Dynamic optical coherence tomography evaluation in locally advanced basal cell carcinoma during sonidegib treatment.

BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer in the Caucasian population. It has a multifactorial pathogenesis, in which constitutive activation of the Sonic Hedgehog signalling (SHH) pathway (via mutations in PTCH1 or SMO genes) represents by far the most common genetic aberration. The introduction of vismodegib and sonidegib, two SHH pathway inhibitors, changed the therapeutic approach of locally advanced and metastatic BCCs. EADO's (European Association of Dermato-Oncology) new staging system refers to these as 'difficult-to-treat' BCCs. OBJECTIVE: The aim was to evaluate sonidegib's effectiveness in patients affected by difficult-to-treat BCCs by using non-invasive diagnostic techniques. METHODS: We retrospectively evaluated 14 patients (4 females, 10 males; mean age 77 ± 11 years) affected by difficult-to-treat BCCs treated with oral sonidegib 200 mg/day that were followed with total body videodermoscopy (V-Track, Vidix 4.0) and dynamic optical coherence tomography (D-OCT, VivoSight Dx) since May 2022. Considering the risk of rhabdomyolysis routine blood tests, especially for creatine kinase concentrations, were performed. All treated patients were inserted in the BasoCare database, which aims to offer support to patients taking sonidegib. Complete and partial responses were evaluated by the overall reduction of the number of lesions and their individual sizes. Safety was evaluated by assessing the occurrence and severity of adverse reactions. RESULTS: Eighty per cent achieved complete clearance and 75% reduction of diameter. D-OCT scans performed at every follow-up showed concordance with clinical appearance and demonstrated reduction of hyporeflective structures, that is, islets of tumour cells and overall improvement of morphology. CONCLUSION: Sonidegib can be considered an effective treatment option in cases where surgery or radiotherapy would be unfeasible or has previously failed, although pigmented lesions did not show complete clearance, suggesting that there are factors other than the SHH pathway involved in tumour growth. Videodermoscopy and D-OCT were useful in the quick and seamless follow-up of lesions and added valuable information in assessing efficacy.

Vulval hidradenoma papilliferum: a clinical and dermoscopic study.

Hidradenoma papilliferum (HP) is a rare, slow-growing, benign adnexal tumour with apocrine differentiation. It usually affects the anogenital region in adult women and is clinically polymorphous, mimicking other benign or malignant neoformations. The dermoscopic features of vulval HP have not been reported yet. We report the clinical and dermoscopic features in a case series of histopathologically proven vulval HPs. Dermoscopy may be a useful tool for the diagnosis of vulval HP. To our knowledge, our paper represents the first report of dermoscopic findings in a series of vulval HPs in a multiracial population.

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.

Daylight-Photodynamic Therapy for the Treatment of Actinic Keratosis in Different Seasons.

BACKGROUND: non-melanoma skin cancer (NMSC) is the most common malignancy, whose public health significance is often unrecognized. Its incidence continues to grow at an alarming rate, becoming an occupational disease. Available treatments alternative to surgery include: photodynamic therapy, electrochemiotherapy, cryotherapy, ablative lasers, 5-fluorouracil, imiquimod, ingenol mebutate, and diclofenac. Each of these options has its advantages and disadvantages. Photodynamic therapy (PDT), using topically applied photosensitizer precursors such as methylaminolaevulinate (MAL), is a useful nonsurgical treatment, well accepted by patients, but the main limitation is pain. Recently, in order to overcome this limit, visible light irradiation photherapy was considered. AIM: we report our experience comparing conventional PDT (406 patients) with daylight-mediated PDT (D-PDT) 240 patients with multiple actinic keratoses (AK), afferent to our photodynamic outpatients clinic from September 2013 to June 2014. MATERIALS AND METHODS: to establish predictors for the clinical response to conventional PDT and daylight PDT (DPDT), a retrospective study on 646 patients was performed. The following parameters have been evaluated: sex, age, anatomic site of the primary tumor and local skin reactions. We used the Spearmen's coefficient between the clinical response and the predictors analyzed; while Odds Ratio (OR) was performed to evaluate general clinical response and local skin reaction between PDT and D-PDT patients. Subsequently, we performed a sub-analysis, focusing to the anatomical sites, and we subdivided anatomical sites in face and scalp, nose, trunk, and extremities. RESULTS: a total of 406 patients treated with PDT and 240 patients treated with D-PDT, were enrolled in the current report. The median age was 71 years in PDT and 73 years in D-PDT. The mean clinical response in PDT was of 74.4% and 95% in D-PDT. Performing OR between PDT and D-PDT, according to the clinical response, we found a better behavior in patients treated with D-PDT (P < 0.03); the same significance was maintained according to the presence or absence of local skin reaction (P < 0.0002). Using no parametric Spearman's Coefficient test among predictive factors and the therapeutical response we found that D-PDT showed a better clinical response in patients with AK size ≥ 0.6 mm (P < 0.03), while this evidence was not present in PDT. The nose remained in both PDT and DPDT the main anatomical site with a better clinical response to the treatment. CONCLUSION: Since efficacy of D-PDT is comparable or superior to conventional type, but is simpler and better appreciated by patients, in our opinion it may be used routinely to treat sun exposed multiple AKs especially in sun damaged skin also for aesthetic purposes.

Improvement of survival in patients with melanoma and non-melanoma skin cancers compared to patients without double cutaneous malignancies.

OBJECTIVE: The worldwide incidence of cutaneous malignant melanoma (MM) has been rising steadily over the past 30 years. At the same time non-melanoma skin cancers (NMSC) are the most prevalent type of cancer in United States and Europe. Up to date, no paper has explored the influence on the general survival in patients with MM and NMSC. We decided to perform a study with the aim to evaluate the different survival in patients with MM-NMSC compared to control patients (MM-CTRL). PATIENTS AND METHODS: To evaluate prognosis in both groups, we analyzed disease-free survival (DFS) and overall survival (OS).Kaplan-Meier product was performed for the survival analysis. Median DFS was 73 months in group and 72 months in MM-CTRL patients (p = 0.4); while, median OS was 74.2 months in MM-NMSC patients and 63.1 in MM-CTRL (p < 0.001). Also at Odds-Ratio (OR), the statistical significance was maintained (p < 0.007) with a better prognostic value for MM-NMSC. RESULTS: Among group patients, the ones with a basal cell carcinoma showed a batter behavior, than the ones with squamous cell carcinoma (p = 0.01). CONCLUSIONS: Patients with MM-NMSC showed a better survival than MM-CTRL patients (p < 0.001). The causes of this improved survival are still unknown; probably the endogenous immune response can play a pivotal role in this class of patients. However, further studies are necessary to better understand this phenomenon, not yet explored in literature.

Evaluation of Ingenol mebutate efficacy for the treatment of actinic keratosis with Antera 3D camera.

OBJECTIVE: Cumulative exposure of the skin to ultraviolet radiation promotes mutation in keratinocytes and their abnormal growth led to the formation of scaly lesions, called actinic keratoses (AKs). Its incidence is growing at an emerging rate, becoming a worldwide problem especially for occupational ultraviolet (UV) rays exposure. Detectable lesions are often associated with field changes, where the surrounding skin is altered and subclinical lesions may be present. Thus, a field-directed therapy, such as topical treatment, should be preferred for the prevention of invasive cancer development. A retrospective analysis was made, evaluating the efficacy of ingenol-mebutate gel, using a novel device the 3D in vivo optical skin Imaging (Antera 3D, Miravex, Ireland). PATIENTS AND METHODS: We included all patients with multiple non-hypertrophic Aks, to whom it was prescribed ingenol-mebutate gel, applied at the dosages of 0.015 for lesions in the scalp/face (for 3 consecutive days) and at the dosage of 0.05% for lesions in the trunk and/or extremities (for 2 consecutive days). RESULTS: A reduction of the lesions and of median hemoglobin levels, after a follow-up of 60 days, was observed in 100% of patients. CONCLUSIONS: Ingenol mebutate gel, the last topical molecule appeared in the Italian market showed its efficacy using Antera 3D also in terms of hemoglobin reduction. Therefore, this camera could be considered an useful tool for the identification of the area to be treated and for therapeutic follow-up.

Association between autoimmune disease and cutaneous melanoma with regard to melanoma prognosis.

BACKGROUND: An association between autoimmune disease and malignant melanoma (MM) has often been reported in the literature as a positive prognostic factor for MM. Consequently, we evaluated the influence of different autoimmune diseases on the prognosis of MM. AIM: To evaluate the prognosis of patients with MM who also had an autoimmune disorder, whether tumour-associated, paraneoplastic or drug-induced. METHODS: Autoimmune diseases were classified and analysed as tumour-associated, paraneoplastic or drug-induced. Patients were enrolled according to their clinicopathological features and matched with control groups. Kaplan-Meier analysis was used to estimate disease-free survival (DFS) and overall survival (OS), and log-rank test was used to evaluate differences between the survival curves. RESULTS: In total, 49 patients with MM and tumour-associated autoimmune disease were included in our analysis. No case of paraneoplastic autoimmune disease was detected. The survival analyses showed a range of results, from a worsening of DFS and OS to a lack of any difference. In a second analysis, we separately analysed patients who developed autoimmune disorders after starting adjuvant therapy with interferon-α; we did not find significant differences between these patients and the untreated patients. CONCLUSIONS: Autoimmune disease, whether tumour-associated or drug-induced, was not associated with better prognosis in patients with MM. The results suggest that the reported relationship between autoimmunity and MM may be a result of individual variation in sensitivity to the autoimmune disease, the tumour or the treatments.

Multiple painful papulo-nodular lesions: clinical pitfall.

A 43-year-old male presented with multiple (>10) painful, papulo-nodular lesions, associated with paresthesia, over the face, neck and trunk, appeared 15 years prior and increased with time. The patient's brother has cutaneous leiomyomas and testicle cancer, his mother underwent hysterectomy for symptomatic leiomyomas while his maternal grandfather died from aggressive renal cell carcinoma at age 57 years. The patient reported that he had removed a kidney cancer 5 years prior. Dermoscopy, histologic evaluation and genetical analysis were done and Hereditary leiomyomatosis and renal cell carcinoma was diagnosed.

Drug cutaneous side effect: focus on skin ulceration.

Skin ulcers are defined as tissue loss interesting the deeper layers of the dermis and hypodermis, with low tendency to spontaneous healing. They cause disability related to pain, risk of infection and amputation, chronic management, requiring working absence with notably economic burden. The major cause is often related to underlying vascular disease, infections, tumors, autoimmunity, trauma, even if literature occasionally reported several cases of drug inducing skin ulceration. Most of drugs involved are chemotherapy agents and more recently molecular target therapies. Evidences supporting these drugs as the major cause of skin ulcers include delay of onset after therapy initiation, improvement after withdrawal of the drug, recurrence after its reintroduction and, sometimes, simultaneous occurrence of other skin lesions that have previously been reported to be associated with these agents. Attention should be reserved to patients undergoing antineoplastic agents, especially if previously affected by predisposing comorbidities, considering such side effect as possible differential diagnosis for skin ulceration in neoplastic patients.

Basal cell carcinomas in a young woman with Steinert's disease.

Steinert's disease or Myotonic dystrophy type I (DM1) is an autosomal dominant disease characterized by myotonia, muscular dystrophy, cataracts, hypogonadism, frontal balding, and electrocardiographic alterations.Several tumors have been associated with DM1 such as pilomatricoma, thymomas and insulinomas. Herein, we describe the unusual onset of multiple basal cell carcinomas in a young woman with DM1.

Melanoma detection in Italian pigmented lesion clinics.

AIM: Accuracy in melanoma detection is important to recognize early curable melanomas and to minimize the unnecessary excision of benign lesions. The aim of this paper was to evaluate melanoma screening accuracy of Italian pigmented lesion clinics in terms of number needed to excise (NNE), melanoma thickness, and number of melanomas diagnosed during patient follow-up. METHODS: Information on all skin tumors excised in 2011 were extracted from the databases of the participating centers. Information whether the lesion was excised at the baseline examination or during patient follow-up was recorded, as well as the overall number of patients examined in each center in 2011. RESULTS: After e-mail solicitation, 22 of 40 centers agreed to participate. A total of 8229 excised lesions were collected. The overall number of examined patients was 86.564, thus 9.5% of screened patients had a lesion removed. Of the excised lesions, 866 were diagnosed as melanoma (1% of examined patients) and 5311 (88.9%) were melanocytic nevi. Three NNE were calculated giving values of 7.9 excised lesions to find 1 melanoma, 7.1 melanocytic lesions to find 1 melanoma, and 3.7 lesions to find 1 skin malignancy. The median melanoma thickness was 0.6 mm, with only 15.1% of melanomas ≥ 1 mm of thickness. Melanomas detected over time were 96 (11.1%; mean thickness, 0.3 mm), with 15.6% of lesions excised after short-term follow-up and 84.4% after long-term follow-up. CONCLUSION: The NNE values comparable to those achieved in specialized clinical settings and the high number of early melanomas diagnosed at the baseline examination or during patient follow-up indicate a high level of accuracy in melanoma screening achieved by Italian pigmented lesion clinics.

Topical promethazine side effects: our experience and review of the literature.

Promethazine hydrochloride is a first-generation H1 receptor antagonist, antihistamine, and antiemetic medication that can also have strong sedative effects. The apparent ability of topical H1r/2r antagonists to target epidermal H1/2r was translated into increased efficacy in the treatment of inflammatory dermatoses, likely due to decreased inflammation and enhanced barrier function.

Male tuberculous mastitis: a rare entity.

A 28-year old male presented to our clinic complaining of a recent onset of a painful right breast lump with redness and nipple discharge. Fine-needle aspiration biopsy revealed caseating granulomas, with a culture positive for Mycobacterium tuberculosis. He was found to have a positive PPD, but no other site of pulmonary or extra-pulmonary tuberculosis was identified. Treatment with anti-tuberculous drugs lead to complete clinical resolution of the breast lesion. The breast is a rare site of extra-pulmonary tuberculosis (TB), comprising only 0.1% of all cases. TB is re-emerging in the Western world with the increasing prevalence of immunosuppressive disorders. Increasing immigration rates and widespread travel are further contributing to TB globalization. With the re-emergence of TB, atypical forms are appearing, with an increase in the proportion of extra-pulmonary disease and a widening of the age range at presentation. Tuberculous mastitis(TM) is found mostly in young, multiparous women. Male TM is extremely rare, and accounts for only 4% of all cases. This strikingly lower incidence in males points towards a significant role of parity, pregnancy and lactation as likely predisposing factors. Although a rare disease, TM is an important differential diagnosis for breast cancer. A high index of suspicion is the cornerstone for diagnosis. Awareness of this condition is important not only for dermatologists, but for surgeons, radiologists and pathologists, as well. Clinicians are encouraged to provide a careful assessment of the breasts, an important organ also in men.

Acute generalized exanthematous pustulosis during antituberculosis therapy.

Acute generalized exanthematous pustulosis (AGEP) is a significant adverse cutaneous reaction most often induced by drugs and by acute infections. Its clinical hallmark is the sudden onset of multiple, disseminated, non-follicular, sterile pustules on an erythematous background usually arising in intertriginous folds, associated with fever, massive neutrophilia and sometimes eosinophilia. Antitubercular therapy is described as an uncommon cause of AGEP. We report the onset of disseminated non-follicular sterile pustules on an erythematous background in a 68-year-old man receiving a combination of isoniazid, pyrazinamide and rifampicin that may have been the etiologic agents. A thorough history, including a medication history, with clinicopathologic correlation is crucial in patients presenting with acute diffuse pustular lesions.

Serum concentrations of IL-2, IL-6, IL-12 and TNF-α in patients with alopecia areata.

Alopecia areata (AA) has been represented as a restricted T cell-mediated autoimmune disease. Several studies have shown that cytokines may play an important role in its pathogenesis although many pathways exist. We investigated cytokine (IL-2, IL-6, IL-12, and TNFα) levels in peripheral blood mononuclear cell (PBMC) of 105 patients with different grade and duration of alopecia areata, to confirm that T-cell responses in AA is regulated via mechanisms of peripheral T-cell tolerance. We observed that IL-12 levels are higher for patients with bigger extensions and tend to increase according to the duration of the AA; TNFα instead, is more related to the gender of the patients and to the duration. Therefore abnormalities in cytokines production, showed by our results, may suggest that T-cell responses in AA scalp are closely regulated via mechanisms of peripheral T-cell tolerance and therefore confirm that this disease has an immuno-pathogenesis. Our aim is to shed light upon the complexity of AA underlying mechanisms and indicate pathways that may suggest future treatments.

Safety and efficacy of Adalimumab in the treatment of moderate to severe palmo-plantar psoriasis: an open label study.

INTRODUCTION: Psoriasis of the hands and feet is highly debilitating and difficult to treat. Lesions are very painfull, disabilitating and impair quality of life of patients. Most treatment options have limited efficacy, short duration of response and several adverse events. OBJECTIVE: To investigate the safety and efficacy of Adalimumab in the management of palmo-plantar psoriasis. PATIENTS AND METHODS: Adults patients with moderate to severe palmoplantar psoriasis were enrollend in this trial. They received a 6 courses of Adalimumab 40 mg 1 vial every 2 weeks. The study consisted of treatment period of 12 weeks (Weeks 1-12). Safety and efficacy were assessed at weeks 0.6 and 12. PGA (Physician's Global Assesment) and DLQI were used to measure the efficacy. Primary end point of the study was to evaluate patients who achieved a reduction in PGA at week 12. The secondary end point was to evaluate patients who achieved a 50% reduction in PGA at week 12. The tertiary end point evaluated patients who achieved a PGA rating of clear or almost clear. RESULTS: Of 11 patients enrolled 6 showed overall improvement of at least one point of PGA at week 12; 4 of them obtained a PGA of 0 while 5 patient of 11 a ≥ 50% improvement from the beginning of the study. 8 patients showed an increase in quality of life score while receiving the drug at week 12. No serious adverse events were reported during the study. CONCLUSION: Continuous treatment with Adalimumab for 12 weeks was safe and efficacious in this open-label clinical trial of patients with palmoplantar psoriasis.

Finasteride, 1 mg daily administration on male androgenetic alopecia in different age groups: 10-year follow-up.

Finasteride 1 mg is indicated for the treatment of men with androgenetic alopecia (AGA). However, more than 5 years efficacy and safety has not been previously reported. To assess the efficacy over 10 years in different age groups of men with AGA. 118 men, between 20 and 61 years, with AGA receiving finasteride (1 mg/day), were enrolled in this uncontrolled study. Efficacy evaluation was assessed with standardized global photographs at T0,T1,T2,T5,T10. Statistical analysis was made using frequency tables and evaluating the chi-square index with its p-value. Better improvements are observed in patients older than 30 years (42.8% aged between 20 and 30 years did not improve also after 10 years) or with higher AGA grades (58.9% for AGA grade IV and 45.4% for AGA grade V had the first improvement just after 1 year). In 21% of cases, the treatment continuation beyond 5 years provided better results. Side effects were referred by 6% of the patients; nevertheless, some of them went on with treatment because of the great results. In our opinion, the result after the first year can help in predicting the effectiveness of the treatment. Its efficacy was not reduced as time goes on; in fact, a big proportion of subjects unchanged after 1 year, improved later on, maintaining a positive trend.