By Dr Maxton Bergin
Reflectance confocal microscopy (RCM), sometimes described as an optical biopsy, is most useful when a skin lesion remains diagnostically equivocal after clinical examination and dermoscopy, and when additional non-invasive information could reasonably change the decision between immediate biopsy and non-invasive management.
The central role of RCM is diagnostic. It provides high-resolution imaging of living skin without removing tissue, but it does not universally replace surgical biopsy or histopathology. Histopathology remains the definitive assessment when tissue diagnosis is clinically required.¹⁻⁴
For referrers, the practical question is not whether every uncertain lesion should undergo RCM. It is whether RCM is likely to add enough useful diagnostic information to alter management safely.
What is reflectance confocal microscopy?
Reflectance confocal microscopy is a non-invasive optical imaging technique that produces images of living skin at cellular resolution. A focused low-power laser is used to image the epidermis and superficial dermis in horizontal optical sections.¹˒⁴
RCM can visualise individual cells and microscopic architectural patterns without cutting the skin. This is why it is sometimes referred to as an optical biopsy. However, it cannot provide the complete histopathological information required for every lesion.¹˒⁴
In practice, RCM is an adjunct to clinical examination and dermoscopy. It is most valuable when these initial assessments narrow the differential diagnosis but do not provide sufficient confidence to decide whether biopsy is necessary.¹⁻³
When should a clinician consider referral?
Consider referral for confocal microscopy when a lesion remains clinically or dermoscopically equivocal, and the result is likely to influence whether immediate biopsy is required.
The following situations are commonly appropriate.
Equivocal pigmented lesions
RCM is particularly suited to pigmented lesions where clinical examination and dermoscopy leave meaningful uncertainty. These are lesions with one or more concerning features but without clear-cut evidence of melanoma or a confidently benign diagnosis.¹˒²
The best candidates are often lesions with low to moderate pre-test probability of malignancy, where a further diagnostic layer may safely improve confidence. RCM should not be used to delay biopsy for a lesion with strong clinical or dermoscopic features of melanoma.¹˒⁴
Diagnostic uncertainty after dermoscopy
Dermoscopy remains the core second-level assessment for suspicious lesions. However, some lesions remain difficult to classify after dermoscopy, especially when there are mixed, subtle or partially regressed structures.²˒⁵
In this setting, RCM may help identify cellular and architectural features that support a benign diagnosis or increase concern sufficiently to support biopsy.¹˒²˒⁵
Facial lesions and cosmetically sensitive sites
RCM can be particularly useful for selected lesions on the head and neck, including the face, nose, eyelids, lips and ears, where benign and malignant lesions may overlap clinically and where a surgical biopsy may leave a visible scar or affect delicate anatomy.⁶˒⁷
A large study examining clinical indications found RCM was most useful for lesions on the head and neck, lesions on chronically sun-damaged skin and lesions showing regression on dermoscopy.⁶
Difficult-to-classify lesions on sun-damaged skin
Chronically sun-damaged facial skin can create a challenging background of pigmentation, vascular change and irregular structures. This may make distinction between benign lentigines, pigmented actinic keratoses, lentigo maligna and other lesions more difficult.⁶˒⁷
RCM can provide additional diagnostic information in selected lesions on sun-damaged skin, particularly when clinical and dermoscopic assessment remain equivocal.⁶˒⁷
Selected suspected melanoma
RCM can provide useful additional information for selected lesions in which melanoma is considered but cannot be confidently diagnosed or excluded after clinical examination and dermoscopy.¹˒²˒⁵
This does not mean RCM should be used to defer biopsy in a lesion that is clinically highly suspicious for melanoma. Where clinical concern is high, immediate biopsy remains appropriate.¹˒⁴
Selected suspected basal cell carcinoma
RCM may also provide additional diagnostic information for selected suspected basal cell carcinomas, especially when clinical and dermoscopic findings are uncertain.⁸
A Cochrane review found potentially useful diagnostic performance in studies of equivocal basal cell carcinoma lesions, but also concluded that evidence for RCM in keratinocyte cancer diagnosis remained limited and should be interpreted carefully.⁸ RCM should therefore be considered as an adjunct in selected cases, not as a universal diagnostic replacement for biopsy.
Lesions with existing clinical or dermoscopic images
Existing photographs and dermoscopic images can improve the usefulness of an RCM assessment by documenting the lesion’s history and features before referral. They may help the reviewing clinician correlate the RCM findings with the lesion’s surface structures and clinical context.
Where available, include previous clinical photographs, dermoscopic images, lesion history and the specific diagnostic question in the referral.
When RCM may not be appropriate
RCM is not the right next step for every lesion. Referral may be less appropriate when:
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the lesion clearly requires immediate biopsy based on clinical or dermoscopic suspicion;
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the lesion is nodular, deeply infiltrative or likely to extend beyond the imaging depth of RCM;
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marked hyperkeratosis, crusting, ulceration or bleeding prevents adequate optical imaging;
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the lesion is on thick acral skin, such as the palms or soles, where the stratum corneum can limit imaging depth;
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histopathological assessment is required regardless of the RCM result;
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imaging would introduce an unnecessary delay to definitive investigation.¹˒⁴˒⁹
RCM is primarily limited to the epidermis and superficial dermis. Resolution decreases with depth, and the technique cannot reliably determine Breslow thickness.⁴˒⁹
A practical safeguard is to treat a discordance between clinical concern, dermoscopy and RCM as a reason for further evaluation, not reassurance. If the lesion remains concerning or uncertain, biopsy is appropriate.
RCM, dermoscopy and biopsy are complementary tools
RCM, dermoscopy and biopsy should not be viewed as competing tests.
A practical diagnostic sequence is:
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Clinical examination establishes lesion history, symptoms, morphology, risk factors and overall clinical context.
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Dermoscopy provides magnified assessment of pigment, vascular and structural patterns.
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RCM is considered when the lesion remains equivocal and the result could change the immediate management decision.
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Biopsy is performed when tissue diagnosis is necessary or uncertainty persists.¹⁻⁵
Not every lesion requires every step. The appropriate pathway depends on clinical suspicion, lesion morphology, anatomical location, dermoscopic findings, patient circumstances and whether RCM is likely to provide clinically useful additional information.
Can RCM reduce unnecessary biopsies?
In carefully selected equivocal lesions, RCM can improve diagnostic specificity and may reduce the number of benign lesions excised unnecessarily.¹˒²˒¹⁰
A randomised clinical trial of 3,165 patients found that adjunctive RCM reduced the number needed to excise by 43.4% compared with standard assessment. In practical terms, fewer lesions had to be removed to detect each melanoma, while aggressive melanomas present at baseline were identified.¹⁰
A Cochrane review found that, in equivocal lesion studies, RCM had higher specificity than dermoscopy while maintaining similar sensitivity. This suggests that RCM may help clinicians identify some benign lesions that would otherwise be removed, but it does not mean RCM is infallible or that biopsy can be avoided whenever RCM appears reassuring.¹
The clinical objective is better lesion selection for biopsy—not fewer biopsies at any cost. A biopsy that is clinically indicated should never be deferred simply to avoid a scar or procedure.
What happens after referral to Skintel?
Skintel is a diagnostic skin imaging service. It does not provide treatment for skin cancer.
Following referral, the lesion is assessed using the imaging modality or modalities considered appropriate for the diagnostic question. Where RCM is performed, the images are interpreted by an accredited skin cancer doctor alongside the available clinical and dermoscopic information.
A diagnostic report is prepared and returned to the referring clinician. The patient then returns to their GP, dermatologist, skin cancer doctor or other treating clinician for discussion of the result, biopsy where indicated, treatment and ongoing management.
A practical rule for referral
Consider RCM referral when all of the following apply:
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the lesion is diagnostically equivocal after clinical examination and dermoscopy;
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RCM is technically feasible for the lesion;
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additional cellular-level imaging has a reasonable likelihood of changing the decision between immediate biopsy and non-invasive management;
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referral will not delay clinically necessary tissue diagnosis.
Conversely, proceed directly to biopsy when a lesion is strongly suspicious, unsuitable for RCM, requires tissue information regardless of imaging, or remains uncertain after non-invasive assessment.
Frequently Asked Questions
When should you refer for confocal microscopy?
Refer for confocal microscopy when a lesion remains equivocal after clinical examination and dermoscopy, and when RCM is likely to change whether immediate biopsy is needed.¹˒² RCM is particularly useful for selected difficult-to-classify pigmented lesions, facial lesions and lesions on chronically sun-damaged skin.⁶˒⁷ It should not delay biopsy of a lesion that is strongly suspicious for melanoma or another skin cancer.
What lesions are suitable for confocal microscopy?
Suitable lesions are usually flat or only slightly raised lesions that can be imaged adequately at the epidermis and superficial dermis.¹˒⁴ RCM is commonly used for equivocal pigmented lesions and selected lesions on the head and neck or sun-damaged skin.⁶˒⁷ Nodular, heavily crusted, ulcerated, bleeding or hyperkeratotic lesions may be unsuitable.⁴˒⁹
Can confocal microscopy diagnose melanoma?
Confocal microscopy can provide additional diagnostic information for selected equivocal lesions and may support or increase concern for melanoma.¹˒² However, it is not a universal replacement for biopsy. If melanoma is strongly suspected clinically or dermoscopically, or if RCM findings remain concerning or uncertain, biopsy and histopathology are required.¹˒⁴
Can optical biopsy replace a skin biopsy?
No. Optical biopsy is a non-invasive imaging examination that can add detail without removing tissue, but it does not replace biopsy whenever histopathological assessment is clinically required.¹˒⁴ RCM cannot adequately assess every lesion, has limited imaging depth and cannot provide complete tumour staging information. Biopsy remains the definitive next step when clinical suspicion is high or uncertainty persists.
When should a suspicious mole be biopsied immediately?
A suspicious mole should be biopsied without unnecessary delay when clinical or dermoscopic features create strong concern for melanoma, when it is changing rapidly, bleeding, ulcerated, nodular or otherwise unsuitable for RCM.¹˒⁴ RCM is intended for selected diagnostically equivocal lesions, not for postponing biopsy when tissue diagnosis is clearly required.
How accurate is reflectance confocal microscopy?
Reflectance confocal microscopy can improve diagnostic accuracy in selected equivocal lesions, particularly when added to clinical examination and dermoscopy.¹˒² A systematic review reported pooled sensitivity of 93% and specificity of 76% for melanoma diagnosis in clinically equivocal lesions, although results vary across settings and depend on image quality and reader expertise.² RCM is therefore an adjunct, not a stand-alone guarantee.
Can RCM help avoid unnecessary biopsies?
Yes, RCM may help avoid some unnecessary biopsies in appropriately selected equivocal lesions by improving recognition of benign patterns.¹˒¹⁰ This does not mean that the aim is simply fewer biopsies. The aim is to biopsy lesions that require tissue diagnosis promptly while avoiding procedures that are unlikely to change care when non-invasive assessment provides sufficient reassurance.
Is confocal microscopy useful for facial lesions?
Yes, confocal microscopy can be especially helpful for selected equivocal lesions on the face and other cosmetically sensitive sites.⁶˒⁷ These areas often have sun damage that complicates dermoscopic assessment, and an unnecessary biopsy may leave a visible scar. RCM can add diagnostic information, but biopsy remains appropriate if the lesion is suspicious or cannot be confidently classified.
What happens during an optical biopsy?
During an optical biopsy, a small confocal imaging head is placed gently against the lesion to capture high-resolution images of the upper layers of living skin.¹˒⁴ The examination is non-invasive and does not involve needles, cutting or stitches. Images are interpreted alongside clinical and dermoscopic findings, and the referring clinician receives a report to guide the next management step.
How do I refer a patient for confocal microscopy?
Refer with a concise clinical history, lesion location, duration and evolution, relevant risk factors, the clinical and dermoscopic differential diagnosis, and the specific diagnostic question. Include high-quality clinical and dermoscopic images where available. This gives the imaging clinician the context needed to determine whether RCM is likely to be useful and to interpret images alongside the referral question.
Disclaimer
All information is general and not intended as a substitute for professional advice.
References
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Dinnes J, Bamber J, Chuchu N, et al. Reflectance confocal microscopy for diagnosing cutaneous melanoma in adults. Cochrane Database Syst Rev. 2018;12(12):CD013190. doi:10.1002/14651858.CD013190.pub2.
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Xiong YQ, Ma S, Li X, Zhong X, Duan C, Chen Q. Systematic review of diagnostic accuracy of reflectance confocal microscopy for melanoma diagnosis in patients with clinically equivocal skin lesions. Br J Dermatol. 2016;175(5):930-939. doi:10.1111/bjd.14850.
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Guitera P, Menzies SW. State of the art of reflectance confocal microscopy for melanoma diagnosis. J Am Acad Dermatol. 2020;83(6):1535-1545.
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Dickman AM, et al. Reflectance confocal microscopy: principles, basic terminology, clinical indications, limitations, and practical considerations. J Am Acad Dermatol. 2021;84(1):1-15.
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Waddell A, Star P, Guitera P. Advances in the use of reflectance confocal microscopy in melanoma. Melanoma Manag. 2018;5(1):MMT06. doi:10.2217/mmt-2018-0001.
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Pellacani G, Longo C, Malvehy J, et al. Clinical indications for use of reflectance confocal microscopy for skin cancer diagnosis. JAMA Dermatol. 2016;152(10):1097-1103.
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Guitera P, et al. Reflectance confocal microscopy in the diagnosis of facial pigmented lesions. Br J Dermatol. 2012;166(4):825-832.
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Dinnes J, Bamber J, Chuchu N, et al. Reflectance confocal microscopy for diagnosing keratinocyte skin cancers in adults. Cochrane Database Syst Rev. 2018;12(12):CD013191. doi:10.1002/14651858.CD013191.
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Rajadhyaksha M, Marghoob AA, Rossi A, et al. Introduction to reflectance confocal microscopy and its use in clinical practice. Dermatol Pract Concept. 2017;7(4):1-7.
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Pellacani G, Pampena R, Longo C, et al. Effect of reflectance confocal microscopy for suspect lesions on diagnostic accuracy in melanoma: a randomized clinical trial. JAMA Dermatol. 2022;158(7):754-762. doi:10.1001/jamadermatol.2022.1539.
