Insights into Mutation Effect in Three Poikiloderma with Neutropenia Patients by Transcript Analysis and Disease Evolution of Reported Patients with the Same Pathogenic Variants.

PURPOSE: Poikiloderma with neutropenia (PN) is a genodermatosis currently described in 77 patients, all presenting with early-onset poikiloderma, neutropenia, and several additional signs. Biallelic loss-of-function mutations in USB1 gene are detected in all molecularly tested patients but genotype-phenotype correlation remains elusive. Cancer predisposition is recognized among PN features and pathogenic variants found in patients who developed early in life myelodysplasia (n = 12), acute myeloid leukemia (n = 2), and squamous cell carcinoma (n = 2) should be kept into account in management and follow-up of novel patients. This will hopefully allow achieving data clustered on specific mutations relevant to oncological surveillance of the carrier patients. METHODS: We describe the clinical features of three unreported PN patients and characterize their USB1 pathogenic variants by transcript analysis to get insights into the effect on the overall phenotype and disease evolution. RESULTS: A Turkish boy is homozygous for the c.531delA deletion, a recurrent mutation in Turkey; an adult Italian male is compound heterozygous for two nonsense mutations, c.243G>A and c.541C>T, while an Italian boy is homozygous for the splicing c.683_693+1del variant. The identified mutations have already been reported in PN patients who developed hematologic or skin cancer. Aberrant mRNAs of all four mutated alleles could be identified confirming that transcripts of USB1 main isoform either carrying stop codons or mis-spliced may at least partially escape nonsense-mediated decay. CONCLUSIONS: Our study addresses the need of gathering insights on genotype-phenotype correlations in newly described PN patients, by transcript analysis and information on disease evolution of reported patients with the same pathogenic variants.

Complete response to anti-PD-1 nivolumab in massive skin metastasis from melanoma: efficacy and tolerability in an elderly patient.

The advent of immune checkpoint inhibitors anti-PD-1/PD-L1 has delivered new and effective treatment options with proven clinical benefits for patients affected by metastatic melanoma. The 30-40% of treated patients experience an objective tumour regression, with a significantly prolonged survival and an improved quality of life. Here, we report a case of a 75-year-old Caucasian woman affected by a massive cutaneous metastasis from a BRAF wild-type melanoma who experienced multiple relapses after surgery and repeated electrochemotherapy treatments. A poor response was observed after systemic therapy with ipilimumab, whereas a marked reduction in the lesion size was obtained during the treatment with nivolumab, with an objectively complete response after 6 months. Therapy was well tolerated, without immune-related side effects. During treatment, LDH levels decreased up to the standard values. Our experience confirms the good efficacy and the safety of anti-PD-1 nivolumab for the treatment of relapsed or refractory massive skin lesions, also in elderly patients.

The efficacy of minocycline in inflammatory dermatoses: a case of prurigo pigmentosa of prepubescent onset in Western world.

We present a 21-year-old Italian girl with an 8-year history of missed diagnosed prurigo pigmentosa (PP) successfully treated with short monotherapy with minocycline. PP is an inflammatory disease characterized by recurrent pruritic erythematous papules followed by reticular hyperpigmentation usually located on the trunk. About 300 cases of PP have been described mainly in Japan, whereas only few cases have been reported in Italy. This report shows that minocycline is rapidly effective probably through its ability to scavenge reactive oxygen species and to inhibit the chemotaxis and neutrophil function. Other than its ethnic rarity, this case is very interesting because it is the third case of PP in Caucasian patient with prepubescent onset.

Temporal correlation between the first melanoma and the first noncutaneous tumor in CKDN2A genotyped patients.

CDKN2A pathogenic variants are well known to be associated with cutaneous melanoma and noncutaneous tumors (NCTs). Herein, we investigated the temporal correlation between the first cutaneous melanoma and NCT both in CDKN2A mutation carriers (MUT) and in wild-type melanoma patients, a poorly explored issue to date. Two hundred forty-five cutaneous melanoma patients were genotyped for the CDKN2A gene and divided into 51 MUT and 189 wild-type; the remaining five variant carriers were excluded from the analyses. MUT developed a significantly higher number of cutaneous melanoma than wild-type, while 13.7% in both genotyped groups received a diagnosis of at least one malignant NCT, without statistically significant differences. The onset of the first cutaneous melanoma preceded that of the first malignant or benign NCT in both MUT and wild-type patients by an average of 4.5 and 3.02 years, respectively. Considering only malignant tumors, the diagnosis of melanoma preceded that of the first NCT on an average of 8 and 4.34 years, in MUT and wild-type patients respectively. We emphasize the relevance to adopt a global vision for the primary and secondary surveillance of patients affected by cutaneous melanoma, not only limited to high-risk for multiple primary skin cancers but also to NCT that may develop several years after the diagnosis of the first cutaneous melanoma.

COVID-19 first lockdown and outpatient hospital setting: a single center, real life study focusing on pattern changes in patients' ethnicities and treated dermatoses.

BACKGROUND: During the first Italian lockdown period, the imponent amount of hospital COVID-19 patients forced the healthcare system to re-organize visits but no information are available on outpatient ethnical patterns. Here we evaluated healthcare management changes on dermatological outpatient non-surgical settings visits during the SARS-CoV-2 pandemic. METHODS: In this retrospective study we collected data of scheduled, performed and not-performed visits, together with patients' characteristics (i.e., age, gender) with a particular attention for ethnicities among the outpatients accessing during the first Italian lockdown (March 5-April 30, 2020). Then, we compared these data with the corresponding ones in 2019 (before COVID-19 pandemic). RESULTS: During the Italian lockdown the dermatological department registered a great decrement (-83.5%, P<0.001) in visits compared to the corresponding time period in 2019. Performed and scheduled visits to non-oncological stable patients together with emergency accesses to dermatology decreased. Non-Italian patients decreased accesses, especially the South East Asians (-70.4%) and North Africans (-90.0%). CONCLUSIONS: Hospitals policy and mass media deeply condition the public opinion, and this aspect may explain a different access to the hospital among non-Italian patients. Telemedicine should be promoted especially among non-Italian communities in Italy to overgo patients' skepticism and incentivize prevention and early treatment in dermatological conditions.

North Italy: Welcome to the Tropics!

We describe a case of cutaneous Larva Migrans in an 8-year-old Caucasian girl. The lesion appeared ten days after a bath in the river in a valley in the north-east of Piedmont. The patient was successfully treated with Albendazole 400 mg daily for 5 days. Autochthonous cases are rare, particularly in northern Italy. Probably the high temperatures and the high degree of humidity favored by the climate changes to which Europe is subjected are favorable to the development of larvae. The diagnosis of cutaneous Larva Migrans should, therefore, be considered also in individuals who have not traveled in geographic areas at risk for the climate.

Melanoma-prone families: new evidence of distinctive clinical and histological features of melanomas in CDKN2A mutation carriers.

Germline mutations on the CDKN2A gene, the most important known genetic factors associated with cutaneous melanomas (CMs), predispose carriers to multiple primary CMs (MPMs) with higher frequency and younger onset compared to non-carriers. Most of the largest published studies concerning clinical and histological characteristics of CMs with CDKN2A mutation carriers did not specify if the described CMs are first or subsequent to the first, and they used sporadic CMs from non-genotyped patients as controls. We conducted a single-centre observational study to compare clinical and histological CM features of 32 unrelated carriers (MUT) of 5 germline CDKN2A mutations (one of which was never previously described) compared to 100 genotyped wild-type (WT) patients. We stratified the data based on time of diagnosis, anatomical site and histological subtype of CMs, demonstrating several significant unreported differences between the two groups. MUT developed a higher number of dysplastic nevi and MPMs. We proved for the first time that anatomical distribution of CMs in MUT was independent of gender, unlike WTs. MUTs developed in situ and superficial spreading melanomas (SSMs) more frequently, with significantly higher number of SSMs on the head/neck. In MUTs, Breslow thickness was significantly lower for all invasive CMs. When CMs were stratified on the basis of the time of occurrence, statistical significance was maintained only for SSMs subsequent to the first. In WTs, Clark level was significantly higher, and ulceration was more prevalent than in MUTs. Significant differences in ulceration were observed only in SSMs. In nodular CMs, we did not find differences in terms of Breslow thickness or ulceration between WTs and MUTs. In situ CMs developed 10 years earlier in MUTs with respect to WTs, whereas no significant differences were observed in invasive CMs. In contrast to those reported previously by other authors, we did not find a difference in skin phototype.

An unusual cutaneous infection caused by Mycobacterium marinum.

Introduction.Mycobacterium marinum is a non-tubercular mycobacterium residing in fresh or salt water (in tropical or temperate areas); it is a fish and human pathogen, and in immunocompromised patients can cause severe cutaneous and subcutaneous infections. Case presentation. A 46-year-old white man who underwent immunosuppressive therapy was admitted to our department in May 2016 for skin lesions previously diagnosed as 'unusual erysipelas'. We rejected the hypothesis of erysipelas, due to the clinical features, and our diagnostic hypotheses were oriented towards sporotrichosis, atypical mycobacteriosis, cutaneous tuberculosis and cutaneous sarcoidosis. Histological examination performed after a skin biopsy was compatible with a diagnosis of sporotrichosis. However, PCR performed on fresh tissue demonstrated the presence of M. marinum. Conclusion. The case reported is interesting for the unusual clinical localization and modality of infection. The patient became infected by contact with contaminated remains or in the sea, in a geographical area not endemic for M. marinum. The previous state of immunosuppression favoured infection; however, the presence of M. marinum in this area suggests a possible tropicalization of the water of the Mediterranean Sea. To our knowledge, this case is the only one reported in the literature with this modality of infection and in that geographical area.