Prognostic factors in head and neck melanoma according to facial aesthetic units.

BACKGROUND: Head and neck melanoma is a clinical challenge. Indeed, cutaneous head and neck melanoma shows a worse prognosis in comparison to melanomas of other body sites. Although the emphasis on facial cosmetic preservation plays a pivotal role in comparison to other body areas, specific Facial Aesthetic Units (FAU) could also play a key role in the prognostic evaluation of the malignancy. METHODS: The aim of the current study was to evaluate the general outcome and clinicopathological features of head and neck melanoma and to detect prognostic differences according to each FAU. The Kaplan-Meier product was used to calculate survival curves, while Cox proportional-hazard regression was performed to evaluate the predictive value of each FAU. RESULTS: A total of 221 head and neck melanoma patients was included in our analysis. In the nasal FAU, we found a high rate of local recurrence, which affected significantly disease-free survival. The worse prognosis was observed in melanoma of the scalp, which showed a greater tendency to skip metastases in internal organs. Moreover, we found that scalp showed a low incidence of non-melanoma skin cancers, if compared to other FAU, highlighting that the scalp local milieu might play a more prominent role in melanoma biology than chronic UV exposition. CONCLUSIONS: Although FAUs have an aesthetic function, they could also play a role in the evaluation and follow-up of melanoma.

Vitamin D and melanoma: state of the art and possible therapeutic uses.

Despite the presence of several studies in literature, the real connection between vitamin D serological levels, vitamin D receptor and melanoma remains unclear, probably because of the complex correlation between vitamin D and melanoma. Indeed, UV radiations are not reported as the main risk factor for melanoma in non-sun-exposed, while systemic immunosuppression, anatomical and physiological features may contribute to malignancy. Therefore, the correlation between melanoma cells in sun-exposed areas and vitamin D, as well as vitamin D receptor could be different from the one in melanoma of sun-shielded sites. These differences may also explain the controversial results reported in the literature regarding the correlation between melanoma and vitamin D, as well as the different outcomes in melanoma patients treated with vitamin D as adjuvant therapy. The aim of this review is to highlight the most recent findings about vitamin D and melanoma, focusing on the anatomic site of the primary tumor as well as on the possible therapeutic uses of vitamin D in melanoma patients.

Mast cells and cancer.

Mast cells (MCs) are a potent proangiogenic factor in tumors, they product several pro-angiogenic factors such as fibroblast growth factor 2 (FGF-2), vascular epithelial growth factor (VEGF), tryptase and chymase. Tryptase is a serine protease classified as α-tryptase and ß-tryptase, both produced by MCs. Tryptase degrades the tissues, playing an important role in angiogenesis and in the development of metastases. Serum tryptase increases with age, with increased damage to cells and risk of developing a malignancy and it could be considered the expression of a fundamental role of MCs in tumor growth or, on the contrary, in the antitumor response. Many biomarkers have been developed in clinical practice for improving diagnosis and prognosis of some neoplasms. Elevated tryptase levels are found in subgroups of patients with haematologic and solid cancers. In the current review, we want to update the perspectives of tryptase as a potential biomarker in daily practice in different neoplasms.

Dermatofibrosarcoma protuberans: when the age makes the difference.

BACKGROUND: Dermatofibrosarcoma protuberans is a malignant tumor that affects exclusively the skin. It is a low-grade malignant tumor of subcutaneous tissues, characterized by a local recurrence but it seldom metastasizes. This study aimed to evaluate the impact of different clinical parameters on disease free survival and overall survival of dermatofibrosarcoma protuberans patients. METHODS: A retrospective study of data including seventeen cases of dermatofibrosarcoma protuberans (eleven male, six female) retrieved from the files of the Dermatology Clinics of La Sapienza University, Rome. We evaluated three clinical parameters (age, sex and anatomic site of the primary tumor) using the Kaplan-Meier product and the Log-Rank Test. RESULTS: The results highlighted that patients with an age ≤49 years showed a median disease free survival of 36 months, while patients with an age ≥50 years of 4 months (P<0.0003). In addition, performing Rank-correlation, only the variable age (P<0.0001) reached the statistical significance. Regarding overall survival, performing Rank-correlation only the variable age reached the statistical significance (P=0.02). CONCLUSIONS: Our data suggests that age has a statistically significant role on disease free survival and overall survival of dermatofibrosarcoma protuberans patients.

Skin lesions in patients treated with imatinib mesylate: a 5-year prospective study.

Imatinib mesylate (IM) represents the first-line treatment of patients with chronic myeloid leukemia (CLM) or gastrointestinal stromal tumor (GIST). It presents several side effects. However, less than 10% are nonhematologic including nausea, vomiting, diarrhea, muscle cramps, and cutaneous reactions. The aim of our study was to identify data regarding IM cutaneous adverse effects (AEs) to improve the clinical diagnosis and management of the more frequent side effects. Skin examination should be done before and during IM treatment so that AEs can be diagnosed and treated early with less impact on chemotherapy treatments and on the quality of life of the patient.

Cancer surveillance series: role of demographic aspects, altitude and latitude in the extracutaneous malignant melanoma in a residential study.

BACKGROUND: Extracutaneous melanoma (ECM) is a very rare malignancy and its biology differs from that of cutaneous melanoma. Residential studies can offer an important contribution to the study of this disease. METHODS: We characterized the distribution of ECM according to residential and demographic baseline characteristics. We computer-searched patients that removed an ECM, and we analyzed all demographic and residential parameters. Disease free survival (DFS), date of death or last follow-ups were evaluated. The same parameters were analyzed using hazards-regression. Finally, we used the multiple regressions between DFS and the predictors. RESULTS: A total of 44 ECM patients were included in our analysis. Median DFS was of 10 months; at Log-Rank Test and Cox-hazard regression, the variable age (P<0.01; P<0.004) and latitude (P<0.02; P<0.006) reached a statistical significance; at multiple logistic regression, the significance was instead maintained only for the variable age. General OS was of 42 months at Log-Rank Test age (P<0.001), as well as latitude (P<0.006) maintained its significance at hazard-regression. CONCLUSIONS: Demographic and residential aspects can play an important role in the study of this rare disease, supporting the assumption that ECM are generated by processes actually unknown, as demonstrated in our results compared with those of the literature.

Clinicopathological features, vitamin D serological levels and prognosis in cutaneous melanoma of shield-sites: an update.

Intermittent sun exposure and sunburns are strongly related to the development of melanoma (MM); however, MM can also arise in non-sun exposed areas, where other biological pathways may cause the disease, with different outcomes. At the same time, evidences of serum levels of vitamin D in melanoma patients according to sun-exposed or not-sun-exposed areas are still lacking, especially if compared with the percentage of BRAF mutation. We performed a retrospective analysis with patients registered in our electronic database and an observational study in patients with a recent diagnosis of MM. Performing Kaplan-Meier product and log-rank test, median disease-free survival was 78 months in non-shield-sites (NST-MM) patients and 20.5 months in shield-sites (ST-MM) patients (p < 0.0001); also in the long term, a better behavior was observed for NST-MM (80 vs. 42 months; p < 0.0001). Among 87 melanoma patients with a recent history of MM (≤30 days), we found that ST-MM patients showed lower values of vitamin D compared with NST-MM patients. Regarding BRAF status, a BRAF mutation was present in 13 % of ST-MM and in 41 % of NST-MM. Performing Mc-Nemar test, we found a statistical significant correlation between low serum levels of vitamin D in ST-MM and low percentage of BRAF mutation (p = 0.03), as well as between serum levels of vitamin D and high percentage of BRAF mutation in NST-MM (p < 0.001). All these aspects confirm that in ST-MM, other pathways play pivotal points, if compared with NST-MM.

Thin melanoma and late recurrences: it is never too thin and never too late.

In the absence of risk factors, thin melanomas (TM) present a long-term survival; however, recurrences may occur. We describe the predictive clinicopathological features of patients with metastatic TM. Kaplan-Meier product was performed for the survival analysis, while Cox proportional hazards regression was used to evaluate the effect of the clinicopathological features on disease-free survival (DFS) and overall survival (OS). Median DFS of the entire cohort was 26 months and three patients developed late metastases. Nine patients developed extra-nodal metastases as first recurrence, while cases of positive sentinel lymph node biopsy (SLNB) were not found. DFS and OS varied according to the clinicopathological features, but only ulceration remained the main statistical significance value. According to our results, a hypothetical use of SLNB in TM without other risk factors is not currently feasible. No consensus exists as to which patients with TM are at risk for metastases or late recurrences.

Appearance of malignant melanoma after a non-cutaneous cancer diagnosis.

BACKGROUND: The aim of this study is to find the associations between malignant melanoma (MM) and other non-cutaneous malignancies and to see whether there are possible correlations between them. METHODS: We analysed a sample of 1720 patients collected by our melanoma database, to identify patients with both MM and non-cutaneous primary cancer (NCC). The incidence rate (IR) included in our database was calculated as the ratio between the observed patients with NCC and those with MM. RESULTS: A total of 74 patients, with both NCC and MM, were included in our analysis, corresponding to 4.30% of patients with MM present in our melanoma database. After breast cancer (24.3%; IR = 1:4), the most common malignancies were lymphomas (14.8%; IR = 1:4), renal cell carcinoma (13.5%; IR = 1:7), thyroid cancer (9.4%; IR = 1:11), and prostatic carcinoma (8.1%; IR = 1:12), followed by other cancers. Among patients with lymphomas, most patients (72.7%) had a non-Hodgkin lymphoma. Our study shows a high coexistence of multiple malignancies in patients with MM. CONCLUSION: Although we cannot definitively confirm a true association between non-skin cancers and MM, we believe that there are sufficient links for further investigation in order to identify new aetiological factors and therapeutic targets for these cancers.

Predictors and survival in patients with melanoma brain metastases.

Brain metastases (BM) are one of the most frequent neurological complications of cancers. Melanoma is the third most common tumor to metastasize to the brain with a reported incidence of 10-40 %, and many patients have subclinical BM (>73 %). We computer-searched the clinical records of all our patients registered into a database to identify patients that presented or developed BM. A total of 49 patients with melanoma BM were included in our analysis. General time to brain metastases (TTBM) was 23 months. The nonparametric test between TTBM and the single variables showed an association between TTBM and Breslow thickness (p < 0.0076; Spearman's coefficient-0.411), ulceration (p = 0.0656; Spearman's coefficient-0.287) and positive sentinel lymph node (p < 0.0015; Spearman's coefficient-0.475). Performing multiple regression, positive SLN remained the only, statistically significant, predictive variable (p < 0.01). Regarding the first melanoma site, the axial sites were more likely to develop BM than peripheral ones (p < 0.001). The analysis of brain metastasis survival (BMS) with Kaplan-Meier curves has resulted in a median survival rate of 6 months (range 1-134 months) and was strongly related to response to treatment, number of parenchymal lesions, presence or absence of symptoms. The results of the current analysis revealed clinical and primary tumor characteristics associated with the development of BM, TTBM, and BMS. The SNL was found to be the strongest predictor for BM development.

Melanoma with unknown primary: report and analysis of 24 patients.

In the literature, there are some papers reporting on patients with metastatic melanoma from an unknown primary lesion (MUP). The pathogenesis of this phenomenon and the prognosis of these patients are still debatable. Therefore, we reviewed our casistics on MUP patients. We identified 24 MUP patients out of all patients registered into a melanoma database from June 1996 to June 2011. The incidence was 1.4%. We compared the survival rate of all patients with MUP stage III-IV with all patients with metastatic melanoma known primary (MMKP) stage III-IV observing a clear survival improvement for MUP patients in front of MMKP patients (p<0.01). In a second instance, we compared stage III MUP patients with only lymph nodal involvement with stage III MMKP patients with only lymph nodal involvement, and again we found statistically significant better survival for MUP patients (p<0.05). In this retrospective study, the number of lymph nodes involved (p=0.8), the sex (p=0.9), and S100 value (p=0.2) were not statistically relevant for prognosis. The better prognosis for these patients is very similar to better survival rate for metastatic melanoma patients and vitiligo. This correlation may be in accord with the hypothesis of a regression of primary lesion by immunological system of the host and also the median age of patients at the time of diagnosis, commonly older than melanoma patients, may correspond to a long period of immunological interferences between the host and the melanoma disease.