THYROID CANCER STRUCTURED REPORTING PROTOCOL (2 …

THYROID CANCER

STRUCTURED REPORTING

PROTOCOL

(2nd Edition 2020)

Incorporating the:

International Collaboration on Cancer Reporting (ICCR)

2 Structured Reporting Protocol for Thyroid Cancer 2nd edition

Carcinoma of the Thyroid Dataset www.ICCR-Cancer.org

Core Document versions:

• ICCR dataset: Carcinoma of the Thyroid 1st edition v1.0

• AJCC Cancer Staging Manual 8th edition

• World Health Organization (2017) Classification of Tumours of Endocrine

Organs (4th edition). Volume 10

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


ISBN: 978-1-76081-423-6

Publications number (SHPN): (CI) 200280

Online copyright

© RCPA 2020

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

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

subject to the following terms and conditions:

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

whole or in part, for profit or commercial gain.

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

notice in full.

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

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

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

checklist. References and acknowledgments must be maintained in any

reproduction or copy in full or part of the Protocol.

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

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

included as part of the checklist.

• Guidelines are optional and those which are deemed not applicable may

be removed.

• 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.

• 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.

• Formatting changes in regard to font, spacing, tabulation and sequencing

may be made.

• 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: June 2020, 2nd Edition (version 2.0)


Disclaimer

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

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

information for specific cancers. 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. It 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 circumstances. Users are responsible

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

purpose of the protocols.

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

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

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

prohibits the exclusion of that term, condition or warranty, then such term, condition

or warranty is not excluded. To the extent permitted by law, the College's liability

under or for breach of any such term, condition or warranty is limited to the resupply

or replacement of services or goods.


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

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

Definitions .................................................................................. 8

Introduction................................................................................ 11

Authority and development ............................................................ 15

1 Pre-analytical ......................................................................... 18

2 Specimen handling and macroscopic findings .............................. 23

3 Microscopic findings ............................................................... 27

4 Ancillary studies findings ........................................................ 39

5 Synthesis and overview ........................................................... 41

6 Structured checklist ................................................................ 43

7 Formatting of pathology reports ................................................ 58

Appendix 1 Pathology request form for thyroid tumours .................... 59

Appendix 2 Guidelines for formatting of a pathology report ................ 63

Appendix 3 Example of a pathology report ..................................... 64

Appendix 4 WHO histological classification of tumours of the thyroid

gland .............................................................................. 66

Appendix 5 Histological tumour type............................................. 68

Appendix 6 AJCC Staging Grouping ............................................. 71

References ................................................................................. 72


Scope

This protocol contains standards and guidelines for the preparation of structured

reports for thyroid resection specimens for carcinoma. Core needle biopsies and

metastasis to the thyroid gland are not included. Non-invasive follicular thyroid

neoplasm with papillary-like nuclear features (NIFTP), tumours of uncertain

malignant potential (UMP), thyroid carcinomas arising from struma ovarii, thyroid

carcinomas arising in thyroglossal duct cysts are included in this protocol. Sarcomas

and lymphomas are dealt with in separate protocols.

This protocol is designed for the reporting of a total thyroidectomy or a single

laterality specimen i.e. left or right. If both are submitted separately or if surgeries

are done at different time points (e.g. completion thyroidectomy after initial

lobectomy), then separate protocols should be completed. If multiple carcinomas are

found in the same specimen, the protocol should be completed for the most clinical

relevant tumour which is the one with the highest T stage and/or the one that has

the most aggressive histologic features. For example, in the case of a papillary

thyroid carcinoma with gross extension into muscle associated with a papillary

carcinoma without adverse histologic features, the protocol should be filled for the

tumour with gross extra-thyroid extension. The less aggressive tumour should be

reported with a description limited to basic histopathologic features (such as size and

location) under the tumour focality element. If tumours of different lineage coincide

in the same specimen, then a protocol should be completed for each of these

tumours. For example, if a lobectomy contains separate medullary and papillary

carcinoma, a protocol should be completed for each of these carcinomas.

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 thyroid cancer, whether as

a minimum data set or fully comprehensive report.

https://www.rcpa.edu.au/getattachment/a3c04ea0-3f34-48a3-86a6-f5bc18345f12/Protocol-Soft-tissue-tumour-resections.aspx

https://www.rcpa.edu.au/getattachment/f32439ee-36ed-4f19-a9cf-a7759e2a60a6/Protocol-haematopoietic-and-lymphoid-tissue.aspx


Abbreviations

AJCC American Joint Committee on Cancer

ATA American Thyroid Association

CAP College of American Pathologists

CD Cluster of differentiation

CEA Carcinoembryonic antigen

CI Capsular invasion

ENE Extranodal extension

ETE Extrathyroidal extension

FC Follicular carcinoma

FNA Fine needle aspiration

FTC Follicular thyroid carcinoma

HPF High power field

ICCR International Collaboration on Cancer Reporting

IHI Individual Healthcare Identifier

LIS The laboratory information system

LVI Lymphovascular invasion

MEN Multiple endocrine neoplasia

S Standard

G Guide

mm Millimetres

MRN Medical Record Number

NCCN National Comprehensive Cancer Network

NHI New Zealand National Health Identifier

NHMRC National Health and Medical Research Council

NIFTP Non-invasive follicular thyroid neoplasm with papillary-like nuclear features

PAX8 Paired box 8

PBS Pharmaceutical Benefits Scheme

PDTC Poorly differentiated thyroid carcinomas

PTC Papillary thyroid carcinoma

RAI Radioiodine

RCPA Royal College of Pathologists of Australasia

RCPath UK Royal College of Pathologists United Kingdom RET Rearranged during transfection proto-oncogene SI International System of Units

TNM tumour-node-metastasis

TTF Thyroid transcription factor-1

UICC International Union Against Cancer

UK United Kingdom

UMP Uncertain malignant potential

VI Vascular invasion

WHO World Health Organization

http://en.wikipedia.org/wiki/International_System_of_Units


Definitions

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

protocol. Readers should take particular note of the definitions for ‘standard’,

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

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

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

histological assessment.

Clinical

information

Patient information required to inform pathological assessment,

usually provided with the specimen request form, also referred to

as ‘pre-test information’.

Commentary Commentary is text, diagrams or photographs that clarify the

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

examples and help with interpretation, where necessary (not every

standard or guideline has commentary).

Commentary is used to:

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

reproducibility

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

with clinical management or prognosis of the specific cancer).

• cite published evidence in support of the standard or guideline

• state any exceptions to a standard or guideline.

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

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

guideline), numbered to be consistent with the relevant standard

or guideline, and with sequential alphabetic lettering within each

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

General

commentary

General commentary is text that is not associated with a specific

standard or guideline. It is used:

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

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

in the protocol as items of potential importance, for which there

is currently insufficient evidence to recommend their inclusion.

(Note: in future reviews of protocols, such items may be

reclassified as either standards or guidelines, in line with

diagnostic and prognostic advances, following evidentiary

review).


Guideline Guidelines are recommendations; they are not mandatory, as

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

that are unanimously agreed should be included in the dataset but

are not supported by National Health and Medical Research Council

(NHMRC) level III-2 evidence.1 These elements may be clinically

important and recommended as good practice but are not yet

validated or regularly used in patient management.

Guidelines include key information other than that which is

essential for clinical management, staging or prognosis of the

cancer such as macroscopic observations and interpretation, which

are fundamental to the histological diagnosis and conclusion e.g.

macroscopic tumour details, block identification key, may be

included as either required or recommended elements by

consensus of the expert committee. Such findings are essential

from a clinical governance perspective, because they provide a

clear, evidentiary decision-making trail.

Guidelines are not used for research items.

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

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

Macroscopic

findings

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

unaided eye.

Microscopic

findings

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

morphological assessment.

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

response or lack of response to a particular therapy.

Prognostic

factor

A prognostic factor is a measurement that is associated with

clinical outcome in the absence of therapy or with the application

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

natural history of the disease.

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

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

staging or prognosis of the cancer. These elements will either have

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

factors in the NHMRC levels of evidence1 document). In rare

circumstances, where level III-2 evidence is not available an

element may be made a Standard where there is unanimous

agreement in the expert committee. An appropriate staging system

e.g. Pathological TNM staging would normally be included as a

required element. These elements must be recorded and at the

discretion of the pathologist included in the pathology report

according to the needs of the recipient of the report.

The summation of all standards represents the minimum dataset

for the cancer.


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

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

Structured

report

A report format which utilises standard headings, definitions and

nomenclature with required information.

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

Synthesis Synthesis is the process in which two or more 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.


Introduction

Thyroid cancer

Thyroid cancer is the most common endocrine cancer in Australia and in other parts

of the world. This malignancy is more common in women than in men and occurs

primarily in young and middle-aged adults, with approximately 122,000 new cases

per year worldwide.1

Thyroid cancers, like benign thyroid diseases, usually present as a thyroid nodule

and/or enlargement of the thyroid gland. In many instances, it is very difficult to

differentiate them from benign thyroid lesions clinically. Thyroid nodules are common

clinically (prevalence of approximately 5%) and even more common on ultrasound

examination (prevalence of approximately 25%).2 About 1% of thyroid nodules are

malignant.

Pathological reporting of resection specimens for thyroid cancer provides information

both for the clinical management of the affected patient, for research, and for the

evaluation of the health care system. In thyroid cancer, there are many different

histological types. Papillary carcinoma is the most common type, accounting for more

than 80-90% of thyroid malignancies.2, 33

Many subtypes of papillary carcinoma have

been described and some are known to have prognostic significance. Also, follicular

lesions including follicular carcinoma, minimally invasive follicular carcinoma, Hürthle

cell carcinoma, follicular variant of papillary carcinoma, follicular adenoma, Hürthle

cell carcinoma and adenomatous nodule often are difficult to differentiate. Some

patients with thyroid cancer can progress to a more aggressive metastatic form of

thyroid cancer with a high mortality.4 Therefore, recognition of pathological

parameters in thyroid cancer is very important for the management of these

patients.

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 developed2,4 around


the world. Both the United Kingdom,5 and United States6 have produced standardised

cancer reporting protocols or ‘datasets’ for national use for many years.

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

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

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

timely treatment based on accurate and complete information.

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

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

International Collaboration on Cancer Reporting

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

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

American Pathologists (US CAP) and Royal College of Pathologists United Kingdom

(RCPath UK) Colleges of Pathology and the Canadian Association of Pathology -

Association Canadienne des Pathologistes (CAP-ACP) in association with the

Canadian Partnership Against Cancer (CPAC), was established to explore the

possibilities of a collaborative approach to the development of common,

internationally standardised and evidence-based cancer reporting protocols for

surgical pathology specimens.

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

significant benefits for patients and efficiencies for organisations through the ease

and completeness of data capture7-10 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

Carcinoma of the Thyroid 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 Carcinoma of the Thyroid.



ICCR dataset elements for Carcinoma of the Thyroid are included verbatim. ICCR

Core elements are mandatory and therefore represented as standards in this

document. ICCR Non-core 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:

S3.01 The histological tumour type must be recorded.

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

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

logo e.g.

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

as central, left lateral, right lateral or bilateral.

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

should be submitted for histological examination.

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

Checklist

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

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

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

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

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

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

Report format

The structure provided by the following chapters, headings and subheadings

describes the elements of information and their groupings, but does not necessarily

represent the format of either a pathology report (Chapter 7) or checklist

(Chapter 6). These, and the structured pathology request form (Appendix 1) are

templates that represent information from this protocol, organised and formatted

differently to suit different purposes.



Key documentation

• ICCR dataset: Carcinoma of the Thyroid 1st edition v1.0

• Guidelines for Authors of Structured Cancer Pathology Reporting Protocols,

Royal College of Pathologists of Australasia, 200911

• World Health Organization (2017) Classification of Tumours of Endocrine

Organs (4th edition). Volume 1012

Changes since the last edition

Inclusion of ICCR Core and Non-core elements.


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

protocol.

This 1st edition of the protocol is an amalgam of two separate processes:

• This protocol is based on the ICCR dataset – Carcinoma of the Thyroid 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.

1. 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.

Expert committee

Prof Jane Dahlstrom (Lead Author, Chair of Head and Neck and Endocrine Group),

Pathologist

Dr John Turchini Pathologist

A/Prof Ruta Gupta, Pathologist

Prof Alfred Lam (Lead author 1st edition), Pathologist

Prof Anthony J. Gill, Pathologist

Prof Klaus-Martin Schulte, Endocrine Surgeon

A/Prof Michael Elliott, Head and Neck Surgeon

A/Prof Rory Clifton-Bligh, Endocrinologist Prof Christopher J. Nolan, Endocrinologist

Editorial manager

Christina Selinger, PhD, Royal College of Pathologists of Australasia

Acknowledgements

The Thyroid expert committee wish to thank all the pathologists and clinicians who

contributed to the discussion around this document.


Stakeholders

ACT Cancer Registry

ACT Health

Anatomical Pathology Advisory Committee (APAC)

Australian and New Zealand Endocrine Surgeons (ANZES)

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

Endocrine Society of Australia (ESA)

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

Northern Territory Cancer Registry

Public Pathology Australia


Queensland Cooperative Oncology Group (QCOG)

Representatives from laboratories specialising in anatomical pathology across

Australia

Royal Australasian College of Physicians (RACP)

Royal Australasian College of Surgeons (RACS)

Royal Australian and New Zealand College of Radiologists (RANZCR)

Royal Australian College of General Practitioners (RACGP)

Royal College of Pathologists of Australasia (RCPA)

South Australia Cancer Registry

Southern Cancer Network, Christchurch, New Zealand

Standards Australia

Tasmanian Cancer Registry

Victorian Cancer Registry

Western Australia Clinical Oncology Group (WACOG)

Western Australian Cancer Registry

Development process

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

for Authors of Structured Cancer Pathology Reporting Protocols.11

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

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

components denoted with the ICCR logo.


1 Pre-analytical This chapter relates to information that should be recorded on receipt of the

specimen in the laboratory.

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

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

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

the reporting of thyroid tumours 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.13

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 the patient identifies

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

Māori in New Zealand. This is in support of government

initiatives to monitor the health of those who identify as

indigenous, particularly in relation to cancer.

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

Medical Record Number as well as a national health number

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

Healthcare Identifier (IHI) (Australia) or the National

Healthcare Index (New Zealand).

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

be recorded verbatim.

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

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

format.

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

however, in a small number of cases the pathologist may

exercise discretion regarding the inclusion of provided

clinical information, for instance, possibly erroneous

information or information that may impact on patient

privacy. In such case reference should be made as to the

location of the complete clinical information e.g. ‘Further

clinical information is available from the scanned request

form.’


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

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 can provide key information

regarding the clinical presentation of the patient. Follow up

may be required with the principal clinician for a number of

reasons:

• The clinical assessment and staging may be incomplete

at the time of biopsy.

• The pathology request is often authored by the clinician

performing the 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 clinicians should be recorded together with the

source of that information.


Figure 1. Anatomy of the thyroid gland. Used with the permission of the American Joint

Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, 8th Edition (2017) published by Springer Science and Business Media LLC, www.springerlink.com.14

Figure 2. Topological definition of lymph node levels in the neck. Used with the

permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, 8th Edition (2017) published by Springer Science and Business Media LLC, www.springerlink.com.14

http://www.springerlink.com/



Figure 3. Two views of T3: on the left, tumour more than 4 cm in greatest

dimension limited to the thyroid (categorised as T3a); on the right, a

tumour of any size with gross extrathryroidal extension invading only strap

muscles (sternohyoid, sternothyroid, thyrohyoid or omohyoid muscles)

(categorised as T3b). Used with the permission of the American Joint Committee on Cancer

(AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, 8th Edition (2017) published by Springer Science and Business Media LLC, www.springerlink.com.14

Figure 4. T4a is defined as gross extrathyroidal extension invading

subcutaneous soft tissues, larynx, trachea, oesophagus, or recurrent

laryngeal nerve from a tumour of any size. Used with the permission of the American

Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, 8th Edition (2017) published by Springer Science and Business Media LLC, www.springerlink.com.14




Figure 5. Cross-sectional diagram of three different parameters of T4a:

tumour invading subcutaneous soft tissues; tumour invading trachea;

tumour invading oesophagus. Used with the permission of the American Joint Committee on

Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, 8th Edition (2017) published by Springer Science and Business Media LLC, www.springerlink.com.14

Figure 6. T4b is defined as gross extrathyroidal extension invading

prevertebral fascia or encasing the carotid artery or mediastinal vessels

from a tumour of any size. Cross-sectional diagram of two different

parameters of T4b: tumour encases carotid artery; tumour invades vertebral

body. Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois.

The original source for this material is the AJCC Cancer Staging Manual, 8th Edition (2017) published by Springer Science and Business Media LLC, www.springerlink.com.14




2 Specimen handling and macroscopic findings

This section 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.

Specimen handling

➢ Detailed fixation and specimen handling instructions are available from

the RCPA online Cut-up Manual:

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

➢ The specimen must be handled in a systematic and thorough

fashion to ensure completeness and accuracy of pathological

data.

Macroscopic findings

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

S2.02 Clinical information must be recorded.

CS2.02a Any clinical information relevant to the thyroid disease

should be recorded.

If a pre-operative fine needle aspiration (FNA) or core biopsy

has been performed, this should be recorded, and the results

of that biopsy briefly stated. If imaging has been performed,

this should be recorded, and the results briefly stated.

Previous thyroid surgery or medical treatments like anti-

thyroid drug or radioactive iodine should be noted. Previous

exposure of the neck to radiotherapy (e.g. for treatment of

Hodgkin lymphoma) should be noted. The indication for

performing the surgery should be recorded as many thyroid

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


cancers are found incidentally in thyroid specimens removed

for a purpose other than cancer.

Family history of thyroid cancers or features of other

endocrine tumours or syndromes should be recorded. (Refer

to ICCR guidelines for full commentary.)

Clinical or biochemical evidence of hyperthyroidism or

hypothyroidism should be noted.

S2.03 The operative procedure must be recorded.

CS2.03a Cases with lobectomy followed by completion thyroidectomy

in the same operative procedure should be classified as total

thyroidectomies. Other procedures include completion

thyroidectomy, central compartment resection or lateral

neck node dissection. (Refer to ICCR guidelines for full

commentary.)

CS2.03b Surgical management of thyroid tumours consists of either

enucleation, lobectomy (removal of a lobe), a

hemithyroidectomy (resection of lobe and isthmus), subtotal

thyroidectomy (leaving 2 g of tissue on one side), near total

thyroidectomy (leaving 0.5-2.0 g tissue on one side) or total

thyroidectomy.

S2.04 Any operative findings should be recorded.

CS2.04a It is expected that the surgeon will provide information in

regard to the presence or absence of gross extrathyroidal

extension (ETE) at the time of the surgical procedure, as

well as to the completeness of excision. Gross ETE is a

crucial element in staging systems.15,16 The pathologist

should indicate if the intra-operative data on gross ETE or

margin completeness is not available at the time of

pathology reporting.

S2.05 The specimen(s) submitted and laterality must be recorded.

CS2.05a The nature of the specimen and laterality (in lobectomy

specimens and node dissection) must be reported.

G2.01 The specimen should be weighed and findings recorded.

S2.06 Tumour focality must be recorded.

CS2.06a Multifocal lesions (defined as more than one tumour focus)

are not uncommon in patients with papillary carcinoma and

medullary carcinoma. They must be reported.

S2.07 The tumour sites must be recorded, where possible.

CS2.07a The thyroid may give rise to more than 1 or multiple foci of

the same type of carcinoma, designated as per the American

Joint Committee on Cancer (AJCC) and Union for

International Cancer Control (UICC) guidelines with the

descriptor ‘(m)’.15,16 The designation of the tumour site and

http://www.iccr-cancer.org/datasets/published-datasets/endocrine-organs/phaeochromocytoma-and-paraganglioma-tnm8



this protocol are applicable to the dominant excised

carcinoma. The dominant tumour is defined as the most

clinically relevant tumour because of its aggressiveness

and/or its higher T stage. As such, it is often, but not

necessarily, the largest tumour. In cases of multiple lesions,

the tumour characteristics of a second focus may be relevant

and contribute to patient management, particularly if they

are of a different histologic type (i.e. tumour 1 is papillary

carcinoma and tumour 2 is medullary carcinoma). A second

protocol should be generated for these instances. For

additional tumour foci that do not alter management, only

basic histopathological features (such as size and location)

may be reported at the pathologist’s discretion.

S2.08 The macroscopic description of any lesion(s) in the specimen

must be recorded.

CS2.08a Where there are multiple lesions, the total number of

lesions must be recorded, and each lesion should be

identified and described.

CS2.08b For each lesion, the location, appearance, the borders

(encapsulated or infiltrative), size (greatest dimension),

and distance from the nearest excision margin must be

recorded.

CS2.08c Thyroid cancer can be an incidental finding in thyroid

glands surgically removed for reasons other than thyroid

cancer.

G2.02 The appearance of the thyroid other than the lesion(s) detected

should be documented.

S2.09 A block identification key listing the nature and origin of all

tissue blocks must be recorded.

CS2.09a The origin/designation of all tissue blocks should be recorded

and it is preferable to document this information in the final

pathology report. This is particularly important should the

need for internal or external review arise. The reviewer

needs to be clear about the origin of each block in order to

provide an informed specialist opinion. 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. Photography of macroscopic

specimens is considered best practice. Annotation of

captured images can be very helpful and aids with review of

the case later. It can also provide useful information in the

context of multidisciplinary meetings.

Recording the origin/designation of tissue blocks also

facilitates retrieval of blocks, for example for further

immunohistochemical or molecular analysis, research studies

or clinical trials.


Because of the importance of resection margin status, it is

recommended that all surgical surfaces are painted prior to

specimen dissection. Occasionally different colours can be

used to identify specific surgical margins. This information

should also be recorded in the block key.

G2.03 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.

CG2.03a 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.

CG2.03b Much of the information recorded in a traditional

macroscopic narrative is covered in the standards and

guidelines above and in many cases, no further description

is required.


3 Microscopic findings

Microscopic findings relate to purely histological (morphological) assessment.

Information derived from multiple investigational modalities, or from two or more

chapters, is described in Chapter 5.

S3.01 The histological tumour type must be recorded.

CS3.01a All tumours of the thyroid should be given a type based on

the most recent edition of the World Health Organization

(WHO) Classification of Tumours of Endocrine Organs.17 (See

also Appendix 4).

CS3.01b The more common types are papillary carcinoma, follicular

carcinoma, Hürthle cell carcinoma, medullary carcinoma,

anaplastic carcinoma and poorly-differentiated carcinoma. It

is important to note that other types of benign and

malignant tumours can occur in the thyroid gland.

CS3.01c For follicular carcinoma and Hürthle cell carcinoma, it is

important to define the carcinoma based on the extent of

capsular and/or vascular invasion.

Follicular carcinomas and Hürthle cell carcinomas are divided

into widely invasive and minimally invasive type.

Widely invasive follicular and Hürthle cell carcinomas show

infiltration of thyroid cancer cells outside the capsule of the

lesion.

Minimally invasive (encapsulated) follicular and Hürthle cell

carcinoma show significant focal invasion of the tumour

capsule. It is important to indicate whether there is capsular

invasion, vascular invasion or both. The number of foci of

capsular or vascular invasion should be noted. (See figures

7, 8, and 9).

Invasion must be differentiated from entrapments of follicles

in the capsule and the pseudo-invasive changes following

fine needle aspiration.

CS3.01d Minimally invasive follicular or Hürthle cell carcinomas with

capsular invasion alone behave like benign tumours. The

presence of vascular invasion should be noted.14,18

CS3.01e For poorly-differentiated carcinoma, the pattern should be

dominant for the carcinoma to be placed in this category,

but foci of poor differentiation should also be reported.19

CS3.01f For papillary, follicular/Hürthle cell or poorly-differentiated

thyroid carcinomas, the presence of even a minor

undifferentiated component should be noted as having a

component of anaplastic carcinoma as this confers a poorer

prognosis.4


CS3.01g For papillary carcinoma, there are 15 histological variants

documented by WHO.14 Some variants have prognostic

significance, while others do not.

Papillary microcarcinoma (≤10 mm in diameter), is not

thought to have a significant risk of recurrence or

metastasis.16 On the other hand, tall cell and columnar cell

variants may show more aggressive clinical behaviour than

conventional papillary thyroid carcinoma.

Some variants, in particular, encapsulated follicular variant,

oncocytic variant, etc. may be difficult to differentiate from

other tumours. It is recommended that expert opinion be

sought if there are uncertainties.

CS3.01h For carcinomas of follicular differentiation, the carcinoma is

classified as Hürthle cell carcinoma if more than 75% of the

carcinoma is composed of oncocytic cells.14 The 4th edition

WHO classification defines this carcinoma as Hürthle cell

carcinoma as they have different clinical and genetic

features from follicular carcinoma.

CS3.01i For poorly differentiated and undifferentiated anaplastic

carcinomas, minor components of papillary, follicular or

Hürthle cell carcinoma should be mentioned.

CS3.01j In familial medullary carcinoma, the tumour is preceded by

expansion of the C cell population, termed familial C cell

hyperplasia that is thought to be neoplastic.17 The C cells are

normally found in the upper and middle thirds of the lobes,

so immunostaining of sections from these areas may be

helpful in suggesting familial disease, although the

thresholds for diagnosis are a matter of debate.18-19 From a

practical point of view, the presence of multiple groups or

nodules of C cells in sections that do not contain the main

tumour is suggestive of C cell hyperplasia. It should be

noted, however, that secondary C cell hyperplasia may occur

in several other circumstances such as

hyperparathyroidism,20 Hashimoto’s thyroiditis19 and around

tumours of follicular origin.21 It remains important for the

pathologist to identify C cell hyperplasia, as it remains one of

the clinical settings in which patients should have genetic

testing for mutations in the RET protooncogene.22

S3.02 The tumour dimensions must be recorded.

CS3.02a The dimension is that of the microscopically proven

dominant tumour, based upon a reconciliation of the

imaging, macroscopic and microscopic findings. The

dominant tumour (largest tumour) is defined as the most

clinically relevant tumour because of its aggressiveness

and/or its higher T stage (such as extension to outside

thyroid). As such, it is often, but not necessarily, the largest

tumour. Tumour size has an impact on prognosis and is a


component of TNM staging. For example, papillary

carcinomas measuring 10 mm or less are associated with an

excellent prognosis, while tumours measuring over 40 mm

are associated with a worse prognosis.20 If the exact tumour

size cannot be measured, the report should mention the

reason such as specimen fragmentation or a grossly positive

margin.

CS3.02b For multifocal tumours, the mm measurements of each foci

must not be combined, as this would artificially increase the

‘T’ stage.

CS3.02c The size of each lobe of the thyroid and isthmus (if present)

must be determined.

S3.03 Mitotic activity must be recorded in poorly-differentiated thyroid

carcinoma.

CS3.03a The mitotic status should be reported in every thyroid

carcinoma since it is an essential defining criterion for poorly

differentiated thyroid carcinomas (PDTC) regardless of the

definition used for this entity.21,22 The vast majority of

thyroid carcinomas have a very low mitotic rate and a

mitotic count is required only in those cases with elevated

mitotic activity (≥3 mitoses/2 mm2). Mitotic count (using

mm2) should be performed in the area of highest mitotic

activity in 10 consecutive high power fields (HPFs).23,24 The

Ki-67 proliferation rate has been shown to correlate with

outcome.25,26 It has not been utilized in the commonly used

definitions of poorly differentiated thyroid carcinomas and

thus is not a required element. It can however guide the

pathologist to the area of highest mitotic activity.

G3.01 The histological tumour grade should be recorded.

CG3.01a The grade in thyroid carcinomas of follicular cell origin

(including both papillary and follicular carcinoma) impacts

outcome significantly. It can, however, be deduced from the

histologic type along with increased mitotic activity and

tumour necrosis, therefore this item is designated as non-

core.

S3.04 Whether the capsule of the thyroid is intact or not must be

recorded.

CS3.04a The presence of a fibrous capsule or a well demarcated

tumour border (i.e. well circumscribed tumour edge directly

adjacent to benign thyroid parenchyma with no intervening

capsule) is a crucial element in thyroid carcinomas. In

follicular and Hürthle cell tumours, the invasion of the

capsule and its vessels define malignancy.17 Even in

biologically aggressive carcinomas such as poorly

differentiated carcinoma, the presence of a capsule was


shown to convey a better outcome.22 When a tumour

infiltrates the surrounding non-neoplastic parenchyma and is

not completely encapsulated/well demarcated, it should be

labelled as infiltrative. Infiltrative papillary carcinomas are

different from their encapsulated counterparts with regard to

metastatic spread (propensity for nodal rather than distant

metastasis) and genetic mutations (BRAF V600E rather than

RAS mutations).27

S3.05 The presence of capsular invasion must be recorded.

CS3.05a There is no consensus as to the definition of capsular

invasion (CI). While there is universal agreement that

complete transgression of the capsule constitutes CI,28

complete as opposed to partial transgression of the capsule

may suffice for diagnosis of CI.29 Figure 7 depicts the various

histologic appearances associated with the presence or

absence of CI. According to Chan (2007),28 a given

neoplasm should not be diagnosed as carcinoma if complete

capsular penetration cannot be proven after extensive

sampling except in the following circumstance. This situation

occurs when a satellite tumour nodule, morphologically

similar to the main tumour, is lying just outside the tumour

capsule (Figure 7e). This appearance results from failure to

identify the point of capsular penetration. It is noteworthy

that not all authors agree that these satellite nodules

represent CI.30 In equivocal cases of CI, the entire capsule,

irrespective of tumour size, should be processed in the

attempt to clarify whether CI is present. Deeper sections (at

least three levels) of the representative paraffin block(s)

should be performed in the areas of concern in order to

exclude CI.28 Despite enhanced histologic examination, there

are cases where the presence of CI is questionable. In this

instance the term uncertain CI should be used. There is no

need to report on the number of foci of CI since it has not

been shown to have clinical value.

S3.06 The presence of lymphatic and blood vessel invasion must be

recorded.

CS3.06a The majority of authors agree that blood vessel invasion

(BVI), also termed angioinvasion, should involve capsular or

extra-capsular vessels in encapsulated tumours (Figure 8).

In infiltrative tumours partially encapsulated or totally

lacking a capsule, BVI can be present within the tumour

nodule. These images (Figure 8) depict intracapsular BVI

with tumour thrombus attached to the vessel wall, covered

by endothelium or associated with fibrin. Tumour thrombus

covered by endothelial cells qualifies as BVI (Figure 8b).

However, endothelialization is not a requirement if the

tumour is attached to the vessel wall (Figure 8c) or admixed

with a fibrin thrombus (Figure 8d). If the tumour is

encapsulated, intra-tumoural or subcapsular vessels do not

https://link.springer.com/article/10.1007%2Fs12105-009-0109-2#Fig2






qualify for BVI and should not be interpreted as such

(Figure 8a). One study has raised the caveat that tumour

cells within vascular lumina unassociated with thrombus, and

tumour cells underlying intact endothelium could represent

‘pseudoinvasion’ given the fenestrated endothelial network

of endocrine organs.31 When this more stringent criterion of

BVI is applied, the incidence of BVI in differentiated thyroid

carcinoma decreased drastically from 7-62%32-36 to 3%,31

while the risk of distant metastasis in association with the

mere existence of BVI becomes 35%. This latter approach

has not been validated by additional studies and may fail to

identify a significant proportion of thyroid tumours with BVI,

focal or extensive, that should be classified as carcinoma

based on the presence of invasion, and that may benefit

from appropriate risk stratification and/or additional

therapies.

The consensus opinion is that the criteria used in Figure 8 to

define BVI should be utilised. In regard to the extent of BVI,

several papers have shown that the presence of 4-5 foci of

BVI in encapsulated follicular/Hürthle cell carcinoma confers

a much worse outcome than lower number of LVI foci.18,37,38

The 2015 American Thyroid Association (ATA) guidelines

classify a patient in a high risk category, if having 4 foci or

more of vascular invasion (VI), while focal BVI (<4 foci) in

an intrathyroidal follicular carcinoma will put the patient in

low risk group.39 More importantly, the National

Comprehensive Cancer Network (NCCN) 2019 guidelines

have defined minimal vascular invasion as a few foci (1-4) of

VI, and does not mandate radioiodine (RAI) administration in

an intrathyroidal, well defined, follicular or Hürthle cell

carcinoma, with minimal VI.40 Consequently, it is important

to report the extent of BVI in encapsulated thyroid

carcinoma by counting the foci of BVI. It is noteworthy that

most papers that validated the importance of BVI cut-offs

have counted individual vessel sections invaded by tumour

separately, as different foci. In regard to papillary thyroid

carcinoma (PTC), the presence of BVI was shown to impart

poorer outcome.35 Furthermore any focus of VI in PTC will

put the patient in an intermediate risk category according to

the 2015 ATA guidelines.39 It is therefore mandatory to

report on the status of BVI in PTC (i.e. core item). There is

no evidence that the number of BVI foci impact on prognosis

in non-encapsulated PTC. Counting the BVI foci in non-

encapsulated PTC is therefore not a core item. It is however

a core item in those PTC who are completely encapsulated.

(Refer to ICCR guidelines for full commentary.)

S3.07 The presence of necrosis must be recorded.

CS3.07a Tumour necrosis should be reported in every thyroid

carcinoma since it is an essential defining criterion for PDTC

regardless of the definition used for this entity.21,22 Tumour




necrosis is defined as coagulative or comedo-necrosis and

should be differentiated from infarct-like necrosis related to

previous FNA or ischemic changes within the tumour.

Reactive changes seen in the latter two situations such as

hyalinization or fibrosis, haemorrhage, hemosiderin laden

macrophages, cholesterol clefts or calcification, should be

separated from coagulative necrosis.

S3.08 The presence of extrathyroidal extension must be recorded.

CS3.08a Extrathyroidal extension (ETE), defined as tumour extension

beyond the thyroid capsule into the adjacent soft tissue, is a

common pathologic finding in papillary thyroid carcinomas.41

ETE has long been considered as an adverse prognostic

factor with an increased risk of recurrence and mortality.41-44

It can be further subdivided into two categories: 1) minimal

(or microscopic) ETE, identified in roughly half of all PTC45

which is invasion into the immediate perithyroidal soft

tissue, detected solely at microscopic level and not

appreciated clinically or grossly at the time of surgery; and

2) extensive (or gross) ETE, present in around 10% of

cases45 that is defined as gross direct extension of the

carcinoma into strap muscles (e.g. sternohyoid,

sternothyroid, thyrohyoid, and omohyoid muscles),

subcutaneous tissue, adjacent viscera (e.g. larynx, trachea,

and oesophagus), or recurrent laryngeal nerve, and is

typically established clinically by imaging or during the

operation. These two categories of ETE bear different

prognostic values: the risk of recurrence associated with

minor extrathyroidal extension is approximately 3 to 9%,46-52

compared with 23 to 40% risk of recurrence in patients with

gross ETE.46,47,49-51,53,54 Furthermore, several studies have

shown that microscopic ETE is not an independent predictor

for persistent disease, recurrence free survival and disease

specific survival.45,48,49,52,54-56 NCCN 2019 guidelines

recommend completion thyroidectomy and post-operative

RAI for lesions with gross ETE, while low-dose RAI using 30

mCi of iodine 131 is optional for patients with a primary

tumour of <4 cm, clinical M0 and minor ETE.40 Histologically,

the thyroid gland is devoid of a well-defined capsule in many

areas along its periphery, and the follicles are often

intermingled with adipose tissue or even skeletal muscle.57

Therefore, the very definition of microscopic ETE is

problematic and subjective, and a universally accepted

pathologic criterion for ETE is lacking. The fact that

microscopic ETE is associated with poor interobserver

agreement57 and does not affect recurrence and survival

raise concerns of whether microscopic ETE alone is sufficient

to upstage a patient. Because of all the above, in the 8th

edition AJCC and UICC staging systems, microscopic ETE has

been removed entirely from the staging system of

differentiated thyroid carcinoma.15,16 Gross ETE invading

strap muscles only, by a tumour of any size, will be staged


as pT3b, while gross ETE with invasion into subcutaneous

soft tissue, larynx, trachea, oesophagus, or recurrent

laryngeal nerve will be staged as pT4a. In view of the above,

the pathologists’ role is

1) to mention in their report the ETE seen histologically

(whether microscopic or gross) and

2) communicate with the surgeon in regards to staging,

since the determination of gross ETE is done intra-

operatively.

CS3.08b The pathological staging (T stage) depends on the size of the

cancer and the extent of involvement of thyroid gland and

adjacent tissues.

The extension into peri-thyroid soft tissue and the

sternohyoid muscles is recorded as T3, regardless of the size

of the cancer.

Cancer extending beyond the thyroid capsule into

subcutaneous soft tissue, larynx, trachea, oesophagus or

recurrent laryngeal nerve, etc. should be recorded as T4.

S3.09 The margin status must be recorded.

CS3.09a The margin status of a surgical resection for thyroid

carcinoma is a core element and can be divided into three

categories: R0 resection (microscopically negative margin),

R1 resection (grossly complete resection with microscopically

positive margin), and a R2 resection (grossly positive margin

or incomplete resection).15 The surgeon should communicate

macroscopic status of the margins to the pathologist.

Histologically, a positive margin is defined by the presence of

tumour cells at the inked tissue border and/or the outer

aspect of the thyroid gland.58-61 Several studies have shown

that microscopically positive margin is not an independent

predictor for recurrence and disease free survival, especially

after adjusting for tumour stage and ETE.59-61 Taken these

into consideration, the current ATA guideline has only

included incomplete R2 resection into the risk stratification

as a feature of high risk lesions.39 In contrast, the NCCN

2019 guideline has included any positive resection margin as

one of the criteria to recommend completion

thyroidectomy.40 (Refer to ICCR guidelines for full

commentary.)

S3.10 The presence, location and status of lymph nodes must be

recorded.

CS3.10a Increasing evidence has shown that various characteristics

of nodal metastases, e.g. number, size, and extranodal

extension (ENE), may provide additional prognostic

information. Thus, detailed features of nodal disease ought

to be included in the pathology report, and be considered in



risk stratification and staging systems.55,62-69 A meta-analysis

by Randolph et al (2012) has shown that small volume

subclinical microscopic pathologic N1 disease, i.e. five or

fewer subcentimeter metastatic lymph nodes, conveys little

prognostic impact on recurrence free survival and disease

specific survival in patients with PTC, compared with

clinically evident macroscopic nodal disease involving more

than 5 lymph nodes, especially those with ENE.62 The

greatest dimension of the largest metastatic deposit in a

lymph node should be measured. It is accepted it can be

difficult to distinguish multiple small metastases in one large

deposit. Many authors recommend measuring the greatest

dimension end to end in a single slide including

discontinuous deposits.70 Taking this data into consideration,

the NCCN 2019 guidelines no longer recommend completion

thyroidectomy and post-operative RAI in small volume pN1a

disease, i.e. <5 involved nodes with metastasis <2 mm in

largest dimension.40 Histologic features of the nodal

metastasis that have been incorporated in the ATA initial risk

stratifications included number of involved lymph nodes (>5

is considered as intermediate risk) and size of the metastatic

lymph nodes (≥3 cm as high risk). The presence of

psammoma bodies alone in a node is subject to controversy.

While some practicing pathologists do not consider these as

metastasis, we are in agreement with the College of

American Pathologists in considering these lymph nodes as

positive for metastatic carcinoma.23

Extranodal extension is not an uncommon finding, being

reported in up to 12% of PTC overall and 33% of nodal

metastatic PTC.55,66 Similar to ETE, a well-defined,

consensus, histologic diagnostic criterion for ENE is currently

lacking.23,71 A study by Du et al (2016) has shown that

involvement of perinodal adipose tissue appears to be the

most consistent diagnostic criteria of ENE, being considered

by eleven participating endocrine pathologists as ENE.71

However, the overall agreement in diagnosing ENE is only

fair among expert pathologists.71 Nevertheless, studies have

repeatedly demonstrated the association between ENE and

persistent and/or recurrence disease.55,62-68 Hence, it is

important to document ENE in the pathology report of a

differentiated thyroid carcinoma.

A seven-compartment nomenclature is used to define

anatomic lymph nodes compartments. Central neck refers to

level VI (peri-thyroidal, paralaryngeal, paratracheal, and

prelaryngeal (Delphian)) and VII (upper mediastinal). Lateral

neck refers to level I (submental/submandibular), II (upper

jugular), III (mid jugular), IV (lower jugular) and V

(posterior triangle).72

At the current time, no additional special techniques should

be used other than routine histology for the assessment of

nodal metastases (i.e. sentinel lymph node-type protocols


are not advocated). However, confirmation by

immunohistochemical staining, including thyroglobulin or

Thyroid transcription factor-1 (TTF-1) for papillary carcinoma

and calcitonin and neuroendocrine markers (e.g.

chromogranins, synaptophysin, carcinoembryonic antigen

(CEA), CD56) for medullary carcinoma, may be required.

CS3.10b If regional lymph nodes are identified, the location must be

specified.

CS3.10c The total number of lymph nodes sampled must be stated.

CS3.10d The number of lymph nodes containing metastatic tumour

must be stated.

CS3.10e The presence and sites of lymph node metastases of thyroid

carcinoma, affect the pathological staging (N stage) of

thyroid cancer.

G3.02 The presence of C-cell hyperplasia should be recorded.

CG.02a The presence of C-cell hyperplasia may suggest hereditary

disease and should therefore be reported in specimens

harbouring medullary thyroid carcinoma.

S3.11 The parathyroid gland status must be recorded.

CS3.11a The number and status of the parathyroid glands in the

specimen should be stated to support surgical quality

assurance.

CS3.11b The presence of parathyroid tissue may provide correlation

with the clinical data on calcium status.

S3.12 The presence or absence of histologically confirmed distant

metastases must be recorded.

CS3.12a The presence of histologically confirmed distant metastasis is

a key component of staging.2,3

S3.13 The presence or absence of coexistent pathological

abnormalities in the thyroid gland should be recorded.

CS3.13a The presence of chronic lymphocytic thyroiditis, follicular

adenoma, Hürthle cell adenoma, NIFTP and nodular

hyperplasia for example can help explain the

clinical/imaging/cytologic findings.

CS3.13b Hashimoto’s thyroiditis, lymphocytic thyroiditis, diffuse

parenchymatous goitre and nodular hyperplasia, etc. are

common additional findings and may help elucidate the

aetiological relationship or the differential diagnosis.


G3.03 Any additional relevant microscopic comments should be recorded.

Figure 7. Capsular invasion (CI)

Schematic drawing for the interpretation of the presence or absence of CI. The

diagram depicts a follicular neoplasm (orange) surrounded by a fibrous capsule

(green).

a) bosselation on the inner aspect of the capsule does not represent CI;

b) sharp tumour bud invades into but not through the capsule suggesting

invasion requiring deeper sections to exclude;

c) tumour totally transgresses the capsule invading beyond the outer contour of

the capsule qualifying as CI;

d) tumour clothed by thin (probably new) fibrous capsule but already extending

beyond an imaginary (dotted) line drawn through the outer contour of the

capsule qualifying as CI;

e) satellite tumour nodule with similar features (architecture, cytomorphology)

to the main tumour lying outside the capsule qualifying as CI;

f) Follicles aligned perpendicular to the capsule suggesting invasion requiring

deeper sections to exclude

g) follicles aligned parallel to the capsule do not represent CI;

h) mushroom-shaped tumour with total transgression of the capsule qualifies as

CI;

i) mushroom-shaped tumour within but not through the capsule suggests

invasion requiring deeper sections to exclude;

j) neoplastic follicles in the fibrous capsule with a degenerated appearance

accompanied by lymphocytes and siderophages does not represent CI but

rather capsular rupture related to prior fine needle aspiration.


Modified from Chan JKC; Chapter 18 Tumours of the thyroid and parathyroid glands.

Diagnostic Histopathology of Tumours. 3rd ed. Fletcher CDM, editor. London, England:

Churchill Livingston; 2007. p. 997–1078. Reproduced with permission.

Figure 8. Vascular invasion (VI): Schematic drawing for the interpretation of

the presence or absence of VI.

The diagram depicts a follicular neoplasm (green) surrounded by a fibrous capsule

(blue).

a) Bulging of tumour into vessels within the tumour proper does not constitute VI.

b) Tumour thrombus covered by endothelial cells in intracapsular vessel qualifies as

VI.

c) Tumour thrombus in intracapsular vessel considered as VI since it is attached to

the vessel wall.

d) Although not endothelialized, this tumour thrombus qualifies for VI because it is

accompanied by a fibrin thrombus.

e) Endothelialized tumour thrombus in vessel outside the tumour capsule represents

VI.

f) Artefactual dislodgement of tumour manifesting as irregular tumour fragments

into vascular lumen unaccompanied by endothelial covering or fibrin thrombus.

Modified from Chan JKC; Chapter 18 Tumours of the thyroid and parathyroid glands.

Diagnostic Histopathology of Tumours. 3rd ed. Fletcher CDM, editor. London, England:

Churchill Livingston; 2007. p. 997–1078. Reproduced with permission.


Figure 9. Encapsulated Hürthle cell carcinoma

Encapsulated Hurtle cell carcinoma with multiple foci of microscopic vascular invasion

(VI) and no gross invasion.

In some classification schemes, these tumours are labelled as minimally invasive

while others will use terms such as encapsulated angioinvasive Hürthle cell

carcinomas or encapsulated Hürthle cell carcinomas with extensive angioinvasion to

stress their potential for aggressive behaviour. This 50 year old patient developed

bone metastases 10 years after thyroidectomy.

A. Low power view showing multiple microscopic foci of VI in tumour capsule

(arrow) and immediately outside the capsule.

B. High power view of a tumour thrombus (arrow) attached to vessel wall and

covered by endothelial cells.

Reproduced with permission from Springer Science+Business Media: Ghossein R.

Update to the College of American Pathologists Reporting on Thyroid Carcinomas

Head and Neck Pathol (2009) 3:86–93.73


4 Ancillary studies

Ancillary studies may be used to determine lineage, clonality or disease classification

or subclassification; as prognostic biomarkers; or to indicate the likelihood of patient

response to specific biologic therapies.

G4.01 The findings of any ancillary studies, where performed, should be

recorded.

CG4.01a Ancillary studies may be used to determine lineage, disease

classification or subclassification; as prognostic biomarkers;

or to indicate the likelihood of patient response to specific

biological therapies.

In cases in which the diagnosis is suspected to be medullary

carcinoma, immunostaining for calcitonin, chromogranin,

synaptophysin, CEA and thyroglobulin may be performed to

confirm the diagnosis. The calcitonin, CEA, chromogranin

and synaptophysin immunostains are also helpful to identify

C-cell hyperplasia.

Thyroglobulin, TTF-1 and paired box 8 (PAX8) may indicate

that a tumour is of follicular cell origin. TTF-1 is more

sensitive than thyroglobulin however, TTF-1 can be positive

in other cancers such as lung adenocarcinoma and small cell

carcinoma of any primary site. Anaplastic thyroid carcinoma

is negative for thyroglobulin, positive focally for TTF-1 in a

small percentage of cases, but labels for PAX-8 in a

substantial number of cases.74

It is not possible to differentiate benign and malignant

thyroid tumours by using immunohistochemistry. (Refer to

ICCR guidelines for full commentary.)

Molecular analyses are currently being performed to identify

targets in tumour refractory to radioactive iodine therapy. An

immunostain for the BRAF V600E mutation is an easy to

perform, robust and rapid assay to select patients for BRAF

inhibitor therapy as well as confirm diagnosis of some

papillary thyroid carcinomas.

CG4.01b Uncommon tumours (e.g. angiosarcoma, carcinoma showing

thymus-like differentiation, paraganglioma, etc.) can occur in

the thyroid gland. Immunohistochemistry (CD31, CD5,

GATA-3, etc.) can help with a definitive diagnosis.

G4.02 Results of any molecular investigation should be incorporated into the

pathology report.

CG4.02a Molecular investigation can be useful in the management of

patients with medullary thyroid carcinoma.



Germline mutations of the rearranged during transfection

proto-oncogene (RET) gene identify patients at risk for

mutation-specific thyroidal and extrathyroidal

manifestations, in particular MEN2a and MEN2b. The strong

genotype-phenotype correlation guides management and

prognosis of germline carriers. Somatic RET mutations

occur in up to 70% of sporadic medullary thyroid

carcinoma patients.

CG4.02b Ancillary tests performed externally may contain

information needed for compliance with National Pathology

Accreditation Advisory Council (NPAAC) and RCPA

requirements, that are not relevant to cancer reporting

protocols. The specific elements of an ancillary study report

needed for cancer reporting include the following:

• laboratory performing the test,

• substrate (e.g. cytology smears, fluid in special media,

paraffin block, fresh tissue, etc.),

• method (where relevant),

• results,

• conclusion (usually a text field), and

• person responsible for reporting the ancillary test.

CG4.02c Documentation of all relevant ancillary study findings is

essential for overarching commentary (see Synthesis and

Overview, Chapter 5), in which the significance of each

finding is interpreted in the overall context of the case.


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 descriptors – 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

according to the most recent TNM staging system of the AJCC

Cancer Staging Manual. (See Appendices 5 and 6).

CS5.01a The staging applies to all tumour types, including anaplastic

carcinoma, which hitherto had automatically been staged as

stage 4 irrespective of all other details.

The UICC TNM 8th edition staging applies to carcinomas and

includes papillary, follicular, poorly differentiated, Hürthle

cell (oncocytic), anaplastic, and medullary carcinoma.16

Multifocal tumours (≥2 foci) of all histological types should

be designated (m), with the largest and/or most invasive

focus determining the classification, e.g. pT2(m).

CS5.01b In thyroid cancer, staging is also informed by patient age

and cancer type.

CS5.01c A dedicated staging system is employed in young patients

(age <55) with differentiated thyroid cancer, i.e. papillary

and follicular carcinoma.

CS5.01d Anaplastic thyroid carcinoma is stage IV but being

subdivided to stage IVA, IVB and IVC based on the criteria of

AJCC TNM 8th edition.14

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:

a. Specimen type

b. Tumour laterality and site


c. Tumour type

d. Tumour stage

e. Completeness of excision

S5.03 The reporting system must provide a field for free text or

narrative in which the reporting pathologist can give

overarching case comment.

CS5.03a This field may be used, for example, to:

– list results of any relevant ancillary tests,

– document any noteworthy adverse gross and/or

histological features,

– express any diagnostic subtlety or nuance that is

beyond synoptic capture, and

– 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’.


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 thyroid cancer. For

emphasis, standards (mandatory elements) are formatted in bold font.

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

but with the following restrictions:

a. All standards and their respective naming conventions,

definitions and value lists must be adhered to.

b. Guidelines are not mandatory but are recommendations ,

and where used, must follow the naming conventions,

definitions and value lists given in the protocol.

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

according to the LIS capabilities and as described in Functional

Requirements for Structured Pathology Reporting of Cancer Protocols.75

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

report format, the structured checklist is usually best

formatted to follow the pathologist’s 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.

44

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

on request form

Text

OR

Information not provided

OR

Structured entry as below:

CLINICAL INFORMATION

Previous history of thyroid

tumour or related

abnormality

Text

Relevant biopsy/cytology

results

Text

Imaging findings Text

Previous surgery/therapy Text

Relevant family history Text

Presence of clinical

syndrome

Text

G1.01 Copy To doctors recorded Text

S1.03 Pathology accession number Alpha-numeric

S1.04 Principal clinician Text

45

G1.02 Other clinical information

received

Text

Macroscopic findings

S2.01 Specimen labelled as Text

S2.02 Clinical information Text

S2.03 Operative procedure Not specified

OR

Multi selection value list (select all that

apply):

• Total thyroidectomy

• Near total thyroidectomy

• Hemithyroidectomy

• Lobectomy

• Isthmusectomy

• Partial excision*

• Lymph node dissection

• Other, specify

*Note: Anything less than a lobectomy excluding

isthmusectomy, including substernal excision.

If partial excision, specify the

type if possible.

Type of partial excision Text

S2.04 Operative findings Single selection value list:

• Not specified

• Intra-operative macroscopic evidence of

extrathyroidal extension

If intra-operative macroscopic

evidence of extrathyroidal

extension is present, specify

location and tissue invaded.

If R2 excision is observed,

specify the location.

46

o Yes, specify location and tissue

invaded

o No

o Information not available

• Intra-operative impression of

completeness of excision

o R0/R1

o R2, specify location

o Information not available

• Other, specify

S2.05 Specimen(s) submitted Single selection value list:

• Not specified

OR


apply):

• Thyroid gland

o Left

o Right

o Isthmus

• Parathyroid gland(s)

• Lymph node(s), specify site(s) and

laterality

• Other, specify site(s) and laterality

G2.01 Specimen weight Numeric: ___g

47

S2.06 Tumour focality Single selection value list:

• Cannot be assessed, specify

• Unifocal

• Multifocal

If multifocal, specify the number

of tumours (if >5 state such, but

no need to specify the number)

Number of tumours in

specimen

Numeric: ____

S2.07 Tumour site

Single selection value list:

• Not specified

OR


apply):

• Lobe

o Left

o Right

• Isthmus

• Pyramidal lobe

• Soft tissue or muscle, specify site(s) and

laterality

• Other, specify site(s) and laterality

Describe tumour focality for the

most clinically relevant tumour.

S2.08 Macroscopic description Text

G2.02 Thyroid appearance Text

S2.09 Block identification key Text

G2.03 Other macroscopic comments Text

Microscopic findings

48

S3.01 Histological tumour type

Single selection value list from WHO

Classification of Tumours: Pathology and

Genetics of Tumours of Endocrine Organs

(2017).


• Papillary thyroid carcinoma

o Classic (usual, conventional)

o Cribriform-morular variant

o Diffuse sclerosing variant

o Encapsulated variant

o Encapsulated/well-demarcated

follicular variant with invasion

o Infiltrative follicular variant

o Hobnail variant

o Microcarcinoma

o Oncocytic variant

o Solid variant

o Tall cell variant

o Warthin-like variant

o Other variant, specify

• Follicular thyroid carcinoma (FTC)

o FTC, minimally invasive

o FTC, encapsulated angioinvasive

o FTC, widely invasive

• Hürthle (oncocytic) cell tumours

49

o Hürthle cell carcinoma, minimally

invasive

o Hürthle cell carcinoma,

encapsulated angioinvasive

o Hürthle cell carcinoma, widely

invasive

• Poorly differentiated thyroid carcinoma

• Anaplastic thyroid carcinoma

• Squamous cell carcinoma

• Medullary thyroid carcinoma

• Mixed medullary and follicular thyroid

carcinoma

• Mucoepidermoid carcinoma

• Sclerosing mucoepidermoid carcinoma

with eosinophilia

• Mucinous carcinoma

• Spindle epithelial tumour with thymus-like

differentiation

• Intrathyroid thymic carcinoma

• Other, specify

S3.02 Microscopic tumour

dimension



OR

Numeric: ___mm maximum tumour dimension

(largest tumour)

OR

50

Additional dimensions (largest tumour)

____mm x ____mm

S3.03 Mitotic activity Single selection value list:

• Not identified/low (<3 mitoses/2 mm2)

• High (>3 mitoses/2 mm2)


Note: 2 mm2 approximates 10 high power fields

on some microscopes

If high mitoses, specify number

of mitoses per 2 mm2

Numeric: ___ mitotic figures/2 mm2

G3.01 Histological grade Single selection value list:

• Well differentiated

• Poorly differentiated

• Undifferentiated/anaplastic

S3.04 Tumour encapsulation /

circumscription


• Encapsulated

• Infiltrative

• Other, specify

S3.05 Capsular invasion Single selection value list:

• Not applicable

• Uncertain

• Not identified

• Present


S3.06 Lymphatic invasion Single selection value list:


• Not identified

51

• Present

Vascular invasion Single selection value list:

• Not identified

• Present, for encapsulated neoplasms

o Focal, <4 foci

o Extensive, >4 foci

• Extrathyroidal blood vessel invasion

o Not identified

o Present

• Small vessel, not otherwise classifiable


S3.07 Necrosis Single selection value list:

• Not identified

• Present

S3.08 Extrathyroidal extension


• Cannot be assessed

• Not identified

OR


apply):

• Invasion into perithyroid fibroadipose

tissue

• Invasion into skeletal muscle

52

• Invasion into subcutaneous soft tissue,

larynx, trachea, oesophagus or recurrent

laryngeal nerve

• Invasion into prevertebral fascia or

encasing the carotid artery or mediastinal

vessel

S3.09 Margin status


• Not involved

• Involved, specify (anterior or posterior)


If not involved by invasive

carcinoma record the distance of

tumour to closest margin

If involved by invasive

carcinoma specify the anterior or

posterior margin, if possible

Distance to closest margin Numeric: __mm

Margin (anterior or posterior) Text

S3.10 LYMPH NODE STATUS No nodes submitted or found

OR


• Not involved

• Involved

Record the number of LN

examined.

If involved, specify the number

of positive LN

Number of lymph

nodes examined

Number cannot be determined

OR

Numeric: ___

Number of positive

lymph nodes

Numeric: ___ Not required if number cannot

be determined is entered above.

Location of involved lymph

nodes

Text

53

Greatest dimension of

largest lymph node with

metastasis

Numeric: __mm

Greatest dimension of

largest metastatic focus in

lymph node

Numeric: __mm

Extranodal extension (ENE) Single selection value list:

• Not identified

• Present

• Cannot be determined

If ENE present, specify number

of nodes

G3.02 C-cell hyperplasia Single selection value list:

• Not identified

• Present

• Unilateral

• Bilateral

S3.11 Parathyroid gland status


• Not identified

• Present

o Normal

o Involved by carcinoma

o Hypercellular/enlarged

If present, specify the number of

parathyroid gland(s) found and

the location of any removed

parathyroid glands (e.g. right

upper or lower lobe).

Number of parathyroid

gland(s)

Numeric: __

S3.12 Distant metastases Single selection value list:

• Not identified

54

• Not assessed

• Present, specify site(s)

S3.13 Coexistent pathological

abnormalities

None identified

OR

Multi select value list :

• Nodular hyperplasia

• Diffuse hyperplasia

• Dyshormonogenetic goitre

• Chronic lymphocytic thyroiditis

• Follicular adenoma

• Hürthle cell adenoma

• Non-invasive follicular thyroid neoplasm

with papillary-like nuclear features

(NIFTP)

• Other, specify

G3.03 Additional microscopic comment Text

Ancillary findings

G4.01 Ancillary studies


• Not performed

• Performed, specify

Results Text

G4.02 Molecular studies Text

Synthesis and overview

S5.01 PATHOLOGICAL STAGING

(AJCC 8TH EDITION)

55

TNM descriptors Multi select value list :

• m - multiple primary tumours

• r – recurrent

• y – post therapy

Primary tumour (pT)* Single select value list :

TX Primary tumour cannot be assessed

T0 No evidence of primary tumour

T1 Tumour <2 cm in greatest dimension

limited to the thyroid

T1a Tumour <1 cm in greatest dimension

limited to the thyroid

T1b Tumour >1 cm but <2 cm in greatest

dimension limited to the thyroid

T2 Tumour >2 cm but <4 cm in greatest

dimension limited to the thyroid

T3 Tumour >4 cm limited to the thyroid, or

gross extrathyroidal extension invading

only strap muscles

T3a Tumour >4 cm limited to the thyroid

T3b Gross extrathyroidal extension invading

only strap muscles (sternohyoid,

sternothyroid, thyrohoid, or omohyoid

muscles) from a tumour of any size

T4 Includes gross extrathyroidal extension

beyond the strap muscles

T4a Gross extrathryroidal extension invading

subcutaneous soft tissues, larynx, trachea,

oesophagus, recurrent laryngeal nerve from

a tumour of any size

T4b Gross extrathyroidal extension invading

prevertebral fascia or encasing the carotid

artery or mediastinal vessels from a tumour

of any size

All categories may be

subdivided: (s) solitary tumour

and (m) multifocal tumour (the

largest tumour determines the

classification).

56

Regional lymph node (pN) Single selection value list:

NX Regional lymph nodes cannot be

assessed

N0 No evidence of locoregional lymph node

metastasis

N0a One or more cytologically or

histologically confirmed benign lymph

nodes

N0b No radiologic or clinical evidence of

locoregional lymph node metastasis

N1 Metastasis to regional nodes

N1a Metastasis to level VI or VII

(pretracheal, paratracheal, or

prelaryngeal/Delphian, or upper

mediastinal) lymph nodes. This can be

unilateral or bilateral disease.

N1b Metastasis to unilateral, bilateral or

contralateral lateral neck lymph nodes

(levels I, II, III, IV or V) or

retropharyngeal lymph nodes

S5.02 Year and edition of staging

system

Numeric: year

AND

Text: Edition e.g. 1st, 2nd etc.

G5.01 Diagnostic summary

Include:

a. Operative procedure

b. Tumour site

c. Histological tumour type

d. Tumour stage

e. Margin status

Text

S5.03 Overarching comment Text

57

G5.02 Edition/version number of the

RCPA protocol on which the

report is based

Text

58

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.

59

Appendix 1 Pathology request form for thyroid tumours

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 thyroid tumour specimens

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

• gender

• identification and contact details of requesting doctor

• date of request

• Document 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.

• 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 Individual Healthcare Identifier (IHI) (Australia) or the

National Healthcare Index (New Zealand).

➢ The Australian Healthcare identifiers i.e. Healthcare Provider Identifier -

Individual (HPI-I) and Healthcare Provider Identifier - Organisation (HPI-

O) should be used, where possible, to identify the requesting doctor.

60

Clinical Information

➢ Surgical handling procedures affect the quality of the specimen.

• The specimen should be fixed in 10% neutral buffered formalin as

soon as possible after resection or after tissue banking (if applicable).

• It is useful for the surgeon to identify the anatomical orientation of

the thyroid.

➢ Any previous history of thyroid/endocrine tumour or related

abnormality must be recorded.

➢ • Clinical or biochemical evidence of hyperthyroidism or hypothyroidism

should be noted.

➢ • Clinical features associated with thyroid lesion such as change in size,

presence of hoarse voice, stridor, swallowing difficulties, presence of

pain.

➢ If a pre-operative biopsy, or cytology has been performed, this

must be recorded.

➢ • If a pre-operative FNA or core biopsy has been performed, this should

be recorded and the results of that biopsy briefly stated. .

Any imaging findings must be recorded.

• If imaging has been performed, this should be recorded and the

results briefly stated.

➢ Any previous surgery or therapy should be recorded.

➢ • Previous thyroid surgery or medical treatments like anti-thyroid drug

or radioactive iodine should be noted. Previous exposure of the neck

to radiotherapy (e.g. for treatment of Hodgkin lymphoma) should be

noted. The indication for performing the surgery should be recorded

as many thyroid cancers are found incidentally in thyroid specimens

removed for a purpose other than cancer.

➢ Any relevant family history should be recorded.

➢ • Family history of thyroid cancers or features of other endocrine

tumours or syndromes should be recorded. It is worth noting that

gastrointestinal manifestations of an endocrine syndrome may

present before identification of an endocrine tumour.

➢ The presence of the clinical syndrome be recorded.

• Relevant clinical information suggestive of the presence of clinical

syndromes, in pargicular multiple endocrine neoplasia type 2A and

type 2B that are associated with increased risk of medullary cancer of

thyroid (e.g. phaeochromocytoma, hyperparathyroidism, neuromas)

and any evidence (clinical or biochemical) of endocrine hyperfunction

or hypofunction should be included.

61

➢ Any other clinical information should be included, if appropriate.

• Space for free text should be included to encourage reporting

of ambiguity, or for the addition of other comments.

62

Example Request Information Sheet

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

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

63

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.76

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.76

• Reduce ‘clutter’ to a minimum.76 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.

64

Appendix 3 Example of a pathology report

66

Appendix 4 WHO histological classification of tumours of the thyroid gland

Follicular adenoma 8330/0

Hyalinizing trabecular tumour 8336/1*

Other encapsulated follicular-patterned thyroid tumours

Follicular tumour of uncertain malignant potential 8335/1*

Well-differentiated tumour of uncertain malignant potential 8348/1*

Non-invasive follicular thyroid neoplasm with papillary-like nuclear features 8349/1*

Papillary thyroid carcinoma (PTC)

Papillary carcinoma 8260/3

Follicular variant of PTC 8340/3

Encapsulated variant of PTC 8343/3

Papillary microcarcinoma 8341/3

Columnar cell variant of PTC 8344/3

Oncocytic variant of PTC 8342/3

Follicular thyroid carcinoma (FTC), NOS 8330/3

FTC, minimally invasive 8330/3

FTC, encapsulated angioinvasive 8339/3*

FTC, widely invasive 8330/3

Hürthle (oncocytic) cell tumours

Hürthle cell adenoma 8290/0

Hürthle cell carcinoma 8290/3

Poorly differentiated thyroid carcinoma 8337/3

Anaplastic thyroid carcinoma 8020/3

Squamous cell carcinoma 8070/3

Medullary thyroid carcinoma 8345/3

Mixed medullary and follicular thyroid carcinoma 8346/3

Mucoepidermoid carcinoma 8430/3

Sclerosing mucoepidermoid carcinoma with eosinophilia 8430/3

Mucinous carcinoma 8480/3

Ectopic thymoma 8580/3

Spindle epithelial tumour with thymus-like differentiation 8588/3

Intrathyroid thymic carcinoma 8589/3

Paraganglioma and mesenchymal/stromal tumours

Paraganglioma 8693/3

Peripheral nerve sheath tumours (PNSTs)

Scwannoma 9560/0

67

Malignant PNST 9540/3

Benign vascular tumours

Haemangioma 9120/0

Cavernous haemangioma 9121/0

Lymphangioma 9120/0

Angiosarcoma 9120/3

Smooth muscle tumours

Leiomyoma 8890/0

Leiomyosarcoma 8890/3

Solitary fibrous tumour 8815/1

Haematolymphoid tumours

Langerhans cell histiocytosis 9751/3

Rosai-Dorfman disease

Follicular dendritic cell sarcoma 9758/3

Primary thyroid lymphoma

Germ cell tumours

Benign teratoma (grade 0 or 1) 9080/0

Immature teratoma (grade 2) 9080/1

Malignant teratoma (grade 3) 9080/3

Secondary tumours

The morphology codes are from the International Classification of Diseases for Oncology

(ICD-O).77 Behaviour is coded /0 for benign tumours; /1 for unspecified, borderline, or

uncertain behaviour; /2 for carcinoma in situ and grade III intraepithelial neoplasia; and

/3 for malignant tumours.

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

changes in our understanding of these lesions.

*These new codes were approved by the IARC/WHO Committee for ICD-O.

From WHO Classification of Tumours Pathology and Genetics. Tumours of

Endocrine Organs 2017, Volume 10, 4th Edition. IARC.17

© World Health Organisation/International Agency for Research on Cancer (IARC). Reproduced with permission

68

Appendix 5 Histological tumour type

Papillary carcinoma

Papillary carcinoma is the most common carcinoma type and consists of numerous

named variants, though only a few of these currently have sufficient evidence to be

considered clinically and biologically relevant. Thus efforts should be made to flag or

document the following variants when present:

• Classic (usual, conventional)

• Encapsulated/well demarcated follicular variant with invasion

• Infiltrative follicular variant

• Tall cell variant

• Cribriform-morular variant

• Diffuse sclerosing variant

• Encapsulated variant

• Microcarcinoma

Classical papillary thyroid carcinoma (PTC), tall cell and microcarcinoma variants

Classic (usual, conventional) papillary carcinoma is the most common and ‘default’

variant of papillary carcinoma. Tall cell variant of papillary carcinoma is a more

aggressive variant that has a higher prevalence of BRAF mutations and is more

frequently refractory to radioactive Iodine therapy.78-80 Papillary microcarcinomas are

defined by their size (≤1 cm) and are extremely indolent and often incidental.17 In this

protocol, it is recommended but not required that they are subtyped according to their

cytoarchitectural features (e.g. papillary microcarcinoma, classical)

Follicular variant and related lesions

Follicular variant of papillary carcinoma is important to document because it has recently

been substratified based on outcome into completely encapsulated/well demarcated and

infiltrative follicular variants which completely or partially lack a capsule. Infiltrative

follicular variants have a behaviour similar to classic papillary carcinoma, particularly in

terms of propensity for nodal metastasis, while the behaviour of encapsulated/well

circumscribed follicular variant is more indolent, especially if non-invasive.81,82

Many non-invasive encapsulated/well circumscribed follicular variants of papillary thyroid

carcinoma can now be reclassified under the new designation NIFTP. This shift in

nomenclature arose as an effort to encourage conservative management of these lesions

given their extremely low risk of structural recurrence.83 It is noteworthy that the impact

of this change worldwide varies according to countries. For example, many cases

designated as NIFTP today were labelled in parts of Asia including Australia, as follicular

adenomas and thus this new designation will have little effect on the practice of these

pathologists. NIFTP remains an actionable surgical disease, albeit with a more

conservative approach. As NIFTP is not overtly malignant, it is technically not required to

report these under this cancer protocol. However it is encouraged to include them in the

overall pathology report, though only limited parameters are relevant, namely size,

laterality, and margin status.

It must be noted that not all tumours previously designated as non-invasive follicular

69

variant of papillary thyroid carcinoma would qualify as NIFTP.83 Several exclusionary

criteria have been put forth in the initial publication of this entity in order to ensure that

the NIFTP category remains indolent83 and are as follows: solid/trabecular or insular

growth ≥30%, ≥1% true papillary growth (for more explanation see below), psammoma

bodies, tumour necrosis, ≥3 mitosis/10 HPFs at 400x magnification, tall cell, columnar,

or cribriform morular morphology. A key requirement for a NIFTP diagnosis is that the

entire lesional border has been submitted for histologic evaluation. When a tumour fulfils

these inclusion and exclusion criteria, NIFTP designation is appropriate. Of note,

subcentimeter NIFTP and NIFTP with oncocytic features have been shown to have an

outcome similar to NIFTP.84,85

Multifocal NIFTP has not been well validated yet. In view of the small number of articles

on these NIFTP scenarios, some pathologists do not label these unusual forms of this

entity as NIFTP. In these situations, our opinion is that the designation, NIFTP, is not

absolutely contraindicated. NIFTP is still an evolving diagnosis, and certain problematic

areas have already been noted such as the quantification of true papillae. Because the

initial criterion of <1%83 papillae was noted to be subjective and difficult to apply, there

was a suggestion that even 1 well-formed papilla as defined above should be considered

exclusionary.86 Studies are underway to resolve this issue. When an encapsulated non-

invasive follicular patterned lesion with PTC nuclei does not fulfil the NIFTP inclusion

criteria, they can be labelled as encapsulated variant. This variant is defined in the most

recent WHO as an architecturally and cytologically typical PTC that is totally

encapsulated but in the opinion of this expert panel it can be used to label encapsulated

non-invasive follicular patterned lesions with PTC nuclei that do not meet the NIFTP

criteria.17

If an encapsulated follicular patterned tumour has questionable capsular/vascular

invasion, the term of uncertain malignant potential (UMP) is used as a qualifier. These

tumours are not required to be reported using this thyroid cancer protocol since their

malignant potential has not been demonstrated yet. When the nuclear features of PTC

are absent, these lesions are labelled as follicular tumour of uncertain malignant

potential (FTUMP) while if PTC nuclei are questionable or present the designation well

differentiated tumour of uncertain malignant potential (WTUMP) is used.17

Diffuse sclerosing variant and cribriform-morular variants

The cribriform morular variant is a biologically distinct variant characterised by APC or

beta-catenin mutations and shows an association with familial adenomatous polyposis

coli, in some cases preceding recognition of colon polyps or other extracolonic

manifestations.87 Diffuse sclerosing variant is a locoregionally aggressive variant with a

high rate of nodal metastasis and locoregional recurrence, though overall survival is

good possibly because of the young age of the patients. Nonetheless, this variant

appears to necessitate more aggressive initial surgical management including more

extensive node dissection.88

Other variants that may have prognostic and therapeutic value but are rare and not well

validated include:

• Clear cell

• Hobnail variant

• Oncocytic or oxyphilic

• Solid

Follicular and Hürthle (oncocytic) cell carcinomas

Follicular carcinoma is a well-differentiated carcinoma type defined by invasiveness in

the absence of diagnostic nuclear features of papillary thyroid carcinoma. The diagnosis

of follicular carcinoma and its distinction from follicular adenoma primarily depends on

70

the identification of invasion of the tumour capsule and/or vascular spaces.

The most recent WHO classification subdivide these carcinomas into minimally invasive

(capsular invasion only), encapsulated angioinvasive (any focus of vascular invasion)

and widely invasive. The latter is defined as grossly apparent extensive invasion of the

thyroid and/or extra-thyroid tissue with often prominent vascular invasion.17 These

widely invasive carcinomas are often characterised by loss of encapsulation and multiple

invasive fronts radiating from the epicenter of the tumour. Hürthle cell carcinoma is

defined as a tumour composed of 75% of oncocytes lacking the nuclear features of

papillary carcinoma demonstrating capsular and/or vascular invasion.17 In the most

recent WHO classification of endocrine tumours, Hürthle cell carcinoma is no longer

considered a variant of follicular carcinoma because of different (overall more

aggressive) behaviour, different molecular profile and less radioactive iodine avidity.17

The definition of minimally invasive, angioinvasive and widely invasive Hürthle cell

carcinoma mirrors those of follicular carcinoma.

Although pathologists can diagnose benign from malignant thyroid tumours with very

high accuracy, there are extremely rare cases with distant metastasis in a setting of

non-invasive follicular and Hürthle cell carcinoma even after complete sampling of the

tumour capsule.89 There are also very rare instances of regional nodal metastases

without primary thyroid carcinoma found.90

While the majority of thyroid cancers are well differentiated, a subset are poorly

differentiated (historically known as insular, or trabecular, carcinoma) or undifferentiated

(anaplastic). These tumour types represent progression to a more aggressive phenotype

and are often seen with co-existent or antecedent well-differentiated carcinoma. While

detailed histomorphologic review is beyond the scope of this protocol, salient features of

both tumour types are listed below.

Poorly differentiated thyroid carcinomas (PDTC)

Poorly differentiated thyroid carcinomas (PDTC) have a prognosis in between the well

differentiated indolent papillary thyroid carcinoma and the often fatal anaplastic

carcinoma. According to the most recent WHO classification, poorly differentiated

carcinomas are tumours that display a solid, trabecular, and/or insular growth pattern,

and show 1 or more of the following: 3 or more mitoses per 10 HPF, tumour necrosis,

and nuclear convolution (without other nuclear features seen in papillary carcinoma).17,21

As defined, PDTC is not the only tumour type that has prognostic features intermediate

between well- differentiated and undifferentiated (anaplastic) carcinoma.17 Other tumour

types, including tall cell papillary carcinoma, can have guarded prognosis. Grading

(based on high mitotic count and necrosis as used at Memorial Sloan-Kettering Cancer

Center) identifies aggressive thyroid tumours of intermediate prognosis, regardless of

their cytoarchitectural features.17,22 Of note, encapsulated poorly differentiated thyroid

carcinomas appear to have a more favourable prognosis than unencapsulated tumours,

particularly if they show no capsular or vascular invasion with adequate sampling.22,24

Anaplastic (undifferentiated) carcinoma

Undifferentiated carcinoma represents the most extreme form of tumour progression and

consists of a high-grade malignancy with spindled, pleomorphic, squamoid, or even

rhabdoid morphology.91 Undifferentiated carcinoma is almost invariably rapidly lethal. A

better differentiated component such as PTC or Hürthle cell carcinoma may be found and

its presence should be mentioned.

71

Appendix 6 AJCC Staging Grouping

Separate stage groupings are recommended for papillary or follicular (differentiated),

medullary, and anaplastic (undifferentiated) carcinoma.

Differentiated

Stage And T is… And N is… And M is… When age

at diagnosis

is…

Stage I Any T Any N M0 <55 years

Stage II Any T Any N M1 <55 years

55 YEARS AND OLDER

Stage I T1 N0/NX M0 >55 years

Stage II T1 N1 M0 >55 years

Stage I T2 N0/NX M0 >55 years

Stage II T2 N1 M0 >55 years

Stage II T3a/T3b Any N M0 >55 years

Stage III T4a Any N M0 >55 years

Stage IVA T4b Any N M0 >55 years

Stage IVB Any T Any N M1 >55 years

Anaplastic carcinoma

Stage IVA T1-T3a N0/NX M0

Stage IVB T1-T3a N1 M0

Stage IVB T3b Any N M0

Stage IVB T4 Any N M0

Stage IVC Any T Any N M1

Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The

original source for this material is the AJCC Cancer Staging Manual, 8th Edition (2017) published by Springer Science and Business Media LLC, www.springerlink.com.


72

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