Reflectance Confocal Microscopy Allows in Vivo Real-time Noninvasive Assessment of the Outcome of Methyl Aminolaevulinate Photodynamic Therapy of Basal Cell Carcinoma

M. Venturini; R. Sala; S. Gonzàlez; P.G. Calzavara-Pinton


The British Journal of Dermatology. 2013;168(1):99-105. 

In This Article

Abstract and Introduction


Background Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is an approved noninvasive treatment option for basal cell carcinoma (BCC). In vivo reflectance confocal microscopy (RCM) is a noninvasive imaging technique that has proved useful for in vivo real-time cytomorphological analysis of BCC cells infiltrating the epidermis.

Objectives To investigate the use of in vivo RCM to assess the persistence of BCC cells surviving MAL-PDT.

Methods In vivo RCM images of 20 biopsy-proven BCCs were taken before patients underwent a treatment cycle with MAL-PDT. Follow-up after 3 months was performed using clinical examination, RCM and conventional dermoscopy. Treated areas also underwent a targeted 3-mm punch biopsy for standard haematoxylin and eosin histology stain to establish the clinical and instrumental correlation of the treatment outcome.

Results Three months after PDT, clinical examination established that two out of 20 BCCs were persistent; dermoscopy found three out of 20 residual BCCs, but RCM showed that one of these lesions was a false positive, and showed persistent BCC foci in five out of 20 lesions. Histological analysis of targeted biopsies confirmed these results.

Conclusions RCM provided noninvasive, early detection of incipient recurrences of BCC after MAL-PDT. RCM findings steered targeted biopsies and surgical removal, or a new MAL-PDT, of these subclinical recurrences with minimal invasiveness.


Basal cell carcinoma (BCC) is the most common skin tumour in humans, although differences of incidences between phototypes do exist. In the U.S.A. the incidence rate of BCC is estimated to be 1 million cases each year, and increasing.[1]

Although surgery is still considered the 'gold standard' treatment for BCC, a few noninvasive treatment approaches are available to treat superficial BCCs and thin nodular BCCs (< 2 mm in depth). Among them, topical photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) has proven to be as effective as surgery, but with better cosmetic results.[2] The clinical response is generally assessed during follow-up visits by visual inspection, sometimes helped by dermoscopy. If persistent foci are noted, the lesion is removed surgically or another MAL-PDT session is prescribed. However, if a recurrence is seen when the tumour has grown enough to be diagnosed clinically, or if one or more biopsies is needed, the major clinical advantages of PDT, which are lack of invasiveness and optical cosmetic results, are lost. Therefore, diagnostic techniques that enable the imaging of recurrences at subclinical stages may allow tumours to be surgically removed, or retreated with MAL-PDT at an initial phase of development, minimizing the patient's discomfort and maximizing the chance of maintaining an optimal cosmetic result.

In vivo reflectance confocal microscopy (RCM) is a noninvasive in vivo technique for real-time imaging of the epidermis and superficial dermis[3] that has been previously reported to facilitate the in vivo evaluation of BCC, with high sensitivity (from 83·9% to 91·6%) and specificity (from 95·7% to 97%).[4–20]

The aim of this study was to investigate the use of in vivo RCM to assess the response of BCC treated with MAL-PDT.