TUMOURS OF THE OESOPHAGUS AND GASTRO-OESOPHAGEAL JUNCTION STRUCTURED REPORTING PROTOCOL (1st Edition, 2013) Core Document versions: • • AJCC Cancer Staging Manual 7th edition (including errata corrected with 5th reprint 10th Aug 2010). World Health Organization Classification of Tumours Pathology and Genetics of Tumours of the Digestive System, 2010, 4th edition ISBN: 978-1-74187-710-6 Publications number (SHPN): (CI) 120056 Online copyright © RCPA 2013 This work (Protocol) is copyright. You may download, display, print and reproduce the Protocol for your personal, non-commercial use or use within your organisation subject to the following terms and conditions: 1. The Protocol may not be copied, reproduced, communicated or displayed, in whole or in part, for profit or commercial gain. 2. Any copy, reproduction or communication must include this RCPA copyright notice in full. 3. With the exception of Chapter 6 - the checklist, no changes may be made to the wording of the Protocol including any Standards, Guidelines, commentary, tables or diagrams. Excerpts from the Protocol may be used in support of the checklist. References and acknowledgments must be maintained in any reproduction or copy in full or part of the Protocol. 4. In regard to Chapter 6 of the Protocol - the checklist: o The wording of the Standards may not be altered in any way and must be included as part of the checklist. o Guidelines are optional and those which are deemed not applicable may be removed. o Numbering of Standards and Guidelines must be retained in the checklist, but can be reduced in size, moved to the end of the checklist item or greyed out or other means to minimise the visual impact. o Additional items for local use may be added but must not be numbered as a Standard or Guideline, in order to avoid confusion with the RCPA checklist items. o Formatting changes in regard to font, spacing, tabulation and sequencing may be made. o Commentary from the Protocol may be added or hyperlinked to the relevant checklist item. Apart from any use as permitted under the Copyright Act 1968 or as set out above, all other rights are reserved. Requests and inquiries concerning reproduction and rights should be addressed to RCPA, 207 Albion St, Surry Hills, NSW 2010, Australia. First published: February 2013, 1st Edition (version 1.0) ii Disclaimer The Royal College of Pathologists of Australasia ("College") has developed these protocols as an educational tool to assist pathologists in reporting of relevant information for specific cancers. While each protocol includes “standards” and “guidelines” which are indicators of ‘minimum requirements’ and ‘recommendations’, the protocols are a first edition and have not been through a full cycle of use, review and refinement. Therefore, in this edition, the inclusion of “standards” and “guidelines” in each document are provided as an indication of the opinion of the relevant expert authoring group, but should not be regarded as definitive or as widely accepted peer professional opinion. The use of these standards and guidelines is subject to the clinician’s judgement in each individual case. The College makes all reasonable efforts to ensure the quality and accuracy of the protocols and to update the protocols regularly. However subject to any warranties, terms or conditions which may be implied by law and which cannot be excluded, the protocols are provided on an "as is" basis. The College does not warrant or represent that the protocols are complete, accurate, error-free, or up to date. The protocols do not constitute medical or professional advice. Users should obtain appropriate medical or professional advice, or where appropriately qualified, exercise their own professional judgement relevant to their own particular circumstances. Users are responsible for evaluating the suitability, accuracy, currency, completeness and fitness for purpose of the protocols. 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To the extent permitted by law, the College's liability under or for breach of any such term, condition or warranty is limited to the resupply or replacement of services or goods. iii Contents Scope ................................................................................................................. v Abbreviations .................................................................................................... vi Definitions ........................................................................................................ vii Introduction .......................................................................................................1 Authority and development ................................................................................4 1 Pre-analytical ...........................................................................................7 2 Specimen handling and macroscopic findings ..........................................9 3 Microscopic findings ............................................................................... 19 4 Ancillary studies findings ....................................................................... 23 5 Synthesis and overview.......................................................................... 29 6 Structured checklist ............................................................................... 37 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 ................67 Appendix 3 Example of a pathology report .......................................... 68 Appendix 4 WHO Classificationa of oesophageal tumours ....................70 References ....................................................................................................... 72 iv Scope This protocol contains standards and guidelines for the preparation of structured reports for oesophageal and gastro-oesophageal junctional carcinomas. Oesophagectomy and oesophago-gastrectomy specimens are included in this document and a separate protocol is available for reporting endoscopic resections. Endoscopic biopsy specimens are excluded. Structured reporting aims to improve the completeness and usability of pathology reports for clinicians, and in particular to improve decision support for cancer treatment. The protocol provides a framework for reporting of any oesophageal and gastro-oesophageal junctional (GOJ) carcinomas whether as a minimum data set or fully comprehensive report. This approach also allows easy extraction of relevant information for cancer registries and for clinical, translational and basic research. However the structured report allows flexibility in the report to reflect the inherent issues of oesophageal and gastro-oesophageal junctional carcinomas with an allowance to include any appropriate additional information as free text. The report will allow optional elements for reporting relevant immunohistochemical and molecular results. v Abbreviations AJCC American Joint Committee on Cancer OAC Oesophageal adenocarcinoma GOJ Gastro-oesophageal junction PBS Pharmaceutical Benefits Scheme RCPA Royal College of Pathologists of Australasia SCC Squamous cell carcinoma TNM tumour-node-metastasis UICC International Union Against Cancer WHO World Health Organization vi Definitions The table below provides definitions for general or technical terms used in this protocol. Readers should take particular note of the definitions for ‘standard’, ‘guideline’ and ‘commentary’, because these form the basis of the protocol. Ancillary study An ancillary study is any pathology investigation that may form part of a cancer pathology report but is not part of routine histological assessment. Clinical information Patient information required to inform pathological assessment, usually provided with the specimen request form, also referred to as “pre-test information”. Commentary Commentary is text, diagrams or photographs that clarify the standards (see below) and guidelines (see below), provide examples and help with interpretation, where necessary (not every standard or guideline has commentary). Commentary is used to: • define the way an item should be reported, to foster reproducibility • explain why an item is included (e.g. how does the item assist with clinical management or prognosis of the specific cancer). • cite published evidence in support of the standard or guideline • state any exceptions to a standard or guideline. In this document, commentary is prefixed with ‘CS’ (for commentary on a standard) or ‘CG’ (for commentary on a guideline), numbered to be consistent with the relevant standard or guideline, and with sequential alphabetic lettering within each set of commentaries (eg CS1.01a, CG2.05b). General commentary Guideline General commentary is text that is not associated with a specific standard or guideline. It is used: • to provide a brief introduction to a chapter, if necessary • for items that are not standards or guidelines but are included in the protocol as items of potential importance, for which there is currently insufficient evidence to recommend their inclusion. (Note: in future reviews of protocols, such items may be reclassified as either standards or guidelines, in line with diagnostic and prognostic advances, following evidentiary review). Guidelines are recommendations; they are not mandatory, as indicated by the use of the word ‘should’. Guidelines cover items vii 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. Guidelines are not used for research items. In this document, guidelines are prefixed with ‘G’ and numbered consecutively within each chapter (eg G1.10). Macroscopic findings Measurements, or assessment of a biopsy specimen made by the unaided eye. Microscopic findings In this document, the term ‘microscopic findings’ refers to histomorphological assessment. Predictive factor A predictive factor is a measurement that is associated with response or lack of response to a particular therapy. Prognostic factor A prognostic factor is a measurement that is associated with clinical outcome in the absence of therapy or with the application of a standard therapy. It can be thought of as a measure of the natural history of the disease. Standard Standards are mandatory, as indicated by the use of the term ‘must’. 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 (eg 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 viii 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. ix Introduction Oesophageal and Gastro-oesophageal Junction Cancer Oesophagectomy and oesophagogastrectomy specimens include all types of oesophageal carcinomas and carcinomas that straddle the junction of the oesophagus and the proximal stomach. The classification of gastro-oesophageal junctional (GOJ) carcinomas is difficult in practice. The AJCC guide includes the GOJ tumours and those of proximal 5cm stomach that extend into the GOJ in the group of oesophageal adenocarcinoma (OAC) and GOJ cancers.1 Separate stage groupings have been recommended for squamous and adenocarcinomas. It is likely that some tumours that originate in the proximal stomach present as gastro-oesophageal junctional cancers, and will be reported using the protocol below. Oesophageal and gastro-oesophageal junctional (GOJ) carcinoma can be of either squamous or glandular type. There are differences with regards to geographic distribution, epidemiology, aetiology and prognosis for these two histological subtypes. In developed nations the incidence and the prevalence of oesophageal, gastro-oesophageal junctional and proximal cardiac adenocarcinomas have been on the rise during the last decades. The incidence was considered to be highest in the UK, Australia, the Netherlands and the USA. In Asia and Africa OAC was considered uncommon but an increase has been reported lately.2 Oesophageal cancer is number 8 on the list of most common cancers worldwide and the sixth most common cause of death from cancer.3 In Australia oesophageal cancer is the 9th most common cancer and one of the top 10 causes of cancer mortality in males.4 Alcohol and smoking are risk factors for many cancers. In Australia in 2001, cancers attributed to excessive alcohol consumption accounted for 3.2% and those attributed to smoking for 12.0% of all new cases. Oesophageal cancer is high up in the list of such cancers.4 Barrett oesophagus has been singled out as the most important risk factor for OAC. Chronic gastro-oesophageal reflux disease predisposes to Barrett oesophagus. Adenocarcinomas of the GOJ share many characteristics with those of the distal oesophagus in countries where distal oesophageal adenocarcinomas are more common. However there appear to be geographical variations whereby in some Asian countries GOJ cancers have more similarities with proximal cardiac cancers than distal oesophageal cancers.5 While using the same protocol for this entire group of malignancies it is important to recognize that there are inherent biological differences within the group especially with regards to location and the type of cancer. Importance of histopathological reporting The role of the histopathologist in the management of OAC and GOJ carcinomas is to produce an accurate histological assessment that will inform clinicians about prognosis and the need for additional treatment. The most common types of 1 specimens encountered include oesophagogastrectomy, oesophagectomy and endoscopic resections (a separate protocol is available). Survival is dependent mainly on disease stage. Pathological assessment of surgical resection specimens should include salient features of OAC and GOJ carcinomas that are important for staging such as tumour type, depth of invasion and lymph node involvement.6 Similar to rectal carcinomas, oesophageal cancers have shown an increased risk of both local and systemic recurrences consequent to incomplete resections.7-8 Several studies have demonstrated that a negative circumferential margin is associated with improved survival.9-10 Given the fact that the only curative treatment for oesophageal and GOJ cancer is complete surgical resection of the primary tumour, it is imperative that all above relevant information and adequacy of surgical margins is provided in the report. Recently it has been established that certain molecular markers such as HER2 play an important role in target therapy for GOJ cancers. Herceptin therapy has shown a significant survival benefit for HER2 over-expressed, advanced/metastatic GOJ cancers.11 Currently pathologists may be expected to report on HER2 status of GOJ cancers upon request by clinicians. Benefits of structured reporting It is not uncommon to find inconsistencies in pathology reports within single institutions, across organisations, states and countries. The single most effective way to overcome this situation is to create a standardised reporting system that will ensure that key pathological features necessary for patient management and prognostication are included. It is also desirable to document important features for the purposes of audits, tumour registries and research in a systematic fashion. The College of American Pathologists (CAP), Association of Directors of Anatomic and Surgical Pathology (ADASP) and the Royal College of Pathologists (United Kingdom) have recently published protocols for the reporting of OAC.12-14 These protocols by themselves or with modifications to suit local needs have been used in recent years in Australia and New Zealand. A uniform modified protocol prepared in agreement with all parties involved in patient management is needed to cater for local requirements. This publication aims to fulfil this need incorporating relevant, currently available evidence-based information and collective suggestions and expert opinions of a multidisciplinary group. The intention is to provide pathologists with a minimum dataset and guidelines that are comprehensive and easy to use. It is hoped that this will help the clinicians to manage the patients optimally. The structured report aims at "guiding/teaching" to ensure that reporting is up to a desired standard, "enhancing" the practice of pathology with regards to oesophageal cancer, "inducing" the clinicians to undertake appropriate management and "promoting" advanced oesophageal and GOJ cancer research in Australia. 2 Design of this protocol This protocol defines the relevant information to be assessed and recorded in a pathology report for tumours of the oesophagus and gastro-oesophageal junction. Mandatory elements (standards) are differentiated from those that are not mandatory but represent best practice (guidelines). Also, items suited to tick boxes are distinguished from more complex elements requiring free text or narrative. The structure provided in the following chapters, headings and subheadings describe the elements of information and their groupings, but does not necessarily represent the format of either a pathology report (Chapter 7) or a 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. It should be noted that if the resection specimen contains two or more primary carcinomas (as indicated by the term ‘synchronous carcinomas’ on the reporting checklist) then a separate reporting checklist must be completed for each primary carcinoma. Key documentation • Guidelines for Authors of Structured Cancer Pathology Reporting Protocols15 • The Pathology Request-Test-Report Cycle — Guidelines for Requesters and Pathology Provider16 • WHO Classification of tumours, Pathology and Genetics of Tumours of the Digestive System, 2010, 4th edition17 • AJCC Cancer Staging Manual, 7th edition, 20101 Changes since the last edition Not applicable. 3 Authority and development This section provides details of the committee involved in developing this protocol and the process by which it was developed. Protocol developers This protocol was developed by an expert committee, with assistance from relevant stakeholders. Expert committee Clinical Prof Priyanthi Kumarasinghe (Chair and lead author), Pathologist Dr Ian Brown, Pathologist Dr Amanda Charlton, Pathologist A/Prof Bastiaan deBoer, Pathologist A/Prof Robert Eckstein, Pathologist Dr Krishna Epari, Surgeon Dr Anthony Gill, Pathologist Prof Alfred Lam, Pathologist Prof Gregory Lauwers, Pathologist Dr Spiro Raftopoulos, Gastroenterologist A/Prof Timothy Price, Medical Oncologist International Liaison Dr Mary K Washington, Chair of the Gastrointestinal Tumors Cancer Committee, College of American Pathologists Acknowledgements The oesophageal and gastro-oesophageal junction tumour expert committee wish to thank all the pathologists and clinicians who contributed to the discussion around this document. 4 Stakeholders ACT Health Anatomical Pathology Advisory Committee (APAC) Australian Association of Pathology Practices Inc (AAPP) Australian Cancer Network Australian Commission on Safety and Quality in Health Care Cancer Australia Cancer Control New Zealand Cancer Council ACT 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 Clinical Oncology Society of Australia (COSA) Department of Health and Ageing Gastroenterological Society of Australia GESA Grampians Integrated Cancer Services (GICS) Independent Review Group of Pathologists Health Informatics Society of Australia (HISA) Medical Software Industry Association (MSIA) National Coalition of Public Pathology (NCOPP) National E-Health Transition Authority (NEHTA) National Pathology Accreditation Advisory Council (NPAAC) National Round Table Working Party for Structured Pathology Reporting of Cancer. New Zealand Guidelines Group (NZGG) New Zealand Ministry of Health New Zealand Society of Gastroenterology (NZSG) NSW Department of Health 5 Peter MacCallum Cancer Institute Queensland Cooperative Oncology Group (QCOG) Representatives from laboratories specialising in anatomical pathology across Australia Royal Australasian College of Physicians (RACP) Southern Cancer Network, Christchurch, New Zealand Southern Melbourne Integrated Cancer Service (SMICS) Standards Australia The Medical Oncology Group of Australia The Royal Australasian College of Surgeons (RACS) The Royal Australian and New Zealand College of Radiologists (RANZCR) The Royal Australian College of General Practitioners (RACGP) The Royal College of Pathologists of Australasia (RCPA) Victorian Cooperative Oncology Group (VCOG) Western Australia Clinical Oncology Group (WACOG) Secretariat Meagan Judge, Royal College of Pathologists of Australasia Development process This protocol has been developed following the nine-step process set out in Guidelines for Authors of Structured Cancer Pathology Reporting Protocols.15 Where no reference is provided, the authority is the consensus of the expert group. 6 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 Oesophagus and Gastrooesophageal Junction 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 S1.02 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.18 This document specifies the minimum information to be provided by the requesting clinician for any pathology test. CS1.01b The patient’s ethnicity must 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. CS1.01c The patient’s health identifiers may include the patient’s Medical Record Number as well as a national health number such as a patient’s Medicare number (Australia), Individual Healthcare Identifier (IHI) (Australia) or the National Healthcare Identifier (New Zealand). 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 atomically. 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 requesting clinician (identified under S1.01) may be the doctor who performs the surgery or biopsy, and may not be the person with overall responsibility for investigating and managing the patient. Identification of the principal clinician is essential, to ensure that pathological and clinical information is communicated effectively. 7 CS1.04b Knowledge of the clinical presentation is an essential part of the WHO classification yet it may not be available 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 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. S1.05 The surgeon’s name and contact details must be recorded. G1.01 Any clinical information received in other communications from the requestor or other clinician should be recorded together with the source of that information. 8 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. Specimen handling 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 when the pathologist is sure that the diagnostic process including the measurement of maximum depth of invasion and other important parameters that influence patient prognosis and management will not be compromised. As a safeguard, research use of the specimen may be put on hold until the diagnostic process is complete so that the specimen can be retrieved. The specimen must be handled in a systematic and thorough fashion to ensure completeness and accuracy of pathological data. • Specimen reception: specimens are best received without delay either fresh or in formalin. This allows optimal orientation and sampling of non-fixed tissue e.g. tumour bank, research. Where receipt of fresh specimen is impractical, the specimen should be sent in an adequate volume of formalin (approximately 10 times greater than the tissue volume) depending on local approach.19 • Specimen measurement and fixation: generally the specimen should be pinned out on corkboard, measurements of length taken (see Specimen Inspection below), and then fully fixed in an adequate volume of formalin (generally overnight) before dissection and block-taking. In cases where the specimen is not opened initially, a “wick” inserted into the lumen will aid fixation. • Specimen inspection: the external aspect should be inspected for any visible tumour prior to inking of the entire circumferential margin. The nature and extent of any peri-oesophageal tissue should be described. Any surgical tears or defects should be recorded. The length of the tubular oesophagus, and of any included stomach, along the greater and lesser curvatures, should be recorded, if not previously recorded prior to fixation. • Specimen dissection: there are 2 recommended methods of opening the oesophagus: 1. If, by inspection and palpation, the tumour is not circumferential, the oesophagus can be opened longitudinally with scissors, taking care to avoid cutting into the tumour. This allows better assessment of the mucosal surface of the tumour and 9 oesophagus. 2. If, by inspection and palpation, the tumour is circumferential, it should be “bread-sliced” transversely, similar to the method used for rectal cancers. This gives better assessment of the circumferential margin. For further details see Figure S2.11 below. 3. A photograph of the specimen is recommended All lymph nodes must be harvested and examined histologically. • In completely resected carcinomas, lymph node status is the most important independent prognostic indicator.20-22,23 • Regional lymph nodes include supraclavicular nodes, upper paratracheal nodes, posterior mediastinal nodes, lower paratracheal nodes, aortopulmonary nodes, anterior mediastinal nodes, subcarinal nodes, middle paraoesophageal nodes, lower paraoesophageal nodes, pulmonary ligament nodes, tracheobronchial nodes, diaphragmatic nodes, paracardial nodes, left gastric nodes, common hepatic nodes, splenic nodes and coeliac nodes. Other lymph node groups are non-regional nodes. • Individually labelled lymph nodes should be reported separately. • Lymph nodes may be more difficult to locate following chemoradiotherapy. 10 Figure SH1 Lymph node map for oesophageal cancer.* 1 Supraclavicular zone 8L Lower paraesophageal 2R Right Upper Paratracheal 9 Pulmonary ligament 2L Left Upper Paratracheal 10R Right tracheobronchial 3P Posterior mediastinal 10L Left tracheobronchial 4R Right Lower Paratracheal 15 Diaphragmatic 4L Left Lower Paratracheal 16 Paracardial 5 Aortopulmonary 17 Left gastric 6 Anterior mediastinal 18 Common hepatic 7 Subcarinal 19 Splenic 8M Middle paraesophageal 20 Celiac *Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Sixth Edition (2002) published by Springer Science and Business Media LLC, www.springerlink.com. 11 Macroscopic findings S2.01 The type of resection must be recorded. CS2.01a Options include: • Pharyngolaryngo-oesophagectomy • Oesophagectomy • Oesophago-gastrectomy • Other (specify) S2.02 All linear measurements are in SI units, unless explicitly stated. S2.03 The specimen dimensions must be recorded. CS2.03a Record the length of the tubular oesophagus, and the stomach, along the greater curve if present (see Specimen Inspection in Specimen Handling above). The stomach can be recognised by the presence of rugal folds on the mucosal surface, and serosa on the outer surface. Note that the resected oesophagus shrinks considerably both before and after fixation, making measurements shorter than in vivo measurements.24 For the purposes of this protocol it is generally expected that measurements will be made after fixation. S2.04 The tumour site (location) must be recorded. CS2.04a It is often not feasible for the pathologist to identify the level of the tumour within the oesophagus without information from the surgeon. The pathologist must record the distance of the proximal edge of the tumour from the proximal end of the specimen. For tumours located entirely within the oesophagus, the distance between the distal edge of the tumour and the gastro-oesophageal junction must be recorded (see CS2.04c). For tumours straddling the gastro-oesophageal junction, the distance of the midpoint of the tumour from the gastro-oesophageal junction must be recorded. This, in conjunction with the overall length of the tumour, will determine whether the tumour is classified and staged using this protocol or the RCPA gastric cancer protocol. CS2.04b Tumours having their midpoint within 5cm of the gastrooesophageal junction, the so-called gastric “cardia”, that extend into the oesophagus (macroscopically or microscopically) are staged using the oesophageal cancer protocol; see figure S2.04. 12 CS2.04c Figure S2.04 S2.05 G2.01 Stage as oesophageal carcinoma The maximum tumour dimension must be recorded CS2.05a Tumour size is based on macroscopic assessment, confirmed or amended on microscopy. This is of particular relevance where the macroscopic size may be difficult to assess, such as after chemoradiotherapy and in cases of diffuse carcinoma. CS2.05b Maximum tumour length has been shown to correlate with survival.23,25 The maximum tumour thickness may be recorded. CG2.01a G2.02 The gastro-oesophageal junction can be identified as the point where the tubular oesophagus meets the upper limit of the gastric rugal folds. If this mucosal landmark is obscured by extensive tumour involvement or columnar lined oesophagus, the junction can be located at the highest point of the peritoneal reflection on the serosal surface of the stomach. Tumour thickness is based on macroscopic assessment, confirmed or amended on microscopy. The gross appearance of the tumour should be recorded. 13 S2.06 CG2.02a An attempt should be made to assess whether the tumour is restricted to mucosa, muscularis propria, or involves the adventitia or serosa. CG2.02b Prior chemoradiotherapy or endoscopic resection may result in scarring and loss of grossly recognisable tumour. The distance from the tumour to the nearest proximal or distal margin (cut end) must be recorded. CS2.06a S2.07 S2.08 Tumour distance to margins is based on macroscopic assessment, confirmed or amended on microscopy. This is of particular relevance where the macroscopic size may be difficult to assess, such as after chemoradiotherapy and in cases of diffuse carcinoma. The distance of the tumour from the circumferential margin of the oesophagus must be recorded. CS2.07a The distance is used as a guide to subsequent microscopic assessment. CS2.07b Tumour involving the circumferential resection margin by gross examination is classified as R2. Involvement of any adjacent structures must be recorded. CS2.08a Involvement of pleura, pericardium, diaphragm, gastric serosa, or other adjacent structures, upstages oesophageal carcinoma to T4. Refer to Figure S2.08 below. 14 Figure S2.08 Anatomic cancer classification for oesophageal cancer. Anatomic cancer classification is by depth of cancer invasion (T) and regional lymph node classification (N), defined by absence (N0) or presence (N1) of cancer-positive lymph nodes. Distant metastasis (M) not illustrated.26 Reproduced with permission. S2.09 The presence or absence of Barrett mucosa must be recorded. CS2.09a Glandular mucosa can usually be distinguished from squamous mucosa by naked eye inspection. CS2.09b Thickening, congestion and superficial ulceration within the glandular or squamous mucosa may be due to dysplasia or in situ carcinoma. CS2.09c The presence of Barrett mucosa should be confirmed by microscopy. G2.03 The length of Barrett mucosa within the tubular oesophagus should be recorded. S2.10 Additional specimens such as labelled lymph nodes/donuts must be recorded. S2.11 The nature and site of all blocks must be recorded. CS2.11a A diagram or photograph showing the sites of blocks taken 15 may be helpful. CS2.11b Proximal and distal resection margins should be sampled, usually parallel to the cut edge. If the tumour is very close to the margin, perpendicular slices can aid microscopic measurement. The central part of the tumour is cut in serial 3mm slices, and the slices laid out sequentially (figure S2.11). Select blocks of tumour to show the greatest depth of invasion, and tumour closest to the circumferential (radial) margin. Sample gastric serosa if close to the tumour. Take blocks to show involvement of other tissues/organs if present on the specimen, eg pleura. CS2.11c At the proximal and distal ends of the tumour, take perpendicular blocks. This will help to show the relation of the tumour to neoplastic precursors such as Barrett oesophagus, and glandular or squamous dysplasia. CS2.11d Unless obliterated by tumour, sample the squamoglandular junction and the junction of tubular oesophagus and stomach, to assess for Barrett oesophagus. CS2.11e Take a sample of uninvolved oesophagus and stomach above and below the tumour to assess for tumour precursors such as Barrett oesophagus, glandular and squamous dysplasia, and Helicobacter pylori infection. CS2.11f In cases of intramucosal carcinoma or high grade intraepithelial neoplasia there may be little or no gross abnormality. In such cases, clinical and radiological data regarding tumour location should be obtained to guide sampling. Extensive sampling of the tumour site may be required, with examination of blocks at multiple levels (figure S2.11). CS2.11g Preoperative chemotherapy may result in the shrinkage or complete loss of macroscopic abnormality.27 In the absence of macroscopic tumour, clinical and radiologic data regarding tumour location is used to localise sampling. Following slicing, thickening or fibrosis in the submucosa and muscularis propria may indicate the site of previous tumour. If no carcinoma is found in the initial blocks, then examine three further levels of each block. If there is still no carcinoma found, then in most cases, embedding of the whole site is required before a complete response to neoadjuvant therapy can be reported. CS2.11h All macroscopically uninvolved nodes should be completely embedded. Macroscopically involved nodes require only one slice embedded for confirmation. 16 Figure S2.11 Recommended blocks for histology in resected oesophageal neoplasms Recommended blocks for histology in resected oesophageal neoplasms. (A) Oesophagectomy specimen. (B) Oesophago-gastrectomy specimen containing tumour above the gastro-oesophageal junction. (C) Oesophago-gastrectomy specimen containing tumour at the gastro-oesophageal junction. (D) Resected specimen for high grade dysplasia/in situ carcinoma. Shaded blocks represent the recommended minimum number to be sampled (A) and (C).28 Reproduced with permission. G2.04 A descriptive or narrative field should be provided to record any macroscopic information that is not recorded in the above standards 17 and guidelines, and that would normally form part of the macroscopic description. CG2.04a The traditional macroscopic narrative recorded at the time of specimen dissection is often reported separately from the cancer dataset. Although this remains an option, it is recommended that macroscopic information be recorded within the overall structure of this protocol. CG2.04b 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. 18 3 Microscopic findings This section relates to purely histological (morphological) assessment. Information derived from multiple investigational modalities, or from two or more chapters, is described in Chapter 5. S3.01 Tumour location must be recorded. CS3.01a The tumour location should be explicitly recorded after microscopic confirmation as the confirmed location after microscopic examination may be different to the macroscopic impression. In the AJCC classification tumours “arising in the stomach <5cm from the gastro-oesophageal junction and crossing the gastro-oesophageal junction are staged using the TNM system for oesophageal adenocarcinoma”. In the event that the location on microscopic evaluation involves the oesophagus, even when not obvious macroscopically, then the cancer is reported using the oesophageal cancer structured report if they are within the 5cm of the proximal stomach ("cardia"). By adhering to the AJCC classification1, it is recognised that there will be tumours that are present in the proximal stomach, which appear to be of gastric origin (eg unassociated with Barrett oesophagus and predominantly located in the stomach), will be somewhat artificially placed into the category of tumours of the “oesophagus and gastro-oesophageal junction”. Such tumours are reported using the protocol for oesophageal cancer. Nevertheless, in reporting such tumours it is recommended that the likelihood that such tumours may have arisen within the stomach is recorded. S3.02 Histological tumour type must be recorded. CS3.02a The histological type of the tumour should be recorded based on the current WHO classification.17 These types are: • Squamous cell carcinoma • Adenocarcinoma • Adenoid cystic carcinoma • Adenosquamous carcinoma • Basaloid squamous cell carcinoma • Mucoepidermoid carcinoma • Spindle cell (squamous) carcinoma 19 CS3.02b S3.03 • Verrucous (squamous) carcinoma • Undifferentiated carcinoma The revised TNM staging system for oesophageal carcinomas incorporates tumour grade and histologic type in the stage groupings. Mixed histologic types, such as adenosquamous carcinomas, are staged using the squamous cell carcinoma stage grouping. Histologic grade must be recorded. CS3.03a The tumour should receive a histological grade a based on the AJCC classification1: • Grade X Grade cannot be assessed – stage grouping as G1 • Grade 1 Well differentiated • Grade 2 Moderately differentiated • Grade 3 Poorly differentiated • Grade 4 Undifferentiated – stage grouping as G3 squamous For adenocarcinomas: • Grade 1 – is comprised of greater than 95% of tumour composed of glands. • Grade 2 - 50% to 95% of tumour composed of glands • Grade 3 - 49% or less of tumour composed of glands. Glandular structures are absent in undifferentiated tumours.17 CS3.03b Mucoepidermoid carcinoma and adenoid cystic carcinoma of the oesophagus are not graded. Signet-ring cell carcinoma is classified as grade 3. Small cell carcinoma and undifferentiated carcinoma are classified as grade 4. G3.01 The pattern of growth should be recorded. a Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer Science and Business Media LLC, www.springerlink.com. 20 CG3.01a The pattern of growth should be recorded as either: 1. Expanding: Tumour cells grow en masse by expansion resulting in tumour nodules, or 2. Infiltrating: Tumour cells penetrate individually and widely resulting in diffuse infiltration of the oesophagus. S3.04 Tumour size must be specified. CS3.04a S3.05 A final estimate of the maximum dimension of the tumour is given based on both the macroscopic and histological findings. The depth of invasion must be recorded. CS3.05a The level of invasion relative to the anatomical layers of the oesophagus (lamina propria, muscularis mucosae, submucosa, muscularis propria and adventitial connective tissue) must be recorded. (Refer to Figure S2.08). S3.06 The presence or absence of peritoneal involvement must be recorded. S3.07 The presence or absence of pleural involvement must be recorded. S3.08 The presence or absence of vascular space invasion in small (lymphatic and capillary) and large (vein and artery) caliber vessels as well as perineural growth must be recorded. G3.02 The presence or absence of tumour budding may be recorded. CG3.02a Tumour budding can be defined as the presence of single cells or small groups of less than 5 undifferentiated cells at the invasive front of the carcinoma. More than 5 tumour buds per square mm has been proposed as a high rate of tumour budding. There is early evidence suggesting that tumour budding may represent an adverse prognostic indicator. However, at the current time there is insufficient evidence to support its routine reporting and it should be considered investigational.29 S3.09 The degree of regression after preoperative chemoradiation must be recorded. CS3.09a The following schema, though based on a study originally applied to rectal cancer, is recommended by the College of American Pathologists1 as is the same as that endorsed by the RCPA for gastric carcinoma. In the absence of other widely used schemas, the following grading system is recommended. Grade 0: Complete Response – No viable cancer cells Grade 1: Moderate response - Single cells or small 21 groups of cancer cells Grade 2: Minimal response – Residual cancer outgrown by fibrosis Grade 3: Absent response – Minimal or no tumour kill; extensive residual cancer. S3.10 The distance of carcinoma from the proximal, distal and radial/circumferential margins must be recorded. CS3.10a For most oesophageal cancers, the radial margin of the oesophagus will commonly be the closest margin. Away from the gastro-oesophageal junction, the only radial/circumferential margins are the lesser omental ligaments and the greater omental resection margin. CS3.10b If the tumour shows microscopic involvement of the excision margin (R1 resection) this should be explicitly stated. Otherwise the distance of the tumour from the resection margin (circumferential and end margins both) should be stated. G3.03 If submitted, state whether the donut is involved by tumour or not. S3.11 The number of lymph nodes involved and the total number received must be recorded. S3.12 CS3.11a Record the number of lymph nodes from the main resection specimen, and the regional nodes from each separately labelled specimen should be recorded. CS3.11b According to the AJCC1, a “tumour nodule with smooth contour in regional node area” is classified as a positive node. Note that similar nodules on the peritoneal surface are considered M1. The presence or absence of Barrett mucosa, squamous or glandular dysplasia, gastritis, eosinophilic oesophagitis or other pathologies must be specified. CS3.12a G3.04 If Barrett mucosa or dysplasia involves a margin this should be stated. The estimated distance of dysplasia from the closest margin should be stated. Any additional relevant microscopic comments should be recorded. 22 4 Ancillary studies findings Ancillary investigations in tumours of the gastro-oesophageal junction or oesophagus can potentially serve the following purposes: 1) to predict response to medical therapy; 2) to aid tumour classification; 3) to detect a genetic aetiology for the cancer; 4) to provide prognostic information; and 5) to establish the presence or absence of an infectious co-factor. G4.01 The results of any ancillary tests performed should be incorporated into the pathology report. CG4.01a Therapeutic guidance Surgical resection has long been the first line of treatment for oesophageal cancer, however, local recurrence rates approach 60% and a ‘surgery alone’ approach is only recommended for non cervical T1 lesions. The addition of adjuvant radiotherapy and chemotherapy is recommended for all other cases30. Targeted therapy is currently being investigated as an addition to these regimes and for the treatment of metastatic disease. Of the potential targets trialled to date, epithelial growth factor receptor - EGFR (Her1 and Her2) and vascular endothelial growth factor - VEGF surface receptor antagonists have shown the most promise. a. Her 2 (EGFR-2)10,28-30 Her 2 over expression is reported in approximately 15 25% of gastric/gastro-oesophageal junction (GOJ) adenocarcinomas in Western countries including in Australia (range 2-45% for gastric/GOJ and 9-60% for oesophagus).11,31 The 2010 ToGA study found that trastuzumab-based therapy offered a significant survival advantage for patients with HER2 overexpressing locally advanced, recurrent or metastatic gastric and gastrooesophageal junctional adenocarcinomas compared to conventional therapy alone. Currently the relevance in true oesophageal adenocarcinomas and squamous carcinomas is unclear. However it is likely that pathologists will be required to determine the Her 2 status in biopsy or resection material in GOJ and gastric cancers as well as in metastatic sites. Currently immunohistochemistry (IHC) and in-situ hybridisation (ISH) testing is performed concurrently in an accredited laboratory in Australia to select the patients who are eligible for trastuzumab based treatment. National guidelines for testing and criteria for negative and positive HER2 status in gastric/GOJ cancers are based on the current scientific evidence and both local and international expert opinions.32-33 It should be noted methods/interpretation of HER-2 positivity for gastric/GOJ cancers differs importantly from that for breast cancer, and that application of breast cancer 23 scoring will significantly under-report the proportion of HER-2 positive oesophagitis gastric cancer.34 Hence a modified IHC scoring and ISH cut-off levels are adopted.35 In Australia a positive HER2 result requires a combination of IHC2+ or a IHC3+ score and a positive ISH result. The high level of heterogeneity noted in these cancers has resulted in many difficulties in interpretation of results. Table G4.01 (i) below is a guide to assess protein expression by IHC. Figure G4.01 (iii) shows an example of HER2 gene amplification by silver in situ hybridisation (SISH) and heterogeneity. b. EGFR -1 Over expression of EGFR -1 is found in 1/3 to 2/3 of oesophageal adenocarcinoma and squamous cell carcinoma (SCC). To date, clinical trials using the EGFR-1 antagonist, cetuximab, have revealed varied results. At this stage, assessment of EGFR-1 expression is not warranted. c. VEGF VEGF is over expressed in 30 – 60% of oesophageal adenocarcinoma. Over expression is associated with higher tumour stage and poorer survival.36 In non selected patients, the VEGF antagonist bevacizumab has shown promising results when added to multimodality treatment. At this time, assessment of VEGF status is not required. d. Others Other molecular targets undergoing clinical trial and/or being considered for clinical trial and potentially requiring assessment of protein expression by pathologists include: other EGFRs, cyclooxygenase-2 (COX-2), mammalian target of rapamycin (mTOR), heat shock protein 90 (Hsp90), and PI3K/Akt, matrix metalloproteinases, insulinlike growth factor receptor (IGFR) and regulators of the cell cycle e.g. cyclins and nuclear factor κβ. There is evidence that high levels of microsatellite instability predict a poor response to alkylating chemotherapy in colorectal carcinoma, however, there is conflicting data in oesophageal adenocarcinoma and MSI testing (or mismatch repair marker immunohistochemistry) is not warranted at this stage.37 CG4.01b Aid to tumour classification At present, no specific ancillary tests are routinely recommended for oesophageal tumour classification. In the case of occasional poorly differentiated carcinoma, mucin stains (positive, albeit often focal, in adenocarcinoma) and p63 and/or p40 (ΔNp63) (positive in SCC) may help distinguish SCC from adenocarcinoma and basaloid 24 squamous carcinoma from adenoid cystic carcinoma. Spindle cell (squamous) carcinoma will express cytokeratin, aiding distinction from primary sarcomas and melanoma. Immunohistochemical stains may be performed to identify phenotypes. MUC2, CD10 and CDX2 are known to be positive in intestinal phenotype and MUC5AC and MUC6 in gastric phenotypes. The significance of this has not been determined.38-39 CG4.01c Detection of inherited cases Familial cases of oesophageal cancer are uncommon. In many cases an underlying genetic disease is already evident (eg Tylosis or achalasia predisposing to oesophageal SCC). The approximately 5% of oesophageal adenocarcinomas that arise on the basis of microsatellite instability, are due to sporadic hypermethylation related silencing of MLH-1 gene and do not represent Lynch syndrome.37 Because of the rarity of genetically defined predisposing conditions, ancillary investigation is not required. CG4.01d Prognostic markers40 Most data exists for oesophageal adenocarcinoma and has found that expression or identification of the following markers to predict survival - Epidermal growth factor receptors (1 and 2 - Her2/neu): Transforming growth factor (TGF α and β1); P53, Ki-67, Cyclin dependent kinase inhibitor 1 (p21); B-cell lymphoma 2 (bcl-2); Cyclooxygenase-2 (COX-2); Nuclear factor-κB (NF-κB); Vascular endothelial growth factor (VEGF); Tissue inhibitor of metalloproteinase (TIMP) and microsatellite instability (MSI). At present, routine testing for all or any of these markers is not warranted. Several studies have investigated the prognostic utility of whole genome expression array profiling and micro RNA expression profiling in oesophageal cancer. Either or both techniques have potential future utility in prediction of patient survival, prediction of response to preoperative therapy and to guide therapy. For Squamous cell carcinoma, apart from staging, Ki-67 appears to be able to stratify the patients into prognostic groups.41 However, this method has not been widely used. CG4.01e Infectious co-factor There is considerable data on the role of HPV infection in the development of oesophageal SCC. Some of this is conflicting, however, it appears that identification of HPV is uncommon in western countries (<5%) but may be more frequent (30-50%) in high oesophageal SCC prevalence 25 regions such as in parts of China.42 The presence of HPV does not correspond to a particular morphology. It is currently unknown whether HPV detection and/or p16 expression will predict radiotherapy response as it does for upper aerodigestive tract SCC. At this stage routine evaluation of HPV status and/or p16 is not required. 26 Table G4.01 (i) Score Surgical specimen HER2 scoring (immunohistochemistry) table Biopsy specimen HER2 status (protein overexpression) No reactivity or membranous reactivity in <10% of tumour cells No reactivity or no membranous reactivity in any tumour cell 0 Faint/barely perceptible membranous reactivity in ≥ 10% of tumour cells; cells are reactive only in part of their membrane Tumour cell cluster with a faint/barely perceptible membranous reactivity irrespective of percentage of tumour cells stained 1+ Negative Weak to moderate complete, basolateral or lateral membranous reactivity in ≥ 10% of tumour cells Tumour cell cluster with a weak to moderate complete, basolateral or lateral membranous reactivity irrespective of percentage of tumour cells stained 2+ Equivocal Strong complete, basolateral or lateral membranous reactivity in ≥ 10% of tumour cells Tumour cell cluster with a strong complete, basolateral or lateral membranous reactivity irrespective of percentage of tumour cells stained 3+ Positive 27 Negative Figure G4.01 (ii) IHC for HER2 demonstrating heterogeneous patterns Score 3+ Left score 1+ Right score 3+ Mix of scores 1+, 2+ and 3+ 3 1 1 0 3 28 Figure G4.01 (iii) HER2 gene amplification by SISH on the right half of the tumour in contrast to non-amplification on the left half. This example also highlights HER2 heterogeneity. 29 Table G4.01 (iv) Morphologic and immunohistochemical features of dysplasia Pattern of dysplasia Intestinal (adenomatous) Morphologic features - Columnar cells - Hyperchromatic, pencillate, stratified nuclei See figure G4.01(iv) - Dense eosinophilic cytoplasm Gastric foveolar - Cuboidal to (non adenomatous) columnar cells with pale clear to light See figure G4.01(v) eosinophilic cytoplasm - Hyperchromatic round to oval nuclei - Prominent nucleoli if high grade - Cytological Hybrid features intermediate between the above patterns - Or an intimate admixture of both - Resembling Serrated colorectal serrated lesions - Poorly characterised at present - Closely packed Pyloric gland tubules lined by cuboidal to columnar epithelium with pale to eosinophilic ground glass cytoplasm - Round basal nuclei - Nucleoli easily visible MUC2 MUC5ac MUC6 CDX-2 Villin CD10 + ± - + + + - + rare - - - ± + ± ± ± ± ?(+) ?(+) ? ?(+) ? ? - + (surface) + - - - 30 Figure G4.01(v) H&E Intestinal panel CDX-2 MUC2 Figure G4.01(vi) VILLIN Gastric foveolar panel H&E CDX-2 MUC5ac VILLIN 31 5 Synthesis and overview Information that is synthesised from multiple modalities and therefore cannot reside solely in any one of the preceding chapters is described here. For example. tumour stage is synthesised from multiple classes of information – clinical, macroscopic and microscopic. By definition, synthetic elements are inferential rather than observational, often representing high-level information that is likely to form part of the report ‘Summary’ or ‘Diagnosis’ section in the final formatted report. Overarching case comment is synthesis in narrative format. 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. 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 (7th Edition).1 (See Tables S5.01a, b, c and d below.) Table S5.01a AJCC primary tumour definitions for tumours of the oesophagus and oesophagogastric junction. b Primary Tumour (T)** TX Primary tumour cannot be assessed T0 No evidence of primary tumour Tis High grade dysplasia*** T1 Tumour invades lamina propria, muscularis mucosae, or submucosa T1a Tumour invades lamina propria or muscularis mucosae T1b Tumour invades submucosa T2 Tumour invades muscularis propria T3 Tumour invades adventitia T4 Tumour invades adjacent structures T4a Resectable tumour invading pleura, pericardium, or diaphragm T4b Unresectable tumour invading other adjacent structures, such as aorta, vertebral body, trachea etc ** (1) At least maximal dimension of the tumour must be recorded and (2) multiple tumours require the T(m) suffix. *** High grade dysplasia includes all noninvasive neoplastic epithelia that was formerly called carcinoma in-situ, a diagnosis that is no longer used for columnar mucosae anywhere in the gastrointestinal tract. Table S5.01b AJCC regional lymph node classifications for tumours of b Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer Science and Business Media LLC, www.springerlink.com. 32 the oesophagus and oesophagogastric junction. c Regional Lymph Nodes (N)* NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Metastasis in 1-2 regional lymph nodes N2 Metastasis in 3-6 regional lymph nodes N3 Metastasis in seven or more regional lymph nodes * Number must be recorded for the total number of regional nodes sampled and total number of reported nodes with metastasis. Table S5.01c AJCC distant metastasis classifications for tumours of the oesophagus and oesophagogastric junction.c Distant Metastasis (M) M0 No distant metastasis M1 Distant metastasis NOTE that the designation "MX" has been dropped from the 7th edition of the AJCC/UICC TNM system. The terminology pM1 (distant metastases present) can only be used by pathologists on the basis of pathological assessment of a relevant tissue sample. The pathologist may not be in possession either of the clinical information that indicates a cM1 stage or of specimens received from other procedures that indicate a pM1 stage. In such situations pM staging may not be reported. Thus there must be a recognition that staging based on examination of the resection specimen may not reflect the stage of disease in the patient. This can be indicated in the “synthesis and diagnostic summary” section of the report by including a statement such as: Note: the staging given is based on examination of the specimens received. Stage IV cannot normally be assigned on these examinations. Note that positive peritoneal cytology is classified as M1. Often this is separately reported. Positive cytology would change the stage group to stage IV. This information if available should be indicated in the report preferably as a comment. Table S5.01d AJCC/UICC pathological stage grouping for tumours of the oesophagus and oesophagogastric junction.c c Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer Science and Business Media LLC, www.springerlink.com. 33 Anatomic Stage/Prognostic Groups Squamous cell carcinoma* Stage T N M Grade Tumour Location ** O Tis N0 M0 1, X Any IA T1 N0 M0 1, X Any IB T1 N0 M0 2-3 Any T2-3 N0 M0 1, X Lower, X T2-3 N0 M0 1, X Upper, middle T2-3 N0 M0 2-3 Lower, X T2-3 N0 M0 2-3 Upper, middle T1-2 N1 M0 Any Any T1-2 N2 M0 Any Any T3 N1 M0 Any Any T4a N0 M0 Any Any IIIB T3 N2 M0 Any Any IIIC T4a N1-2 M0 Any Any T4b Any M0 Any Any Any N3 M0 Any Any Any Any M1 Any Any IIA IIB IIIA IV * Or mixed histology including a squamous component or NOS. ** Location of the primary cancer is defined by the position of the upper (proximal) edge of the tumour in the oesophagus. 34 Adenocarcinoma Stage T N M Grade O Tis (HGD*) N0 M0 1, X IA T1 N0 M0 1-2, X IB T1 N0 M0 3 T2 N0 M0 1-2, X IIA T2 N0 M0 3 IIB T3 N0 M0 Any T1-2 N1 M0 Any T1-2 N2 M0 Any T3 N1 M0 Any T4a N0 M0 Any IIIB T3 N2 M0 Any IIIC T4a N1-2 M0 Any T4b Any M0 Any Any N3 M0 Any Any Any M1 Any IIIA IV *HGD, high grade dysplasia. S5.02 The year of publication and edition of the cancer staging system used in S5.01 must be included in the report. G5.01 The ‘Diagnostic summary’ section of the final formatted report should include: G5.02 o Tumour location o Histologic type o Tumour grade o Tumour size o Lymph nodes o Stage o Involved or close margins (includes tumour less than 1mm from margin) A field for free text or narrative in which the reporting pathologist can give overarching case comment must be provided. CG5.02a 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 35 pending. CG5.02b Use of this field is at the discretion of the reporting pathologist. 36 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 Data Set” for oesophageal tumours. For emphasis, standards (mandatory elements) are formatted in bold font. S6.01 The structured checklist provided below 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 G6.02 The order of according to described in Reporting of 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. Where the checklist is used as a report template (see G6.01), the principles in Chapter 7 and Appendix 2 apply. CG6.02a G6.03 information and design of the checklist may be varied the laboratory information system (LIS) capabilities and as Functional Requirements for Structured Pathology Cancer Protocols.43 All extraneous information, tick boxes and unused values should be deleted. 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. 37 Values in italics are conditional on previous responses. Values in all caps are headings with sub values. S/G Item description Response type Conditional Clinical information and surgical handling S1.01 Demographic information provided S1.02 Clinical information provided on request form Text OR Structured entry as below: Tumour location Operative procedure Multi select value list (select all that apply): • cervical oesophagus • upper thoracic • middle thoracic • lower thoracic • gastro-oesophageal junction Single selection value list: • Pharyngolaryngo-oesophagectomy • Oesophagectomy • Oesophago-gastrectomy • Other 38 If other, record the details. S/G Item description Response type Details Operative method of oesophagogastrectomy Extent of lymphadenectomy Preoperative therapy Text Single selection value list: • 3 Stage (eg McKeown) • 2 Stage (eg Ivor-Lewis) • 1 Stage (eg Sweet) • Trans-hiatal Single selection value list: • Three field • Two field • Two field (Infra-carinal) • Conservative Single selection value list: Type Involvement of adjacent Conditional • Administered • Not administered Single selection value list: • Preoperative chemotherapy • Preoperative radiotherapy • Preoperative chemoradiotherapy Text 39 If administered, record type S/G Item description Response type Conditional Single selection value list: If present, provide details organs Distant metastases Details Existence of residual cancer New primary cancer or recurrence • Absent • Present Text Single selection value list: • Absent • Present (R2) Single selection value list: • New primary • Recurrence – regional • Recurrence - distant S1.03 Pathology accession number Alpha-numeric S1.04 Principal clinician caring for the patient Text S1.05 Surgeon’s name & contact details Text G1.01 Additional information Text Macroscopic findings 40 S/G Item description Response type Conditional S2.01 Type of resection Single selection value list: If other, record the details. Details S2.03 S2.04 • Pharyngolaryngo-oesophagectomy • Oesophagectomy • Oesophago-gastrectomy • Other Text Length of tubular oesophagus Numeric: ___mm Length of greater curve stomach (if present) Numeric: ___mm Tumour site Multi select value list (select all that apply): • cervical oesophagus • upper thoracic • middle thoracic • lower thoracic • gastro-oesophageal junction Proximal edge of tumour to proximal end of specimen Numeric: ___mm Distal edge of tumour to gastro-oesophageal junction Numeric: ___mm 41 S/G Item description Response type Conditional Midpoint of tumour to gastro-oesophageal junction Numeric: ___mm Conditional on gastrooesophageal junction being selected above. S2.05 Maximum tumour dimension Numeric: ___mm G2.01 Maximum tumour thickness Numeric: ___mm G2.02 Gross appearance of tumour Text S2.06 Distance of tumour to nearest proximal or distal margin (cut end) Numeric: ___mm OR Not identifiable OR Involved S2.07 Distance of tumour to circumferential margin Numeric: ___mm OR Not identifiable OR Involved S2.08 Involvement of adjacent structures Not involved If other, provide details OR Multi select value list (select all that apply): 42 S/G Item description Response type Details S2.09 Barrett mucosa Conditional • Pleura • Peritoneum • Pericardium • Diaphragm • Aorta • Carotid vessels • Azygos vein • Trachea • Left or right main bronchus • Vertebral body • Perioesophageal tissue • Other Text Single selection value list: • Absent • Present If present, consider G2.03 G2.03 Length of Barrett mucosa Numeric: ___mm Conditional on the presence of Barrett mucosa in S2.09 S2.10 Additional specimens Single selection value list: If submitted, describe • Not submitted 43 S/G Item description Response type • Description Conditional Submitted Text S2.11 Nature and site of all blocks Text G2.04 Other macroscopic comment Text Microscopic findings S3.01 S3.02 Tumour location Histologic type Multi select value list (select all that apply): • cervical oesophagus • upper thoracic • middle thoracic • lower thoracic • gastro-oesophageal junction Single selection value list: • Squamous cell carcinoma • Adenocarcinoma • Adenoid cystic carcinoma • Adenosquamous carcinoma 44 If other, record details S/G Item description Response type Details S3.03 Histologic grade Conditional • Basaloid squamous cell carcinoma • Mucoepidermoid carcinoma • Spindle cell (squamous) carcinoma • Verrucous (squamous) carcinoma • Undifferentiated carcinoma • Other Text If Adenocarcinoma (from S3.02): Single selection value list: • Grade X Grade cannot be assessed • Grade 1 Well differentiated (greater than 95% of tumour composed of glands). • Grade 2 Moderately differentiated (50% to 95% of tumour composed of glands) • Grade 3 Poorly differentiated (49% or less of tumour composed of glands). • Grade 4 Undifferentiated If Squamous cell carcinoma, adenosquamous carcinoma, basaloid squamous cell carcinoma, Spindle cell (squamous) carcinoma and Verrucous (squamous) carcinoma (from S3.02): 45 Conditional on Adenocarcinoma, Squamous cell carcinoma, adenosquamous carcinoma, basaloid squamous cell carcinoma, Spindle cell (squamous) carcinoma and Verrucous (squamous) carcinoma being selected in S3.02. S/G Item description Response type Conditional Single selection value list: • Grade X • Grade 1 Well differentiated • Grade 2 Moderately differentiated • Grade 3 Poorly differentiated • Grade 4 Undifferentiated Note 1. Grade X tumours are grouped as grade 1 carcinomas. 2. Mucoepidermoid carcinoma and adenoid cystic carcinoma of the oesophagus are not graded. 3. If small cell carcinomas OR undifferentiated carcinoma record grade as 4. Signet-ring cell carcinoma is classified as grade 3. G3.01 Pattern of growth Single selection value list: • Expanding • Infiltrating S3.04 Maximum tumour dimension Numeric: ___mm S3.05 Depth of invasion Single selection value list: • lamina propria 46 S/G S3.06 S3.07 S3.08 Item description Peritoneal involvement Pleural involvement Lymphatic and capillary space invasion Vein and artery space invasion Perineural invasion G3.02 Tumour budding Response type Conditional • muscularis mucosae • submucosa • muscularis propria • adventitial connective tissue Single selection value list: • Absent • Present Single selection value list: • Absent • Present Single selection value list: • Absent • Present Single selection value list: • Absent • Present Single selection value list: • Absent • Present Single selection value list: 47 S/G S3.09 S3.10 Item description Degree of regression (AJCC) Response type • Absent • Present Conditional Single selection value list: • Grade 0: Complete Response – No viable cancer cells • Grade 1: Moderate response - Single cells or small groups of cancer cells • Grade 2: Minimal response – Residual cancer outgrown by fibrosis • Grade 3: Absent response – Minimal or no tumour kill; extensive residual cancer SURGICAL MARGIN STATUS Distance of carcinoma to proximal margin Numeric: ___mm OR Involved (R1) Distance of carcinoma to distal margin Numeric: ___mm OR Involved (R1) 48 S/G Item description Response type Distance of carcinoma to radial/circumferential margin Numeric: ___mm Conditional OR Involved (R1) G3.03 S3.11 Donut Single selection value list: • Not involved • Involved LYMPH NODE STATUS Main resection specimen Numeric: Number of LN’s AND If positive, record the number of positive nodes. Single selection value list: Number of positive nodes Separately labelled specimen(s) • Negative • Positive Numeric: ___ Text: record site as per labelling AND Numeric: Number of LN’s 49 If positive, record the number of positive nodes. S/G Item description Response type Conditional AND Single selection value list: • Negative • Positive Notes: Note that the number of Lymph Nodes and whether any are positive will need to be repeated for each separately labelled specimen received. Number of positive nodes Numeric: ___ Note: Note that the number of positive Lymph Nodes will need to be repeated for each site received with positive nodes. S3.12 Other pathologies Multi select value list (select all that apply): • Barrett mucosa • Squamous or glandular dysplasia • Gastritis • Eosinophilic oesophagitis • Other 50 If ‘other’, record details If Barrett mucosa or dysplasia record margin involvement If dysplasia, record the distance of dysplasia to closest margin S/G Item description Response type Details Margin involvement Distance of dysplasia to closest margin G3.04 Other microscopic comment Conditional Text Single selection value list: • Involved • Not involved Numeric: ___mm Text Ancillary test findings G4.01 ANCILLARY TESTS Performed Test type eg IHC, MUC etc Single selection value list: • No • Yes Text If yes, record test type If IHC, record the antibodies Note: Test result type, result and interpretive comment will need to repeat for each ancillary test performed. 51 S/G Item description Response type Antibodies Result Conditional List (as applicable) all: • Positive antibodies • Negative antibodies • Equivocal antibodies Text Note: Test result type, result and interpretive comment will need to repeat for each other ancillary test performed. Interpretive comment Text Note: Test result type, result and interpretive comment will need to repeat for each other ancillary test performed. Synthesis and overview S5.01 AJCC TUMOUR STAGING Primary tumour category Single selection value list: TX T0 Tis T1 T1a Primary tumour cannot be assessed No evidence of primary tumour High grade dysplasia*** Tumour invades lamina propria, muscularis mucosae, or submucosa Tumour invades lamina propria or muscularis 52 S/G Item description Response type T1b T2 T3 T4 T4a T4b Conditional mucosae Tumour invades submucosa Tumour invades muscularis propria Tumour invades adventitia Tumour invades adjacent structures Resectable tumour invading pleura, pericardium, or diaphragm Unresectable tumour invading other adjacent structures, such as aorta, vertebral body, trachea etc Note (1) At least maximal dimension of the tumour must be recorded and (2) multiple tumours require the T(m) suffix. *** High grade dysplasia includes all noninvasive neoplastic epithelia that was formerly called carcinoma in-situ, a diagnosis that is no longer used for columnar mucosae anywhere in the gastrointestinal tract. Regional lymph node Single selection value list: NX N0 N1 N2 N3 Regional lymph nodes cannot be assessed No regional lymph node metastasis Metastasis in 1-2 regional lymph nodes Metastasis in 3-6 regional lymph nodes Metastasis in seven or more regional lymph nodes 53 S/G Item description Response type Conditional Note * Distant metastasis Single selection value list: M0 M1 Pathological stage grouping Number must be recorded for the total number of regional nodes sampled and total number of reported nodes with metastasis. No distant metastasis Distant metastasis For Squamous cell carcinoma: Single selection value list: Stage O IA IB IIA IIB IIIA IIIB T N M Grade Tumour Location ** Tis (HGD) T1 T1 T2-3 T2-3 T2-3 T2-3 T1-2 T1-2 T3 T4a T3 N0 N0 N0 N0 N0 N0 N0 N1 N2 N1 N0 N2 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 1, X 1, X 2-3 1, X 1, X 2-3 2-3 Any Any Any Any Any Any Any Any Lower, Upper, Lower, Upper, Any Any Any Any Any 54 X middle X middle S/G Item description Response type IIIC IV T4a T4b Any Any Conditional N1-2 Any N3 Any M0 M0 M0 M1 Any Any Any Any Any Any Any Any Note * Or mixed histology including a squamous component or NOS. ** Location of the primary cancer is defined by the position of the upper (proximal) edge of the tumour in the oesophagus. For Adenocarcinoma Single selection value list: Stage O IA IB IIA IIB IIIA T Tis (HGD*) T1 T1 T2 T2 T3 T1-2 T1-2 T3 N N0 N0 N0 N0 N0 N0 N1 N2 N1 55 M M0 M0 M0 M0 M0 M0 M0 M0 M0 Grade 1, X 1-2, X 3 1-2, X 3 Any Any Any Any S/G Item description Response type Conditional T4a N0 T3 N2 T4a N1-2 T4b Any Any N3 IV Any Any *HGD, high grade dysplasia. IIIB IIIC S5.02 G5.01 Year and edition of staging system Diagnostic summary Numeric: year AND Text: Edition eg 1st, 2nd etc Text Include: o Tumour location G5.02 o Histologic type o Tumour grade o Maximum tumour dimension o Lymph nodes o Stage o Involved or close margins (includes tumour less than 1mm from margin) Overarching comment Text 56 M0 M0 M0 M0 M0 M1 Any Any Any Any Any Any 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. 57 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 Oesophagus and Gastro-oesophageal Junction 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 should be provided with the specimen. • • Items relevant to cancer reporting protocols include: • patient name • date of birth • sex • identification and contact details of requesting doctor • date of request The patient’s ethnicity should be recorded, if known. In particular whether the patient is of aboriginal or Torres Strait islander origin. This is in support of a government initiative to monitor the health of indigenous Australians particularly in relation to cancer. The patient’s health identifiers should be provided. • The patient’s health identifiers may include the patient’s Medical Record Number as well as a national health number such as a patient’s Medicare number (Australia), Individual Healthcare Identifier (IHI) (Australia) or the National Healthcare Identifier (New Zealand). Clinical Information The tumour location/site should be recorded. • Select all that apply: • cervical oesophagus 58 • upper thoracic • middle thoracic • lower thoracic • gastro-oesophageal junction Refer to Figure A1 below. • Cancers whose midpoint is in the lower thoracic oesophagus, GOJ or within the proximal 5cm of the stomach (cardia) that extend into the GOJ or oesophagus are staged as carcinoma of the oesophagus. (Refer to Figure S2.04). All other cancers with a midpoint in the stomach lying more than 5cm distal to the GOJ or those within 5cm of the GOJ but not extending into the GOJ or oesophagus are staged using the gastric (non-GOJ) cancer staging system.1 • It should be noted that true gastric proximal (cardia) tumours are rare; most involve the GOJ and should therefore be staged using the oesophageal cancer staging system.1 Figure A1 Anatomy of oesophageal cancer primary site Anatomy of oesophageal cancer primary site, including typical endoscopic measurements of each region measured from the incisors. Exact measurements are dependent on body size and height. 59 Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer Science and Business Media LLC, www.springerlink.com. The type of operation or procedure should be recorded. • • Pharyngolaryngo-oesophagectomy • Oesophagectomy • Oesophago-gastrectomy • Other (specify) The operative method of the oesophago-gastrectomy may be recorded. • Choose from one of the following: Choose from one of the following: • 3 Stage (eg McKeown) • 2 Stage (eg Ivor-Lewis) • 1 Stage (eg Sweet) • Trans-hiatal The extent of lymphadenectomy should be recorded.44 • There is a general lack of uniformity as to what the term lymphadenectomy in oesophageal cancer surgery means. For the purposes of this protocol the definitions provided by Jamieson et al44 will be used: Radical lymphadenectomy procedures i. Three-field lymphadenectomy with lymph node resection encompassing upper abdominal (D2), inferior, middle, and superior mediastinal lymph nodes, and inferior cervical nodes. ii. Two-field lymphadenectomy, which is the same as the above with the exception of removal of the cervical nodes. iii. Infracarinal 2-field lymphadenectomy which omits both cervical lymph nodes and a formal superior mediastinal nodal dissection. Conservative lymphadenectomy in which only the nodes in direct proximity to the tumour, the oesophagus, and upper stomach are removed. • Choose from one of the following: • Three field • Two field • Two field (Infra-carinal) 60 • If preoperative therapy has been administered, this should be recorded. • • Preoperative chemotherapy • Preoperative radiotherapy • Preoperative chemoradiotherapy Involvement of adjacent organs, either resected or not resected, is required for assessment of the tumour (T) stage. Unless obvious, the area of involvement should be marked with a suture or other marker. The presence of any distant metastases should be recorded. • 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. • Additional specimens taken eg peritoneal nodules, liver biopsy, other etc should be labelled and recorded separately. • The presence of positive peritoneal cytology is classified as metastatic disease. This information should be provided to the reporting pathologist, in part because the diagnosis may have been made at a different laboratory. The Surgeon’s opinion on the existence of local residual cancer following the operative procedure should be recorded. • Choose from one of the following: The involvement of adjacent organs should be recorded. • Conservative 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). It allows for residual tumour status (R) to be reported by the pathologist following microscopic assessment of the surgical margins. Residual microscopic disease is reported as R1. Record if this is a new primary cancer or a recurrence of a previous cancer, if known. • The term recurrence defines the reappearance or metastasis of cancer (of the same histology) after a disease free period. Recurrence should be classified as regional (local) recurrence or distant metastasis. 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. 61 • This information will provide an opportunity for previous reports to be reviewed during the reporting process, which may provide valuable information to the pathologist. This information also has implications for recording cancer incidence and evidence based research. Any additional relevant information should be recorded. • 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. Surgical handling The specimen must be capable of orientation if the status of specific surgical margins is critical in determining the need for, or extent of, further surgery. • The specimen should be sent to the laboratory in the fresh state without delay where possible. • The laboratory should be informed if the specimen is likely to be received outside normal working hours. • Where a specimen is unable to be received by the laboratory (eg outside normal working hours), it should be opened by the surgeon, contents drained, and placed in an adequate volume of formalin based solution. The specimen should be sent to the laboratory intact where possible. • Where there are no anatomical landmarks, specimen orientation may be indicated with marking sutures or other techniques. If a specimen is orientated, the orientation should be indicated on the specimen request form (this may be facilitated by the use of a diagram). When a specimen needs to be opened eg to confirm adequate surgical margins or tumour localisation, the specimen should be opened by a single longitudinal incision and should avoid cutting through tumour if at all possible. Lymph nodes must be labelled clearly, identifying the site. • Lymph nodes taken separately from the resection specimen must be labelled as to site. (Refer to Figure A2 below). 62 Figure A2 Lymph node map for oesophageal cancer.* _ 1 Supraclavicular zone 8L Lower paraesophageal 2R Right Upper Paratracheal 9 Pulmonary ligament 2L Left Upper Paratracheal 10R Right tracheobronchial 3P Posterior mediastinal 10L Left tracheobronchial 4R Right Lower Paratracheal 15 Diaphragmatic 4L Left Lower Paratracheal 16 Paracardial 5 Aortopulmonary 17 Left gastric 6 Anterior mediastinal 18 Common hepatic 7 Subcarinal 19 Splenic 8M Middle paraesophageal 20 Celiac Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Sixth Edition (2002) published by Springer Science and Business Media LLC, www.springerlink.com. 63 Any other additional tissue eg donut, must be labelled clearly, identifying the site. 64 Example Request Information Sheet 65 The above Request Information Sheet is published to the RCPA website. 66 Appendix 2 Guidelines for formatting of a pathology report Layout Headings and spaces should be used to indicate subsections of the report, and heading hierarchies should be used where the LIS allows it. Heading hierarchies may be defined by a combination of case, font size, style and, if necessary, indentation. • Grouping like data elements under headings and using ‘white space’ assists in rapid transfer of information.39 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. • • • Configuring reports in such a way that they ‘chunk’ data elements into a single unit will help to improve recall for the clinician.39 ‘Clutter’ should be reduced to a minimum.45 Thus, information that is not part of the protocol (e.g. billing information, Snomed codes, etc) should not appear on the reports or should be minimized. Injudicious use of formatting elements (e.g. too much bold, underlining or use of footnotes) constitutes 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. 67 Appendix 3 Example of a pathology report 68 69 Appendix 4 WHO Classificationa of oesophageal tumours Epithelial tumours Premalignant lesions Squamous Intraepithelial neoplasia (dysplasia), low grade Intraepithelial neoplasia (dysplasia), high grade 8077/0* 8077/2 Glandular Dysplasia (intraepithelial neoplasia), low grade Dysplasia (intraepithelial neoplasia), high grade 8148/0* 8148/2 Carcinoma Squamous cell carcinoma Adenocarcinoma Adenoid cystic carcinoma Adenosquamous carcinoma Basaloid squamous cell carcinoma Mucoepidermoid carcinoma Spindle cell (squamous) carcinoma Verrucous (squamous) carcinoma Undifferentiated carcinoma 8070/3 8140/3 8200/3 8560/3 8083/3 8430/3 8074/3 8051/3 8020/3 Neuroendocrine neoplasmsb Neuroendocrine tumour (NET) NET G1 (carcinoid) NET G2 Neuroendocrine carcinoma (NEC) Large cell NEC Small cell NEC Mixed adenoneuroendocrine carcinoma 8240/3 8249/3 8246/3 8013/3 8041/3 8244/3 Mesenchymal tumours Granular cell tumour Haemangioma Leiomyoma Lipoma Gastrointestinal stromal tumour Kaposi sarcoma Leiomyosarcoma 9580/0 9120/0 8890/0 8850/0 8936/1 9140/3 8890/3 70 Melanoma Rhabdomyosarcoma Synovial sarcoma 8720/3 8900/3 9040/3 Lymphomas Secondary tumours a b * The morphology code of the International Classification of Diseases for Oncology (ICD-O). 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