Lentigo maligna (LM) is an in situ form of melanoma that grows very slowly radially and eventually can progress into invasive lentigo maligna melanoma (LMM). The gold standard treatment for LM is wide local excision but surgery is not always feasible due to elderly age of the patients and location on cosmetically sensitive head and neck area. Alternative, non-surgical therapies have been investigated with varying results.
Basal cell carcinoma (BCC) is the most common skin cancer among whites in Western countries and approximately 7% of all BCCs contain melanin, being clinically pigmented. Pigmented BCCs may be difficult to distinguish from melanoma and other melanocytic tumours even for an experienced dermatologist.
The dissertation consists of three separate studies. Study I was a randomized double-blind trial intended to compare clinical efficacy, tolerability and cost- effectiveness of two photosensitizers, 5-aminolaevulinic acid nanoemulsion (BF-200 ALA) and methyl-5-aminolaevulinate (MAL) in daylight photodynamic therapy (DL-PDT) for AKs. Altogether 69 patients with 767 mild to moderate AKs were given a single DL-PDT treatment in a randomized split-face setting. In a follow-up of 12 months, BF-200 ALA was more effective than MAL, clearing 79.7% vs. 73.5% of all AKs. The tolerability of both treatments was very good, with no difference in pain, cosmetic outcome or patient preference, but BF-200 ALA caused more intense local skin reactions.
Study II was a prospective study intended to investigate the efficacy of ablative fractional laser (AFL)-assisted PDT in the treatment of LM. BF-200 ALA was used as a photosensitizer. Ten biopsy-verified LM lesions were treated with AFL-assisted PDT three times at two-week intervals. Four weeks after the last PDT treatment all LM lesions were surgically excised for histopathological evaluation. The complete histopathological clearance rate was seven out of ten lesions (70%). Some severe and unanticipated skin reactions occurred after PDT sessions.
Study III was a prospective diagnostic study piloting hyperspectral imaging (HSI) and convolutional neural network (CNN) for differential diagnosis of pigmented skin lesions. A total of 26 pigmented lesions were imaged with HSI in vivo and then surgically excised for histopathological evaluation. HSI images were divided into two halves, one of which was used for the training of the CNN and the other for the classification task. For two-class classifier (melanocytic tumours vs. pigmented BCCs) using majority of the pixels to predict the class of the lesion, we obtained high sensitivity of 100%, specificity of 90% and positive predictive value (PPV) of 94% for diagnosis of melanocytic tumours.
The results of this thesis permit the following conclusions: 1) BF-200 ALA is more effective than MAL in DL-PDT for mild to moderate AKs and is slightly more cost-effective than MAL. BF-200 ALA caused more intense local skin reactions, which could affect the tolerability of the treatment. 2) AFL-assisted PDT showed good efficacy of 70% for lentigo maligna in terms of histopathological clearance. It could be considered a minimally invasive alternative treatment for LM in cases where surgery is not an option. 3) a CNN classifier can accurately and pixel-wise differentiate melanocytic tumours from pigmented BCCs in hyperspectral images. A larger sample dataset with multiple tumour types and a separate training dataset is warranted in the future to confirm these preliminary results.
The doctoral dissertation of M.D. Janne Räsänen in the field of dermatology and allergology titled Novel Methods for the Treatment and Diagnosis of Skin Cancers and their Precursors will be publicly examined at the Faculty of Medicine and Health Technology of Tampere University at 12 o'clock on Friday 3 September, 2021. The venue is Arvo building auditorium F115, address: Arvo Ylpön katu 34. Professor Veli-Matti Kähäri from University of Turku will be the opponent while Professor Teea Salmi will act as the custos.
The event can be followed via remote connection
The dissertaion is available online at
http://urn.fi/URN:ISBN:978-952-03-2050-8
Photo: Maaria Nikunen