Publications by authors named "Nicola Pimpinelli"

122 Publications

Single ALA-PDT irradiation induces increase in mast cells degranulation and neuropeptide acute response in chronic venous ulcers: A pilot study.

Photodiagnosis Photodyn Ther 2021 Feb 15:102222. Epub 2021 Feb 15.

Department of Health Sciences, Division of Dermatology, University of Florence, Italy.

Background: The behavior of mast cells, their interaction with neuronal cells or nerve fibers, the expression of neuropeptides and the distribution of skin neuronal cells or nerve fibers after ALA-PDT treated vs untreated chronic wounds were investigated.

Methods: Nineteen patients suffering from chronic venous ulcers (CVU) were enrolled in this study. Skin samples from wound bed before and after irradiation with ALA-PDT were taken. All specimens were anonymized and analyzed by immunohistochemistry.

Results: After completion of ALA-PDT, mast cells showed an increase of degranulation index and expression of NGF and VIP. Amongst all the neuronal mediators tested, all except for SP showed an increase of cellular expression after ALA-PDT therapy.

Conclusion: Our study shows preliminary evidences that ALA-PDT induces rapid recruitment of mast cells around dermal fibers in chronic venous ulcers. This finding is also associated with increase in expression of multiple peripheral neuropeptides except SP by skin neuronal cells. ALA-PDT may promote healing of chronic venous ulcers via stimulation of quiescent peripheral nerves, possibly after release of inflammatory molecules by degranulating mast cells.
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http://dx.doi.org/10.1016/j.pdpdt.2021.102222DOI Listing
February 2021

Retrospective data from a dedicated outpatient dermatology clinic for hemato-oncology patients.

Int J Dermatol 2021 Feb 11. Epub 2021 Feb 11.

Section of Dermatology, Department of Health Sciences, University of Florence, Florence, Italy.

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http://dx.doi.org/10.1111/ijd.15462DOI Listing
February 2021

Italian expert-based recommendations on the use of photo(chemo)therapy in the management of mycosis fungoides: Results of an e-Delphi consensus.

Photodermatol Photoimmunol Photomed 2021 Jan 18. Epub 2021 Jan 18.

Dip. Scienze della Salute, sezione Dermatologia, Universita' degli Studi di Firenze, Firenze, Italy.

Background: Phototherapy is a mainstay for the treatment of MF. However, there is scarce evidence for its use, mostly due to the lack of a unified schedule.

Aims: The primary aim of this study was to establish the first structured, expert-based consensus regarding the indications and technical schedules of NB-UVB and PUVA for MF. The secondary aim was to determine the consensus level for each specific item.

Materials & Methods: E-delphi study. Item-specific expert consensus was defined as the number of "Totally Agree" results to ≥80% of the panelists. Cronbach alpha index ≥0.7 was used as a measure of homogeneity in the responses among questions related to the same topic.

Results: Overall, there was a high homogeneity among responders (0.78). On specific topics, the highest grade was observed for technical items (0.8) followed by indications for early (0.73) and advanced stages (0.7).

Conclusions: Items related to the most canonical indications of phototherapy and to treatment schedules showed the highest agreements rates. There is consensus about the use of standardized treatment schedules for the induction and consolidation phases for NB-UVB and PUVA in MF.
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http://dx.doi.org/10.1111/phpp.12658DOI Listing
January 2021

Complete remission with brentuximab vedotin in a case of primary cutaneous gamma-delta T-cell lymphoma relapsed after allogeneic stem cell transplantation.

Int J Dermatol 2021 Jan 7. Epub 2021 Jan 7.

Section of Dermatology, Department of Health Sciences, University of Florence Medical School, Florence, Italy.

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http://dx.doi.org/10.1111/ijd.15393DOI Listing
January 2021

Phenotypical Markers, Molecular Mutations, and Immune Microenvironment as Targets for New Treatments in Patients with Mycosis Fungoides and/or Sézary Syndrome.

J Invest Dermatol 2021 Mar 5;141(3):484-495. Epub 2020 Nov 5.

Dermatologic Clinic, Department of Medical Sciences, University of Turin, Turin, Italy.

Primary cutaneous lymphomas encompass a wide spectrum of rare lymphoproliferative disorders originating in the skin, among which, mycosis fungoides (MF) is the most common subtype. The treatment of this disease is based on skin-directed therapies eventually in association with biologic response modifiers in the early phases, whereas in patients with the advanced stages, several therapeutic strategies can be used including mono and/or polychemotherapy and bone marrow transplantation. In recent years, the identification of specific markers (phenotypical, immunological, and molecular) has led to the development of several studies (including two randomized phase III trials). The results of these studies are modifying our therapeutic strategy toward a personalized treatment approach in which the clinical characteristics of the patients and tumor-node-metastasis-blood stage are considered together with the expression of specific markers (i.e., a CD30-positive expression for the use of brentuximab vedotin). This review will provide a comprehensive scenario of the main phenotypical, molecular, and immunological markers related to MF pathogenesis and disease evolution, which could represent the target for the development of innovative effective treatments in this disease.
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http://dx.doi.org/10.1016/j.jid.2020.07.026DOI Listing
March 2021

Prognostic significance of Bcl-2 expression in primary cutaneous B-cell lymphoma: a reappraisal.

G Ital Dermatol Venereol 2020 Oct 16. Epub 2020 Oct 16.

Dermatology Unit, Department of Health Sciences, University of Florence Medical School, Florence, Italy.

Introduction: Bcl-2 family protein plays an important role in apoptosis and its overexpression is protects neoplastic cell from apoptotic stimuli. Cutaneous B-cell lymphoma are rare non-Hodgkin lymphomas and can be classified in primary forms, featuring an exclusive skin-involvement at diagnosis, and cutaneous spread of a nodal disease. Such a distinction is not trivial, owing to different prognosis (indolent vs. aggressive) and therapeutic management.

Evidence Acquisition: Bcl-2 expression at immunohistochemistry can be crucial in differential diagnosis between cutaneous and systemic disease, as well as between the different primary cutaneous forms.

Evidence Synthesis: In the last few years, an animated debate on the prognostic role of BCL-2 overexpression at molecular analysis have been developed in cutaneous B-cell lymphoma.

Conclusions: Bcl-2 expression have a diagnostic role more than prognostic in primary cutaneous B-cell lymphomas.
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http://dx.doi.org/10.23736/S0392-0488.20.06622-5DOI Listing
October 2020

Intellectual Disability and Hidradenitis Suppurativa.

Dermatology 2020 Oct 9:1-3. Epub 2020 Oct 9.

Section of Dermatology, Department of Health Sciences, University of Florence, Florence, Italy,

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http://dx.doi.org/10.1159/000510655DOI Listing
October 2020

Anetoderma secondary to cutaneous mastocytosis: a rare occurrence?

G Ital Dermatol Venereol 2020 Sep 17. Epub 2020 Sep 17.

Division of Dermatology and Venereology, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy.

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http://dx.doi.org/10.23736/S0392-0488.20.06596-7DOI Listing
September 2020

Reply to E. Hindié.

J Clin Oncol 2020 09 23;38(27):3238-3240. Epub 2020 Jul 23.

Andrea Maurichi, MD, Melanoma and Sarcoma Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy; Rosalba Miceli, PhD, Medical Statistics, Biometry and Bioinformatics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy; Hanna Eriksson, MD, PhD, Department of Oncology, Theme Cancer, Karolinska University Hospital, and Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden; Julia Newton-Bishop, MD, FRCP; Jérémie Nsengimana, PhD; and May Chan, PGD, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, United Kingdom; Andrew J. Hayes, MA, MBBS, MD, PhD and Kara Heelan, MB, BCH, BAO, MRCPI, MD, Sarcoma and Melanoma Units and Skin Unit, The Royal Marsden National Health Service (NHS) Foundation Trust, London, United Kingdom; David Adams, PhD, Experimental Cancer Genetics, Wellcome Trust Sanger Institute, Hinxton, United Kingdom; Roberto Patuzzo, MD, Melanoma and Sarcoma Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy; Francesco Barretta, MS, PhD, Medical Statistics, Biometry and Bioinformatics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy; Gianfranco Gallino, MD, Melanoma and Sarcoma Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy; Catherine Harwood, MA, MD, PhD, FRCP and Daniele Bergamaschi, PhD, Queen Mary University of London, London, United Kingdom; Dorothy Bennett, FMedSci, PhD, Molecular and Clinical Sciences Research Institute, St George's, University of London, London, United Kingdom; Konstantinos Lasithiotakis, MD, PhD, York Teaching Hospital NHS Foundation Trust, York, United Kingdom and Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy; Paola Ghiorzo, MD, PhD and Bruna Dalmasso, MD, University Hospital of Genoa, Genoa, Italy; Ausilia Manganoni, MD and Francesca Consoli, MD, University Hospital of Brescia, Brescia, Italy; Ilaria Mattavelli, MD; Consuelo Barbieri, MD; and Andrea Leva, MD, Melanoma and Sarcoma Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy; Umberto Cortinovis, MD, Plastic and Reconstructive Surgical Unit, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy; Vittoria Espeli, MD and Cristina Mangas, MD, PhD, Istituto Oncologico Svizzera Italiana, Ospedale Regionale Bellinzona e Valli, Bellinzona, Switzerland; Pietro Quaglino, MD; Simone Ribero, MD, PhD; and Paolo Broganelli, MD, University Hospital of Turin, Turin, Italy; Giovanni Pellacani, MD, University Hospital of Modena, Modena, Italy; Caterina Longo, MD, Arcispedale S. Maria Nuova, Reggio Emilia, Italy; Corrado Del Forno, MD, University Hospital of Pavia, Pavia, Italy; Lorenzo Borgognoni, MD and Serena Sestini, MD, Ospedale S. Maria Annunziata, Tuscan Cancer Institute, Florence, Italy; Nicola Pimpinelli, MD, PhD and Sara Fortunato, MD, Division of Dermatology, University of Florence, Florence, Italy; Alessandra Chiarugi, MD and Paolo Nardini, MD, Institute for Cancer Research and Prevention, Florence, Italy; Elena Morittu, PhD and Antonio Florita, PhD, Scientific Director's Office, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy; Mara Cossa, MD, PhD; Barbara Valeri, MD; Massimo Milione, MD, PhD; and Giancarlo Pruneri, MD, Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy; Odysseas Zoras, MD, PhD, University Hospital of Heraklion, Heraklion, Greece; Andrea Anichini, PhD and Roberta Mortarini, PhD, Immunobiology of Human Cancers Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy; and Mario Santinami, MD, Melanoma and Sarcoma Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.

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http://dx.doi.org/10.1200/JCO.20.01460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499609PMC
September 2020

Novel Therapeutic Approaches and Targets for the Treatment of Atopic Dermatitis.

Curr Pharm Biotechnol 2021 ;22(1):73-84

Dermatology Unit, Department of Health Sciences, University of Florence, Florence, Italy.

Background: Atopic Dermatitis is one of the most common inflammatory skin diseases, with an estimated prevalence of 2.1-4.9% in adults. Recently, advances in Atopic Dermatitis understanding have highlighted the role of inappropriate Th2 cell activation as principally involved in its pathogenesis. Other immune pathways seem to play a key role in the complex Atopic Dermatitis pathophysiology. The anti-IL-4/IL-13 was the first monoclonal antibody approved for the treatment of moderate to severe atopic dermatitis in adult patients whose disease is resistant to other therapies. Following its interesting results in terms of efficacy and safety, new therapies are in development.

Methods: Monoclonal antibodies targeting IL-5, IL-13, IL-17, IL-22, IL-23, IL-31 and TSLP are currently under investigation on patients with moderate to severe Atopic Dermatitis patients. Moreover, small molecules like anti-PDE4 and JAK inhibitors may also represent other treatment possibilities.

Results: In this section, we present data available on the efficacy and safety of newer molecules for the treatment of Atopic Dermatitis.

Conclusion: The extreme clinical heterogeneity and the chronic progression of Atopic Dermatitis need for newer, safer and more effective treatments, able to control the disease and to improve the quality of life of affected patients. Dupilumab, and the other monoclonal antibodies and small molecules currently under investigation aim to improve the clinical management of Atopic Dermatitis.
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http://dx.doi.org/10.2174/1389201021666200611112755DOI Listing
February 2021

Is biologic treatment of hidradenitis suppurativa during the COVID-19 pandemic different from psoriasis biologic treatment?

J Dermatolog Treat 2020 Jun 19. Epub 2020 Jun 19.

Department of Health Sciences, Section of Dermatology, University of Florence, Florence, Italy.

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http://dx.doi.org/10.1080/09546634.2020.1771256DOI Listing
June 2020

Factors Affecting Sentinel Node Metastasis in Thin (T1) Cutaneous Melanomas: Development and External Validation of a Predictive Nomogram.

J Clin Oncol 2020 05 13;38(14):1591-1601. Epub 2020 Mar 13.

Melanoma and Sarcoma Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori di Milano, Milan, Italy.

Purpose: Thin melanomas (T1; ≤ 1 mm) constitute 70% of newly diagnosed cutaneous melanomas. Regional node metastasis determined by sentinel node biopsy (SNB) is an important prognostic factor for T1 melanoma. However, current melanoma guidelines do not provide clear indications on when to perform SNB in T1 disease and stress an individualized approach to SNB that considers all clinicopathologic risk factors. We aimed to identify determinants of sentinel node (SN) status for incorporation into an externally validated nomogram to better select patients with T1 disease for SNB.

Patients And Methods: The development cohort comprised 3,666 patients with T1 disease consecutively treated at the Istituto Nazionale Tumori (Milan, Italy) between 2001 and 2018; 4,227 patients with T1 disease treated at 13 other European centers over the same period formed the validation cohort. A random forest procedure was applied to the development data set to select characteristics associated with SN status for inclusion in a multiple binary logistic model from which a nomogram was elaborated. Decision curve analyses assessed the clinical utility of the nomogram.

Results: Of patients in the development cohort, 1,635 underwent SNB; 108 patients (6.6%) were SN positive. By univariable analysis, age, growth phase, Breslow thickness, ulceration, mitotic rate, regression, and lymphovascular invasion were significantly associated with SN status. The random forest procedure selected 6 variables (not growth phase) for inclusion in the logistic model and nomogram. The nomogram proved well calibrated and had good discriminative ability in both cohorts. Decision curve analyses revealed the superior net benefit of the nomogram compared with each individual variable included in it as well as with variables suggested by current guidelines.

Conclusion: We propose the nomogram as a decision aid in all patients with T1 melanoma being considered for SNB.
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http://dx.doi.org/10.1200/JCO.19.01902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213590PMC
May 2020

Tuscan Consensus on the diagnosis, treatment and follow up of adult atopic dermatitis.

G Ital Dermatol Venereol 2020 Jun 10;155(3):253-260. Epub 2020 Mar 10.

Unit of Allergological and Pediatric Dermatology, Department of Health Sciences, University of Florence, Florence, Italy.

Atopic dermatitis (AD) is an inflammatory disease with a chronic-relapsing course that is intensely itchy. A correct diagnosis of AD in adults and consequently appropriate clinical therapeutic management is a critical issue for extreme clinical expression heterogeneity and various grades of disease severity. In order to ensure high levels of care and standardization of clinical therapeutic management of Adult AD, the decision was taken to create an AD Tuscan Consensus Group (the Group), to work on and validate a consensus based regional clinical-therapeutic management model. The aims of the Group were to find agreement on the criteria for diagnosis, scoring of severity, multidisciplinary approach and treatment of adult atopic dermatitis and to create an easier way for patients to access specialized dermatology outpatient services and importantly to reduce waiting lists and costs related to the management of AD. The Tuscan Consensus Group adopted a simplified Delphi method, in three principal steps: 1) literature metanalysis and critical review of patient's clinical experience to identify the main areas considered questionable or uncertain; 2) discussion of those areas requiring consensus and statement definition through four different sub-committees (diagnosis, severity evaluation, scoring and comorbidities); 3) a consensus based simplified process with final approval of each statement by plenary vote with approval >80% of the participants. The Group here presents and discusses the consensus based recommendation statements on adult atopic dermatitis.
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http://dx.doi.org/10.23736/S0392-0488.19.06527-1DOI Listing
June 2020

Second neoplasm in cutaneous T-cell lymphoma patients: a marker of worse prognosis?

G Ital Dermatol Venereol 2019 Dec 4. Epub 2019 Dec 4.

Dermatology Unit, Department of Health Sciences, University of Florence Medical School, Florence, Italy.

Background: Epidemiologic studies have shown that cutaneous T-cell lymphoma (CTCL) patients have an increased risk of the development of a second neoplasm (SN). The aim of our study was to evaluate the risk of SN and to correlate any possible change in CTCL course after the diagnosis of a subsequent neoplasm.

Methods: A ten-year retrospective study was carried out in two centres (Bologna and Florence) all the patients who developed a SN six months at least after a CTCL were included. Two groups were selected: Group 1 featuring patients who developed a SN and Group 2 characterised by patients affected by MF age and sex-matched with Group 1 (control group). Data concerning any stage change after SN, time between MF and SN onset, modified Severity Weighted Assessment Tool (mSWAT) score before and after SN, concerning Group 1 and after a median time of 36 months in Group 2 were analysed.

Results: Thirteen patients were detected. Before SN onset, early MF patients were mainly present, while SN cases in advanced-stage (ten patients) were observed. SN type predominant was lung cancer, along with prostate and pancreatic cancer, while isolated cases presenting with vulvar, colon, mammalian, prostate cancer along with Hodgkin's Lymphoma. Mean mSWAT at MF diagnosis and after SN showed a significant difference (p value=0.0037). After SN diagnosis, nine patients experienced an MF stage progression and ten patient died at follow up.

Conclusions: In all the instances, statistical analysis showed that mean mSWAT score before/after SN diagnosis had a significantly difference (p value=0.0037) suggesting that patients with a SN may have a worse clinical outcome. By secreting immunosuppressive cytokines or recruiting immunosuppressive cells, a sort of mutual help between the two neoplasms may be prompted. Our data suggest that SN development in MF patients may be regarded as a worse prognostic marker.
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http://dx.doi.org/10.23736/S0392-0488.19.06510-6DOI Listing
December 2019

Melanoma survival with classification and regression trees analysis: a complement for the communication of prognosis to patients.

G Ital Dermatol Venereol 2019 Jun 17. Epub 2019 Jun 17.

Romagna Cancer Registry, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Forlì-Cesena, Italy.

Background: Prognostic factors in cutaneous melanoma are commonly evaluated by the Cox proportional hazard model. However, the interpretation of the effect of multiple variables is not straightforward. Classification and Regression Trees Analysis (CART), which allows a more friendly data evaluation, could be a valid integration of the message from Cox model.

Methods: The CART algorithm splits up data, creating a "tree" of groups of patients with different profiles for risk of death. Results are easy to interpret in clinical practice. A total of 2,692 patients with invasive cutaneous melanoma registered in Romagna (northern Italy) between 1993-2012 and followed-up until the end of 2013 were included. The Cox model and CART analysis were applied to sex, patient age, histological subtype, Breslow's tumour thickness, ulceration, site of disease, and Clark level.

Results: The CART analysis identified 15 categories which were collapsed into five classes with statistically different survival. The best prognostic group (10-year observed survival, 99.1%) included subjects with Breslow's thickness ≤ 0.78 mm and age 16-81 years. The worst prognostic group (10-year observed survival, 35.8%) comprised subjects with thickness ≥ 3.75 mm and age 16-96 years. According to the Cox model, patient age, histological subtype, Breslow thickness, ulceration, and site of disease had a significant independent prognostic value.

Conclusions: CART and Cox models provided consistent results. CART seemed friendlier in its interpretation and it could facilitate the communication of risk.
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http://dx.doi.org/10.23736/S0392-0488.19.06402-2DOI Listing
June 2019

Primary cutaneous CD8+ CD30+ lymphoproliferative disorder in a patient with acquired CD4 immunodeficiency.

G Ital Dermatol Venereol 2019 Jun 12. Epub 2019 Jun 12.

Dermatology Unit, Department of Health Sciences, University of Florence Medical School, Florence, Italy.

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http://dx.doi.org/10.23736/S0392-0488.19.06367-3DOI Listing
June 2019

Melanoma diagnosis: traumatic impact of the event on the patient.

G Ital Dermatol Venereol 2019 Jun 12. Epub 2019 Jun 12.

Division Dermatology, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy.

Background: The aim of our study was to consider the distressing impact of the diagnosis in a group of patients with metastatic melanoma, and the effects it could have on the quality of life of the patients.

Methods: We proposed a Impact Event Scale (IES-R) to a group of 31 patients. The patients were positive to the Distress Thermometer (DS), and accepted the psychological support. After six months from the start of the treatment we made a semi-structured interview of 10 multiple choice questions.

Results: Sixtyfive (65) % women and 50% men report that all the event related to the disease, cause emotions that recall the disease. Eightytwo (82) % women, compared to 50% men, report that the thought of their medical condition tends to affect their quality of sleep; the patients report feelings of anger and irritation (41% of the women and 78% of the men).

Conclusions: The traumatic aspects following the diagnosis of melanoma burst powerfully into the life of these patients, who show different reactions, also according to gender.
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http://dx.doi.org/10.23736/S0392-0488.19.06348-XDOI Listing
June 2019

Blastic Plasmacytoid Dendritic Cell Neoplasm: State of the Art and Prospects.

Cancers (Basel) 2019 Apr 28;11(5). Epub 2019 Apr 28.

Division of Diagnostic Haematopathology, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141 Milano, Italy.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare tumour, which usually affects elderly males and presents in the skin with frequent involvement of the bone-marrow, peripheral blood and lymph nodes. It has a dismal prognosis, with most patients dying within one year when treated by conventional chemotherapies. The diagnosis is challenging, since neoplastic cells can resemble lymphoblasts or small immunoblasts, and require the use of a large panel of antibodies, including those against CD4, CD56, CD123, CD303, TCL1, and TCF4. The morphologic and in part phenotypic ambiguity explains the uncertainties as to the histogenesis of the neoplasm that led to the use of various denominations. Recently, a series of molecular studies based on karyotyping, gene expression profiling, and next generation sequencing, have largely unveiled the pathobiology of the tumour and proposed the potentially beneficial use of new drugs. The latter include SL-401, anti-CD123 immunotherapies, venetoclax, BET-inhibitors, and demethylating agents. The epidemiologic, clinical, diagnostic, molecular, and therapeutic features of BPDCN are thoroughly revised in order to contribute to an up-to-date approach to this tumour that has remained an orphan disease for too long.
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http://dx.doi.org/10.3390/cancers11050595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562663PMC
April 2019

Time trends and age-period-cohort analysis of cutaneous malignant melanoma incidence rates in the Romagna Region (northern Italy), 1986-2014.

Melanoma Res 2020 04;30(2):198-205

Romagna Cancer Registry, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola (FC), Italy.

After a long-term increase, the incidence of cutaneous malignant melanoma has stabilized recently or even decreased in several populations of North-western Europe, USA, Canada, Australia and New Zealand, but not in southern Europe. The incidence trends of primary invasive cutaneous malignant melanoma (International Classification of Diseases, 10th revision, codes C43.0-C43.9) in the Romagna Region (northern Italy, 1.2 million inhabitants) for the period 1986-2014 were analysed with an age-period-cohort modelling approach. The series included 2466 men and 2481 women, a total of 4947 patients. Using the method of model building, the best-fitting models were found to be an age-drift model for men and an age-period model for women. Among men, the age-specific incidence rates increased in each successive cohort born between 1916 and 1981 with an attenuation of the trend for younger ones in the last cohorts. Among younger women, a slight decrease occurred for the cohorts born after 1961. For men, the quasi-parallel appearance of incidence curves by age group and cohort on a log scale suggested that the observed change was explained by a linear cohort effect. For women, the curves tended to overlap, suggesting an interaction between age and cohort that could be explained as a nonlinear period effect. In conclusion, the long-term upward incidence trend in the study area is stabilizing among women and an attenuation of the increasing trend is occurring among younger men in the most recent cohorts. These observations need to be confirmed with longer-term studies.
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http://dx.doi.org/10.1097/CMR.0000000000000570DOI Listing
April 2020

EGFR/uPAR interaction as druggable target to overcome vemurafenib acquired resistance in melanoma cells.

EBioMedicine 2019 Jan 2;39:194-206. Epub 2019 Jan 2.

Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Viale G.B. Morgagni, 50, 50134 Florence, Italy.

Background: BRAF inhibitor (BRAF-I) therapy for melanoma patients harboring the V600E mutation is initially highly effective, but almost all patients relapse within a few months. Understanding the molecular mechanisms behind BRAF-I responsiveness and acquired resistance is therefore an important issue. Here we assessed the role of urokinase type plasminogen activator receptor (uPAR) as a potentially valuable biomarker in the acquisition of BRAF-I resistance in V600E mutant melanoma cells.

Methods: We examined uPAR and EGFR levels by real time PCR and western blot analysis. uPAR loss of function was realized by knocking down uPAR by RNAi or using M25, a peptide that uncouples uPAR-integrin interaction. We investigated uPAR-β1integrin-EGFR association by co-immunoprecipitation and confocal immuno-fluorescence analysis. Acquired resistance to BRAF-I was generated by chronic exposure of cells to vemurafenib.

Findings: We proved that uPAR knockdown in combination with vemurafenib inhibits melanoma cell proliferation to greater extent than either treatment alone causing a decrease in AKT and ERK1/2 phosphorylation. Conversely, we demonstrated that uPAR enforced over-expression results in reduced sensitivity to BRAF inhibition. Moreover, by targeting uPAR and EGFR interaction with an integrin antagonist peptide we restored vemurafenib responsiveness in melanoma resistant cells. Furthermore, we found significant detectable uPAR and EGFR levels in tumor biopsies of 4 relapsed patients.

Interpretation: We disclosed an unpredicted mechanism of reduced sensitiveness to BRAF inhibition, driven by elevated levels of uPAR and identified a potential therapeutic strategy to overcome acquired resistance.

Funds: Associazione Italiana Ricerca sul Cancro (AIRC); Ente Cassa di Risparmio di Firenze.
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http://dx.doi.org/10.1016/j.ebiom.2018.12.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355443PMC
January 2019

Management of severe bio-radiation dermatitis induced by radiotherapy and cetuximab in patients with head and neck cancer: emphasizing the role of calcium alginate dressings.

Support Care Cancer 2019 Aug 19;27(8):2957-2967. Epub 2018 Dec 19.

Radiation Oncology, Azienda Ospedaliero - Universitaria Careggi, University of Florence, largo Brambilla 3, 50134, Florence, Italy.

Purpose: Severe bio-radiation dermatitis may develop in patients treated with concurrent radiotherapy and cetuximab for head and neck squamous cell carcinoma. The aim of our work was to report on the impact of a grade-specific management approach on treatment tolerability.

Methods: Concomitant radiotherapy and cetuximab was prescribed for patients deemed ineligible for cisplatin-based chemoradiation. Since 2014, an advanced wound care nursing team was established in our clinic to implement a standardized policy for skin toxicity. A central role of calcium alginate dressings was defined in our management algorithm. The correlation between patient, disease, and treatment features with severe bio-radiation dermatitis and treatment tolerability was evaluated.

Results: Between 2007 and 2018, 51 patients were treated at our center with radiotherapy and cetuximab. The incidence of G3/G4 bio-radiation dermatitis was 43.1%. Comparing two consecutive cohorts of 26 and 25 patients treated before and after January 2014, respectively, the adoption of a grade-specific dermatitis management allowed to improve treatment tolerability. A mean radiation treatment interruption of 8.42 days (SD, 6.73; 95% CI 5.7-11.1) was reduced to 0.86 days (SD, 2.66; 95% CI - 0.28-2.02) in the more recent group (p < 0.0001). Mean relative dose intensity of cetuximab was also significantly higher (86.3% vs 74.5%, p = 0.0226).

Conclusions: Routine involvement of an advanced wound care management team and early consideration for calcium alginate dressings in case of moist desquamation should be warranted to ensure high compliance to radiotherapy and cetuximab in patients with head and neck cancer.
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http://dx.doi.org/10.1007/s00520-018-4606-2DOI Listing
August 2019

Eosinophilic dermatosis of hematologic malignancy: A retrospective cohort of 37 patients from an Italian center.

J Am Acad Dermatol 2019 07 5;81(1):246-249. Epub 2018 Dec 5.

Division of Dermatology, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy.

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http://dx.doi.org/10.1016/j.jaad.2018.11.048DOI Listing
July 2019

Clindamycin as unique antibiotic choice in Hidradenitis Suppurativa.

Dermatol Ther 2019 03 21;32(2):e12792. Epub 2018 Dec 21.

Department of Surgery and Translational Medicine, Section of Dermatology, University of Florence, Florence, Italy.

The rifampicin (RF)-clindamycin (CL) combination is recommended as first line therapy in moderate to severe Hidradenitis Suppurativa (HS) by European S1 guidelines. Although prolonged use of RF should be discouraged, there are currently few alternatives to this combination therapy. The aim of the present study was to assess retrospectively the efficacy of oral CL monotherapy in patients diagnosed with HS. In the period January 2017-May 2018, 31 HS patients who received a 300 mg b.i.d. oral dose of CL were studied retrospectively. Efficacy of the treatment was evaluated by comparing the main HS severity scores (Sartorius score modified by Revuz, Hidradenitis Suppurativa Physician Global Assessment [HS-PGA] and International Hidradenitis Suppurativa Severity Score System [IHS4]) before (W0) and after (W12) CL oral therapy. CL efficacy was demonstrated by the extreme and significant reduction of all three disease severity parameters during the 12-week period (p ≤ .01). There was also a statistically significant change in the mean visual analogue scale for pain. The present study demonstrates the efficacy of oral CL monotherapy as RF-sparing regimen alternative to RF-CL combination in a selected group of patients.
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http://dx.doi.org/10.1111/dth.12792DOI Listing
March 2019

Blastic plasmacytoid dendritic cell neoplasm: genomics mark epigenetic dysregulation as a primary therapeutic target.

Haematologica 2019 04 31;104(4):729-737. Epub 2018 Oct 31.

Division of Haematopathology, IEO European Institute of Oncology IRCCS, Milan, Italy.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy for which there is still no effective therapy. In order to identify genetic alterations useful for a new treatment design, we used whole-exome sequencing to analyze 14 BPDCN patients and the patient-derived CAL-1 cell line. The functional enrichment analysis of mutational data reported the epigenetic regulatory program to be the most significantly undermined (<0.0001). In particular, twenty-five epigenetic modifiers were found mutated (e.g. was the most frequently affected (28.6% of cases). To evaluate the impact of the identified epigenetic mutations at the gene-expression and Histone H3 lysine 27 trimethylation/acetylation levels, we performed additional RNA and pathology tissue-chromatin immunoprecipitation sequencing experiments. The patients displayed enrichment in gene signatures regulated by methylation and modifiable by decitabine administration, shared common H3K27-acetylated regions, and had a set of cell-cycle genes aberrantly up-regulated and marked by promoter acetylation. Collectively, the integration of sequencing data showed the potential of a therapy based on epigenetic agents. Through the adoption of a preclinical BPDCN mouse model, established by CAL-1 cell line xenografting, we demonstrated the efficacy of the combination of the epigenetic drugs 5'-azacytidine and decitabine in controlling disease progression .
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http://dx.doi.org/10.3324/haematol.2018.202093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442957PMC
April 2019

Tuscan consensus on the use of UVBnb phototherapy in the treatment of psoriasis.

G Ital Dermatol Venereol 2019 Apr 29;154(2):99-105. Epub 2018 Oct 29.

Section of Dermatology, Department of Clinical Medicine and Immunological Science, University of Siena, Siena, Italy.

Psoriasis (PSO) is traditionally defined as an immune-mediated, inflammatory dermatological disease characterized by a chronic-relapsing course and associated with multifactorial inheritance (genetic predisposition and influence of various environmental factors). Considered until recently a dermatological disease only, today PSO is correctly known as a systemic one because of the involvement of multiple organs with important impact on social life and relationships. PSO is found in the 0.3-4.6% of the world's population, while its prevalence in the Italian population is estimated at 2.8%. Therefore, if we consider that in Tuscany more than 100,000 people out of 3,672,202 suffer of psoriasis, it is of paramount importance to focus on a shared clinical and therapeutic protocol to manage the disease. With the aim of ensuring diagnostic-therapeutic suitability, high levels of care and standardization of treatment, a unique clinical-therapeutic management model has been developed and validated in Tuscany, involving all accredited regional dermatological centers. Among the possible alternatives to be implemented in the treatment of patients with mild, moderate-severe psoriasis, UVBnb phototherapy is widely used alone or in association with other systemic and non-systemic devices. Despite this, there is still no universally shared therapeutic protocol. In this context the CO.FO.TO working group (Consensus Fototerapia Toscana) is born with the aim of defining and validating the main guidelines in the use of phototherapy with UVBnb in psoriasis; the guidelines are based both on the real-life experience of the different centers of reference in the region and on the revision of the recent literature.
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http://dx.doi.org/10.23736/S0392-0488.18.06223-5DOI Listing
April 2019

Granular IgA Deposits in the Skin of Patients with Coeliac Disease: Is it Always Dermatitis Herpetiformis?

Acta Derm Venereol 2019 01;99(1):78-83

Department of Surgery and Translational Medicine, Section of Dermatology, University of Florence, IT-50129 Florence, Italy.

Coeliac disease is an immune-mediated enteropathy driven by gluten, which can be associated with dermatitis herpetiformis. The presence of granular IgA deposits, detected by direct immunofluorescence, is the hallmark of dermatitis herpetiformis; nevertheless, IgA deposits have also been demonstrated in healthy skin of patients with coeliac disease. The main objective of this study was to investigate whether IgA deposits could be found in the skin of patients with coeliac disease who have non-dermatitis herpetiformis inflammatory skin diseases. Direct immunofluorescence was performed on perilesional skin biopsies of 6 patients with coeliac disease with non-dermatitis herpetiformis inflammatory skin diseases and, as control, on 12 non-coeliac patients with inflammatory skin diseases. IgA deposits were found in all of the patients with coeliac disease, but were absent in the control group. In conclusion, IgA deposits may be considered an immunopathological marker for coeliac disease; therefore, patients with coeliac disease showing skin manifestations with positive direct immunofluorescence should be investigated carefully in order to make a differential diagnosis between dermatitis herpetiformis and other non-dermatitis herpetiformis inflammatory skin diseases.
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http://dx.doi.org/10.2340/00015555-3001DOI Listing
January 2019

Cutaneous squamous cell carcinoma. Italian Guidelines by SIDeMaST adapted to and updating EADO/EDF/EORTC guidelines.

G Ital Dermatol Venereol 2018 Dec 11;153(6):747-762. Epub 2018 Jun 11.

Department of Dermatology, Spedali Civili di Brescia, University of Brescia, Brescia, Italy.

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, accounting for 20% of all cutaneous malignancies, and has an increasing incidence in the elderly as well as in the younger population. Although most cSCC is treated with simple therapeutic procedures, advanced cSCC can lead a significant risk for morbidity, negative impact on quality of life, and death. Proper management includes distinguishing between high-risk and low-risk lesions and determining treatment accordingly. A collaboration of multidisciplinary Italian experts has given birth to these recommendations on cSCC diagnosis and management, based on a critical review of the literature, existing European (EADO-EDF-EORTC) guidelines and the expert's experience. Topics covered include diagnostic path and histopathologic assessment, tumor staging, surgical and nonsurgical procedures, follow-up and management of localized and advanced disease.
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http://dx.doi.org/10.23736/S0392-0488.18.06093-5DOI Listing
December 2018

Idiopathic follicular mucinosis: can dermoscopy be helpful?

G Ital Dermatol Venereol 2018 Jun;153(3):440-441

Unit of Dermatology, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.

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http://dx.doi.org/10.23736/S0392-0488.17.05552-3DOI Listing
June 2018