Is Confocal Microscopy a Valuable Tool in Diagnosing Nodular Lesions?

A Study of 140 Cases

C. Longo; F. Farnetani; S. Ciardo; A.M. Cesinaro; E. Moscarella; G. Ponti; I. Zalaudek; G. Argenziano; G. Pellacani


The British Journal of Dermatology. 2013;169(1):58-67. 

In This Article

Abstract and Introduction


Background Nodular lesions pose diagnostic challenges because nodular melanoma may simulate all kinds of melanocytic and nonmelanocytic lesions. Reflectance confocal microscopy (RCM) is a novel technique that allows visualization of the skin at nearly histological resolution although limited laser depth penetration hampers visualization of the deep dermis.

Objectives We sought to assess whether the diagnostic accuracy of RCM was comparable to histopathology for the diagnosis of nodular lesions, and to identify possible limitations of this technique.

Methods We retrospectively evaluated 140 nodules by means of RCM while blinded from the histopathological diagnosis. At the end of the study the patient codes were broken and the evaluations were matched with histopathological diagnosis before performing statistical analysis.

Results The study consisted of 140 nodular lesions (23 'pure' nodular melanomas, nine melanoma metastases, 28 BCCs, six invasive SCCs, 32 naevi, 14 seborrhoeic keratoses, 17 dermatofibromas, five vascular lesions and six other lesions). RCM correctly diagnosed 121 of 140 lesions (86·4%); eight of 140 (5·7%) lesions revealed discordance between histopathology and confocal microscopy. Eight of the 140 (5·7%) cases were not evaluable by means of RCM due to the presence of ulceration or hyperkeratosis and three cases showed a nonspecific pattern. Interestingly, confocal microscopy reached a 96·5% sensitivity and 94·1% specificity (area under curve 0·970) (95% CI 0·924–1·015) (P < 0·001) for the diagnosis of melanoma.

Conclusions The study is retrospective and lesions were not included on the basis of their diagnostic difficulty. Despite the limited laser depth penetration of RCM, this imaging tool represents an effective instrument in diagnosing nodular lesions; however, for fully ulcerated lesions or when a marked hyperkeratosis is present, biopsy should always be performed. Prospective studies on difficult-to-diagnose nodules should be performed to analyse further the pros and cons of RCM in skin cancer diagnosis.


Reflectance confocal microscopy (RCM) is a relatively new imaging tool that provides horizontal scanning of the skin at nearly histological resolution.[1,2] It has been applied in several skin diseases and predominantly in skin oncology,[3–8] where it has been proven to increase the specificity of difficult-to-diagnose lesions.

Reflectance confocal microscopy uses a diode laser as a source of monochromatic and coherent light, which penetrates into the skin and illuminates a small point inside the tissue.[1] Then, the light is reflected, goes through a small pinhole and generates an image in the detector. The pinhole collects reflected light emanating only from the focal region (confocal); thus, light from out-of-focus planes is rejected at the pinhole. The contrast in RCM images relies on the differences in the refractive index of the tissue; therefore, structures with a higher refractive index (melanin, collagen and keratin) appear brighter in RCM. The deeper a skin section is the more laser power is needed to penetrate the skin. The laser power employed by RCM (near-infrared wavelength of 830 nm) causes no damage to tissue, but limits the imaging depth to 200 μm, which corresponds to the papillary dermis. Higher laser power would provide an increased signal and contrast but would be dangerous for the skin (higher temperature) and the resolution will be poor.

The limited laser penetration depth of the instrument has led to the assumption that nodular lesions with a prevailing dermal component are not suitable for RCM diagnosis, as an evaluation of the 'informative' dermal component is hampered. However, nodular lesions belonging to both melanocytic and nonmelanocytic tumours have been explored by means of RCM,[2,9,10] albeit extensive studies on this topic are still lacking.

The aim of our study is to elucidate the feasibility of RCM in diagnosing nodular lesions to define the role of this tool in this field in clinical practice.