Operational classification of cutaneous squamous cell carcinomas based on unsupervised clustering of real cases by experts.

BACKGROUND: There is currently no staging system for cutaneous squamous cell carcinoma (cSCC) that is adapted to decision-making and universally used. Experts have unconscious ability to simplify the heterogeneity of clinical situations into a few relevant groups to drive their therapeutic decisions. Therefore, we have used unsupervised clustering of real cases by experts to generate an operational classification of cSCCs, an approach that was successful for basal cell carcinomas. OBJECTIVE: To generate a consensual and operational classification of cSCCs. METHOD: Unsupervised independent clustering of 248 cases of cSCCs considered difficult-to-treat. Eighteen international experts from different specialties classified these cases into what they considered homogeneous clusters useful for management, each with freedom regarding clustering criteria. Convergences and divergences between clustering were analysed using a similarity matrix, the K-mean approach and the average silhouette method. Mathematical modelling was used to look for the best consensual clustering. The operability of the derived classification was validated on 23 new practitioners. RESULTS: Despite the high heterogeneity of the clinical cases, a mathematical consensus was observed. It was best represented by a partition into five clusters, which appeared a posteriori to describe different clinical scenarios. Applicability of this classification was shown by a good concordance (94%) in the allocation of cases between the new practitioners and the 18 experts. An additional group of easy-to-treat cSCC was included, resulting in a six-group final classification: easy-to-treat/complex to treat due to tumour and/or patient characteristics/multiple/locally advanced/regional disease/visceral metastases. CONCLUSION: Given the methodology based on the convergence of unguided intuitive clustering of cases by experts, this new classification is relevant for clinical practice. It does not compete with staging systems, but they may complement each other, whether the objective is to select the best therapeutic approach in tumour boards or to design homogeneous groups for trials.

Surgery after sonidegib treatment achieves complete response in locally advanced basal cell carcinoma of the face.

Basal cell carcinoma accounts for 75% of skin cancers worldwide and is the most common malignancy in Caucasians. Since chronic ultraviolet exposure is the major risk factor for its development, sun-exposed areas such as the face are frequently affected. The gold-standard treatment is surgical excision. Radiotherapy may be considered in selected cases such as unresectable primary tumors. In some patients, when the risk of a significant functional/cosmetic deficit advises against both surgery and radiotherapy, target therapy (hedgehog pathway inhibitors) can be administered alone or in a neoadjuvant setting, to reduce the tumor size and make it eligible for surgery. Vismodegib as a neoadjuvant treatment before surgery has been investigated in a single, multicentre, open-label, phase II trial (VISMONEO); however, sonidegib has not yet been evaluated in this setting. We report the cases of two patients with locally advanced basal cell carcinoma of the face who achieved complete remission with sonidegib followed by a more limited surgical excision than would have been needed without target therapy.

Line-field confocal optical coherence tomography of cutaneous vascular lesions: Morphological assessment and histopathological correlations.

BACKGROUND: Cutaneous vascular lesions (VLs) are benign or malignant processes involving blood and/or lymphatic vessels, usually readily diagnosed with dermoscopy. However, cases showing unclear clinical/dermoscopic findings may require further investigations. Line-field confocal optical coherence tomography (LC-OCT) is a new, non-invasive imaging technique displaying high resolution and deep penetration. The aim of this study was to describe the LC-OCT features of the most common benign and malignant VLs and to correlate them with histopathological substrates. METHODS: Clinical, dermoscopic, LC-OCT and histopathological images of VLs were retrospectively collected. Detailed LC-OCT description and histopathological correlations were produced for different types of VLs. RESULTS: The study included 71 VLs belonging to 50 caucasian patients [31 (62%) females; median age 56.8 (30-83) years] study lesions included 25 cherry haemangiomas, 15 angiokeratomas, 10 thrombosed haemangiomas, six pyogenic granulomas, five venous lakes, four targetoid haemosiderotic haemangiomas, four Kaposi's sarcomas and two extraungual glomus tumours. LC-OCT detected increased dermal vascularity, assuming different size and shape according to the particular type of VLs. LC-OCT criteria correlated well to established histopathologic findings. CONCLUSION: The results of our preliminary observations indicate that in vivo evaluation with LC-OCT may provide practical clues for the identification of the vascular nature of a lesion and its differential diagnosis.

The role of postoperative radiotherapy in eccrine porocarcinoma: a multidisciplinary systematic review.

OBJECTIVE: Eccrine porocarcinoma (EPC) is a malignant adnexal tumor accounting for about 0.005% of skin tumors. The standard treatment of EPC is the complete surgical excision of the primary lesion and of the clinically involved lymph nodes. There is limited evidence regarding the role of radiotherapy (RT) in managing EPC after surgery. Therefore, the aim of this multidisciplinary systematic review is to analyze the available evidence about postoperative RT in the curative treatment of EPC. MATERIALS AND METHODS: A systematic search strategy was launched trough the main scientific databases including PubMed, Scopus and Cochrane. An additional manual search and a chain citation were performed about potentially relevant papers. The key words used for the search included "eccrine porocarcinoma", "porocarcinoma", "radiotherapy", "radiation therapy", "adjuvant radiotherapy" and "postoperative radiotherapy". RESULTS: A total of 104 publications were identified and 14 papers were included in the final analysis. The only articles found on adjuvant RT in EPC were case reports published between 1996 and 2019. There was a slight female prevalence (57% female/43% male) with a mean age of 65 years (range 37-85). Head-and-neck region was the most frequently involved anatomical site followed by legs. CONCLUSIONS: Adjuvant radiotherapy after surgical removal of EPC could be considered in cases with positive or close margins and in cases with unfavorable histological features. In view of limited literature data and the rarity of EPC the best treatment sequence should always be discussed within the frame of a multidisciplinary setting. ADVANCES IN KNOWLEDGE: adjuvant radiotherapy after surgical removal of EPC could be considered in cases with positive or close margins and in cases with unfavorable histological features.

Treatment approaches of advanced cutaneous squamous cell carcinoma.

Common primary cutaneous squamous cell carcinoma (CSCC) accounts for 20% of keratinocyte cancers that is usually successfully treated with surgery or radiotherapy. In a minority of cases, CSCC lesions may progress to locally advanced or metastatic disease that may be difficult to be treated causing significant morbidity and mortality. Chemotherapies and targeted therapy with anti-epidermal growth factor receptor antibodies have been used off-label in small studies and case reports of advanced CSCC, but data are scarce and response short-lived. Recently, two PD-1 immune checkpoint inhibitors, cemiplimab and pembrolizumab, have been approved for the treatment of advanced CSCC; specifically the former can be administered in patients with locally advanced and metastatic tumours, while the latter in case of recurrent metastatic CSCC. The introduction of immune checkpoint inhibitors represents a breakthrough in the treatment of CSCC, since numerous clinical trials showed that these agents may provide remarkable clinical benefit with an acceptable safety profile, in a high-need population who had no standard of care. In addition, real-world studies are needed to validate the results observed in clinical trials and numerous clinical trials in the neoadjuvant or adjuvant setting are ongoing. Finally, further studies should investigate predictive biomarkers useful to better select patients to maximize the treatment efficacy.