Melanoma has one of the fastest rising incidence rates of any cancer. It accounts
for a small percentage of skin cancer cases but is responsible for the majority of
skin cancer deaths. Early detection and treatment is key to improving survival; however,
anxiety around missing early cases needs to be balanced against appropriate levels
of referral and excision of benign lesions. Used in conjunction with clinical or dermoscopic
suspicion of malignancy, or both, reflectance confocal microscopy (RCM) may reduce
unnecessary excisions without missing melanoma cases. To determine the diagnostic
accuracy of reflectance confocal microscopy for the detection of cutaneous invasive
melanoma and atypical intraepidermal melanocytic variants in adults with any lesion
suspicious for melanoma and lesions that are difficult to diagnose, and to compare
its accuracy with that of dermoscopy. We undertook a comprehensive search of the following
databases from inception up to August 2016: Cochrane Central Register of Controlled
Trials; MEDLINE; Embase; and seven other databases. We studied reference lists and
published systematic review articles. Studies of any design that evaluated RCM alone,
or RCM in comparison to dermoscopy, in adults with lesions suspicious for melanoma
or atypical intraepidermal melanocytic variants, compared with a reference standard
of either 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). We contacted authors of included studies where information related
to the target condition or diagnostic threshold were missing. We estimated summary
sensitivities and specificities per algorithm and threshold using the bivariate hierarchical
model. To compare RCM with dermoscopy, we grouped studies by population (defined by
difficulty of lesion diagnosis) and combined data using hierarchical summary receiver
operating characteristic (SROC) methods. Analysis of studies allowing direct comparison
between tests was undertaken. To facilitate interpretation of results, we computed
values of specificity at the point on the SROC curve with 90% sensitivity as this
value lies within the estimates for the majority of analyses. We investigated the
impact of using a purposely developed RCM algorithm and in‐person test interpretation.
The search identified 18 publications reporting on 19 study cohorts with 2838 lesions
(including 658 with melanoma), which provided 67 datasets for RCM and seven for dermoscopy.
Studies were generally at high or unclear risk of bias across almost all domains and
of high or unclear concern regarding applicability of the evidence. Selective participant
recruitment, lack of blinding of the reference test to the RCM result, and differential
verification were particularly problematic. Studies may not be representative of populations
eligible for RCM, and test interpretation was often undertaken remotely from the patient
and blinded to clinical information. Meta‐analysis found RCM to be more accurate than
dermoscopy in studies of participants with any lesion suspicious for melanoma and
in participants with lesions that were more difficult to diagnose (equivocal lesion
populations). Assuming a fixed sensitivity of 90% for both tests, specificities were
82% for RCM and 42% for dermoscopy for any lesion suspicious for melanoma (9 RCM datasets;
1452 lesions and 370 melanomas). For a hypothetical population of 1000 lesions at
the median observed melanoma prevalence of 30%, this equated to a reduction in unnecessary
excisions with RCM of 280 compared to dermoscopy, with 30 melanomas missed by both
tests. For studies in equivocal lesions, specificities of 86% would be observed for
RCM and 49% for dermoscopy (7 RCM datasets; 1177 lesions and 180 melanomas). At the
median observed melanoma prevalence of 20%, this reduced unnecessary excisions by
296 with RCM compared with dermoscopy, with 20 melanomas missed by both tests. Across
all populations, algorithms and thresholds assessed, the sensitivity and specificity
of the Pellacani RCM score at a threshold of three or greater were estimated at 92%
(95% confidence interval (CI) 87 to 95) for RCM and 72% (95% CI 62 to 81) for dermoscopy.
RCM may have a potential role in clinical practice, particularly for the assessment
of lesions that are difficult to diagnose using visual inspection and dermoscopy alone,
where the evidence suggests that RCM may be both more sensitive and specific in comparison
to dermoscopy. Given the paucity of data to allow comparison with dermoscopy, the
results presented require further confirmation in prospective studies comparing RCM
with dermoscopy in a real‐world setting in a representative population. What is the
diagnostic accuracy of the imaging test reflectance confocal microscopy (RCM) for
the detection of melanoma in adults? What was the aim of the review? The aim of this
Cochrane Review was to find out how accurate reflectance confocal microscopy (RCM)
was on its own and used in addition to dermoscopy compared to dermoscopy alone for
diagnosing melanoma. Review authors in Cochrane included 18 publications to answer
this question. Why is improving the diagnosis of melanoma important? Melanoma is one
of the most dangerous forms of skin cancer. Not recognising a melanoma when it is
present (called a false negative test result) delays surgery to remove it, risking
cancer spreading to other parts in the body and possibly death. Diagnosing a skin
lesion as a melanoma when it is not present (called a false positive result) may result
in unnecessary surgery, further investigations, and patient anxiety. What did the
review study? Microscopic techniques are used by skin cancer specialists to allow
a more detailed, magnified examination of suspicious skin lesions than can be achieved
using the naked eye alone. Currently, dermoscopy (a handheld device using natural
light) can be used as part of the clinical examination of suspicious skin lesions.
RCM is a new microscopic technique (a handheld device or static unit using infrared
light) that can visualise deeper layers of the skin compared to dermoscopy. Both techniques
are painless procedures, but RCM is more expensive, time consuming, and requires additional
training. Dermoscopy can be used by general practitioners whereas RCM is likely to
only be used by secondary care specialists in people who have been referred with a
lesion suspicious for skin cancer. We sought to find out whether RCM should be used
instead of, or in addition to, dermoscopy, to diagnose melanoma in any suspicious
skin lesion or only in particularly difficult to diagnose skin lesions. What were
the main results of the review? The review included 18 publications reporting data
for 19 groups of participants with lesions suspected of melanoma. The main results
were based on 16 of the 19 datasets (sets of information and results). The review
included nine datasets with 1452 lesions in people with any suspicious skin lesion,
three of which compared RCM to dermoscopy. The results suggested that in 1000 lesions,
of which 300 (30%) actually are melanoma: ‐ an estimated 396 would have an RCM result
indicating melanoma was present, and of these, 126 (32%) would not be melanoma (false
positive results);
‐ in the same group of 1000 lesions, dermoscopy would produce 406 false positive results,
meaning RCM would avoid unnecessary surgery in 280 lesions compared to dermoscopy;
‐ of the 604 lesions with an RCM result indicating that melanoma was not present (and
324 lesions with a dermoscopy result indicating that melanoma was not present), 30
would actually be melanoma (false negative results). This equated to a false negative
rate of 5% for RCM and 9% for dermoscopy. The review also included seven datasets
with 1177 lesions in people with particularly difficult to diagnose skin lesions,
three of which compared RCM to dermoscopy. The results suggested that if skin specialists
used RCM in a group of 1000 lesions, of which 200 (20%) were actually melanoma: ‐
an estimated 292 would have an RCM result indicating melanoma was present, and of
these, 112 (38%) would not be melanoma (false positive results);
‐ in the same group of 1000 lesions, dermoscopy would produce 408 false positive results,
meaning RCM would avoid unnecessary surgery in 296 lesions compared to dermoscopy;
‐ of the 708 lesions with an RCM result indicating that melanoma was not present (and
412 lesions with a dermoscopy result indicating that melanoma was not present), 20
would actually have melanoma (false negative results). This equates to a false negative
rate of 3% for RCM and 5% for dermoscopy. How reliable were the results of the studies
of this review? In all included studies, the diagnosis of melanoma was made by lesion
biopsy (RCM/dermoscopy positive) (a biopsy involves taking a sample of body cells
and examining them under a microscope), and the absence of melanoma was confirmed
by biopsy or by follow‐up over time to make sure the skin lesion remained negative
for melanoma (RCM/dermoscopy negative)*. This is likely to have been a reliable method
for deciding whether people really had melanoma. Only a small number of studies compared
the accuracy of dermoscopy and RCM. Most were conducted by specialist research teams
with high levels of experience with RCM. Therefore, RCM may have appeared more accurate
than it actually was. Participants in the nine studies of any suspicious lesion may
have had very obvious disease compared to that seen in practice leading to a lower
number of false positive results than would actually occur. It is not possible to
recommend a definition of a positive RCM test that will reliably produce the results
presented here due to differences between studies. Who do the results of this review
apply to? Eleven studies were undertaken in Europe (61%), with the remainder undertaken
in Oceania, North America, or more than one continent. Mean age ranged from 39 to
54.7 years. The percentage of people with melanoma ranged between 1.9% and 41.5% (a
median (midpoint reading) of 19% for difficult to diagnose skin lesions and 32% for
any suspicious lesion). The majority of studies only included people with certain
types of skin lesion. In many studies, it was not clear what tests participants had
received before RCM. What are the implications of this review? RCM appears to be an
accurate test for identifying melanoma, and it may reduce the number of people receiving
unnecessary surgery by up to three‐quarters compared to dermoscopy. There is considerable
variation and uncertainty in results and in study conduct, reducing the reliability
of findings. Use of RCM may be of most benefit in people with particularly difficult
to diagnose lesions rather than people with any lesion suspicious for melanoma. Further
research comparing RCM and dermoscopy in well described groups of people with difficult
to diagnose skin lesions is needed. How up‐to‐date is this review? The review authors
searched for and used studies published up to August 2016. *In these studies, biopsy
or clinical follow‐up were the reference standards (means of establishing final diagnoses).