Cancer of the Exocrine Pancreas, Ampulla of Vater and Distal Common Bile Duct STRUCTURED REPORTING PROTOCOL (2nd Edition 2020)

Incorporating the: International Collaboration on Cancer Reporting (ICCR) Carcinoma of the Exocrine Pancreas Dataset www.ICCR-Cancer.org Core Document versions:

• AJCC Cancer Staging Manual 8th edition, American Joint Committee on Cancer, 2016 • World Health Organization Classification of Tumours, Digestive System Tumours. 5th Edition, 2019 • ICCR dataset: Carcinoma of the Exocrine Pancreas 1st edition v1.0

2 Cancer of the Exocrine Pancreas, Ampulla of Vater and Distal Common Bile Duct Structured Reporting Protocol 2nd edition

ISBN: 978-1-76081-426-7

Publications number (SHPN): (CI) 200283

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© RCPA 2020

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o The wording of the Standards may not be altered in any way and must be included as part of the checklist.

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Apart from any use as permitted under the Copyright Act 1968 or as set out above, all other rights are reserved. Requests and inquiries concerning reproduction and rights should be addressed to RCPA, 207 Albion St, Surry Hills, NSW 2010, Australia.

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

3 Cancer of the Exocrine Pancreas, Ampulla of Vater and Distal Common Bile Duct Structured Reporting Protocol 2nd edition

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 protocols and to update the protocols regularly. However subject to any warranties, terms or conditions which may be implied by law and which cannot be excluded, the protocols are provided on an "as is" basis. The College does not warrant or represent that the protocols are complete, accurate, error-free, or up to date. The protocols do not constitute medical or professional advice. Users should obtain appropriate medical or professional advice, or where appropriately qualified, exercise their own professional judgement relevant to their own particular circumstances. Users are responsible for evaluating the suitability, accuracy, currency, completeness and fitness for purpose of the protocols.

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4 Cancer of the Exocrine Pancreas, Ampulla of Vater and Distal Common Bile Duct Structured Reporting Protocol 2nd edition

Contents

Scope ...... 6

Abbreviations ...... 7

Definitions ...... 8

Introduction ...... 10

Authority and development ...... 13

1 Pre-analytical ...... 17

2 Specimen handling and macroscopic findings ...... 19

3 Microscopic findings ...... 25

4 Ancillary findings ...... 32

5 Synthesis and overview ...... 33

6 Structured checklist ...... 35

7 Formatting of pathology reports ...... 57

Appendix 1 Pathology request information and surgical handling procedures ...... 58

Appendix 2 Guidelines for formatting of a pathology report ...... 61

Appendix 3 Example of a pathology report ...... 62

Appendix 4 WHO Classification of Tumours of the pancreas ...... 64

Appendix 5 WHO Classification of tumours of the small intestine and ampulla ...... 66

Appendix 6 WHO Classification of Tumours of the gallbladder and extrahepatic bile ducts ...... 67

References ...... 68

5 Cancer of the Exocrine Pancreas, Ampulla of Vater and Distal Common Bile Duct Structured Reporting Protocol 2nd edition

Scope

This protocol contains standards and guidelines for the preparation of structured reports for cancer of the exocrine pancreas, ampulla of Vater and distal common bile duct. It excludes cancer of the duodenum apart from those occurring in the periampullary region. Endocrine, haematological and mesenchymal neoplasms occurring within the pancreas have different requirements for reporting and are therefore not covered in this protocol.

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 cancer of the exocrine pancreas, ampulla of Vater and distal common bile duct, whether as a minimum data set or fully comprehensive report. Abbreviations

AJCC American Joint Committee on Cancer

ICCR International Collaboration on Cancer Reporting

LIS Laboratory information system

NOS Not otherwise specified

PanIN Pancreatic intraepithelial neoplasia

R Residual tumour status

RCPA Royal College of Pathologists of Australasia

SMA Superior mesenteric artery

SMV Superior mesenteric vein

TNM Tumour-node-metastasis

UICC Union for International Cancer Control

WHO World Health Organization

7 Cancer of the Exocrine Pancreas, Ampulla of Vater and Distal Common Bile Duct Structured Reporting Protocol 2nd edition

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 not essential for clinical management, staging or prognosis of a cancer, but are recommended. Guidelines include key observational and interpretative findings that are fundamental to the diagnosis and conclusion. Such findings are essential from a clinical governance perspective, because they provide a clear, evidentiary decision-making trail.

8 Cancer of the Exocrine Pancreas, Ampulla of Vater and Distal Common Bile Duct Structured Reporting Protocol 2nd edition

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).

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.

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.

Standard Standards are mandatory, as indicated by the use of the term ‘must’. Their use is reserved for core items essential for the clinical management, staging or prognosis of the cancer and key information (including observations and interpretation) which is fundamental to the diagnosis and conclusion. 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 pre-existing elements are combined, resulting in the formation of something new. The Oxford dictionary defines synthesis as ‘the combination of components or elements to form a connected whole’. In the context of structured pathology reporting, synthesis represents the integration and interpretation of information from two or more modalities to derive new information.

9 Cancer of the Exocrine Pancreas, Ampulla of Vater and Distal Common Bile Duct Structured Reporting Protocol 2nd edition

Introduction

Cancer of the exocrine pancreas, ampulla of Vater and distal common bile duct

Australian data for ‘pancreatic cancer’ show that it is the 5th highest cause of cancer related deaths with a 5 year survival of 9.8%.1 Tumour staging and eligibility for adjuvant therapy depend on tumour origin, emphasising the need to accurately identify and report these tumours accordingly.2-9 The vast majority (90%) of these cancers are adenocarcinomas, which arise in the exocrine pancreas (43-77%), followed by adenocarcinomas of the ampulla (11-12%), distal common bile duct (10-11%) and duodenum (4-5%).2,3,10 The true origin of carcinomas arising in this region may be difficult to determine due to the size of these tumours relative to normal structures, the ‘field effect’ of dysplasia and the ability of carcinomas to colonise epithelial surfaces and mimic dysplasia.11 Nevertheless, an informed decision can be made in many cases through detailed macroscopic and microscopic assessment.12 Endocrine, neuroendocrine, haematological and mesenchymal neoplasms occurring within the pancreas have different requirements for reporting and will not be covered in this protocol.

Benefits of structured reporting The pathology report lays the foundation for a patient’s cancer journey and conveys information which: • Provides the definitive diagnosis • Includes critical information for Tumour-Node-Metastasis (TNM) staging • Evaluates the adequacy of the surgical excision • Provides morphological and biological prognostic markers which determine personalised cancer therapy However, the rapid growth in ancillary testing such as immunohistochemistry, flow cytometry, cytogenetics, and molecular studies, have made the task of keeping abreast of advances on specific cancer investigations extremely difficult for pathologists. The use 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 developed13,14 around the world. Both the United Kingdom,15 and United States16 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.

10 Cancer of the Exocrine Pancreas, Ampulla of Vater and Distal Common Bile Duct Structured Reporting Protocol 2nd edition

International Collaboration on Cancer Reporting The International Collaboration on Cancer Reporting (ICCR), founded in 2011 by the Royal College of Pathologists of Australasia (RCPA), United States College of American Pathologists (US CAP) and Royal College of Pathologists United Kingdom (RCPath UK) Colleges of Pathology Canadian Association of Pathology - Association Canadienne des Pathologistes (CAP-ACP) in association with the Canadian Partnership Against Cancer (CPAC), was established to explore the possibilities of a collaborative approach to the development of common, internationally standardised and evidence-based cancer reporting protocols for surgical pathology specimens. The ICCR, recognising that standardised cancer datasets have been shown to provide significant benefits for patients and efficiencies for organisations through the ease and completeness of data capture17-20 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 carcinomas of the exocrine pancreas 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 exocrine pancreas cancers. ICCR dataset elements for carcinomas of the exocrine pancreas 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.

11 Cancer of the Exocrine Pancreas, Ampulla of Vater and Distal Common Bile Duct Structured Reporting Protocol 2nd edition

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, 200921

• The Pathology Request-Test-Report Cycle — Guidelines for Requesters and Pathology Provider28 • World Health Organization Classification of Tumours, Digestive System Tumours. 5th Edition, 201922 • AJCC Cancer Staging Manual 8th edition, American Joint Committee on Cancer, 201623 • ICCR dataset: Carcinoma of the Exocrine Pancreas 1st edition v1.024

Changes since last edition Inclusion of ICCR Core and Non-core elements.

12 Cancer of the Exocrine Pancreas, Ampulla of Vater and Distal Common Bile Duct Structured Reporting Protocol 2nd edition

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 two separate processes: 1. This protocol is based on the ICCR dataset – Carcinoma of the exocrine pancreas 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. Please note that unlike the RCPA protocol, the ICCR dataset only covers carcinomas of the exocrine pancreas, and not ampulla of Vater and distal common bile duct. 2. Additional elements, values and commentary have been included as deemed necessary by the local expert committee. In addition, the standard inclusions of RCPA protocols e.g. example reports, request information etc., have also been added. 3. This protocol was developed by an expert committee, with assistance from relevant stakeholders.

Authorship – 2nd edition

Dr Caroline Cooper, (lead author), Pathologist Prof Priyanthi Kumarasinghe, (Chair of the GI cancer committee), Pathologist Dr Siaw Ming Chai, Pathologist Prof James Kench, Pathologist A/Prof Andrew Ruszkiewicz, Pathologist Prof Alfred Lam, Pathologist Dr Julie Lokan, Pathologist Dr Keshani De Silva, Pathologist Dr Krishna Epari, Surgeon Dr Mikael Johansson, Surgeon Dr Kevin Jasas, Oncologist Prof Timothy Price, Oncologist

Authorship – 1st edition

Dr Siaw Ming Chai, (lead author), Pathologist

13 Cancer of the Exocrine Pancreas, Ampulla of Vater and Distal Common Bile Duct Structured Reporting Protocol 2nd edition

Dr Ian Brown, Pathologist (Chair of the GI cancer committee), Pathologist Clinical A/Prof Bastiaan de Boer, Pathologist Dr Krishna Epari, Surgeon Dr Anthony Gill, Pathologist Dr Kevin Jasas, Oncologist Dr Mikael Johansson, Surgeon Prof James Kench, Pathologist Clinical Prof Priyanthi Kumarasinghe, Pathologist A/Prof Andrew Ruszkiewicz, Pathologist Dr Mee Ling Yeong, Pathologist Dr Ian Yusoff, Gastroenterologist

Editorial manager

Christina Selinger, PhD, Royal College of Pathologists of Australasia

Acknowledgements

The Pancreas expert committee wish to thank all the pathologists and clinicians who contributed to the discussion around this document.

14 Cancer of the Exocrine Pancreas, Ampulla of Vater and Distal Common Bile Duct Structured Reporting Protocol 2nd edition

Stakeholders

ACT Cancer Registry ACT Health Anatomical Pathology Advisory Committee (APAC) Australasian Gastrointestinal Pathology Society (AGPS) Australasian Gastro-Intestinal Trials Group (AGITG) Australasian Pancreatic Club Australian Commission on Safety and Quality in Health Care Australian Digital Health Agency (ADHA) Australian Institute of Health and Welfare (AIHW) Australian Pathology Cancer Australia Cancer Council ACT Cancer Council Australia and Australian Cancer Network (ACN) Cancer Council NSW Cancer Council Queensland Cancer Council SA Cancer Council Tasmania Cancer Council Victoria Cancer Council Western Australia Cancer Institute NSW Cancer Services Advisory Committee (CanSAC) Cancer specific expert groups – engaged in the development of the protocols Cancer Voices Australia Cancer Voices NSW Clinical Oncology Society of Australia (COSA) Department of Health, Australian Government Gastroenterological Society of Australia (GESA) Health Informatics Society of Australia (HISA) Independent Review Group of Pathologists Medical Oncology Group of Australia (MOGA) Medical Software Industry Association (MSIA) National Pathology Accreditation Advisory Council (NPAAC) New Zealand Cancer Control Agency New Zealand Cancer Registry New Zealand Committee of Pathologists New Zealand Society of Gastroenterology (NZSG)

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Northern Territory Cancer Registry Public Pathology Australia Queensland Cooperative Oncology Group (QCOG) Representatives from laboratories specialising in anatomical pathology across Australasia 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 Southern Melbourne Integrated Cancer Service (SMICS) 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.21

Where no reference is provided, the authority is the consensus of the local expert group for local inclusions, and the ICCR Dataset Authoring Committee for ICCR components denoted with the ICCR logo.

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1 Pre-analytical

This chapter relates to information that should be recorded on receipt of the specimen in the laboratory. The pathologist is reliant on the quality of information received from the clinicians or requestor. Some of this information may be received in generic pathology request forms, however, the additional information required by the pathologist specifically for the reporting of cancers of the exocrine pancreas, ampulla of Vater and common bile duct 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.25 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 Healthcare Index (New Zealand).

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

CS1.02a The request information may be recorded as a single text (narrative) field or it may be recorded in a structured format.

CS1.02b In most cases all clinical information should be transcribed: however, in a small number of cases the pathologist may exercise discretion regarding the inclusion of provided clinical information, for instance, possibly erroneous information or information that may impact on patient privacy. In such case reference should be made as to the location of the complete clinical information e.g. ‘Further clinical information is available from the scanned request form.’

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

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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 principle clinician for a number of reasons: • The clinical assessment and staging may be incomplete at the time of biopsy. • The pathology request is often authored by the clinician performing the surgical excision/biopsy rather than the clinician who is investigating and managing the patient. • The identity of this clinician is often not indicated on the pathology request form In practice therefore, it is important in such cases that the reporting pathologist should be able to communicate with the managing clinician for clarification.

CS1.04b The Australian Healthcare identifiers i.e. Healthcare Provider Identifier - Individual (HPI-I) and Healthcare Provider Identifier - Organisation (HPI-O) should be included, where possible, to identify the principal clinician involved in the patient's care.

G1.02 Any clinical information received in other communications from the requestor or other clinician should be recorded together with the source of that information.

CG1.02a There should be a free text field so that the referring doctor can add anything that is not addressed by the above points, such as previous cancers, risk factors, investigations, treatments and family history.

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2 Specimen handling and macroscopic findings

This chapter relates to the procedures required after the information has been handed over from the requesting clinician and the specimen has been received in the laboratory. Tissue banking

➢ Pathologists may be asked to provide tissue samples from fresh specimens for tissue banking or research purposes. The decision to provide tissue should only be made if the pathologist is sure that the diagnostic process will not be compromised. As a safeguard, research use of the tissue samples may be put on hold until the diagnostic process is complete.

➢ If tissue is sampled for banking or research then this should be done in consultation with a pathologist and recorded in the report in accordance with departmental protocols. 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

➢ The specimen must be handled in a systematic and thorough fashion to ensure completeness and accuracy of pathological data. Macroscopic findings

S2.01 The labelling of the specimen(s) must be clearly recorded.

S2.02 The operative procedure must be recorded.

CS2.02a Information regarding the type of surgical specimen should be recorded. For so-called extended resection specimens, the tissue(s) or organ(s) that are resected en bloc, for example a segment of the superior mesenteric vein or the left adrenal gland, should be clearly indicated. The type and extent of the surgical procedure depends on the site, size and extent of the tumour.

S2.03 Tumour focality must be recorded.

CS2.03a Most tumours are solitary, but multifocal disease can occur. Tumour focality is based on combined macroscopic and microscopic assessment. In case of multiple synchronous tumours in a specimen, the number of tumours should be recorded. A single protocol should be completed, in which the site and dimensions of the individual tumours are recorded. Refer to ICCR dataset for full commentary.

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S2.04 The site of the tumour must be recorded.

CS2.04a Determination of the tumour site is based on clinical information combined with specimen assessment by the pathologist. The uncinate process is considered part of the pancreatic head. In cases of multiple synchronous tumours in a specimen, the number of tumours should be recorded. A single protocol should be completed, in which the site and dimensions of the individual tumours are recorded, while staging should be based on the largest tumour and the overall lymph node status. Refer to ICCR dataset for full commentary.

CS2.04b Detailed macroscopic and microscopic assessment combined with any radiological and clinical information obtained will often allow accurate determination of tumour site.12

S2.05 The tumour dimensions must be recorded.

CS2.05a Assessment is based on macroscopic evaluation and microscopic confirmation/correction. The latter is important, because ductal adenocarcinoma of the pancreas often has a highly dispersed growth pattern,26 and small clusters of cancer cells that are widely separated from the main tumour mass will be missed on macroscopic assessment. Conversely, the microscopic extent may sometimes be less than the apparent macroscopic maximum size because of peritumoural fibrosis. As pT-staging is based on tumour size, it is important that a tumour is measured in three dimensions such that the largest dimension can be correctly identified. Tumours of the body or tail of the pancreas often have their largest dimension along the length of the pancreas. In case of serial sagittal slicing of the pancreatic body and tail, this means that this tumour dimension must be assessed across specimen slices. Similar considerations apply to the measurement of tumours in the pancreatic head. Measurement of the tumour dimensions may be difficult following neoadjuvant treatment, especially when two or more foci of residual tumour tissue are present.27 Two approaches are being used: • Approach 1: measurement of the largest linear dimension of the entire area involved by viable residual tumour cells including intervening non-cancerous tissue, e.g. stroma and/or pancreatic parenchyma or other tissue structures. • Approach 2: measurement of the maximum dimension of each tumour focus and calculation of the sum of these. Both approaches have disadvantages that may lead to incorrect assessment of tumour size. Moreover, the accuracy

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of measurement is also dependent on the extent of tissue sampling. Given the lack of evidence on how to best measure tumour size, there is currently no international consensus. The approach that is used, based on local practice or dependent on the particular case, should be recorded. In case of intraductal papillary mucinous neoplasm with associated invasive carcinoma, only the dimensions of the invasive carcinoma are to be recorded. This rule also applies to invasive carcinoma associated with intraductal oncocytic papillary neoplasm, intraductal tubulopapillary neoplasm, or mucinous cystic neoplasm.

S2.06 A macroscopic tumour description must be provided.

CS2.06a The presence of an exophytic, cystic or mucinous component to the tumour should be described. These findings provide information regarding the nature of either a coexisting preinvasive lesion or the invasive component itself. Tumours of the ampulla must be differentiated from those arising in the second part of the duodenum that invade the ampulla. Identifying the midpoint of duodenal masses and evaluating the presence or absence of involvement of the mucosa of the ampulla may help make this distinction.23 Tumours with their centre located between the confluence of the cystic duct and common hepatic duct and the ampulla of Vater (excluding ampullary carcinoma) are considered distal bile duct tumours (Figure 2).23 For ampullary tumours, a description of whether the tumour is intra-ampullary, mixed intra-ampullary and peri-ampullary (for tumours growing toward the duodenal lumen) or entirely peri-ampullary is recommended.9,28 Anatomy of the ampullary region is complex with numerous normal variants, which should be considered when evaluating these tumours.29,30

CS2.06b For ampullary tumours, level of invasion of ampulla, duodenum, pancreas or other structures are important for staging.

CS2.06c For distal common bile duct, depth of invasion of the bile duct wall, invasion of other structures are also important for staging.

S2.07 The macroscopic distance of tumour to the margins/surfaces must be recorded.

CS2.07a • The distance of tumour to each of the following margins/surfaces (Figures 2 and 3) should be recorded: • Pancreatic transection • Superior mesenteric artery • Posterior pancreatic • Superior mesenteric vein/vascular groove • Anterior pancreatic

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• Bile duct • Proximal intestinal/gastric • Distal intestinal • Other, specify

G2.01 Macroscopic evidence of any other abnormality or co-existing pathology should be recorded.

CG2.01a Examples include cystic lesions, calculi or chronic pancreatitis.

G2.02 Whether or not a tissue block has been taken for research or tissue banking should be recorded.

CG2.02a Pathologists may be asked to provide tissue samples from fresh specimens for tissue banking or research purposes. These should be in accordance with standard laboratory protocols and with appropriate ethics committee approval and patient consent.

G2.03 The availability of any photographs taken during the cut-up process should be noted.

CG2.03a A specimen photograph is particularly useful if the person performing the cut up is not the pathologist reporting the specimen.

S2.08 A differential ink application and block identification key listing the nature and origin of all tissue blocks must be recorded.

CS2.08a The colours of the ink used to designate the various surfaces should be clearly stated in the macroscopic description to guide margin assessment.

CS2.08b The origin/designation of all tissue blocks should be recorded. This information should be documented in the final pathology report and is particularly important should the need for internal or external review arise. Where appropriate specimen photographs and block diagrams should be utilised. If this information is not included in the final pathology report, it should be available on the laboratory computer system and relayed to the reviewing pathologist. Recording the origin/designation of tissue blocks also facilitates retrieval of blocks for further immunohistochemical or molecular analysis, research studies or clinical trials.

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 pancreas.

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CG2.04b 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.

CG2.04c Some of these elements are formally recorded in the ‘Microscopic findings’ (see Chapter 3).

CG2.04d 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.

Figure 1. Diagram highlighting the location of tumours to be staged as distal bile duct tumours. These tumours have an epicentre located between the confluence of the cystic duct and common hepatic duct and the ampulla of Vater (highlighted) (modified from the College of American Pathologists). Reproduced with permission from Amin MB, Edge SB and Greene FL et al (eds) (2017). American Joint Committee on Cancer Staging Manual. 8th ed., Springer, New York.23

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Figure 2: Circumferential surfaces of a pancreatoduodenectomy specimen to be included in the assessment of the margin status: anterior pancreatic surface (red), superior mesenteric vein (SMV) dissection margin (green), superior mesenteric artery (SMA) dissection margin (yellow), posterior dissection margin (blue). Permission courtesy of Mr Paul Brown; from Campbell F and Verbeke CS (2013). Pathology of the pancreas - a practical approach. Springer; London.31

Figure 3. Pancreatoduodenectomy dissection

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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 Tumours should be typed according to the World Health Organization (WHO) Classification of Tumours of the Gastrointestinal Tract, 5th edition, 2019.32 Ductal adenocarcinoma, including its subtypes, account for 90% of all pancreatic malignancies, whereas acinar cell carcinoma makes up less than 2% of all pancreatic cancers in adults. Correct diagnosis of the various subtypes of ductal adenocarcinoma is important, as they may differ in terms of prognosis, response to treatment and molecular profile. Invasive carcinoma that has arisen from a neoplastic precursor lesion, for example from a mucinous cystic neoplasm or intraductal papillary mucinous neoplasm, should be recorded under the corresponding histological tumour type in accordance with the WHO Classification.32

CS3.01b Refer to structured checklist (Chapter 6) for detailed list of subtypes.

S3.02 The histological grading of the tumour must be recorded.

CS3.02a While the WHO and the Union for International Cancer Control (UICC)33/American Joint Committee on Cancer (AJCC)23 each propose a different system for grading of the histological tumour differentiation,23,32-34 grading is highly concordant between both and has a similar predictive value.35 Grading according to the UICC33/AJCC23 systems is recommended, because it is more widely used and less complex than the WHO grading system (i.e. it does not require assessment of mucin production and mitotic activity). Other grading systems have been proposed but have not been adopted widely. The UICC33/AJCC23 system is as follows: • Grade 1: >95% of the tumour is composed of glands • Grade 2: 50-95% of the tumour is composed of glands • Grade 3: <50% of the tumour is composed of glands Histological tumour grade has been shown to have prognostic significance, with grade 3 being an adverse prognostic factor.36-38 By consensus, the histological grade of tumour differentiation is not given for acinar cell carcinoma and acinar cell

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cystadenocarcinoma or for tumours following neoadjuvant treatment.

CS3.02b Other methods of grading pancreatic ductal adenocarcinoma such as the Klöppel and Adsay systems are in use.39,40 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.

CS3.02c Some literature has been published suggesting that tumour budding may be a prognostic factor in pancreatic ductal adenocarcinoma.41-43 The assessment of budding with H&E could be used to better risk stratify patients with pancreatic ductal adenocarcinoma.42

S3.03 The extent of invasion must be recorded.

CS3.03a Following controversy as to whether infiltration of the intrapancreatic common bile duct should be regarded as extrapancreatic extension and difficulties related to the identification of infiltration into the peripancreatic soft tissue, UICC/AJCC TNM 8th editions have introduced tumour size as the exclusive criterion for stages pT1-3.23,33 T4 tumours remain defined by invasion of the common hepatic artery, superior mesenteric artery and/or coeliac axis, which may be considered resectable in highly selected cases with favourable response to neoadjuvant treatment.44 According to some, but not all studies, tumour invasion of named vessels is associated with worse patient outcome,45-48 and the depth of invasion into the vessel wall (tunica adventitia, media, intima, or vascular lumen) is prognostically relevant.49,50 Refer to ICCR dataset for full commentary.

CS3.03b For ampullary tumours, level of invasion of ampulla, duodenum, pancreas or other structures is important for staging.

CS3.03c For distal common bile duct tumours, depth of invasion of the bile duct wall, invasion of other structures is also important for staging.

S3.04 The microscopic tumour site must be recorded.

CS3.04a Tumour site is a synthesis of macroscopic and microscopic findings. The assessment is based on tumour bulk in relation to normal structures and the presence/absence of an associated preinvasive lesion.12,28 Difficulties in assigning tumour site arise due to several factors including: • the ability of periampullary cancers to colonise epithelial surfaces thereby mimicking preinvasive lesions,

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• the relatively large size of invasive cancers that obliterate pre-existing structures and/or lesions, and • the high prevalence of low-grade pancreatic intraepithelial neoplasia, which may complicate assessment of the relative significance of any preinvasive lesions present.11 Any imaging information provided/obtained can also be amalgamated in the final assessment. The labelling of tumour site has important consequences for staging, therapy and prognosis.2-9 Although immunohistochemistry may be used to determine whether an ampullary adenocarcinoma is of pancreaticobiliary or intestinal phenotype, there are currently no markers to assist in the separation of ampullary, distal bile duct and pancreatic adenocarcinomas.51-53

S3.05 The microscopic maximal dimension of tumour must be recorded.

CS3.05a A final estimate of the maximum dimension of the tumour should be given based on both the macroscopic and microscopic findings. Head of pancreas carcinomas can have a highly dispersed pattern of growth. At the invasive front of the tumour it is not uncommon to identify small clusters of or single tumour cells widely separated from the main tumour mass.54 These microscopic foci should be incorporated into the final measurement of maximum tumour dimension.

S3.06 The presence of lymphatic and venous invasion must be recorded.

CS3.06a Tumour invasion of lymphatic and venous vessels represents different biological processes with a different outcome, i.e. lymph node metastasis or distant, blood-borne metastasis. Hence, these features should be recorded separately, in accordance with UICC TNM 8th edition.33 It may be difficult to distinguish between small lymphatics and venous blood vessels, in which case the ‘orphan arteriole’ sign may help with identifying venous invasion. Special stains, in particular elastin stains or immunohistochemistry for caldesmon or podoplanin/D2-40, may also assist the distinction.55 The latter immunohistochemical stains may also be useful to identify the occasional examples of vascular invasion that mimic pancreatic intraepithelial neoplasia.56 While invasion of lymphatic or vascular vessels has been correlated with survival, both in patients who receive neoadjuvant treatment and those who do not, their prognostic value is weaker than that of tumour stage.32,55-58

S3.07 The presence of perineural invasion must be recorded.

CS3.07a Perineural invasion of intrapancreatic nerves and the extrapancreatic neural plexus is a common finding in pancreatic ductal adenocarcinoma. It is an adverse prognostic

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factor both in treatment-naive tumours and following neoadjuvant therapy.59-61

CG3.07b The superior mesenteric nerve plexus is present in the connective tissue surrounding the superior mesenteric artery and is usually resected as part of this margin (otherwise known as the uncinate margin). Invasion of the extrapancreatic neural plexus in the region of the SMA margin is often associated with involved margins and therefore local recurrence.62

S3.08 Response to neoadjuvant therapy must be recorded.

CS3.08a In the past several years, neoadjuvant treatment of pancreatic cancer has entered routine clinical practice. The response to neoadjuvant treatment should be recorded, because it reflects the tissue-based result of clinical intervention. Moreover, complete and near complete response correlate with better patient outcome.63 Several different scoring systems have been proposed.26 The modified Ryan scheme with a 4-point scoring scale64,65 is recommended, because it is based on non-numeric criteria and on the evaluation of the residual cancer (not the proportion of the tumour that has been destroyed), which makes it easier to use. While current evidence does not show a difference in patient outcome between score 2 and score 3,66 it is deemed important to distinguish between patients with a treatment response that is poorer than score 1 but definitely better than score 3, in order to risk-stratify the large number of patients (>80%) who fall into both these categories. For that reason, the modified three-tiered system proposed by Chatterjee,63 which has merged score 2 and 3 into a single group, is not recommended. The introduction of an arbitrary and difficult to implement 5% threshold value is a further disadvantage of the Chatterjee scoring system. Accurate evaluation of tumour regression requires extensive sampling of lesional tissue. In case of complete tumour regression, the entire tumour bed and any adjacent, macroscopically abnormal-looking tissues should be processed for histological examination.

S3.09 The margin status must be recorded.

CS3.09a Margin assessment is based on combined macroscopic and microscopic measurement. Because margin involvement may be a focal, macroscopically indiscernible finding, extensive sampling is important for accurate assessment of the margin status.67 The need for extensive tissue sampling to detect microscopic margin involvement is also supported by molecular studies.68 ‘R1’ is defined by UICC33/AJCC23 TNM as microscopic residual disease, i.e. irrespective of whether tumour is left behind at a surgical resection margin or at a non-surgical tissue plane. Assessment of the R-status should therefore be based on evaluation of all surfaces of the resection specimen, including

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the anterior pancreatic surface and the surface of the superior mesenteric vein groove (Figure 2). Involvement of these surfaces increases the risk of local tumour recurrence and is therefore of prognostic relevance.69 Studies based on a fully standardised, detailed pathology examination protocol that includes evaluation of all surfaces report on a high R1-rate (>70%) that correlates with survival.70-72 Currently, a margin is considered positive if the tumour is at or within 1 millimetre (mm) of the margin (R1). This definition was originally adopted from the protocols for the assessment of rectal cancer, for which a clearance of ≤1 mm was found to be predictive of local recurrence and poor survival. Based on the dispersed growth pattern that is characteristic of pancreatic ductal adenocarcinoma and more pronounced than in rectal cancer,26 a definition based on larger clearances (e.g. 1.5 mm) was proposed and found to be prognostically significant in some studies,73,74 but has not been implemented in diagnostic practice. Because the anterior surface of the pancreas is a peritonealised anatomical surface, involvement of that surface is defined by breaching of the surface, i.e. a clearance of 0 mm. While further evidence is awaited, assessment of the margin status based on R1 defined as 1 mm clearance (0 mm for the anterior surface) is now also recommended by the AJCC and other professional bodies.23,64,75,76 An appropriate definition of microscopic margin involvement (R1) following neoadjuvant treatment has not been established yet.77 Because a clearance of >1 mm does not necessarily reflect absence of microscopic residual disease, it is recommended to record the minimum distance to the relevant margins. The definition of R1 based on 1 mm clearance applies to ductal adenocarcinoma of the pancreas only. There is no evidence that this definition is also appropriate for acinar cell carcinoma, which has a different, often less dispersed growth pattern. It is therefore recommended to record the minimum distance to the closest margin(s). By consensus, diagnosing macroscopic residual disease (R2) is the surgeon’s responsibility, and therefore this data item is not included in the pathology reporting document. The distance of a carcinoma to some of the margins may be large, such that this information is of limited clinical relevance. However, it is recommended to record the clearance to the margins that are closest to, but not involved by, the tumour (non-core).

CS3.09b The anterior surface of the pancreatic head is an anatomical surface, rather than a surgical margin and thus is not considered a margin for the purposes of evaluation of residual disease (R status).

CS3.09c The presence of high grade pancreatic intraepithelial neoplasia (PanIN-3, carcinoma in situ) at a resection margin

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(usually the pancreatic transection margin) should be recorded.78

CS3.09d If present, the grade of dysplasia at the bile duct or mucosal margin should be recorded.

CS3.09e There is currently no data on the risk of recurrence in the situation where intranodal, intravascular or intraneural tumour deposits are transected or within 1 mm of the resection margin. A 2013 survey on pathology reporting of head of pancreas carcinomas conducted in the United Kingdom revealed that the majority (up to 83%) of respondents considered tumour in these areas to represent microscopic involvement of a margin (R1).79 In this scenario, like the analogous situation in colorectal carcinoma, it is recommended that until specific information is available the margin should be recorded as positive with the nodal, intravascular or intraneural nature of the involvement noted.80

S3.10 The lymph node status must be recorded.

CS3.10a Regional lymph nodes that are submitted separately should be reported individually, but the numbers should be included in the above response. Lymph node status is one of the most potent predictors of survival for ductal adenocarcinoma of the pancreas.58,81-86 Based on outcome data, tumours with positive lymph nodes are now categorised as N1 (1-3 positive regional lymph nodes) or N2 (4 or more regional lymph node metastases).23,33,87,88 All lymph nodes in the resection specimen should be examined histologically. The lymph node yield from Whipple resection specimens should be at least 12.89-91 In accordance with the UICC/AJCC23,33 8th edition staging systems, direct invasion of a lymph node by the primary tumour should also be reported as lymph node involvement and included in the above information. It should be noted that there is a discrepancy between UICC33 and AJCC23 8th edition staging systems regarding the assignment of coeliac lymph nodes. While these are considered regional lymph nodes only for cancer in the head of the pancreas by UICC,33 the AJCC regards them as regional lymph nodes exclusively for tumours in the body and tail of the pancreas.23

S3.11 The presence of histologically confirmed distant metastases and their site must be recorded.

CS3.11a Distant metastasis is a strong adverse prognostic factor. Metastasis to extraregional lymph nodes (e.g. paraaortic lymph nodes) is also associated with poor prognosis92-94 and should be recorded as distant metastasis.

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G3.01 The presence of any relevant coexistent pathological abnormalities should be recorded.

CG3.01a The information recorded in this element refers to any diagnostic lesion that is found in addition to the index lesion. In particular, in case of ductal adenocarcinoma arising from an intraductal papillary mucinous neoplasm, the latter should not be recorded as an additional finding but rather the tumour should be documented as ‘intraductal papillary mucinous neoplasm with associated invasive carcinoma’ under ‘Histological tumour type’. If a preinvasive lesion is present, the highest grade of dysplasia should be recorded (low or high grade).

G3.02 Any additional relevant information should be recorded.

CG3.02a There must be a free text field so that the pathologist can add any essential information that is not addressed by the above points.

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4 Ancillary findings

Ancillary studies of exocrine pancreas carcinoma may be 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 Any ancillary testing performed should be noted and the results recorded in the pathology report.

CG4.01a Any ancillary studies should be recorded and specified. Ancillary investigations based on immunohistochemistry or molecular analysis are not recommended for routine diagnostics and are currently considered investigational.

CG4.01b Immunohistochemistry such as CDX2, CK20, MUC1, MUC2 and MUC5AC can be useful to determine the phenotype of ampullary adenocarcinoma (pancreatobiliary or intestinal). However, about 40% show mixed or hybrid phenotypes and many show heterogeneous immunoprofiles.32 Molecular analysis such as Next Generation Sequencing could be considered.

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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).9

CS5.01a TNM staging should be assessed according to the agreed criteria of the UICC33 and AJCC23 8th edition staging systems. The staging system for acinar cell carcinoma is the same as the one used for pancreatic ductal adenocarcinoma. In case of multiple synchronous cancers, the stage should be based on the largest tumour (and recorded as ‘pTm’) and the overall lymph node status. The shift of stage criteria for pT1-3 from tumour size and tumour extent (TNM 7th edition)95,96 to tumour size alone (TNM 8th edition)23,33 was prompted by concerns regarding the reproducibility of the criterion ‘extension beyond the pancreas’.97 In addition, extrapancreatic tumour extension is observed in over 80% of tumours smaller than 20 mm in size, and yet, the associated survival is closer to that of tumours without extrapancreatic extension.98-101 The changes introduced by the UICC33/AJCC23 8th edition staging systems aimed at improving reproducibility of T-stage and a more even stratification of patients across stages without sacrificing prognostic accuracy.102 In addition, an N2 category was added, similar to the pN-staging for other gastrointestinal cancer sites. Several validation studies of the UICC/AJCC 8th edition staging systems have been published.102-105 Whereas most find the revised N-stage to be highly prognostic, only a modest increase in prognostic accuracy is observed for the revised T- stage, which remains a fairly poor predictor of survival.103,104 Future studies will be needed to evaluate the prognostic significance of tumour size following neoadjuvant therapy.106

CS5.01b There are separate staging systems for ampulla of Vater and distal common bile duct.23 Refer to structured checklist (Chapter 6) for detailed staging information for exocrine pancreas, ampulla of Vater and distal bile duct.

S5.02 The year of publication and/or edition of the cancer staging system used in S5.01 must be included in the report.

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G5.01 The ‘Diagnostic summary’ section of the final formatted report could include: a. Operative procedure b. Tumour location(s) c. Tumour type d. Tumour size e. Tumour grade f. Tumour stage g. Lymph nodes status h. Margin status

S5.03 A field for free text or narrative in which the reporting pathologist can give overarching case comment must be provided.

CS5.03a 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.

CS5.03b 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’.

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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 pancreatic 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 laboratory information system (LIS) capabilities and as described in Functional Requirements for Structured Pathology Reporting of Cancer Protocols.107

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.

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.

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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: Neoadjuvant therapy Multi selection value list (select all that apply): • Not administered • Administered o Chemotherapy o Radiotherapy o Other, specify Operative procedure Multi selection value list (select all that apply): • Whipple pancreatoduodenectomy • Pylorus-preserving pancreatoduodenectomy • Distal pancreatectomy • Total pancreatectomy

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• Subtotal pancreatectomy • Pancreatic resection (tick one of the options above, extended with one or more of the following additionally resected organs/structures) o Vein ▪ Superior mesenteric vein ▪ Portal vein o Artery(s) ▪ Superior mesenteric artery ▪ Common hepatic artery ▪ Coeliac trunk • • Other, specify Superior mesenteric vein/Portal Single selection value list: If performed, describe the type vein resection of vascular resection • Not performed

• Performed, specify vascular resection Additional specimens Multi select value list (select all that apply): • Liver biopsy • Peritoneal nodules • Omentum • Gallbladder • Spleen • Other, specify

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Local residual cancer Text postsurgery Involvement of adjacent Text organs New primary cancer or Single selection value list: If regional (local) recurrence or recurrence distant metastasis, describe. • New primary • Regional (local) recurrence • Distant metastases Describe Text Relevant patient or family Text history

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 Operative procedure Multi selection value list (select all that apply): • Whipple pancreatoduodenectomy • Pylorus-preserving pancreatoduodenectomy • Distal pancreatectomy • Total pancreatectomy

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• Subtotal pacreatectomy • Pancreatic resection (tick one of the options above, extended with one or more of the following additionally resectied organs/structures) o Vein ▪ Superior mesenteric vein ▪ Portal vein o Artery(s) ▪ Superior mesenteric artery ▪ Common hepatic artery ▪ Coeliac trunk • Other, specify S2.03 Tumour focality Single selection value list: • Cannot be assessed, specify • Unifocal • Multifocal, specify number of tumours Number of tumours in Numeric: ___ specimen S2.04 Tumour site Single selection value list: • No macroscopically visible tumour OR Multi selection value list (select all that apply):

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• Pancreatic head • Pancreatic body • Pancreatic tail • Pancreatic neck • Bile duct • Ampulla of Vater • Duodenum • Other, specify S2.05 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) Dimensions of additional smaller Numeric: ____mm x ____mm x ____mm tumour foci Method of measurement (in case Single selection value list: of neoadjuvant treatment) • Approach 1 • Approach 2

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Note: See CS2.06a for an explanation of the approaches to the method of measurement following neoadjuvant treatment. S2.06 MACROSCOPIC TUMOUR Note: For multiple tumours the description of DESCRIPTION each focus should be recorded. Text Type of ampullary tumour Single selection value list: Conditional on the tumour being located in the ampullary region • Intra-ampullary • Mixed intra-ampullary and peri-ampullary • Peri-ampullary S2.07 MACROSCOPIC DISTANCE OF Note: For multiple tumours the closest distance TUMOUR TO of any foci should be recorded. MARGINS/SURFACES Pancreatic transection Not applicable OR Numeric: __mm Superior mesenteric artery Not applicable OR • Numeric: __mm Posterior pancreatic Not applicable OR • Numeric: __mm Superior mesenteric Not applicable vein/vascular groove OR

Numeric: __mm

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Anterior pancreatic Not applicable OR Numeric: __mm Bile duct Not applicable OR Numeric: __mm Proximal intestinal/gastric Not applicable OR Numeric: __mm Distal intestinal Not applicable OR Numeric: __mm Other margin/surface Not applicable OR Text: description of margin /surface AND Numeric: __mm G2.01 Evidence of other abnormality Single selection value list: or coexisting pathology • Not present • Present G2.02 Tissue block for research or Single selection value list: tissue bank • Not taken • Taken G2.03 Photographs Single selection value list:

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• Not taken • Available S2.08 Block identification key Text G2.04 Other macroscopic comments Text Microscopic findings S3.01 Histological tumour type Single selection value list from WHO Classification of Tumours of the

Gastrointestinal Tract (2019). Single selection value list:

Exocrine pancreas • Ductal adenocarcinoma o Ductal adenocarcinoma not otherwise specified (NOS) o Colloid carcinoma o Poorly cohesive carcinoma o Signet-ring cell carcinoma o Medullary carcinoma, NOS o Adenosquamous carcinoma o Hepatoid carcinoma o Large cell carcinoma with rhabdoid phenotype o Carcinoma, undifferentiated, NOS o Undifferentiated carcinoma with osteoclast-like giant cells • Acinar cell carcinoma

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o Acinar cell cystadenocarcinoma o Mixed acinar-neuroendocrine carcinoma o Mixed acinar-endocrine-ductal carcinoma o Mixed acinar-ductal carcinoma o Acinar cell carcinoma, NOS • Pancreatoblastoma • Solid pseudopapillary neoplasm of the pancreas o Solid pseudopapillary neoplasm with high-grade carcinoma

Ampulla of Vater • Adenocarcinoma, NOS o Mucinous adenocarcinoma o Signet-ring cell adenocarcinoma o Medullary carcinoma, NOS o Adenocarcinoma, intestinal-type o Pancreatobiliary-type carcinoma o Tubular adenocarcinoma

Distal common bile duct • Adenocarcinoma, NOS o Adenocarcinoma, intestinal type

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o Clear cell adenocarcinoma NOS o Mucinous cystic neoplasm with associated invasive carcinoma o Mucinous adenocarcinoma o Poorly cohesive carcinoma o Intraductal papillary neoplasm with associated invasive carcinoma • Squamous cell carcinoma NOS • Carcinoma, undifferentiated NOS • Adenosquamous carcinoma • Cholangiocarcinoma • Other, specify S3.02 Histological tumour grade Single selection value list: • Not applicable • Grade 1: Well differentiated • Grade 2: Moderately differentiated • Grade 3: Poorly differentiated or undifferentiated • Grade X: Cannot be assessed S3.03 Extent of invasion Single selection value list: • Cannot be assessed • No evidence of primary tumour • No invasion (carcinoma in situ/high grade dysplasia) • Tumour is confined to pancreas

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OR Multi selection value list (select all that apply): • Invasion into ampulla of Vater • Invasion into duodenum • Invasion into common bile duct • Invasion into peripancreatic soft tissues • Invasion into spleen • Invasion into splenic vein/artery • Invasion into vascular resection o Invasion into venous resection, specify which vein o Specify maximum depth of invasion ▪ Tunica adventitia ▪ Tunica media ▪ Tunica intima ▪ Vascular lumen o Invasion into arterial resection, specify which artery(s) ▪ Tunica adventitia ▪ Tunica media ▪ Tunica intima ▪ Vascular lumen • Invasion into coeliac axis

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• Invasion into other adjacent structure(s)/organ(s), specify S3.04 Microscopic tumour site Multi select value list (select all that apply): • Pancreas o Head of pancreas o Neck of pancreas o Body of pancreas o Tail of pancreas • Uncinate process • Ampulla of Vater • Common bile duct (extrapancreatic or intrapancreatic) • Duodenum • Other, specify S3.05 Maximum tumour diameter Numeric: __mm • Note: Record for each tumour identified. S3.06 Lymphatic and venous Single selection value list: invasion • Not identified • Present o Lymphatic channel invasion o Venous invasion S3.07 Perineural invasion Single selection value list: • Not identified • Present

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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 groups of cancer cells (score 1) • Partial response – residual cancer with evident tumour regression (score 2) • Poor or no response – extensive residual cancer with no evident tumour regression (score 3) • Cannot be assessed, specify S3.09 MARGIN STATUS Pancreatic transection Single selection value list: If not involved by invasive margin carcinoma, estimate distance to • Not applicable closest margin • Cannot be assessed

• Involved o Invasive carcinoma o High grade dysplasia • Not involved Distance to closest margin Numeric: __mm Bile duct transection margin Single selection value list: If not involved by invasive carcinoma, estimate distance to • Not applicable closest margin • Cannot be assessed

• Involved

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• Not involved Distance to closest margin Numeric: __mm Gastric/proximal duodenal Single selection value list: If not involved by invasive transection margin carcinoma, estimate distance to • Not applicable closest margin • Cannot be assessed

• Involved • Not involved Distance to closest margin Numeric: __mm Posterior dissection margin Single selection value list: If not involved by invasive carcinoma, estimate distance to • Not applicable closest margin • Cannot be assessed

• Involved • Not involved Distance to closest margin Numeric: __mm Superior mesenteric artery Single selection value list: If not involved by invasive (SMA) dissection margin carcinoma, estimate distance to • Not applicable closest margin • Cannot be assessed

• Involved • Not involved Distance to closest margin Numeric: __mm Superior mesenteric vein Single selection value list: If not involved by invasive (SMV) dissection margin carcinoma, estimate distance to • Not applicable closest margin • Cannot be assessed

49 Cancer of the Exocrine Pancreas, Ampulla of Vater and Distal Common Bile Duct Structured Reporting Protocol 2nd edition

• Involved • Not involved Distance to closest margin Numeric: __mm Anterior pancreatic surface Single selection value list: If not involved by invasive carcinoma, estimate distance to • Not applicable closest margin • Cannot be assessed

• Involved • Not involved Distance to closest margin Numeric: __mm Transection margins of Single selection value list: If not involved by invasive venous resection carcinoma, estimate distance to • Not applicable closest margin • Cannot be assessed

• Involved • Not involved Distance to closest margin Numeric: __mm Transection margins of Single selection value list: If not involved by invasive arterial resection carcinoma, estimate distance to • Not applicable closest margin • Cannot be assessed

• Involved • Not involved Distance to closest margin Numeric: __mm Other margin(s) Text

50 Cancer of the Exocrine Pancreas, Ampulla of Vater and Distal Common Bile Duct Structured Reporting Protocol 2nd edition

Single selection value list: If not involved by invasive carcinoma, estimate distance to • Not applicable closest margin • Cannot be assessed

• Involved • Not involved Distance to closest margin Numeric: __mm S3.10 LYMPH NODE STATUS No nodes submitted or found OR Number of lymph nodes Number cannot be assessed examined OR Numeric: ___ Single selection value list: Record the number of LN examined. • Not involved If involved, specify the number • Involved of positive LN Number of positive lymph Numeric: ___ Not required if number cannot nodes be determined is entered above. S3.11 Distant metastases Single selection value list: • Not identified • Not assessed • Present, specify site(s) G3.01 Coexistent pathological Multi select value list : abnormalities • Chronic pancreatitis • Pancreatic intraepithelial neoplasia, specify highest grade

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• Intraductal papillary mucinous neoplasia, specify highest grade • Neuroendocrine tumour, specify grade • Other, specify G3.02 Additional microscopic comment Text Ancillary findings G4.01 Ancillary studies Single selection value list: • Not performed • Performed, specify 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) PANCREAS Single select value list : TX Primary tumour cannot be assessed T0 No evidence of primary tumour Tis Carcinoma in situ. This includes high-grade pancreatic intraepithelial neoplasia (PanIn- 3), intraductal papillary mucinous neoplasm with high-grade dysplasia, intraductal tubulopapillary neoplasm with high-grade

52 Cancer of the Exocrine Pancreas, Ampulla of Vater and Distal Common Bile Duct Structured Reporting Protocol 2nd edition

dysplasia, and mucinous cystic neoplasm with high-grade dysplasia. T1 Tumour ≤2 cm in greatest dimension T1a Tumour ≤0.5 cm in greatest dimension T1b Tumour >0.5 cm and <1 cm in greatest dimension T1c Tumour 1–2 cm in greatest dimension T2 Tumour >2 cm and ≤4 cm in greatest dimension T3 Tumour >4 cm in greatest dimension T4 Tumour involves celiac axis, superior mesenteric artery, and/or common hepatic artery, regardless of size AMPULLA OF VATER Single selection value list: TX Primary tumour cannot be assessed T0 No evidence of primary tumour Tis Carcinoma in situ T1 Tumour limited to ampulla of Vater or sphincter of Oddi (perishphincteric invasion) and/or into the duodenal submucosa T1a Tumour limited to ampulla of Vater of sphincter of Oddi T1b Tumour invades beyond the sphincter of Oddi (perisphincteric invasion) and/or into the duodenal submucosa

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T2 Tumour invades into the muscularis propria of the duodenum T3 Tumour directly invades the pancreas (up to 0.5 cm) or tumour extends more than 0.5 cm into the pancreas, or extends into peripancreatic or periduodenal tissue or duodenal serosa without involvement of the coeliac axis or superior mesenteric artery T3a Tumour directly invades pancreas (up to 0.5 cm) T3b Tumour extends more than 0.5 cm into the pancreas, or extends into peripancreatic tissue or periduodenal tissue or duodenal serosa without involvement of the coeliac axis or superior mesenteric artery T4 Tumour involves the coeliac axis, superior mesenteric artery, and/or common hepatic artery, irrespective of size

DISTAL BILE DUCT Single selection value list: TX Primary tumour cannot be assessed T0 No evidence of primary tumour Tis Carcinoma in situ/high grade dysplasia T1 Tumour invades the bile duct wall with a depth less than 5 mm

54 Cancer of the Exocrine Pancreas, Ampulla of Vater and Distal Common Bile Duct Structured Reporting Protocol 2nd edition

T2 Tumour invades the bile duct wall with a depth of 5–12 mm T3 Tumour invades the bile duct wall with a depth greater than 12 mm T4 Tumour involves the coeliac axis, superior mesenteric artery, and/or common hepatic artery

Regional lymph node (pN) Single selection value list: NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Metastasis in one to three regional lymph nodes N2 Metastasis in four or more regional lymph nodes S5.02 Year and edition of staging Numeric: year system AND Text: Edition e.g.1st, 2nd etc. G5.01 Diagnostic summary Text Include: a. Operative procedure b. Tumour location(s) c. Tumour type d. Tumour size e. Tumour grade f. Tumour stage

55 Cancer of the Exocrine Pancreas, Ampulla of Vater and Distal Common Bile Duct Structured Reporting Protocol 2nd edition

g. Lymph nodes status h. Margin status S5.03 Overarching comment Text G5.02 Edition/version number of the Text RCPA protocol on which the report is based

56 Cancer of the Exocrine Pancreas, Ampulla of Vater and Distal Common Bile Duct Structured Reporting Protocol 2nd edition

7 Formatting of pathology reports

Good formatting of the pathology report is essential for optimising communication with the clinician, and will be an important contributor to the success of cancer reporting protocols. The report should be formatted to provide information clearly and unambiguously to the treating doctors, and should be organised with their use of the report in mind. In this sense, the report differs from the structured checklist, which is organised with the pathologists’ workflow as a priority. Uniformity in the format as well as in the data items of cancer reports between laboratories makes it easier for treating doctors to understand the reports; it is therefore seen as an important element of the systematic reporting of cancer. For guidance on formatting pathology reports, please refer to Appendix 2. An example of a pathology report is shown in Appendix 3.

57 Cancer of the Exocrine Pancreas, Ampulla of Vater and Distal Common Bile Duct Structured Reporting Protocol 2nd edition

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 cancers of the exocrine pancreas, ampulla of Vater and common bile duct 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 Index (New Zealand).

Clinical Information

➢ Any neoadjuvant therapy administered must be recorded.

➢ • Neoadjuvant treatment can have a profound effect on the morphological findings and has implications for both specimen sampling and histological interpretation. Information regarding the administration of neoadjuvant therapy should therefore always be provided to and recorded by the pathologist.

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➢ The operative procedure must be recorded.

➢ • Information regarding the type of surgical specimen should be recorded. For so-called extended resection specimens, the tissue(s) or organ(s) that are resected en bloc, for example a segment of the superior mesenteric vein or the left adrenal gland, should be clearly indicated. The type and extent of the surgical procedure depends on the site, size and extent of the tumour.

➢ The involvement of adjacent organs must be recorded.

• Involvement of adjacent organs, either resected or not resected, is required for assessment of the tumour (T) stage of the tumour.

➢ 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 macroscopic residual disease at surgical margins or within regions in which resection has not been attempted (R2).

➢ 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 sites of such deposits should be stated.

• 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 relevant patient or family history should be provided.

➢ 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.

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Example Request Information Sheet

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

60 Cancer of the Exocrine Pancreas, Ampulla of Vater and Distal Common Bile Duct Structured Reporting Protocol 2nd edition

Appendix 2 Guidelines for formatting of a pathology report

Layout

Headings and spaces should be used to indicate subsections of the report, and heading hierarchies should be used where the LIS allows it. Heading hierarchies may be defined by a combination of case, font size, style and, if necessary, indentation. Grouping similar data elements under headings and using ‘white space’ assists in rapid transfer of information.108 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.108

• Reduce ‘clutter’ to a minimum.108 Thus, information that is not part of the protocol (e.g. billing information or SNOMED codes) should not appear on the reports or should be minimised.

• Reduce the use of formatting elements (e.g. bold, underlining or use of footnotes) because these increase clutter and may distract the reader from the key information. Where a structured report checklist is used as a template for the actual report, any values provided in the checklist but not applying to the case in question must be deleted from the formatted report. Reports should be formatted with an understanding of the potential for the information to ‘mutate’ or be degraded as the report is transferred from the LIS to other health information systems. As a report is transferred between systems: • text characteristics such as font type, size, bold, italics and colour are often lost • tables are likely to be corrupted as vertical alignment of text is lost when fixed font widths of the LIS are rendered as proportional fonts on screen or in print • spaces, tabs and blank lines may be stripped from the report, disrupting the formatting • supplementary reports may merge into the initial report.

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Appendix 3 Example of a pathology report

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Appendix 4 WHO Classification of Tumours of the pancreas

Benign epithelial tumours and precursors Serous cystadenoma NOS 8551/0 Macrocystic (oligocystic) serous cystadenoma Solid serous adenoma Von Hippel-Lindau syndrome-associated serous cystic neoplasm Mixed serous-neuroendocrine neoplasm Serous cystadenoma NOS 8441/3 Glandular intraepithelial neoplasia, low grade 8148/0 Glandular intraepithelial neoplasia, high grade 8148/2 Intraductal papillary mucinous neoplasm with low-grade dysplasia 8453/0 Intraductal papillary mucinous neoplasm with high-grade dysplasia 8453/2 Intraductal papillary mucinous neoplasm with associated invasive carcinoma 8453/3 Intraductal oncocytic papillary mucinous neoplasm NOS 8455/2* Intraductal oncocytic papillary mucinous neoplasm with associated invasive carcinoma 8455/3* Intraductal tubulopapillary neoplasm 8503/3 Intraductal papillary neoplasm with associated invasive carcinoma Mucinous cystic neoplasm with low-grade dysplasia 8470/0 Mucinous cystic neoplasm with high-grade dysplasia 8470/2 Mucinous cystic neoplasm with associated invasive carcinoma 8470/3

Malignant Ductal adenocarcinoma NOS 8500/3 Colloid carcinoma 8480/3 Poorly cohesive carcinoma 8490/3 Signet-ring cell carcinoma 8490/3 Medullary carcinoma NOS 8510/3 Adenosquamous carcinoma 8560/3 Hepatoid carcinoma 8576/3 Large cell carcinoma with rhabdoid phenotype 8014/3 Carcinoma, undifferentiated, NOS 8020/3 Undifferentiated carcinoma with osteoclast-like giant cells 8035/3 Acinar cell carcinoma 8550/3 Acinar cell cystadenocarcinoma 8551/3 Mixed acinar-neuroendocrine carcinoma 8154/3 Mixed acinar-endocrine-ductal carcinoma 8154/3 Mixed acinar-ductal carcinoma 8552/3

Pancreatoblastoma 8971/3 Serous cystadenocarcinoma 8441/3 Solid-pseudopapillary neoplasm with high-grade carcinoma 8452/3

Pancreatic neuroendocrine neoplasms Pancreatic neuroendocrine microadenoma 8150/0 Neuroendocrine tumour NOS 8240/3 Neuroendocrine tumour, grade 1 8240/3 Neuroendocrine tumour, grade 2 8249/3 Neuroendocrine tumour, grade 3 8249/3 Pancreatic neuroendocrine tumour, non-functioning 8150/3

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Oncocytic neuroendocrine tumour, non-functioning pancreatic Pleomorphic neuroendocrine tumour, non-functioning pancreatic Clear cell neuroendocrine tumour, non-functioning pancreatic Cystic neuroendocrine tumour, non-functioning pancreatic Functioning pancreatic neuroendocrine tumours Insulinoma 8151/3* Gastrinoma 8153/3* VIPoma 8155/3* Glucagonoma 8152/3* Somatostatinoma 8156/3* ACTH-producing tumour 8158/3 Enterochromaffin-cell carcinoid 8241/3 Serotonin-producing tumour 8241/3 Neuroendocrine carcinoma NOS 8246/3 Large cell neuroendocrine carcinoma 8013/3 Small cell neuroendocrine carcinoma 8041/3 Mixed neuroendocrine–non-neuroendocrine neoplasm (MiNEN) 8154/3 Mixed acinar-endocrine carcinoma 8154/3 Mixed acinar-neuroendocrine carcinoma 8154/3 Mixed acinar-endocrine-ductal carcinoma 8154/3

These morphology codes are from the International Classification of Diseases for Oncology, third edition, second revision (ICD-O-3.2).109 Behaviour is coded /0 for benign tumours; /1 for unspecified, borderline, or uncertain behaviour; /2 for carcinoma in situ and grade III intraepithelial neoplasia; /3 for malignant tumours, primary site; and /6 for malignant tumours, metastatic site. Behaviour code /6 is not generally used by cancer registries.

This classification is modified from the previous WHO classification, taking into account changes in our understanding of these lesions.

* Codes marked with an asterisk were approved by the IARC/WHO Committee for ICD-O at its meeting in April 2019.

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

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Appendix 5 WHO Classification of tumours of the small intestine and ampulla

Benign epithelial tumours and precursors

Adenomatous polyp, low-grade dysplasia 8210/0* Adenomatous polyp, high-grade dysplasia 8210/2* Intestinal-type adenoma, low grade 8144/0* Intestinal-type adenoma, high grade 8144/2* Serrated dysplasia, low grade 8213/0* Serrated dysplasia, high grade 8213/2* Non-invasive pancreatobiliary papillary neoplasm with low-grade dysplasia 8163/0 Non-invasive pancreatobiliary papillary neoplasm with high-grade dysplasia 8163/2 Intra-ampullary papillary-tubular neoplasm

Malignant epithelial tumours Adenocarcinoma NOS 8140/3 Mucinous adenocarcinoma 8480/3 Signet-ring carcinoma 8490/3 Medullary carcinoma NOS 8510/3 Adenocarcinoma, intestinal type 8144/3 Pancreatobiliary-type carcinoma 8163/3* Tubular adenocarcinoma 8211/3 Neuroendocrine tumour NOS 8240/3 Neuroendocrine tumour, grade 1 8240/3 Neuroendocrine tumour, grade 2 8249/3 Neuroendocrine tumour, grade 3 8249/3 Gastrinoma NOS 8153/3 Somatostatinoma NOS 8156/3 Enterochromaffin-cell carcinoid 8241/3 Extra-adrenal paranganglioma NOS 8693/3 Neuroendocrine carcinoma NOS 8246/3 Large cell neuroendocrine carcinoma 8013/3 Small cell neuroendocrine carcinoma 8041/3 Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) 8154/3

These morphology codes are from the International Classification of Diseases for Oncology, third edition, second revision (ICD-O-3.2).109 Behaviour is coded /0 for benign tumours; /1 for unspecified, borderline, or uncertain behaviour; /2 for carcinoma in situ and grade III intraepithelial neoplasia; /3 for malignant tumours, primary site; and /6 for malignant tumours, metastatic site. Behaviour code /6 is not generally used by cancer registries.

This classification is modified from the previous WHO classification, taking into account changes in our understanding of these lesions.

* Codes marked with an asterisk were approved by the IARC/WHO Committee for ICD-O at its meeting in April 2019.

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

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Appendix 6 WHO Classification of Tumours of the gallbladder and extrahepatic bile ducts

Benign epithelial tumours and precursors

Adenoma NOS 8140/0 Biliary intraepithelial neoplasia, low grade 8148/0 Biliary intraepithelial neoplasia, high grade 8148/0 Intracystic papillary neoplasm with low-grade intraepithelial neoplasia 8503/0 Intracystic papillary neoplasm with high-grade intraepithelial neoplasia 8503/2 Intracystic papillary neoplasm with associated invasive carcinoma 8503/3 Intraductal papillary neoplasm with low-grade intraepithelial neoplasia 8503/0 Intraductal papillary neoplasm with high-grade intraepithelial neoplasia 8503/2 Intraductal papillary neoplasm with associated invasive carcinoma 8503/3

Malignant epithelial tumours

Adenocarcinoma NOS 8140/3 Adenocarcinoma, intestinal type 8144/3 Clear cell adenocarcinoma NOS 8310/3 Mucinous cystic neoplasm with associated invasive carcinoma 8470/3 Mucinous adenocarcinoma 8480/3 Poorly cohesive carcinoma 8490/3 Intracystic papillary neoplasm with associated invasive carcinoma 8503/3 Squamous cell carcinoma NOS 8070/3 Carcinoma, undifferentiated, NOS 8020/3 Adenosquamous carcinoma 8560/3 Cholangiocarcinoma 8160/3* Neuroendocrine tumour NOS 8240/3 Neuroendocrine tumour, grade 1 8240/3 Neuroendocrine tumour, grade 2 8249/3 Neuroendocrine tumour, grade 3 8249/3 Neuroendocrine carcinoma NOS 8246/3 Large cell neuroendocrine carcinoma 8013/3 Small cell neuroendocrine carcinoma 8041/3 Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) 8154/3

These morphology codes are from the International Classification of Diseases for Oncology, third edition, second revision (ICD-O-3.2).109 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.

67 Cancer of the Exocrine Pancreas, Ampulla of Vater and Distal Common Bile Duct Structured Reporting Protocol 2nd edition

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