Clinical Review

Reflectance Confocal Microscopy: An Overview of Technology and Advances in Telepathology

Cutis. 2015 May;95(5):E39-E46

References

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Reticular Dermis

Further below the stratum corneum (100–350 μm), similar highly reflective collagen fibers and bundles are present, with diameters of 1 to 5 μm and 5 to 25 μm, respectively.^2,3

Adnexal Structures

The limitation of imaging depth by wavelength and intensity restricts visualization to upper portions of sebaceous glands, sweat ducts, and hair shafts within hair follicles.^2,32

Clinical Applications of RCM

Diagnosis of Lesions

Since the inception of RCM, confocal-based diagnostic criteria have been established for allergic and irritant contact dermatitis,^4,5 malignant melanoma,⁶ BCC,⁷ actinic keratosis,⁸ and squamous cell carcinoma.⁸ Much of the research has focused on skin cancers, including the differentiation of benign and malignant skin lesions,^34-38 to help improve clinical diagnostic accuracy, reducing the number of biopsies of benign lesions.^{10,11,28,35,38} In 2008 Guitera et al³⁹ used RCM and dermoscopy to detect melanoma with a sensitivity of 98% and in 2012 determined that biopsies of benign nevi and lesions clinically suspicious for BCC could be reduced by as much as 68% in a series of 710 equivocal lesions.³⁵ In 2014, in a prospective study including more than 1000 patients, Pellacani et al³⁸ demonstrated that biopsies of equivocal benign lesions were reduced by more that 50%, and all of the melanomas and BCCs excised in the study were correctly detected by RCM interpretation. Additionally, in both studies, the sensitivity of the RCM interpretation for detecting BCC was 100%. Amelanotic melanoma can be diagnostically challenging because clinical and dermoscopic features often are nondescript. In 2001, Busam et al¹⁷ successfully used RCM for amelanotic melanoma detection and margin assessment. A subsequent study by Braga et al²⁴ positively demonstrated that RCM may aid in the detection and diagnosis of various solitary pink lesions.

Adjunct to Mohs Micrographic Surgery

When excisional biopsies are impractical, incisional biopsies may be performed, which may lead to sampling errors. Atypical lesions with poorly defined clinical borders dictates standard of care with surgical excision and microscopic evaluation of margins. For malignancies requiring treatment with Mohs micrographic surgery, further staging often is required. These limitations may be overcome with RCM. Early detection of amelanotic malignant melanoma with margin assessment has been successfully demonstrated.¹⁷ Curiel-Lewandroski et al¹⁶ reported 3 successful cases wherein RCM was used for diagnosis and monitoring of topical treatment, delineation of surgical margins, and guidance in tissue-sparing surgical excision with amelanotic melanoma, locally recurrent melanoma, and lentigo maligna melanoma, respectively. In 2013, Guitera et al⁴⁰ demonstrated that mapping lentigo maligna margins prior to Mohs surgery changed the surgical management of 73% of patients in a study that included 37 patients with clinically or dermoscopically visible lesions.

Monitoring Topical Treatment

Unlike conventional histology, RCM does not involve tissue destruction, allowing for longitudinal surveillance when treating a malignancy with topical therapy. In a 2003 case study, RCM was used to confirm a previously diagnosed BCC, map tumor periphery, visualize the inflammatory response to imiquimod cream 5%, and confirm posttreatment clearance. Reflectance confocal microscopy features were confirmed with biopsy before and after treatment, and clinical findings during treatment precisely correlated with RCM findings.¹⁸ A similar study the following year demonstrated the efficacy of imiquimod cream 5% as an adjunct to BCC treatment by reducing or eliminating the lesion size prior to Mohs micrographic surgery, thereby decreasing the resulting surgical defect.¹⁹ To date, several studies have been performed by physicians throughout the world that have used RCM to monitor therapeutic outcomes of topically applied treatments such as imiquimod and hyaluronic acid as well as photodynamic therapy.^41-43

A Clinical Tool

In vivo reflectance confocal microscopy, previously used only in the research setting, is now being used as a clinical tool for the evaluation of lesions suspicious for skin cancer by several academic centers and private practices throughout the United States. With clearance from the US Food and Drug Administration, physicians can use the device clinically for in vivo microscopic examination of skin lesions. The telepathology network allows for images to be acquired by a trained technician in a clinician’s office and then to be evaluated remotely by a diagnostic reader. The clinician can receive a diagnosis in as little as 30 minutes. The potential to noninvasively monitor tumor response to topical therapies, to delineate tumor margins prior to surgery, and to monitor lesions over time is an attractive option to patients.

The technology and telepathology network of RCM continues to be developed as diagnostic criteria are established and diagnostic readers are trained; however, diagnostic confocal features of various lesions have yet to be described, refined, or validated. Consequently, an extensive library of reference images has not yet been constructed.