOGICAL STAGING
(AJCC 8TH EDITION)
TNM descriptors Multi select value list :
• m - multiple primary tumours
• r – recurrent
• y – post therapy
Primary tumour (pT) Single select value list :
TX Primary tumour cannot be assessed
T0 No evidence of primary tumour
Tis Carcinoma in situ, intramucosal carcinoma

(involvement of lamina propria with no
extension through muscularis mucosae)
T1 Tumour invades the submucosa (through

the muscularis mucosa but not into the
muscularis propria)
T2 Tumour invades the muscularis propria
T3 Tumour invades through the muscularis

propria into pericolorectal tissues

T4 Tumour invades* the visceral peritoneum or
invades or adheres** to adjacent organ or
structure
T4a Tumour invades* through the visceral

peritoneum (including gross perforation of
the bowel through tumour and continuous
invasion of tumour through areas of
inflammation to the surface of the visceral
peritoneum)
T4b Tumour directly invades* or adheres** to

adjacent organs or structures
**Direct invasion in T4 includes invasion of other

organs or other segments of the colorectum as a
result of direct extension through the serosa, as
confirmed on microscopic examination (for
example, invasion of the sigmoid colon by a
carcinoma of the cecum) or, for cancers in a
retroperitoneal or subperitoneal location, direct
invasion of other organs or structures by virtue
of extension beyond the muscularis propria (i.e.,
respectively, a tumour on the posterior wall of
the descending colon invading the left kidney or
lateral abdominal wall; or a mid or distal rectal
cancer with invasion of prostate, seminal
vesicles, cervix, or vagina).
**Tumour that is adherent to other organs or

structures, grossly, is classified cT4b. However, if
no tumour is present in the adhesion,
microscopically, the classification should be pT1-
4a depending on the anatomical depth of wall
invasion. The V and L classification should be
used to identify the presence or absence of

vascular or lymphatic invasion whereas the PN
prognostic factor should be used for perineural
invasion.
Regional lymph node (pN) Single selection value list:

NX Regional lymph nodes cannot be
assessed
N0 No regional lymph node metastasis
N1 One to three regional lymph nodes are
positive (tumour in lymph nodes
measuring ≥0.2 mm), or any number of
tumour deposits are present and all
identifiable lymph nodes are negative
N1a One regional lymph node is positive
N1b Two or three regional lymph nodes are
positive
N1c No regional lymph nodes are positive,
but there are tumour deposits in the
• subserosa
• mesentery
• or nonperitonealized pericolic, or
perirectal/mesorectal tissues.
N2 Four or more regional nodes are positive
N2a Four to six regional lymph nodes are
positive
N2b Seven or more regional lymph nodes are
positive
Distant metastasis (pM) Single selection value list:
M0 No distant metastasis by imaging, etc.;
no evidence of tumour in distant sites or
organs (This category is not assigned by
pathologists.)
M1 Metastasis to one or more distant sites
or organs or peritoneal metastasis is

identified
M1a Metastasis to one site or organ is
identified without peritoneal metastasis
M1b Metastasis to two or more sites or
organs is identified without peritoneal
metastasis
M1c Metastasis to the peritoneal surface is
identified alone or with other site or
organ metastases
S5.02 Residual tumour status Single selection value list:
RX: Presence of residual tumour cannot be
assessed
R0: No residual tumour
R1: Microscopic residual tumour
R2: Macroscopic residual tumour at the
primary cancer site or regional nodal
sites. (This designation is not used to
indicate metastatic disease identified but
not resected at surgical exploration.)
S5.03 Year and edition of staging Numeric: year

system
AND
Text: Edition e.g. 1st, 2nd etc
G5.01 Diagnostic summary Text
Include:
a. specimen label
b. tumour site
c. histological tumour type
d. margin status
e. tumour stage

S5.04 Overarching comment Text
G5.02 Edition/version number of the Text
RCPA protocol on which the
report is based

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.

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 colorectal cancer 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.
Also included in this appendix are the procedures that are recommended before
handover of specimens to the laboratory.
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 Identifier
(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 pathology reports. The
presence of a known polyposis syndrome, Lynch-syndrome, chronic
inflammatory bowel disease or any other relevant gastrointestinal
disorder should be recorded and provided to the pathologist, as
awareness of such underlying conditions may influence both

specimen sampling and histological interpretation.
 It may be important to note the presence of previous polyps if they could

indicate an undiagnosed polyposis syndrome (see Table 5).
 The surgeon’s identity and contact details should be recorded.
• Name of operating surgeon, contact details, and date of

operation.
 Perforation and/or obstruction should be recorded.
• Perforation may be more easily appreciated by the surgeon than

the pathologist. Tumour perforation is a prognostic factor in
determining postoperative mortality and long-term survival.
Perforation away from the tumour, related to colonic obstruction
by the tumour, should be distinguished from perforation through
the tumour. Perforation occurring during the course of surgery
should be differentiated from the above and should be identified
as such by the surgeon on the surgical request form.
 The tumour site must be recorded.
• If multiple primary tumours are present, separate protocols

should be used to record tumour site and all following elements
for each primary tumour. Determination of tumour site is based
on clinical information provided on the pathology request form
combined with specimen assessment by the pathologist. Any
significant discrepancy should be discussed with the clinical team
and the tumour site clearly documented by specimen
photography. Recording the anatomical site of tumour allows
correlation with prior endoscopic and radiological investigations,
indicates whether or not a nonperitonealised margin is likely to be
present and defines the presence of regional versus non-regional
lymph nodes. In particular, distinction of colonic from rectal origin
is of importance, given different biologies, clinical features and
management. Every effort should be made, therefore, to
accurately classify a tumour as colonic or rectal in origin.
If a tumour straddles two sites, the site with the greatest tumour
bulk should be recorded. The three taeniae coli of the sigmoid
colon fuse to form the circumferential longitudinal muscle of the
rectal wall, marking the rectosigmoid boundary. If distinction
between the sigmoid colon and rectum is not possible by
pathological assessment, for example owing to advanced tumour
stage obliterating anatomical landmarks, the tumour site can be
recorded based on clinical information available.
Classification as rectosigmoid should be reserved for cases in
which an accurate determination between rectum and sigmoid
cannot be made by pathological assessment and clinical
information regarding site is not available.
• Choose from one of the following:

• caecum

• ascending colon
• hepatic flexure
• transverse colon
• splenic flexure
• descending colon
• sigmoid colon
• rectosigmoid junction
• rectum.
• For synchronous tumours indicate each other site for which a

separate report will be submitted.
 The distance from the anal verge should be recorded (for rectal tumours
only).
• This should be measured in centimetres (by longstanding surgical

convention) using the best available information; rigid
sigmoidoscopy measurements are preferred over digital rectal
examination, operative findings or colonoscopy measurements.
• This measurement allows for the classification of rectal cancers

into upper, mid- and lower third categories, which has a
significant impact on case management.
 The operative procedure must be recorded.
• Information regarding the nature of the operative procedure

should be provided, with any refinements as necessary, for
example the attempted dissection plane in an abdominoperineal
resection. Should the operative specimen include any tissue or
organ not typically submitted within that specimen type, for
example en bloc resection of a segment of intestine or abdominal
wall connective tissue, this should be clearly indicated. Inclusion
of the peritoneal reflection within an anterior resection specimen
distinguishes a low anterior resection from a high anterior
resection.
• Choose from one of the following:

• Total colectomy (with ileorectal anastomosis)
• Proctocolectomy
• Right hemicolectomy
• Extended right hemicolectomy
• Transverse colectomy
• Left hemicolectomy
• Sigmoid colectomy
• Anterior resection (specify whether high or low)
• Hartmann procedure
• Abdominoperineal resection

• Other, specify
 If neoadjuvant therapy has been administered, this must be

recorded.
• Given implications for staging and interpretation of morphological

features related to the primary tumour, it is important that clinical
information is provided to the pathologist regarding the
application of any neoadjuvant therapy, and details of such
therapy, for example radiotherapy and/or chemotherapy, duration
and timing in relation to surgery
• For rectal cancer, preoperative radiotherapy significantly alters

the gross and microscopic appearance of the tumour.
• Short-course and long-course radiotherapy regimes need to be

differentiated because the effects in the resected specimens are
quite different.
 The surgeon’s opinion on the existence of local residual cancer following

the operative procedure should be recorded.
• This item relates to the overall completeness of resection of the

tumour, including evidence of residual disease at surgical margins
or within regions in which resection has not been attempted. It
allows for residual tumour status (R) to be assessed (see
Chapters 2 and 3).
 The involvement of adjacent organs should be recorded.
• With regard to extension of disease into areas which either have

or have not been resected (i.e. involvement of other organs or
tissues by direct spread), it is the responsibility of the surgeon to
report these deposits and, if indicated, mark these areas with a
suture or other marker.
 Record if this is a new primary cancer or a recurrence of a

previous cancer, if known.
• The term recurrence defines the return, reappearance or

metastasis of cancer (of the same histology) after a disease free
period.
Recurrence should be classified as distant metastases or regional
(local) recurrence.
Regional (local) recurrence refers to the recurrence of cancer cells
at the same site as the original (primary) tumour or the regional
lymph nodes.
Distant metastasis refers to the spread of cancer of the same
histologic type as the original (primary) tumour to distant organs
or distant lymph nodes.
• The reporting of metastatic deposits, either resected or not

resected, is required for assessment of the metastatic (M) stage
of the tumour.

• The presence of involved nonregional lymph nodes stages the
tumour as M1.
• This information will provide an opportunity for previous reports

to be reviewed during the reporting process, which may provide
valuable information to the pathologist. This information also has
implications for recording cancer incidence and evidence based
research.
 Any additional relevant information should be recorded.
• A free text field should be completed by the referring doctor to

communicate anything that is not addressed by the above points,
such as previous cancers, risk factors, investigations, treatments
and family history.

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

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 similar data elements under headings and using ‘white space’ assists in rapid
transfer of information.189
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.189
• Reduce ‘clutter’ to a minimum.189 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.

Appendix 3 Example of a pathology report

Appendix 4 WHO Classificationa 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

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).190 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.

Appendix 5 Histological tumour types –
example representative images
Micropapillary carcinoma
Medullary carcinoma (patient with Lynch syndrome)

Rhabdoid carcinoma
Mucinous carcinoma

Signet ring cell carcinoma (intramucosal)
Neuroendocrine carcinoma arising in a tubulovillous adenoma

Large cell neuroendocrine carcinoma
Undifferentiated carcinoma

Adenoma-like carcinoma

Appendix 6 Regression grading systems
Table 6. Comparison of regression grading systems
Descriptive AJCC Mandard191 Becker192 Dworak193

appearance (Ryan)154
No residual 0 (no residual 1 (no residual 1a (complete 4 (no vital

tumour tumour cells) cancer cells) regression, 0% tumour cells
tumour) detected)
Near complete 1 (single cell or 2 (rare cancer 1b (< 10% 3 (scattered

tumour small groups of cells) residual tumour cells -
regression cells) tumour) difficult to find)
Partial tumour 2 (residual 3 (fibrosis 2 (10-50% 2 (scattered

regression cancer with outgrowing residual tumour cells -
desmoplastic residual cancer) tumour) easy to find)
response)
No tumour 3 (extensive 4 (residual 3 (>50% 1

regression residual cancer) cancer residual (predominantly
outgrowing tumour) tumour with
fibrosis) significant
fibrosis and/or
vasculopathy)
5 (cancer with 0 (no

no changes of regression)
regression)

Appendix 6 Practice audits
Structured reporting for colorectal carcinoma presents 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 colorectal
tumours are ideal for performing practice audits.
In some jurisdictions194-196 the following parameters have been helpful for practice audit
and cross practice correlation:
1) frequency of diagnosis of the various WHO subtypes
2) frequency of serosal invasion (pT4a)
3) frequency of venous invasion197
4) frequency of perineural invasion
5) frequency of high-level tumour budding – BD3
6) lymph node yield (how often are ≥12 or more lymph nodes identified in resection
specimens?)196,197
7) MMR immunohistochemistry (how often is MMRD identified?)196

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COLORECTAL CANCER

2 Colorectal Cancer Structured Reporting Protocol 4th edition

Publications number (SHPN): (CI) 200281

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

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

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

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

First published: November 2020, 4th Edition (Version 4.0)

3 Colorectal Cancer Structured Reporting Protocol 4th edition

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

4 Colorectal Cancer Structured Reporting Protocol 4th edition

Authority and development .............................................................................. 14

2 Specimen handling and macroscopic findings ........................................ 20

3 Microscopic findings ............................................................................... 33

4 Ancillary findings ................................................................................... 52

5 Synthesis and overview ......................................................................... 61

6 Structured checklist ............................................................................... 64

7 Formatting of pathology reports ............................................................ 82

Appendix 1 Pathology request information and surgical handling

Appendix 2 Guidelines for formatting of a pathology report ......................... 89

Appendix 3 Example of a pathology report ................................................... 90

Appendix 4 WHO Classificationa of tumours of the colon and rectum 5th

Appendix 5 Histological tumour types – example representative

Appendix 6 Regression grading systems ...................................................... 99

Appendix 6 Practice audits ......................................................................... 100

References ..................................................................................................... 101

5 Colorectal Cancer Structured Reporting Protocol 4th edition

Structured reporting aims to improve the completeness and usability of pathology

AJCC American Joint Committee on Cancer

CRC Colorectal cancer

CRM Circumferential resection margin

HNPCC Hereditary nonpolyposis colorectal cancer

ICCR International Collaboration on Cancer Reporting

LIS Laboratory information system

MiNEN Mixed neuroendocrine-non-neuroendocrine neoplasm

MMR Mismatch repair

MMRD Mismatch repair deficient

MRI Magnetic resonance imaging

MSI Microsatellite instability

NCCN National Comprehensive Cancer Network

NEC Neuroendocrine carcinoma

NET Neuroendocrine tumour

NHMRC National Health and Medical Research Council

PBS Pharmaceutical Benefits Scheme

R Residual tumour status

RCPA Royal College of Pathologists of Australasia

TME Total mesorectal excision

UICC Union for International Cancer Control

WHO World Health Organization

7 Colorectal Cancer Structured Reporting Protocol 4th edition

Clinical Patient information required to inform pathological assessment,

Commentary Commentary is text, diagrams or photographs that clarify the

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

8 Colorectal Cancer Structured Reporting Protocol 4th edition

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

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

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

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

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

9 Colorectal Cancer Structured Reporting Protocol 4th edition

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

Synthesis Synthesis is the process in which two or more preexisting

10 Colorectal Cancer Structured Reporting Protocol 4th edition