Clinical determinants of clinical response to Sonidegib in advanced basal cell carcinoma: a monocenter experience.

OBJECTIVE: The purpose of this study is to evaluate the clinical determinants of complete response in locally advanced basal cell carcinoma (laBCC) patients receiving Sonidegib in a real-life, retrospective, observational study.  Hedgehog pathway inhibitors (Vismodegib and Sonidegib) are approved for the systemic treatment of locally advanced basal cell carcinoma (laBCC). The objective response rate was the primary endpoint of the trials for both drugs. PATIENTS AND METHODS: Adult patients with laBCC treated with Sonidegib at the Dermato-Oncology Unit of IFO San Gallicano between June 2020 and September 2022 were included in the study. Patient, tumor, and treatment characteristics were recorded. The complete response rate was the primary outcome. The median time to the best response and complete response were the secondary outcomes. Treatment-related adverse events (TRAEs) and dose adjustments were recorded. RESULTS: Of the 19 patients included in the study, eight (42.1%) achieved a complete response, seven (36.8%) had a partial response, and four experienced progressive disease (21%). The median time to the best response was 3 months in the group of patients with partial response (range 2.0-4.0, with three patients not evaluable) and 3.5 months in the group of patients with complete response (range 2-5). TRAEs occurred in 14 (73.6%) patients, with 8 (57.1%) reporting ≤2 TRAE categories and 6 (42.8%) >2. A total of 78.9% of patients received a modified treatment schedule; 12.5% of patients who achieved a complete response received full dosage from the beginning to the end of treatment, compared with 27.3% of those with a partial response. CONCLUSIONS: The associations between the clinical outcome of interest (objective response rate) and the clinicopathological and treatment characteristics were evaluated. No statistically significant association was observed. Our analysis confirms the observation that no statistically significant correlation exists between clinical response and Sonidegib alternate dose regimen.

Patient and physician satisfaction in an observational study with methyl aminolevulinate daylight photodynamic therapy in the treatment of multiple actinic keratoses of the face and scalp in six European countries.

BACKGROUND: Guidelines recommend treating actinic keratoses (AKs) as they are recognized as precursors of invasive squamous cell carcinoma. OBJECTIVE: The objective of this study was to collect real-world clinical data on the use of methyl aminolevulinate daylight photodynamic therapy (MAL DL-PDT) for the treatment of face and scalp AK in Europe. METHODS: A prospective, multicenter, non-interventional study was conducted in six European countries in patients receiving a single treatment of MAL DL-PDT for face and/or scalp AK. Patient-reported outcomes were assessed by patient questionnaires at baseline and at 3 months after treatment, efficacy was assessed at 3 months using a 6-point global improvement scale, and adverse events (AE) were recorded at each visit. RESULTS: Overall, 325 patients were enrolled from 52 investigational centres, 314 of whom attended the 3-month visit. Most patients had multiple lesions (58.4% had >10 lesions) with lesions mainly located on the scalp (60.0%) and/or forehead (54.2%). AKs were predominantly grade I (39.4%) or grade II (33.2%), and 10.5% of patients had grade III lesions. The proportions of patients and physicians that were overall satisfied to very satisfied with the MAL DL-PDT treatment were 80.4% and 90.3%, respectively. The vast majority of patients (90.0%) would consider using MAL DL-PDT again if needed. Physician-assessed efficacy at 3 months was at least much improved in 83.5% of patients, with 45.9% of patients requiring no retreatment. Related AEs were reported in 15% of patients. CONCLUSION: Use of MAL DL-PDT for multiple face and/or scalp AKs resulted in high levels of patient and physician satisfaction in clinical practice in Europe, reflecting the good efficacy and high tolerability of this convenient procedure.

Is the prognosis and course of acral melanoma related to site-specific clinicopathological features?

OBJECTIVE: Acral melanoma is an uncommon type of melanoma in Caucasian patients. However, acral melanoma is the most common type of melanoma in African and Asian patients. Comparison analyses between hand-acral melanoma and foot-acral melanoma have been rarely reported in the literature. Acral melanoma is an uncommon melanocytic tumor characterized by an intrinsic aggressiveness, with specific histological and clinicopathological features. Acral melanoma involves the palms, soles and sub-ungueal sites. PATIENTS AND METHODS: A total of 244 patients with acral melanoma were included in our analysis. The current study was performed in three different medical centers: Sapienza University of Rome, San Gallicano Institute of Rome and University of Magna Graecia (Italy). The Kaplan-Meier product was used to estimate survival curves for disease-free survival and overall survival. The log-rank test was used to evaluate differences between the survival curves. Assuming that the effects of the predictor variables are constant over time, the independent predictive factors were assessed by Spearman's test and subsequently data were analyzed performing Cox proportional-hazard regression. RESULTS: In both univariate and multivariate analyses Breslow thickness (p < 0.0001) and ulceration (p = 0.003) remained the main predictors. General BRAF mutation was detected in 13.8% of cases. We found that median Breslow value and the percentage of recurrences were similar in hand-acral melanoma and foot-acral melanoma, as well as there were no differences in both short and long-term. CONCLUSIONS: The absence of differences in survival between hand-acral melanoma and foot-acral melanoma shows that the aggressiveness of the disease is related to distinct mutational rate, as well as to anatomical site-specific features, rather than to the visibility of the primary lesion.

Age-related prevalence and morphological appearance of facial skin tumours: a prospective, cross-sectional, observational, multicentre study with special emphasis on melanocytic tumours.

BACKGROUND: The clinical and histopathological diagnosis of skin tumours arising on the face may be challenging. OBJECTIVE: An improved knowledge about the age-related patterns of facial skin tumours may aid the correct diagnosis and management. METHODS: We conducted a prospective, cross-sectional morphological study to investigate the age-related frequency and morphological variability in facial skin tumours in a cohort of consecutive subjects attending two skin lesion clinics in Italy between June and September 2011. A total of 454 consecutive subjects (249 women; 55.5%) presenting with a total of 1866 facial tumours were enrolled in the study. Of the entire cohort, 54 (11.9%) subjects had no facial lesion. RESULTS: Total body naevus count correlated significantly with the mean number of facial lesions (ρ = 0.289, P < 0.001). The majority of flat lesions were pigmented (1056; 75.70%), compared to palpable (233; 17.40%) and raised lesions (93; 6.90%), the association being statistically significant (Pearson's chi square, P < 0.001. Considering melanocytic tumours only, the frequency of flat lesions significantly decreased with increasing age, while the number of palpable and raised lesions increased with increasing age (chi-square, P < 0.001). This trend was mainly due to naevi, whereby pigmented melanocytic naevi decreased with increasing age. Conversely, the percentage of non- pigmented naevi increased with increasing age (chi-square, P < 0.001). LIMITATIONS: The study was conducted in skin lesion clinics in Italy, thus any general conclusions with respect to common traits or features based on the phenotypic and genetic diversity within the European population cannot be stated. CONCLUSIONS AND RELEVANCE: Our study suggests that a high number of facial naevi could predict a high total naevus count. Moreover, naevi present a different morphological appearance during lifetime being initially flat, small and pigmented and becoming later raised, large and hypopigmented. Instead, lentigo maligna is an intraepidermal proliferation that typically presents as flat, large pigmented macule. A given histopathological diagnosis of a junctional naevus of a flat, facial pigmented macule of an elderly should be critically reviewed and treated with caution.

Typical and atypical dermoscopic presentations of dermatofibroma.

BACKGROUND: Dermatofibroma is a common skin neoplasm that is usually easy to recognize, but in some cases its differentiation from melanoma and other tumours may be difficult. OBJECTIVE: To describe the dermoscopic features of dermatofibromas, with special emphasis on the characteristics of atypical patterns, and to calculate pattern frequency according to the patients age and gender, anatomical site and histopathological subtype. METHODS: Two groups of patients were consecutively seen, one with dermatofibromas that were surgically excised because of clinically and/or dermoscopically equivocal aspects or following patient request, and another with non-equivocal dermatofibromas. Each lesion was scored for previously reported global dermoscopic patterns and for additional features. RESULTS: A typical pattern was observed in 92 of 130 (70.8%) lesions, whereas an atypical pattern, that we named the 'non Dermatofibroma (DF)-like' pattern, was seen in 38 of 130 (29.2%). Atypical dermatofibromas showed features reminiscent of different conditions, such as melanoma in 21(16.2%) cases, vascular tumour in six (4.6%), basal cell carcinoma in five (3.8%), collision tumour in three (2.3%) and psoriasis in three (2.3%). A significant association was found between the 'melanoma-like' pattern/'vascular tumour-like' pattern and males, whereas a trend was observed between the above-mentioned patterns and hemosiderotic/aneurysmal DFs. 'Peripheral pigment network and central white scar-like patch' pattern was found associated with females and classic histopathological variant of DF. CONCLUSION: Dermatofibromas may display different morphological faces. The typical dermoscopic patterns allow a confident diagnosis, whereas a full surgical excision is always recommended in all doubtful cases.

Seven-point checklist of dermoscopy revisited.

BACKGROUND: Most dermoscopic algorithms to diagnose melanoma were established more than 10 years ago and have been tested primarily on clear-cut melanomas and excised melanocytic naevi. OBJECTIVES: To assess the diagnostic performance of pattern analysis and seven-point checklist on lesions that reflect the current clinical setting, compared with a revised seven-point checklist with a lower threshold for excision. METHODS: Eight experienced dermatologists viewed dermoscopic images of 100 excised melanomas, 100 excised naevi and 100 monitored naevi. Each lesion was evaluated by pattern analysis and scored as naevus, melanoma or lesion to be excised. Images were then evaluated using the seven-point criteria, with both standard and revised thresholds for excision. RESULTS: Pooled data using the pattern analysis algorithm showed that 82% of melanomas and 87·5% of monitored naevi were correctly scored as lesion to be excised and benign naevus, respectively. Using the standard and revised thresholds for the seven-point checklist, excision was recommended for 77·9% and 87·8% of the lesions in the melanoma set, respectively. The standard threshold produced 'no excision' recommendations for 85·6% of the monitored naevi, compared with 74·5% using the revised threshold. Pattern analysis, standard seven-point and revised seven-point algorithms resulted in recommendations of 'excision' for 63·6%, 60·3% and 72·0% of the excised naevi, respectively. CONCLUSIONS: The diagnostic approach to naevi and melanoma should be adapted to the current clinical setting, in which patients may present with early-stage melanomas and multiple atypical naevi. To increase sensitivity, a revised seven-point checklist with a lower threshold for excision should be used.

High frequency ultrasound in the preoperative staging of primary melanoma: a statistical analysis.

High frequency sonography has been shown to be a useful tool in the preoperative staging of malignant melanoma. In the present study sonometric and histometric data concerning tumour thickness were compared, using appropriate statistical methods, in order to assess the accuracy of ultrasonography. From December 1997 all pigmented lesions suspected of being melanoma were preoperatively assessed by a 20 MHz ultrasound B scan. The results of these ultrasound examinations were compared with histometric data. Pearson's correlation coefficient and absolute and relative differences were used for statistical analysis. Of the 261 examined lesions, 193 were malignant melanoma. A high correlation between sonometry and histometry was computed (r = 0.95), with an absolute difference of 0.32 +/- 0.03 mm (mean +/- SEM) and a mean relative difference of 27.2% (95% confidence interval 23-31.4%). The highest correlation was found in melanoma > or = 1.51 mm thick and the lowest correlation in melanoma < or = 0.75 mm. In conclusion, the high accuracy of this technique in the preoperative staging of malignant melanoma would offer a basis for defining the surgical margins of > or = 0.76 mm thick lesions. The limited accuracy of sonometry in the preoperative staging of thin melanoma < or = 0.75 mm has emerged by applying adequate statistical methods.

CDKN2A novel mutation in a patient from a melanoma-prone family.

CDKN2A is thought to be the main candidate gene for melanoma susceptibility. Deletion or mutations in the CDKN2A gene may produce an imbalance between functional p16 and cyclin D, causing abnormal cell growth. We here describe a novel mutation consisting of a 1 bp deletion at nucleotide position 201 (codon 67) (CACGGcGCG) resulting in a truncated protein (stop codon 145). The patient, a female subject from a melanoma-prone family, presented at the age of 47 years with a superficial spreading melanoma of the trunk. Her father had colon cancer at the age of 43 years and melanoma at 63 years, her uncle suffered from gastric cancer, and her grandfather had laryngeal cancer.

Cytogenetic follow-up in a case with a primary cutaneous melanoma and five metastatic lesions.

Cytogenetic analyses conducted on several cases of melanoma have contributed to the identification of the chromosomal regions where the sequences responsible for malignant transformation and the evolution of this tumor are probably located. With regard to these problems, it is very important to have the possibility to analyze, through the use of cytogenetics, both the primary melanoma and the metastatic lesions from the same patient. We present a case in which the primary melanoma and five different metastases were studied by using cytogenetics. The primary tumor showed an inversion of chromosome 1 where the p36 region, often proposed in literature as the location of a melanoma susceptibility gene, was involved. Three cutaneous and one lymphonodal metastases presented the same nine clonal chromosomal aberrations. In particular, one is a further rearrangement of the marker present in the primary tumor; another is a deletion of the 9p21pter region in which the p16 gene is located. Our results can provide a contribution to the hypothesis of the location of a candidate gene for melanoma in the 1p36 region and can also underscore the role of the 9p21 region in the progression of melanoma.

Cytogenetic findings in 20 melanomas.

We report cytogenetic studies performed on 20 patients with cutaneous malignant melanoma, characterized by clinical and histological parameters. Cytogenetic analyses were performed on peripheral blood lymphocytes, in order to exclude the presence of constitutional chromosomal aberrations, and on primary cell cultures obtained from neoplastic skin lesions. A metastasis was also cultured in order to characterize chromosome markers. Specific markers found in more than one patient were t(1;14)(q21;q32) and aberrations of the 4q21,8q24 and 10q24q26 regions. The research aims to identify possible subtypes of melanomas related to specific chromosomal markers. It is hoped that this will contribute to understanding of the aetiology and evolution of the disease in order to obtain a more exact classification. We compare our results with the data reported in the literature and discuss the possible role of the cytogenetic analyses in human malignant melanoma.

Mineral fibres and dusts in lungs of subjects living in an urban environment.

We have undertaken a study on 200 autopsy lung samples collected from subjects who lived in the Rome urban area and were not occupationally exposed to mineral dusts. The samples belonged to subjects who died aged between 15 and 65, both male and female. Subjects suffering from diseases and drug addicts were excluded. The purpose of this investigation was to determine whether any correlation existed between subjects' life-style, in particular smoking habits, and the presence of mineral fibres and dusts in their lungs. The data obtained were compared with those on airborne mineral dusts in the environment of the subjects themselves, particularly data on the concentration and types of mineral fibres present in that environment.