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.

Differences in clinicopathological features and distribution of risk factors in Italian melanoma patients.

BACKGROUND: No studies are available in the literature on the distribution of different melanoma features and risk factors in the Italian geographical areas. OBJECTIVE: To identify the differences in clinical-pathological features of melanoma, the distribution of risk factors and sun exposure in various Italian macro-areas. METHODS: Multicentric-observational study involving 1,472 melanoma cases (713 north, 345 centre, 414 south) from 26 referral centres belonging to the Italian Multidisciplinary Group for Melanoma. RESULTS: Melanoma patients in northern regions are younger, with thinner melanoma, multiple primaries, lower-intermediate phototype and higher counts of naevi with respect to southern patients; detection of a primary was mostly connected with a physician examination, while relatives were more involved in the south. Northern patients reported a more frequent use of sunbeds and occurrence of sunburns before melanoma despite sunscreen use and a lower sun exposure during the central hours of the day. CONCLUSIONS: The understanding of differences in risk factors distribution could represent the basis for tailored prevention programmes.

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.

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.

Effect of a single oral dose of 600,000 IU of cholecalciferol on muscle strength: a study in young women.

BACKGROUND: The effect of a single large oral dose of vitamin D on muscle function in young people with vitamin D deficiency has not been investigated so far. AIM: We evaluated the effect of a single oral dose of 600,000 IU of cholecalciferol on muscle strength. SUBJECTS AND METHODS: Eighteen young women with vitamin D deficiency received a single oral dose of 600,000 IU of cholecalciferol. We evaluated changes in maximal voluntary contraction (MVC) and speed of contraction (S) in response to cholecalciferol by using an hand held dynamometer at 3, 15, 30, 60 and 90 days, compared to baseline. RESULTS: We observed no significant change in MVC and S values, a significant increase of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] and a significant decrease in serum parathyroid hormone (PTH) (p<0.001 for all). A significant correlation was found between MVC and S and serum phosphorus (P) after supplementation (p<0.02 and p<0.05, respectively). Conversely, we observed no association between the parameters of muscle strength and 25(OH)D, ionized calcium (Ca2+), PTH and 1,25(OH)2D. CONCLUSIONS: A single dose of 600,000 IU of cholecalciferol does not directly enhance handgrip strength in young women with vitamin D deficiency. More studies are needed on the indirect effect of the hormone on muscle.

Mycosis fungoides: disease evolution of the "lion queen" revisited.

Mycosis fungoides (MF), which represents the most common subtype of primary cutaneous T-cell lymphoma (CTCL), is an epidermotropic lymphoma included as an indolent form in the recent WHO/EORTC classification. From a clinical point of view, the classic disease progression usually is slow and takes over years or even decades, and characterized by the evolution from patches to more infiltrated plaques and eventually to tumours or erythroderma. However, the analysis of the MF disease course has been greatly impaired by the rarity of the disease, thus data about the time course of disease progression and pattern of relapse during time are not well known. In this review, a summary of published data on MF large patients cohorts will be presented, together with the results obtained by a retrospective analysis of clinical features and follow-up data of 1,422 MF patients diagnosed and followed-up from 1975 to 2010 in 27 Italian Centres (Italian Study Group for Cutaneous Lymphoma). From a clinical perspective, the amount of data support the relevance of a stage-tailored, differentiated follow-up strategy, in as much as the TNMB staging appears not only to be associated with different progression rates, but also shows as a new finding a relationship with different patterns of disease progression. From a biological point of view, there is the need to understand the molecular basis of the different clinical pathways of disease progression, to be able to potentially identify at an earlier phase of disease evolution, the patients who are more likely to develop erythroderma or tumour-stage progression. In conclusion, if MF is indeed a true "lion queen", as dermatologists we need to be expert and wise tamers to keep it under control.

Management and follow-up of a patient with Familial Atypical Multiple Mole-Melanoma (FAMMM) Syndrome.

INTRODUCTION: Familial Atypical Multiple Mole-Melanoma Syndrome (FAMMM) is an autosomal dominant genodermatosis characterized by the presence of a high number of dysplastic nevi and family history of melanoma or pancreatic cancer. Melanomas in FAMMM patients tend to occur at a younger age, although they are clinically similar to sporadic melanomas in terms of overall survival. CASE REPORT: A 45 year-old woman with a family history of melanoma, a type II phototype and numerous (>100) nevi was admitted to our Department of Dermatology and Plastic Surgery. Over the past years, the patient underwent several surgical operations to remove pigmented lesions and two are dysplastic nevi. Since 1995, she underwent surgery to remove four melanomas. She is followed for skin examinations including dermoscopy. CONCLUSION: Identifying high-risk patients for melanoma represents a primary objective for the specialists that are involved in the management of this disease, especially in order to enact all the necessary surveillance and follow-up strategies.

Pulmonary mycobacteriosis in a patient affected by mycosis fungoides: a diagnostic and therapeutic challenge.

Among patients with cutaneous T-cell lymphoma (CTCL), sepsis and pulmonary infections are the first cause of death. We report on a patient with CTCL who, after more than 10 years of aggressive antineoplastic treatments, showed extensive pulmonary infiltrations on staging CT scan. Repeated CT scans were inconclusive for an infectious process, and the patient was still asymptomatic. The diagnosis of mycobacteriosis was made on the microbiologic exam of bronchoalveolar lavage. Specific treatment was started with contemporary dosage reduction of chemotherapy. After six months of antibiotic treatment the pulmonary lesions improved, whereas CTCL progressed. Therefore, a new antineoplastic regimen was started obtaining control of CTCL, without aggravation of the pulmonary lesions. We highlight the diagnostic and therapeutic pitfalls encountered when pulmonary mycobacteriosis complicates the course and treatment of CTCL.

[Importance of dermatologic screening within the frame work of a general cancer prevention program]. / Importanza di uno screening dermatologico nell'ambito di un programma di prevenzione oncolologica generale.

BACKGROUND: Skin tumours represent about 11% of all the malignant neoplasms and their frequency is increasing annually. Skin tumours (melanoma, basal and squamous cell carcinoma, etc.) can be used for a good screening activity, but in relation to breast or cervix uteri cancer needs to be better defined. A test on a population of selected patients against skin malignant neoplasms has been carried out in our Centre. All of them had skin lesions and further checks were necessary. METHODS: The diagnostic protocol used in our Centre for Oncological Prevention uses the collection of anamnestic data and an objective examination. Between 1996 and 2000, 222 patients between the ages of 18 and 80 have been selected. All of them had suspected skin lesions. The patients were selected by the oncologist, particularly for pigmentation, asymmetry, irregular borders and heterogeneous colour of their skin lesions. Subsequently, the patients were sent for a further examination to the dermatologist oncologist, who on the basis of the objective dermatological examination with possible dermatoscopy, made a clinical diagnosis of the skin injuries or suggested surgical removal for the histological control of the same. RESULTS: Requested consultations: 222. Exami-nations made: 195. Patients considered: 190. Skin injuries examined: 190. The following skin lesions were identified: melanoma: 4 (2.1%) [2: I Clark level; 2: II Clark level]; basal cell carcinoma: 14 (7.37%); dermatofibrosarcoma: 1 (0.53%); keratoacanthoma: 1 (0.53%); dysplastic nevus: 4 (2.1%); actinic keratosis: 7 (3.68%); benign lesions: 159 (83.68%). CONCLUSIONS: These data were obtained by a screening program and it is therefore not a random study. This study shows interesting results because tumoral skin lesions and in particular melanoma were recognised at early stages. This is more than enough for us to create a specific screening program for skin lesions to cut down the rate of morbidity and mortality.

Cyclosporin A: preliminary results in the treatment of psoriasis.

Cyclosporin A (CYA) has recently attracted the attention of the dermatologists with regard to its use in the treatment of severe psoriasis. We report four cases of psoriasis resistant to conventional therapy. Three patients were affected by chronic plaque psoriasis and one by erythrodermic psoriasis. The initial dosage of CYA was 5 mg/kg/day per os, and was gradually reduced according to the course of the disease. The drug was administered for a period of 6 weeks. All patients showed a significant improvement of the clinical picture. No remarkable clinical side effects were observed. During the trial we took skin biopsies on which we conducted histological and immunohistochemical studies. The efficacy of CYA in the treatment of psoriasis demonstrates the important role of the cell mediated immunity in the pathogenesis of psoriasis.

Efficacy and tolerance of fenticonazole versus miconazole cream.

On the basis of a randomized scheme, 40 patients affected by pityriasis versicolor, candidiasis or dermatophytosis were treated with fenticonazole 2% cream or with miconazole 2% cream. Clinical healing was obtained in 16 patients and there were four improvements in those treated with fenticonazole. In those treated with miconazole there were 14 clinically healed and five improvements. Only in two cases treated with miconazole and in one with fenticonazole, microscopic and cultural analysis had not become negative by the end of treatment. Both drugs were well tolerated. At the end of the study it was concluded that fenticonazole 2% cream is an effective antimycotic with an equal or even higher activity than miconazole.

Classification of non-Hodgkin malignant lymphomas of the skin.

The authors subdivide the primary non-Hodgkin cutaneous malignant lymphomas into "proper" and "non-proper" types. "Proper" lymphomas are those which have in the skin their proper site of localization, and include mycosis fungoides, Pagetoid reticulosis, Baccaredda-Sézary syndrome and possibly lymphomatoid papulosis. They are T-cell lymphomas arising in the papillary dermis, characterized by epidermotropism, having a specific clinical feature in that they are unlikely to be simulated by other cutaneous malignant lymphomas. "Non-proper" lymphomas are those which do not usually arise in the skin, but in various other organs. They are B-, T- or null-cell lymphomas, arising in the middle dermis, infrequently epidermotropic, having a papular-nodular-tumoural clinical feature, which are indistinguishable clinically from other neoplastic types such as plasmacytoma and Hodgkin's disease. The three classifications of non-Hodgkin lymphomas most followed are not directly applicable to cutaneous lymphomas because some of the former are not primarily sited in the skin, and because a follicular morphology is infrequently seen in the latter. Whereas the first classification reported for cutaneous lymphomas utilized malignancy as a criterion, the present classification here proposed utilizes the propriety of the site of localization as the criterion for subdivision into "proper" and "non-proper" types.