Why is improving the diagnosis of skin cancer important?
There are several types of skin cancer. Melanoma is one of the most dangerous forms, so it is important to detect it early and remove it as soon as possible. Failure to recognise melanoma for what it is (known as a false negative test result) can delay treatment, risking the spread of melanoma to other organs in the body and possibly premature death. Other skin cancers, like cutaneous squamous cell carcinoma and basal cell carcinoma, are more localised. However, cutaneous squamous cell carcinoma can spread to other parts of the body, and basal cell carcinoma can cause disfigurement if left untreated. Diagnosing a harmless lesion (a mole or area of skin with an unusual appearance in comparison with the surrounding skin) as skin cancer (a false positive result) may result in unnecessary surgery and other tests that can cause stress and anxiety to the patient. Mistaking one skin cancer for another can lead to the wrong treatment or delays in effective treatment. Thus, the correct diagnosis is important.
What is the aim of the review?
We wanted to find out whether high-frequency ultrasound can help doctors diagnose skin cancer. We found six studies to try and answer this question. Five studies investigated the diagnosis of melanoma and three, basal cell carcinoma.
What was studied in the review?
A number of tools allow skin cancer specialists to examine the skin in more detail than by the naked eye alone. Most skin cancer specialists currently use a dermatoscope, which magnifies the skin lesion using a natural light. Ultrasound is another non-invasive technique that measures sound wave reflections from body tissues. High-frequency ultrasound can produce a good-quality image of structures closer to the skin surface. When used alongside a doctor's examination and dermoscopy, high-frequency ultrasound may help doctors make a more accurate diagnosis.
What are the main results of the review?
The review included six studies: five with 1125 skin lesions suspected of being melanoma, and three with 993 lesions suspected of being basal cell carcinoma. We did not find any studies on the diagnosis of cutaneous squamous cell carcinoma.
The included studies were small and too different from each other to allow reliable estimates of accuracy to be made for identifying melanoma or basal cell carcinoma. Half were not actually designed to establish test accuracy and all can be considered preliminary experiments on the potential value of high-frequency ultrasound. The main value of the studies may be in helping researchers to identify the best ways of interpreting high-frequency ultrasound for the diagnosis of melanoma or basal cell carcinoma for evaluation in future research studies.
How reliable are the results?
Study results are not very reliable when considered collectively. The small number and variability between studies reduces reliability, while all had important limitations. In particular, those taking part in the studies and the way in which the tests were used may not reflect real life situations. In all studies the final diagnosis was confirmed by biopsy. This is likely to have been a reliable method for deciding whether patients really had skin cancer*.
Who do the results of this review apply to?
Studies all took place in Europe, and only one reported participants' average age (55.3 years). The percentage of people with a final diagnosis of melanoma ranged from 14% to 58%, while 8% to 49% had basal cell carcinoma. It was not possible to tell whether doctors suspected skin cancer based on clinical examination alone or both clinical and dermoscopic examination.
What are the implications of this review?
At present, there is not enough good research to draw a conclusion on using high-frequency ultrasound for diagnosing skin cancers. The results of this review suggest that high-frequency ultrasound has potential to separate melanoma or basal cell carcinoma from some harmless types of lesions, but it is still unclear whether it can adequately distinguish these skin cancers from the full range of skin conditions that patients show their doctors in everyday practice. There is a need for more studies investigating high-frequency ultrasound alongside dermoscopy or other microscopic techniques (such as reflectance confocal microscopy) in people with suspicious skin lesions.
How up-to-date is this review?
The review authors searched for and used studies published up to August 2016.
*In these studies biopsy was the reference standard (means of establishing the final diagnosis).
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.
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.
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.
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.
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.
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.
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.