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. 2018 Dec 4;12(12):CD013188.
doi: 10.1002/14651858.CD013188.

High-frequency ultrasound for diagnosing skin cancer in adults

Jacqueline Dinnes  1 , Jeffrey Bamber, Naomi Chuchu, Susan E Bayliss, Yemisi Takwoingi, Clare Davenport, Kathie Godfrey, Colette O'Sullivan, Rubeta N Matin, Jonathan J Deeks, Hywel C Williams; Cochrane Skin Cancer Diagnostic Test Accuracy Group
Affiliations

High-frequency ultrasound for diagnosing skin cancer in adults

Jacqueline Dinnes et al. Cochrane Database Syst Rev. .

Abstract

Background: Early, accurate detection of all skin cancer types is essential to guide appropriate management and to improve morbidity and survival. Melanoma and squamous cell carcinoma (SCC) are high-risk skin cancers with the potential to metastasise and ultimately lead to death, whereas basal cell carcinoma (BCC) is usually localised, with potential to infiltrate and damage surrounding tissue. Anxiety around missing early curable cases needs to be balanced against inappropriate referral and unnecessary excision of benign lesions. Ultrasound is a non-invasive imaging technique that relies on the measurement of sound wave reflections from the tissues of the body. At lower frequencies, the deeper structures of the body such as the internal organs can be visualised, while high-frequency ultrasound (HFUS) with transducer frequencies of 20 MHz or more has a much lower depth of tissue penetration but produces a higher resolution image of tissues and structures closer to the skin surface. Used in conjunction with clinical and/or dermoscopic examination of suspected skin cancer, HFUS may offer additional diagnostic information compared to other technologies.

Objectives: To assess the diagnostic accuracy of HFUS to assist in the diagnosis of a) cutaneous invasive melanoma and atypical intraepidermal melanocytic variants, b) cutaneous squamous cell carcinoma (cSCC), and c) basal cell carcinoma (BCC) in adults.

Search methods: We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists as well as published systematic review articles.

Selection criteria: Studies evaluating HFUS (20 MHz or more) in adults with lesions suspicious for melanoma, cSCC or BCC versus a reference standard of histological confirmation or clinical follow-up.

Data collection and analysis: Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). Due to scarcity of data and the poor quality of studies, we did not undertake a meta-analysis for this review. For illustrative purposes, we plot estimates of sensitivity and specificity on coupled forest plots.

Main results: We included six studies, providing 29 datasets: 20 for diagnosis of melanoma (1125 lesions and 242 melanomas) and 9 for diagnosis of BCC (993 lesions and 119 BCCs). We did not identify any data relating to the diagnosis of cSCC.Studies were generally poorly reported, limiting judgements of methodological quality. Half the studies did not set out to establish test accuracy, and all should be considered preliminary evaluations of the potential usefulness of HFUS. There were particularly high concerns for applicability of findings due to selective study populations and data-driven thresholds for test positivity. Studies reporting qualitative assessments of HFUS images excluded up to 22% of lesions (including some melanomas) due to lack of visualisation in the test.Derived sensitivities for qualitative HFUS characteristics were at least 83% (95% CI 75% to 90%) for the detection of melanoma; the combination of three features (lesions appearing hypoechoic, homogenous and well defined) demonstrating 100% sensitivity in two studies (lower limits of the 95% CIs were 94% and 82%), with variable corresponding specificities of 33% (95% CI 20% to 48%) and 73% (95% CI 57% to 85%), respectively. Quantitative measurement of HFUS outputs in two studies enabled decision thresholds to be set to achieve 100% sensitivity; specificities were 93% (95% CI 77% to 99%) and 65% (95% CI 51% to 76%). It was not possible to make summary statements regarding HFUS accuracy for the diagnosis of BCC due to highly variable sensitivities and specificities.

Authors' conclusions: Insufficient data are available on the potential value of HFUS in the diagnosis of melanoma or BCC. Given the between-study heterogeneity, unclear to low methodological quality and limited volume of evidence, we cannot draw any implications for practice. The main value of the preliminary studies included may be in providing guidance on the possible components of new diagnostic rules for diagnosis of melanoma or BCC using HFUS that will require future evaluation. A prospective evaluation of HFUS added to visual inspection and dermoscopy alone in a standard healthcare setting, with a clearly defined and representative population of participants, would be required for a full and proper evaluation of accuracy.

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Conflict of interest statement

Jac Dinnes: none known. Jeff Bamber: J Bamber has been a member of the advisory board of Michelson Diagnostics and has received payment from Cancer Research UK and the International Breast Ultrasound School and Queen Mary University of London for lectures given. He has received book royalties from John Wiley and Sons, and acknowledges funding from the Engineering and Physical Sciences Research Council, the NIHR Biomedical Research Centre and the Royal Marsden NHS Foundation Trust and Institute of Cancer Research, and the Cancer Research UK Imaging Centre Grant to the Institute of Cancer Research. There was no involvement of grant funders or other sponsors in the study whatsoever. J Bamber is the first named inventor on a patent jointly held by his institution (The Institute of Cancer Research) and The University of Bern. The priority date was 26 July 2012. The PCT publication date was 30 January 2014. A brief description of the invention is as follows: "A method of ultrasound and photoacoustic imaging in which image clutter is reduced, thus improving image quality and penetration depth, by using a localised vibration to tag true signals so as to discriminate them from false signals which occur from sources outside of the imaged region." Naomi Chuchu: none known. Rubeta N Matin: "my institution received a grant for a Barco NV commercially sponsored study to evaluate digital dermoscopy in the skin cancer clinic. My institution also received Oxfordshire Health Services Research Charitable Funds for carrying out a study of feasibility of using the Skin Cancer Quality of Life Impact Tool (SCQOLIT) in non melanoma skin cancer. I have received royalties for the Oxford Handbook of Medical Dermatology (Oxford University Press) and payment from the UK Photopheresis Society for a lecture on cutaneous graft versus host disease (October 2017). I have received payment from Public Health England for the "Be Clear on Cancer" skin cancer report. I have no conflicts of interest to declare that directly relate to the publication of this work." Susan E Bayliss: none known. Yemisi Takwoingi: none known. Clare Davenport: none known. Kathie Godfrey: none known. Colette O'Sullivan: none known. Jonathan J Deeks: none known. Hywel C Williams: H Williams is director of the NIHR HTA Programme. HTA is part of the NIHR, which also supports the NIHR systematic reviews programme from which this work is funded.

Figures

1
1
Sample photographs of superficial spreading melanoma (left), BCC (centre), and cSCC (right). Copyright © 2012 Dr Rubeta Matin: reproduced with permission.
2
2
The principles of B‐mode ultrasound echographic imaging of the skin.
3
3
Modern laptop based DermaScan C (2D). Copyright © 2018 Cortex Technology ApS: reproduced with permission.
4
4
Illustrates the well defined margins, low level and homogenous internal echoes, lack of strong entry echo and lack of acoustic shadowing for melanoma (c. and d.) and contrasting image for BCC (a. and b.) (from Harland 2000, Copyright © 2000 John Wiley and Sons, reproduced with permission)
5
5
Current clinical pathway for people with skin lesions.
6
6
PRISMA flow diagram.
7
7
Risk of bias and applicability concerns graph: review authors' judgements about each domain presented as percentages across included studies
8
8
Risk of bias and applicability concerns summary: review authors' judgements about each domain for each included study
9
9
Forest plot of tests for differentiation of melanoma from other lesions using combinations of HFUS characteristics and quantitative measurements of HFUS outputs
10
10
Forest plot of tests for the differentiation of melanoma from other lesions using HFUS and Doppler US
11
11
Forest plot of tests for the differentiation of BCC from other lesion types using HFUS
1
1. Test
Melanoma ‐ hypoechoic.
2
2. Test
Melanoma ‐ hypoechoic and homogenous.
3
3. Test
Melanoma ‐ hypoechoic and sharp basal margins.
4
4. Test
Melanoma ‐ hypoechoic and sharp lateral margins.
5
5. Test
Melanoma ‐ hypoechoic, homogenous and well defined.
6
6. Test
Melanoma (melanoma vs benign naevi) ‐ hypoechoic, homogenous and well defined.
7
7. Test
Melanoma (melanoma vs seborrhoeic keratosis) ‐ dermal echogenicity ratio < 3.
8
8. Test
Melanoma (melanoma vs seborrhoeic keratosis) ‐ absence of entry echo line.
9
9. Test
Melanoma (melanoma vs seborrhoeic keratosis) ‐ dermal echogenicity ratio < 3 OR absence of entry echo line.
10
10. Test
Melanoma (melanoma vs seborrhoeic keratosis or benign naevi) ‐ absence of entry echo line.
11
11. Test
Melanoma ‐ reflex transmission image contrast/lesional backscatter image relative. Heterogeneity/entry echo image relative heterogeneity.
12
12. Test
Melanoma ‐ HFUS positive OR Doppler positive.
13
13. Test
Melanoma (melanoma vs benign naevi) ‐ HFUS positive OR Doppler positive.
14
14. Test
Melanoma ‐ HFUS positive AND Doppler positive.
15
15. Test
BCC ‐ hypoechoic.
16
16. Test
BCC ‐ hypoechoic and homogenous.
17
17. Test
BCC ‐ hypoechoic and well defined.
18
18. Test
BCC ‐ hypoechoic and sharp basal margins.
19
19. Test
BCC ‐ hypoechoic and sharp lateral margins.
20
20. Test
BCC ‐ hypoechoic, homogenous and well defined.
21
21. Test
BCC ‐ hypoechoic, heterogenous with irregular margins.
22
22. Test
BCC ‐ HFUS positive AND Doppler positive.
See this image and copyright information in PMC

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