Melanoma indotto da farmaci oncologici?

Introduzione Lo sviluppo di melanoma pu\uf2 essere favorito da diversi gruppi di farmaci tra cui diuretici tiazidici, idroclorotiazide, sildenafil. In letteratura \ue8 descritta una maggiore incidenza di nuovi melanomi primari (NPM) nei pazienti oncologici trattati con inibitori BRAF e recentemente \ue8 stato riportato tale evento anche per un paziente in tripla terapia con vemurafenib, cobimetinib e atezolizumab per il melanoma metastatico. Noi presentiamo la nostra casistica di NPM nei pazienti giunti alla nostra osservazione per tossicit\ue0 cutanea in corso di trattamento oncologico. Materiali e Metodi Noi abbiamo cercato nel nostro archivio 2018-2019 quanti casi di NPM sono stati diagnosticati in 1520 pazienti giunti alla nostra osservazione per tossicit\ue0 cutanea da terapie oncologiche. Risultati In 19 mesi abbiamo diagnosticato 6 melanomi in 4 donne e 2 uomini in terapia oncologica. I melanomi si trovavano prevalentemente in zone fotoesposte: 2 tronco, 2 arto superiore, 2 viso. Il loro spessore in media \ue8 stato di 0.5mm: 1 pTis, 4 pT1a, 1 pT1b. I pazienti erano affetti da differenti tumori per i quali erano in terapia oncologica: 1 linfoma non Hodgkin B diffuso a grandi cellule, 1 melanoma, 1 carcinoide tipico polmonare, 1 adenocarcinoma polmonare, 1 carcinoma squamocellulare polmonare, 1 carcinoma mammario duttale infiltrante. Tre pazienti presentavano localizzazione primitiva al polmone ma con diversi istotipi. Tre pazienti (2F e 1 M) presentavano in anamnesi remota problematiche tiroidee: 2 carcinoma papillifero della tiroide e 1 adenoma di Plummer. Un\u2019altra paziente era stata operata anche per carcinoma mammario, carcinoma renale e leiomioma intestinale. Tutti i pazienti erano in corso di terapia oncologica: 1 lenalidomide, 1 trilogy study (vemurafeniv e cobimetinib + atezolizumab/placebo), 1 temozolide, 2 afatinib, 1 epirubicina e ciclofosfamide. Due pazienti sono deceduti. Conclusioni Il melanoma indotto da farmaci si sta rivelando essere un problema di importanza significativa. Per indagare tale fenomeno \ue8 importante spogliare completamente i pazienti in corso di visita dermatologica anche se richiesta per la sola tossicit\ue0 cutanea per effettuare un controllo nevi

The association between pesticide use and cutaneous melanoma: a systematic review and meta-analysis

Background: The incidence of cutaneous melanoma (CM), the deadliest form of skin cancer, has gradually increased in the last decades among populations of European origin. Epidemiological studies suggested that farmers and agricultural workers are at an increased risk of CM because they were exposed to pesticides. However, little is known about the relationship between pesticides and CM. Objectives: To investigate the association between exposure to pesticides and CM by systematically reviewing the literature. Secondary aim was to determine the categories of pesticides mainly involved in CM development. Methods: A systematic review of the literature was performed up to September 2018 using MEDLINE, Embase and Web of Science. Studies assessing CM risk in licensed pesticide applicators were considered. Strict criteria were established to select independent studies and risk estimates; random effect models, taking into account heterogeneity, were applied. A pooled risk estimate for CM was calculated for the use of each type of pesticide and type of exposure. Between-study and estimate heterogeneity was assessed and publication bias investigated. Results: A total of nine studies (two case-controls and seven cohorts) comprising 184 389 unique subjects were included. The summary relative risks for the categories 'herbicides - ever exposure', 'insecticides - ever exposure', 'any pesticide - ever exposure' and 'any pesticide - high exposure' resulted 1.85 [95% confidence interval (CI): 1.01, 3.36], 1.57 (95% CI: 0.58, 4.25), 1.31 (95% CI: 0.85, 2.04) and 2.17 (95% CI: 0.45, 10.36), respectively. Herbicides and insecticides had no between-study heterogeneity (I2 = 0%), while a significant heterogeneity (I2 > 50%) was detected for the high exposure to any pesticide. No indication for publication bias was found. Conclusions: Individuals exposed to herbicides are at an increased risk of CM. Future properly designed observational studies are required to confirm this finding

Micosi fungoide: indagini strumentali e laboratoristiche

Mycosis fungoides: instrumental and laboratory examinations. Cutaneous lymphomas are a group of disorders characterized by localization of malignant lymphocytes to the skin. Approximately two-thirds of these lymphomas are of T-cell origin. The most common form of cutaneous T-cell lymphoma is mycosis fungoides. Several reviews and guidelines on the management of mycosis fungoides have been published. This study reviews the management and the follow-up of early-stage MF according to our experience

Subungual Metastasis from Ovarian Cancer: Case Report and Brief Review of the Literature

Introduction: Visceral solid cancers can metastasize in almost any organ, including the skin and its appendages. Case Presentation: We report here the case of a 19-year-old Caucasian girl carrying a diagnosis of malignant germ cell tumor of the ovary, with pulmonary and brain metastases, that developed a painful red-violaceous subungual papule of the 4th finger of the left hand, associated with an over-curvature of the nail plate. Dermoscopy was characterized initially by different shades of pink and red, while after few weeks, it showed black pigmentation due to subcorneal hematomas, hemorrhagic crusts, and a rainbow pattern. Histology confirmed a diagnosis of a metastasis from a poorly differentiated carcinoma of ovarian origin. Discussion and Conclusion: A brief review on the diagnosis and treatment of subungual metastases is reported

Vitiligo-like lesions in a patient treated with nivolumab for renal cell carcinoma

RATIONALE: The introduction of immune check-point inhibitors (ICIs) in the treatment of solid neoplasms is associated with the need to know and manage a new type of side effects that are commonly defined immune-mediated adverse events. Dermatologic immune-mediated adverse events are relatively common. Vitiligo-like lesions, defined as hypopigmented skin lesions, have already been associated with the use of ICIs in particular in patients with malignant melanoma, probably due to a common autoimmune mechanism against both melanoma cells and normal melanocytes. The onset of vitiligo-like lesions is very rare in non-melanoma patients and nowadays only few cases are described in the literature. PATIENT CONCERNS: We described the case of a heavily pre-treated woman affected by renal cell carcinoma that has been treated with nivolumab for 2 years obtaining a stabilization of disease after an initial mild progression. After 9 months from the beginning of nivolumab, when the disease has reached its maximum stabilization, the patient developed vitiligo-like lesions of the back win halo nevi. DIAGNOSES: Vitiligo like lesion of the back not pre-existing before nivolumab treatment. The etiology was assumed to be nivolumab related as a result of an autoimmune activation against normal melanocytes. INTERVENTIONS: The patient was followed with dermatological evaluations without changes in nivolumab dose and schedule OUTCOMES:: No variations of the described lesions were recorded after the first description. The patients underwent a durable stabilization of her tumor. LESSONS: This case on the one hand is the first case of vitiligo-like lesions associated with ICIs in patients affected by renal cell carcinoma, and on the other hand it seems to confirm that the onset of immumomediate adverse reactions, but in particular vitiligo lesions, can probably be considered a sign of response to immunological treatments probably as a consequence of activation of the immune response

Vitamin D and melanoma and non-melanoma skin cancer risk and prognosis : a comprehensive review and meta-analysis

Vitamin D is formed mainly in the skin upon exposure to sunlight and can as well be taken orally with food or through supplements. While sun exposure is a known risk factor for skin cancer development, vitamin D exerts anti-proliferative and pro-apoptotic effects on melanocytes and keratinocytes in vitro. To clarify the role of vitamin D in skin carcinogenesis, we performed a review of the literature and meta-analysis to evaluate the association of vitamin D serum levels and dietary intake with cutaneous melanoma (CM) and non-melanoma skin cancer (NMSC) risk and melanoma prognostic factors. Twenty papers were included for an overall 1420 CM and 2317 NMSC. The summary relative risks (SRRs) from random effects models for the association of highest versus lowest vitamin D serum levels was 1.46 (95% confidence interval (CI) 0.60-3.53) and 1.64 (95% CI 1.02-2.65) for CM and NMSC, respectively. The SRR for the highest versus lowest quintile of vitamin D intake was 0.86 (95% CI 0.63-1.13) for CM and 1.03 (95% CI 0.95-1.13) for NMSC. Data were suggestive of an inverse association between vitamin D blood levels and CM thickness at diagnosis. Further research is needed to investigate the effect of vitamin D on skin cancer risk in populations with different exposure to sunlight and dietary habits, and to evaluate whether vitamin D supplementation is effective in improving CM survival

Cutaneous side effects and types of dermatological reactions in metastatic melanoma patients treated by immunotherapies or targeted therapies: A retrospective single center study

Immunotherapy and target therapy have revolutionized treatment of stage III/IV melanoma. Both treatments show a favorable toxicity profile even if cutaneous adverse events (AEs) are frequent (30%-40% of cases). This is a retrospective single center cohort study that included patients with stage IV or inoperable stage III metastatic melanoma (AJCC 8th) who received BRAFi + MEKi therapy or immunotherapy with Checkpoint inhibitors. All cutaneous AEs were ascertained by a dermatologist based on clinical and histological findings. The primary outcome was to provide a detailed clinical dermatological classification of cutaneous adverse events and an evaluation of the incidence of skin toxicity in the two arms of therapy (immunotherapy and target therapy). A total of 286 patients with stages III-IV metastatic melanoma were included: 146 received immunotherapy and 140 target therapy. In the immunotherapy cohort, 63 (43.1%) cutaneous reactions were observed while 33 skin reactions (23.6%) were identified in patients treated with target therapy. All the skin toxicities observed were grade I, excepted four cases: an erythema multiforme-like eruption, a grade III psoriasis and two grade III maculopapular rashes. Immunotherapy in older age resulted statistically related to skin toxicities (p = 0.011), meanly in metastatic setting (p = 0.011). Cumulative incidence of skin toxicities was 65.63% in immunotherapy cohort (p = 0.001). Also multivariate logistic regression shows a significant association between skin adverse events and immunotherapy (odds ratio [OR] = 0.50; 95% confidence interval [CI]: 0.29-0.85, p: 0.01) and between cutaneous AEs and metastatic setting (OR = 1.97; 95% CI: 1.04-3.74, p: 0.04). We have also shown that as the age of initiation of therapy increases the probability of developing skin toxicity grows. However, stratifying by type of therapies the effect of age persists only in immunotherapy (OD: 1.04; CI: 1.01-1.06; p: 0.04) while for target therapy age does not affect the onset of skin toxicity (OD 1.01; CI 0.98-1.04; p = 0.42). No differences were shown between patients on target therapy and immunotherapy regarding gender. Patients were also evaluated regarding concomitant therapies and seems that Levotyroxine may be involved in AEs during immunotherapy treatment. More studies are needed to deepen this aspect, also considering the medical history and diverse drug associations. Cutaneous adverse events are characterized by heterogeneous manifestations, are more often seen in patients on immunotherapy and dermatologists can play a crucial role in multidisciplinary care