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.

Serum tryptase levels in patients with psoriasis: a pilot study for a possible useful biomarker.

In psoriasis, biomarkers for disease prognosis and response to treatment may help clinicians to improve patient management. Hence, we decided to evaluate the role of serum tryptase (ST) in a sample of patients with psoriasis. We found higher levels of ST in patients with scalp psoriasis than in those without (6.1 vs. 4.6 ng/mL), in those with palmoplantar psoriasis than in those without (5.3 vs. 5 ng/mL) and, with less significance, in those with psoriatic arthritis than in those without (6.1 vs. 5.1 ng/mL).

Successful use of dupilumab for the treatment of atopic dermatitis on the genitals, a neglected anatomical site.

Atopic dermatitis (AD) is a chronic inflammatory disease that may involve any cutaneous site; involvement of the genital area may greatly impair patients' quality of life but, as the inspection of genitals is not usually conducted during the routine physical examination of patients with AD, the genital presentation of AD is frequently neglected and under-reported. We decided to evaluate the incidence of genital AD in patients with moderate-severe AD and the relative response to anti-interleukin (IL)-4/IL-13 dupilumab. In our study, a high incidence of genital AD emerged but the use of dupilumab allowed a generalized improvement.

Dermoscopy of cutaneous adnexal tumours: a systematic review of the literature.

Cutaneous adnexal tumours (ATs) encompass a variegated group of hamartomas and benign or malignant tumours, originating from the hair follicle, sebaceous, eccrine or apocrine glands that may simulate other cutaneous neoplasms. This study aims to provide a comprehensive overview of the spectrum of clinical and dermoscopic features of ATs, to better define these lesions and assist in the differential diagnosis. We performed a two-step systematic search of the literature in PubMed, Embase and Cochrane Library databases from inception until 4 September 2020. In the first step, we aimed to define histological variants of ATs with descriptions of dermoscopic criteria. The second step included a search for the name of each previously identified AT variants in the same databases adding 'AND (epilum* or dermosc* or dermatosc*)'. All study types in English language reporting dermoscopic images of ATs were included. Collisions between ATs and other inflammatory or neoplastic skin lesions were excluded, with the exception of collisions with a sebaceous nevus. The protocol of this study was prospectively registered in PROSPERO (CRD42021244677). In total, 206 articles met our inclusion criteria, encompassing 372 ATs in 365 patients. Most ATs were apocrine-eccrine (n = 217, 58.3%, n = 173 benign) with a prevalence of poromas (n = 82), followed by follicular ATs (n = 88, 23.7%, n = 83 benign) and sebaceous ATs (n = 67, 18.0%, n = 49 benign). Most patients had a single AT lesion (320, 86.0%), while 42 (11.3%) had multiple ATs. A syndrome causing multiple ATs was identified in 15 patients. Histopathological analysis revealed 82% benign (n = 305) and 18.0% malignant (n = 67). ATs were classified according to their ability to mimic four groups of more common skin tumours: basal cell carcinoma, squamous cell carcinoma, melanocytic lesions and benign cutaneous lesions. Moreover, we have highlighted the ability of malignant variants of ATs to simulate benign skin lesions. This systematic review offers a comprehensive overview of the common clinical and dermoscopic features of follicular, sebaceous and apocrine-eccrine ATs and details possible differential dermoscopic features.

Vipera snakebite in Europe: a systematic review of a neglected disease.

In 2009, snakebites were included in the list of the World Health Organization (WHO) neglected diseases. Dermatological literature lacks current and up-to-date articles about snakebites and their management, despite the fact that dermatologists, especially from rural hospitals, can be called into the emergency room to consult the management of suspected snakebites. In this systematic review, we highlighted the main clinical and laboratory aspects of snakebites from Vipera spp. in Europe, by reviewing 3574 studies initially retrieved from PubMed, Embase and Cochrane CENTRAL databases. Of these, 78 were finally included in the systematic review. We found that the most involved taxon was V. berus in 63.3% and the most involved anatomic site of the bite was the upper limbs 53.1% with fang marks reported in 90.5%. The mean age of the patients was 32.9 years, and bites were slightly more common among males (58.2%). A wound washing was performed in 86.9% of cases before the hospitalization. The most frequently reported grade of envenomation was G2 (42.2%). In addition to local dermatological symptoms (extended erythema, oedema, cutaneous necrosis, hives, purpura, petechiae, acute compartment syndrome), numerous systemic symptoms have also been reported, including fatigue (14.4%), pain (75.3%), fever (49.2%), direct anaphylactoid reaction (5.3%), anxiety (60.8%), cranial nerve neurotoxicity (14.8%), dysesthesia/paraesthesia (7.9%), vomiting (33.7%), abdominal pain (23.3%), diarrhoea (15.4%), dyspnoea (6.3%), proteinuria (10.6%) and haematuria (9.3%). Secondary infections were present in 3.5% and disseminated intravascular coagulation in 3.1% of cases, and fasciotomy was performed in 4.2% cases, while an amputation in 6.9%. Only 0.9% of patients died. Antivenom was administered in 3053 cases. In conclusion, there is a pressing need for robust multi-centre randomized control trials, standardized protocol for snakebite management and antivenom administration across Europe and a National snakebite register for each European country.

Alopecia neoplastica as a sign of visceral malignancies: a systematic review.

Alopecia neoplastica (AN) from visceral tumours is a rare form of cutaneous metastasis in which internal malignancies spread to the scalp. The diagnosis of AN may be very challenging, especially when its onset precedes the diagnosis of the primary tumour. We aimed to improve the knowledge on AN, highlighting that in case of scarring localized alopecia, a differential diagnosis with metastasis should always be considered. We performed a systematic review to describe the main demographic and clinical features associated with AN from visceral malignancies; a survival analysis was also performed. In 118 reports, accounting for 123 patients, we found that women were more affected by AN than men (53.7% vs. 46.3%). The most frequent site of the primary tumour was the gastrointestinal tract (24.4%), followed by breast (17.9%), kidney (8.1%), lung (7.3%), thyroid (7.3%), uterus (6.5%), central nervous system (6.5%), liver (3.3%) and other anatomic areas for 18.7% of cases. Furthermore, in more than half of the cases (66.1%), AN lesions were single and were mainly diagnosed after the primary visceral tumour (71.5%). Finally, survival analysis highlighted a lower progression-free survival in men; while, no significant differences in overall survival were reported among genders. In conclusion, metastatic skin disease should always be taken into consideration when dealing with patients with localized scarring alopecia.

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.

Immunohistochemical expression of VDR is associated with reduced integrity of tight junction complex in psoriatic skin.

BACKGROUND: Cell junctions are crucial for the formation and maintenance of the paracellular barrier and for cell polarity in simple epithelia and endothelia. Altered localization and formation of tissue junction proteins in the epidermis have been described in plaque-type psoriasis. Vitamin D receptor (VDR) is a nuclear hormone involved in anti-proliferative and pro-differentiation pathways in keratinocytes. However, still to date, vitamin D/VDR signalling involved in tissue barrier related to psoriasis remains largely unknown. OBJECTIVE: To study the expression of VDR and tight junctions (TJ) proteins (claudin 1, ZO-1 and occludin) in psoriatic skin, and to correlate the expression of VDR with that of the junctional proteins claudin- 1, occludin and ZO- 1. METHODS: A total of 20 psoriatic tissue samples were included in the analysis. Immunohistochemical studies for VDR, claudin-1, occludin and ZO-1 were performed. RESULTS: We observed a reduction of VDR, claudin-1 and ZO-1 expression in psoriatic skin if compared to normal skin, and the statistical analysis showed a significant correlation between a downgrading of VDR expression and that of claudin-1 (P < 0.005) and ZO-1(P < 0.005). CONCLUSIONS: Our results suggest a new role of VDR in the maintenance of the homeostasis skin barrier. Although the exiguity of our cohort, VDR status appears to be associated with the expression level and functions of TJ proteins, suggesting multiple and different cellular functions of the VDR.

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.

Adenocarcinoma of the cervix associated with a neuroendocrine small cell carcinoma of the cervix in the spectrum of Muir-Torre syndrome.

Muir-Torre syndrome (MTS) is an autosomal genodermatosis that is diagnosed by the presence of at least one sebaceous gland tumor and at least one visceral malignancy. The most frequent visceral malignancies reported in literature are low-grade colon-rectal and genitourinary cancers, with prolonged survival. The authors report the case of a 52-year-old female, with a positive familial history for MTS, who developed a cutaneous sebaceous carcinoma, a synchronous colon-rectal adenocarcinoma, and a metachronous endocervical adenocarcinoma associated with a neuroendocrine small cell carcinoma of the cervix (SCNC), with lymph node metastasis. The rare occurrence in literature of the cervical SCNC and the rarest occurrence of a neuroendocrine carcinoma in the context of a MTS deviate from the usual and low-grade types of cancers normally described with MTS. It should be always appropriate to assess any symptoms that might reveal an underlying malignancy, although not within the spectrum of neoplasms most associated with this rare syndrome.

Melanoma and IFN alpha: potential adjuvant therapy.

Interferon alpha (IFNalpha) is the most used adjuvant treatment in clinical practice for melanoma (MEL) high-medium risk patients; however, the use of IFNalpha has yielded conflicting data on Overall Survival (OS) and disease free survival (DFS) rates. Starting from these considerations, we carried out an analysis on our MEL patients who received adjuvant IFNalpha therapy, in order to identify possible predictors for their outcome. A total of 140 patients were included in our analysis. Patients with Breslow thickness ≤2.00 mm presented a significantly longer mean DFS than patients with Breslow ≥2.01 mm (p = 0.01). Using non- parametric Spearman’s Coefficient test we found association between DFS and Breslow thickness (p < 0.001) and between DFS and ulceration (p = 0.03). Performing Multiple Regression test, Breslow thickness (p < 0.001) remained the only statistically significant predictor. From the OS analysis we found that patients with lower Breslow values ≤ 2.00 mm (p < 0.0001), and absence of ulceration (p <0.004) showed a significantly better long-term survival. From the current analysis we found that the use of low dose IFNalpha is justified only for cutaneous melanoma ≤ 4.01 mm that was not ulcerated; patients with Breslow ≥ 4.01 mm, in our opinion, should not carry out adjuvant treatment with low dose IFNalpha, because its side effects could be higher than the its benefits.

Visceral leishmaniasis revealed by a squamous cell carcinoma in an HIV-1 infected patient.

We present a case of visceral leishmaniasis confirmed after the histological investigation of an ulcerate lesion of the scalp in an HIV-1-infected patient receiving highly active antiretroviral therapy (HAART). Histological examination of the skin lesion revealed a squamous cell carcinoma superinfected by amastigotes of Leishmania infantum from the bloodstream. Because HIV-1-infected individuals can harbour parasitic infections in normal and neoplastic tissue, it is necessary to examine carefully any skin lesions, particularly those with uncommon aspects or a worsening course, to exclude superinfections by unsuspected pathogens.

Lichen sclerosus and the risk of malignant progression: a case series of 159 patients.

AIM AND METHODS: We analyzed 159 stored specimens of Lichen Sclerosus (LS) collected in the period 1999-2011 from 159 patients, in order to evaluate the histological patterns, clinical outcomes and possible associations with malignancies. The histopathologic analysis revealed 145 cases (males and females) with LS alone, 7 in whom penile LS was associated with spinocellular carcinoma (SCC), and 7 in whom LS was associated with a pseudocarcinomatous-hyperplasia (PCH). Extragenital LS was found in 20% (17/85) of the males and 78% (58/74) of the females. In the cases of SCC, immunohistochemical analyses was performed. RESULTS AND CONCLUSION: The results showed very low positivity to p16INK4A and Ki-67; biomolecular PCR was positive in only two cases, and in both cases the non-oncogenic genotype HPV 100 was detected. No important additional risk factors for malignancies were found (e.g., hormones, infections, other autoimmune diseases).