Key points

Introduction

The clinical diagnosis of tumors on the curved surfaces of the face, around the eyes, and on the mucosal surfaces can be difficult, while biopsies and excisions can have functional and aesthetic consequences at these sites. A lower diagnostic accuracy and higher biopsy threshold at these sites could lead to delayed diagnosis of skin cancers that may be more difficult to manage.

Noninvasive imaging technologies have improved upon the accuracy of early diagnosis of skin cancers. However, acquisition of high-quality images with dermoscopy and with wide-probe reflectance confocal microscopy (WP-RCM, VivaScope 1500, CaliberID, Rochester, New York) have been hampered with technical difficulties in these curved, narrow, or relatively inaccessible surfaces. To this end, the newly introduced handheld reflectance confocal microscope (HH-RCM, Vivascope 3000, CaliberID) has a small probe, which allows rapid access to narrow surfaces. The use of the HH-RCM can potentially reduce the number of biopsies performed for benign lesions, while allowing earlier diagnosis of skin cancers, both melanoma and nonmelanoma skin cancers (NMSCs), on the face, eyes, and mucosal surfaces. Other potential applications are the use of HH-RCM for guiding management of skin cancers, such as RCM-guided excisions or laser ablation, and for monitoring response to nonsurgical treatments. This article discusses the technical parameters of the HH-RCM, as well as its advantages and limitations compared with the WP-RCM, and surveys the handful of studies focusing on HH-RCM.

Introduction

The clinical diagnosis of tumors on the curved surfaces of the face, around the eyes, and on the mucosal surfaces can be difficult, while biopsies and excisions can have functional and aesthetic consequences at these sites. A lower diagnostic accuracy and higher biopsy threshold at these sites could lead to delayed diagnosis of skin cancers that may be more difficult to manage.

Noninvasive imaging technologies have improved upon the accuracy of early diagnosis of skin cancers. However, acquisition of high-quality images with dermoscopy and with wide-probe reflectance confocal microscopy (WP-RCM, VivaScope 1500, CaliberID, Rochester, New York) have been hampered with technical difficulties in these curved, narrow, or relatively inaccessible surfaces. To this end, the newly introduced handheld reflectance confocal microscope (HH-RCM, Vivascope 3000, CaliberID) has a small probe, which allows rapid access to narrow surfaces. The use of the HH-RCM can potentially reduce the number of biopsies performed for benign lesions, while allowing earlier diagnosis of skin cancers, both melanoma and nonmelanoma skin cancers (NMSCs), on the face, eyes, and mucosal surfaces. Other potential applications are the use of HH-RCM for guiding management of skin cancers, such as RCM-guided excisions or laser ablation, and for monitoring response to nonsurgical treatments. This article discusses the technical parameters of the HH-RCM, as well as its advantages and limitations compared with the WP-RCM, and surveys the handful of studies focusing on HH-RCM.

Comparison of images acquisition by handheld reflectance confocal microscope and wide-probe reflectance confocal microscopy

The differences between WP-RCM and HH-RCM are summarized ( Table 1 ).

The traditional WP-RCM ( Fig. 1 A) uses an 830 nm laser to acquire images that are characterized by a lateral (horizontal) resolution of less than 1.25 μm and an axial (vertical) resolution of less than 5.0 μm at the center field of view, and a maximal imaging depth of about 250 μm. The WP-RCM images are acquired as single 500 × 500 μm ² optical sections, which can be stitched together via computer software to create a mosaic image along the X-Y axis with a field of view of up to 8 × 8 mm ² . An automated stack of images, acquired along the Z-axis, from the stratum corneum to the superficial dermis, can be obtained at the same location in the lesion. Video streaming of RCM images can also be recorded.

( A ) HH-RCM ( B ) Close-up of HH-RCM probe ( C ) WP-RCM ( D ) Close-up of WP-RCM. The differences between the WP-RCM and HH-RCM are summarized in Table 1 .

( Courtesy of CaliberID, Andover, MA; with permission.)

The HH-RCM ( Fig. 1 B) became commercially available in the United States in 2011. The handheld device also uses an 830 nm laser light source, and its images are characterized by lateral and axial resolution and maximal imaging depth that are comparable to that of the WP-RCM. The HH-RCM has 3 image acquisition modes: single optical sections, image stacks, and video recording. The main differences in acquisition from the WP-RCM are (1) HH-RCM acquires single optical sections that are 750 × 750 μm ² (compared to 500 × 500 μm ² for WP-RCM), and (2) the HH-RCM cannot acquire mosaic images (see Fig. 1 , Table 1 ).

Advantages and limitations of wide-probe reflectance confocal microscope

The WP-RCM has demonstrated high specificity and increased sensitivity in the diagnosis of melanoma and nonmelanoma skin cancers, compared with clinical and dermoscopic examination. Advantages of the WP-RCM include the wide field of view (enables the clinician to evaluate the entire tumor for the overall pattern, size of the lesion, and symmetry of structures and brightness) the presence of built-in navigation guided by dermoscopy, and the systematic navigation and orientation provided by tissue fixation.

However, the WP-RCM requires affixation to flat skin surface of about 2 cm in diameter to obtain high-quality images. If adhesion to the skin is not firm and steady, air bubbles may block the path of RCM laser light and obscure tissue imaging, and skin folding and motion artifacts may reduce image quality and seamlessness. The authors often encounter such imaging technical difficulties when attempting to image lesions on the curved and narrow surfaces of the face (eg, the nose or ear lobe). In other locations, such as around the eyes or at mucosal surfaces, imaging with WP-RCM is inaccessible. This has been a limitation to the use of RCM, since a majority of NMSCs occurs on face.

Additionally, setting up the bulky imaging apparatus and acquiring the images with the WP-RCM are also time consuming, particularly on the face, taking at least 15 minutes. This may pose a barrier for adoption of RCM in the busy dermatologic practices.

Advantages and limitations of handheld reflectance confocal microscope

The HH-RCM has advantages. It is well suited for curved and narrow surfaces because of its small probe, whose tip measures 5 mm in diameter. The HH-RCM allows for imaging of lesions in less accessible sites, such as the medial canthus of the eye or oral or genital mucosa.

The HH-RCM also acquires images faster than the WP-RCM, is lighter in weight, and is relatively easy to handle after some initial practice. Although WP-RCM requires skin preparation by the application of a disposable adhesive window, the HH-RCM can be applied to skin directly with oil immersion fluid, making imaging faster and less cumbersome. As such, it also allows for rapid examination of multiple lesions of concern on the patient. Finally, most of the previously published diagnostic algorithms, delineated for the WP-RCM, can be applied to HH-RCM, since most criteria can be evaluated on optical sections and do not require mosaic image acquisition. The RCM optical sections obtained by both devices are similar in quality and appearance.

The HH-RCM also has inherent limitations. Its optical sections are 1 × 1 mm ² in areas that only allow partial optical sampling of skin lesions. This is in contrast to the WP-RCM, in which adjacent individual optical sections can be pieced together to form large mosaic images up to 8 × 8 mm ² . The limited field of view of HH-RCM may diminish the ability to distinguish between benign melanocytic nevi and melanomas. In the evaluation of melanocytic lesions, the lesion should be viewed as a whole in order to adequately assess the symmetry, circumscription, overall pattern, and RCM features.

That said, when the differential diagnosis is between unrelated pathologic entities, identifying the cellular morphology of the lesion may suffice for diagnosis. For example, HH-RCM can allow distinction between basal cell carcinoma (BCC) from intradermal nevi; similarly, if dendritic pagetoid melanocytes are noted in an HH-RCM stack from the face, the likely diagnosis of a lentigo maligna can be established over a solar lentigo, pigmented actinic keratosis, or lichen planus-like keratosis.

Another disadvantage of the current HH-RCM is that navigation is only guided by the clinical eye, and not by the dermoscopic image of the lesion, nor by the RCM software. In contrast, the WP-RCM has a built-in navigation system, which can be guided by the dermoscopic image; this simplifies orientation and identification of suspicious foci within a lesion.