Term

Definition

Adjuvant therapy or treatment

A treatment given after the main treatment for cancer to reduce the risk of recurrence

Adnexal (in relation to the skin)

Structures in the skin including hair follicles and sebaceous glands

Biopsy

Removal of a sample of tissue from the body to assist in diagnosis or inform the choice of treatment of a disease

Computed tomography (CT)

Imaging technique in which the person lies on a table within a x‐ray gantry. The images are acquired using a spiral (helical) path and banks of detectors, allowing presentation of the internal organs and blood vessels in different projections including 3‐D views

Curettage

Surgical procedure to remove tissue or delineate borders of lesions via scraping

Cutaneous T cell lymphoma

A type of non‐Hodgkin lymphoma of the skin caused by uncontrolled growth of white blood cells

Dermal papilla

Small projections of the dermis into the overlying epidermis giving an undulating pattern and visible as "fingerprints" in hands and feet

Electrodessication

The use of high‐frequency electric currents to cut, destroy or cauterise tissue. It is performed with the use of a fine needle‐shaped instrument

False negative

An individual who is truly positive for a disease, but whom a diagnostic test classifies as disease‐free

False positive

An individual who is truly disease‐free, but whom a diagnostic test classifies as having the disease

Follicular bulge

The portion of the hair follicle that contains the stem cells that give rise to skin cells. It contains the cells needed for wound repair, hair growth and development and tumour development

Histopathology

The study of tissue, usually obtained by biopsy or excision, for example under a microscope

Incidence

The number of new cases of a disease in a given time period

interfollicular epidermis

The part of the skin that lies in between the hair follicles

Local recurrence

Regrowth of a tumour in the area from which it was originally removed

Locoregional recurrence

Regrowth of a tumour in the area from which it was originally removed or in the regional lymph nodes (usually nearest to the original tumour site)

Lymph node dissection

Surgical removal or one or more lymph nodes in the absence of proven involvement with melanoma

Lymph node dissection (lymphadenectomy)

A surgical operation to remove one or more groups of lymph nodes

Lymphoscintigraphy

An imaging technique used to identify the lymph drainage basin, determine the number of sentinel nodes, differentiate sentinel nodes from subsequent nodes, locate the sentinel node in an unexpected location, and mark the sentinel node over the skin for biopsy. It requires the injection of a radio‐isotope into the skin around the biopsy scar and a scan some hours later to determine to which lymph nodes the tracer has travelled

Magnetic resonance imaging (MRI)

A type of scan which uses a magnetic field and radio waves to produce images of sections of the body

Meta‐analysis

A form of statistical analysis used to synthesise results from a collection of individual studies

Metastases/metastatic disease

Spread of cancer away from the primary site to somewhere else through the bloodstream or the lymphatic system

Micrometastases

Metastases so small that they can only be seen under a microscope

Morbidity

Detrimental effects on health

Mortality

Either (1) the condition of being subject to death; or (2) the death rate, which reflects the number of deaths per unit of population in relation to any specific region, age group, disease, treatment or other classification, usually expressed as deaths per 100, 1000, 10,000 or 100,000 people

Multidisciplinary team (MDT)

A team with members from different healthcare professions and specialties (e.g. urology, oncology, pathology, radiology, and nursing). Cancer care in the NHS uses this system to ensure that all relevant health professionals are engaged to discuss the best possible care for that patient

Oncology

The study of cancers. This term also refers to the medical specialty of cancer care, with particular reference to the use of radiotherapy or drugs to treat cancer. The medical specialty is often split into Clinical Oncology (doctors who use radiotherapy and drug treatment) and Medical Oncology (doctors who use drug treatment)

Palpation

Feeling with the fingers or hands as part of a clinical examination of the body

Perineural involvement

Spread or invasion of cancer to the nerves

Positron emission tomography (PET)

A nuclear medicine imaging technique whereby a radioactive glucose (usually ¹⁸FDG) is administered intravenously before a scan is conducted to create an image using colours to show where the FDG (or other radioactive tracer) has been taken up in the body

Prevalence

The proportion of a population found to have a condition

Prognostic factors / indicators

Specific characteristics of a cancer or the person who has it which might affect the patient’s prognosis

Radiotherapy

The use of radiation, usually high energy x‐rays, to control the growth of cancer cells

Recurrence

New cancer cells are detected following treatment. This can occur either at the site of the original tumour or at other sites in the body

Relapse

Where cancer starts to grow again after treatment

Sensitivity

In this context, the proportion of individuals with a disease who have that disease correctly identified by the study test

Sentinel lymph node biopsy

A radioactive tracer and blue dye are injected into the skin surrounding the primary lesion and the 'sentinel' lymph nodes to which the tracer drains are located by imaging (usually lymphoscintigraphy), and then removed and examined for nodal metastatic spread that cannot be detected clinically or on imaging

Specificity

The proportion of individuals without a disease who have the absence of disease correctly identified by the study test (i.e. the study test is negative)

Staging

Clinical description of the size and spread of a patient’s tumour, fitting into internationally agreed categories

Stem cells

Biological cells that can self‐renew and can differentiate into specialised cells; stem cells contribute to maintaining and protecting the skin and allowing hair regrowth

Subclinical (disease)

Disease that is usually asymptomatic and not easily observable, e.g. by clinical or physical examination

Systemic treatment

Treatment, usually given by mouth or by injection, that reaches and affects cancer cells throughout the body rather than targeting one specific area

Ultrasound

A type of scan in which high‐frequency sound waves are used to outline a part of the body

Classification

Criteria^a

T

Tis

Carcinoma in situ

T1

Tumor ≤ 2 cm at largest horizontal width and < 2 high‐risk features

T2

Tumor > 2 cm at largest horizontal width or any size with ≥ 2 high‐risk features

T3

Infiltration of facial and cranial bones

T4

Infiltration of skeletal bone or skull base

N

N0

No regional lymph node metastases

N1

Solitary, ipsilateral lymph node metastasis, maximum diameter ≤ 3 cm

N2a

Solitary, ipsilateral lymph node metastasis, maximum diameter > 3 cm to max. 6 cm

N2b

Multiple, ipsilateral lymph node metastases, all with a maximum diameter ≤ 6 cm

N2c

Multiple, bilateral or contralateral lymph node metastases, all with a maximum diameter ≤ 6 cm

N3

Lymph node metastasis, diameter > 6 cm

M

M0

No distant metastases

M1

Distant metastases

Classification

Criteria ^a

Tis

Carcinoma in situ

T1

0 risk factors

T2a

1 risk factor

T2b

2 to 3 risk factors

T3

4 risk factors or bone invasion

Item

Response (delete as required)

PARTICIPANT SELECTION (1) ‐ RISK OF BIAS

1) Was a consecutive or random sample of participants or images enrolled?

Yes ‐ if paper states consecutive or random

No – if paper describes other method of sampling

Unclear – if participant sampling not described

2) Was a case‐control design avoided?

Yes ‐ if consecutive or random or case‐control design clearly not used

No – if study described as case‐control or describes sampling specific numbers of participants with particular diagnoses

Unclear – if not described

3) Did the study avoid inappropriate exclusions, e.g. needs examples of inappropriate exclusions in this context – for both melanoma and for cutaneous squamous cell carcinoma (cSCC) staging?

Yes ‐ if inappropriate exclusions were avoided

No – if lesions were excluded that might affect test accuracy, e.g. indeterminate results or where disagreement between evaluators was observed

Unclear – if not clearly reported

4) For between‐person comparative (BPC) studies only (i.e. allocating different tests to different study participants such as randomised controlled trials (RCTs)):

• a) were the same participant selection criteria used for those allocated to each test?

Yes ‐ if same selection criteria were used for each index test

No – if different selection criteria were used for each index test

Unclear – if selection criteria per test were not described

N/A – if only one index test was evaluated or all participants received all tests

• b) was the potential for biased allocation between tests avoided through adequate generation of a randomised sequence?

Yes ‐ if adequate randomisation procedures are described

No – if inadequate randomisation procedures are described

Unclear – if the method of allocation to groups is not described (a description of ‘random’ or ‘randomised’ is insufficient)

N/A – if only one index test was evaluated or all participants received all tests

• c) was the potential for biased allocation between tests avoided through concealment of allocation prior to assignment?

Yes ‐ if appropriate methods of allocation concealment are described

No – if appropriate methods of allocation concealment are not described

Unclear – if the method of allocation concealment is not described (sufficient detail to allow a definite judgement is required)

N/A – if only one index test was evaluated

Could the selection of participants have introduced bias?

v FOR NON‐COMPARATIVE (NC) STUDIES

If answers to all of questions 1) and 2) and 3) was ‘Yes’:

Risk is Low

If answers to any one of questions 1) or 2) or 3) was ‘No’:

Risk is High

If answers to any one of questions 1) or 2) or 3) was ‘Unclear’:

Risk Unclear

v FOR BETWEEN‐PERSON COMPARATIVE STUDIES

If answers to all of questions 1) and 2) and 3) and 4) was ‘Yes’:

Risk is Low

If answers to any one of questions 1) or 2) or 3) or 4) was ‘No’:

Risk is High

If answers to any one of questions 1) or 2) or 3) or 4) was ‘Unclear’:

Risk Unclear

PARTICIPANT SELECTION (1) ‐ CONCERNS REGARDING APPLICABILITY

For sentinel lymph node biopsy and imaging tests:

1) Does the study report results for participants unselected by stage of disease or site of primary lesion, i.e. the study does not focus solely on those with a particular stage of disease such as AJCC I or melanoma <=1 mm in thickness?

Yes ‐ if an unrestricted group of participants have been included

No ‐ if a selected group of study participants have been included, e.g. those with clinical stage I disease or only those with thin melanoma

Unclear – if insufficient details are provided to determine the spectrum of included participants

2) Did the study report data on a per‐patient rather than per‐lesion basis?

Yes – if a per‐patient analysis was reported

No – if a per‐lesion analysis only was reported

Unclear – if it is not possible to assess whether data are presented on a per‐patient or per‐lesion basis

For imaging tests only:

3) Does the study focus primarily on participants undergoing primary staging or those undergoing staging for disease recurrence?

Yes ‐ if at least 80% of study participants are undergoing primary staging following diagnosis of a primary cutaneous melanoma or staging of recurrence

No ‐ if less than 80% of study participants are undergoing primary staging following diagnosis of a cutaneous melanoma or staging of recurrence

Unclear – if insufficient details are provided to determine the proportion of patients undergoing primary staging versus those undergoing staging of recurrence

Is there concern that the included participants do not match the review question?

If the answer to question 1) or 2) (and 3)) was ‘Yes’:

Concern is Low

If the answer to question 1) or 2) (and 3)) was ‘No’:

Concern is High

If the answer to question 1) or 2) (and 3)) was ‘Unclear’:

Concern is Unclear

INDEX TEST (2) ‐ RISK OF BIAS (to be completed per test evaluated)

1) Was the index test or testing strategy result interpreted without knowledge of the results of the reference standard?

Yes ‐ if index test described as interpreted without knowledge of reference standard result, or for prospective studies, if index test is always conducted and interpreted prior to the reference standard

No – if index test described as interpreted in knowledge of reference standard result

Unclear – if index test blinding is not described

2) Was the diagnostic threshold at which the test was considered positive prespecified?

Yes ‐ if threshold was prespecified (i.e. prior to analysing study results)

No ‐ if threshold was not prespecified

Unclear ‐ if not possible to tell whether or not diagnostic threshold was prespecified

For imaging tests only:

3) For studies reporting the accuracy of multiple diagnostic thresholds (tumour characteristic or parameter) for the same index test, was each threshold interpreted without knowledge of the results of the others?

Yes ‐ if thresholds were selected prospectively and each was interpreted by a different reader, or if study implements a retrospective (or no) cutoff

No ‐ if study uses prospective threshold and report states reported by same reader

Unclear ‐ if no mention of number of readers for each threshold or if pre‐specification of threshold not reported

N/A ‐ multiple diagnostic thresholds not reported for the same index test

4) For within‐person comparisons (WPC) of index tests or testing strategies (i.e. > 1 index test applied per participant), was each index test result interpreted without knowledge of the results of other index tests or testing strategies?

Yes ‐ if all index tests were described as interpreted without knowledge of the results of the others

No ‐ if the index tests were described as interpreted in the knowledge of the results of the others

Unclear – if it is not possible to tell whether knowledge of other index tests could have influenced test interpretation

N/A – if only one index test was evaluated

Could the conduct or interpretation of the index test have introduced bias?

v FOR NC and BPC STUDIES item 3) / 4) to be added

If answers to questions 1) and 2) was ‘Yes’:

Risk is Low

If answers to either questions 1) or 2) was ‘No’:

Risk is High

If answers to either questions 1) or 2) was ‘Unclear’:

Risk is Unclear

v FOR WPC STUDIES

If answers to all questions 1), 2) for any index test and 3) was ‘Yes’:

Risk is Low

If answers to any one of questions 1) or 2) for any index test or 3) was ‘No’:

Risk is High

If answers to any one of questions 1) or 2) for any index test or 3) was ‘Unclear’:

Risk is Unclear

INDEX TEST (2) ‐ CONCERN ABOUT APPLICABILITY

1) Were thresholds or criteria for diagnosis reported in sufficient detail to allow replication?

This item applies equally to studies using objective and more subjective approaches to test interpretation. For SLNB studies, this requires description of the tracer threshold for identification of the SLN and the histological assessment.

Yes – if the criteria for diagnosis of the target disorder were reported in sufficient detail to allow replication

No – if the criteria for diagnosis of the target disorder were not reported in sufficient detail to allow replication

Unclear – if some but not sufficient information on criteria for diagnosis to allow replication were provided

2) Was the test interpretation carried out by an experienced examiner?

Yes – if the test was interpreted by an experienced examiner as defined in the review protocol

No – if the test was not interpreted by an experienced examiner (see above)

Unclear – if the experience of the examiner(s) was not reported in sufficient detail to judge or if examiners described as 'Expert' with no further detail given

Is there concern that the index test, its conduct, or interpretation differ from the review question?

If answers to questions 1) and 2) was ‘Yes’:

Concern is Low

If answers to questions 1) or 2) was ‘No’:

Concern is High

If answers to questions 1) or 2) was ‘Unclear’:

Concern is Unclear

REFERENCE STANDARD (3) ‐ RISK OF BIAS

1) Is the reference standard likely to correctly classify the target condition?

a) DISEASE POSITIVE ‐ One or more of:

‐ Histological confirmation of metastases following lymph node dissection (or SLNB or core biopsy for imaging studies)

‐ Clinical/radiological follow up to identify clinically detectable disease in a mapped nodal basin (SLNB studies)

‐ Clinical/radiological follow up to identify any metastases (imaging studies) subsequently confirmed on histology

Yes – if all disease positive participants underwent one of the listed reference standards

No – if a final diagnosis for any disease positive participant was reached without histopathology

Unclear – if the method of final diagnosis was not reported for any disease positive participant

b) DISEASE NEGATIVE ‐ One or more of:

‐ Histological confirmation of absence of disease in a mapped nodal basin following lymph node dissection (or following SLNB for imaging studies)

‐ Clinical/radiological follow up of test negative participants

Yes – if at least 90% of disease negative participants underwent one of the listed reference standards

No – if more than 10% of benign diagnoses were reached by concurrent imaging test

Unclear – if the method of final diagnosis was not reported for any participant with benign or disease negative diagnosis

2) Were the histology‐based reference standard results interpreted without knowledge of the results of the index test?

Yes – if the histopathologist was described as blinded to the index test result

No – if the histopathologist was described as having knowledge of the index test result

Unclear – if blinded histology interpretation was not clearly reported

3) Were the reference standard results based on patient follow‐up interpreted without knowledge of the results of the index test?

Yes – if the clinician or radiologist was described as blinded to the index test result

No – if the clinician or radiologist was described as having knowledge of the index test result

Unclear – if blinded interpretation was not clearly reported

Could the reference standard, its conduct, or its interpretation have introduced bias?

If answers to questions 1) and 2) and 3) was ‘Yes’:

Risk is Low

If answers to questions 1) or 2) or 3) was ‘No’:

Risk is High

If answers to questions 1) or 2) or 3) was ‘Unclear’:

Risk is Unclear

REFERENCE STANDARD (3) ‐ CONCERN ABOUT APPLICABILITY

1) Does the study use the same definition of disease positive as the primary review question or is it possible to fully disaggregate data such that data matching the review question can be extracted?

Yes – same definition of disease positive used, or patients can be disaggregated and regrouped according to review definition

No – some patients cannot be disaggregated

For SLNB review – disease positive includes participants with any nodal recurrence (not restricted to clinical recurrence in same nodal basin)

For imaging reviews – participants with nodal versus distant recurrences cannot be disaggregated

Unclear – definition of disease positive not clearly reported

For studies of imaging tests:

2) The result of another imaging test (without patient follow‐up to determine later emergence of disease) was not used as a reference standard

Yes – if imaging‐based diagnosis was not used as a reference standard for any participant

No – if imaging‐based diagnosis was used as a reference standard for any participant

Unclear – if not clearly reported

3) Item on observer experience could be included?

Is there concern that the target condition as defined by the reference standard does not match the review question?

If answers to all questions 1), 2) and 3) was ‘Yes’:

Concern is Low

If answers to any one of questions 1) or 2) or 3) was ‘No’:

Concern is High

If answers to any one of questions 1) or 2) or 3) was ‘Unclear’:

Concern is Unclear

***For teledermatology studies only:

If answers to questions 1) and 3) was ‘Yes’:

Concern is Low

If answers to questions 1) or 3) was ‘No’:

Concern is High

If answers to questions 1) or 3) was ‘Unclear’:

Concern is Unclear

FLOW AND TIMING (4): RISK OF BIAS

1) Was there an appropriate interval between index test and reference standard?

• a) For index test positive participants, was the interval between index test and histological reference standard <= 1 month?

Yes – if study reports <= 1 month between index and histological reference standard

No – if study reports > 1 month between index and histological reference standard

Unclear – if study does not report interval between index and histological reference standard

• b) If reference standard is clinical or imaging‐based follow up of index test negative participants, was there less than 6 months between application of index test(s) and first follow‐up visit?

Yes – if study reports a follow‐up visit within 6 months of application of the index test

No – if study reports the first follow‐up visit beyond 6 months of the index test

Unclear – if study does not report timing of follow‐up visits

2) Did all participants receive the same reference standard?

Yes – if all participants underwent the same reference standard

No – if more than one reference standard was used

Unclear – if not clearly reported

3) Were all participants included in the analysis?

Yes – if all participants were included in the analysis

No – if some participants were excluded from the analysis

Unclear – if not clearly reported

4) For WITHIN‐PERSON COMPARISONS (WPC) of index tests:

Was the interval between application of index tests <= 1 month?

Could the participant flow have introduced bias?

Yes – if study reports <= 1 month between index tests

No – if study reports > 1 month between index tests

Unclear – if study does not report interval between index tests

v FOR NON‐COMPARATIVE and BPC STUDIES

If answers to questions 1) and 2) and 3) was ‘Yes’:

Risk is Low

If answers to any one of questions 1) or 2) or 3) was ‘No’:

Risk is High

If answers to any one of questions 1) or 2) or 3) was ‘Unclear’:

Risk is Unclear

v FOR WITHIN‐PERSON COMPARATIVE STUDIES (WPC)

If answers to all questions 1), 2), 3), and 4) was ‘Yes’:

Risk is Low

If answers to any one of questions 1), 2), 3), or 4) was ‘No’:

Risk is High

If answers to any one of questions 1), 2), 3), or 4) was ‘Unclear’:

Risk is Unclear