Susanna Rossari

Estrogens, estrogen receptors and melanoma

The skin is the largest nonreproductive target tissue on which estrogen plays many beneficial and protective roles. Although neither exogenous hormones nor pregnancy represent significant risk factors for melanoma, epidemiological data suggest a higher survival rate in women with metastatic disease versus men and in premenopausal versus postmenopausal patients. Despite the fact that hyperestrogenic signaling has long been implicated in the initiation and progression of several tumors, the role of estrogens in malignant melanoma is still unclear. The cellular effects of estrogens are mediated by two subtypes of estrogen receptors (ERs). Estrogen receptor β (ERβ), the predominant ER in the skin, antagonizes the proliferative action mediated by estrogen receptor α. According to recent immunohistochemical studies, ERβ protein expression decreases progressively with increased Breslow thickness and results in more invasive melanomas; thus, ERβ immunophenotype may distinguish melanomas linked to poor prognosis from those with a favorable course and lead to melanoma unresponsiveness to both estrogen and anti-estrogen treatment. Therefore, if future large-scale immunohistochemical and molecular studies point towards ERβ as an important factor in malignant melanoma progression, they will open up novel and targeted prognostic and therapeutic perspectives.

Oestrogen receptor beta and melanoma: a comparative study

Background  Oncological research has focused on evaluating oestrogen receptors (ERs) in oestrogen‐related tumours, and understanding the potential role of ERs in the pathophysiology of cancer.

Combined fluorescence-Raman spectroscopic setup for the diagnosis of melanocytic lesions.

Two optical fibre-based probes for spectroscopic measurements on human tissues were designed and developed. The two probes combine fluorescence and Raman spectroscopy in a multimodal approach. The fluorescence excitation was provided by two laser diodes emitting in the UV (378 nm) and in the visible (445 nm) range, while a third source in the NIR (785 nm) was used for Raman. The device was tested on freshly excised human skin biopsies clinically diagnosed as malignant melanoma, melanocytic nevus, or healthy skin. Discrimination of lesions based on their fluorescence and Raman spectra showed good correlation with the subsequent histological examination.

The prognostic impact of the anatomical sites in the 'head and neck melanoma': scalp versus face and neck.

Cutaneous melanoma is a malignant neoplasia with several demographic and histopathological prognostic factors. Many studies stress that the head and neck region has a worse prognosis compared with other localizations, but the reasons for this worse prognosis are unclear. Therefore, the aim of our study is to analyse the poor prognosis of head and neck melanoma (HNM) with respect to the other anatomical sites, considering the face and neck (F&N) and the scalp separately. We carried out a retrospective analysis of 757 melanoma patients. In particular, we studied the prognostic impact of different melanoma skin localizations (head and neck, trunk, upper extremities and lower extremities). Afterwards, we divided HNM into two subgroups, F&N and scalp, to evaluate their impact in the HNM prognosis. Data showed a significantly lower 5-year overall survival probability for HNM (78.9 versus 93.1% for other body sites; P=0.05). Moreover, on analysing the two anatomical areas considered among HNM, we observed a 5-year overall survival of 81.8% for F&N and 66.7% for scalp. HNM has different and worse prognostic features with respect to other sites, but this trend is not only because of scalp melanoma but is also determined by F&N melanoma, which we believe to be underestimated until now.

Multiple primary melanoma: the impact of atypical naevi and follow up

Background  Patients with melanoma are especially encouraged to have regular follow‐up visits with their dermatologist and to perform total‐body skin examination on a routine basis to identify new pigmented lesions or detect significant changes in existing naevi.

Dermoscopy, confocal laser microscopy, and hi-tech evaluation of vascular skin lesions: diagnostic and therapeutic perspectives

Vascular skin lesions comprise a wide and heterogeneous group of malformations and tumors that can be correctly diagnosed based on natural history and physical examination. However, considering the high incidence of such lesions, a great number of them can be misdiagnosed. In addition, it is not so rare that an aggressive amelanotic melanoma can be misdiagnosed as a vascular lesion. In this regard, dermoscopy and confocal laser microscopy examination can play a central role in increasing the specificity of the diagnosis of such lesions. In fact, the superiority of these tools over clinical examination has encouraged dermatologists to adopt these devices for routine clinical practice, with a progressive spread of their use. In this review, we will go through the dermoscopic and the confocal laser microscopy of diagnosis of most frequent vascular lesions (i.e., hemangiomas angiokeratoma, pyogenic granuloma, angiosarcoma) taking into particular consideration the differential diagnosis with amelanotic melanoma.

Dermoscopy pattern of cutaneous angiosarcoma

Auteur(s) : Vincenzo DE GIORGI vincenzo.degiorgi@unifi.it, Marta GRAZZINI, Susanna ROSSARI, Alessia GORI, Alice VERDELLI, Elisa CERVADORO, Torello LOTTI Department of Dermatology, University of Florence, Via della Pergola 60, 50121 Firenze, Italy Cutaneous angiosarcoma (AS) is an aggressive malignant tumor that is generally divided into three clinical subtypes: classical AS (head and neck type), AS arising in the context of Stewart-Treves syndrome, and AS arising in irradiated skin areas [1]. Lymphedema, [...]

Synchronous angiosarcoma, melanoma and morphea of the breast skin 14 years after radiotherapy for mammary carcinoma.

With the improvement in survival after breast cancer there has been increasing interest in the long-term effects of radiotherapy, including the development of tumours. Compared with the general population, breast cancer survivors have a 10-50% higher risk of developing a second cancer. Radiotherapy may play a role in the onset of such lesions. We describe here the case of a 68-year-old woman who developed synchronous cutaneous angiosarcoma, melanoma and morphea of the breast skin and the local area, 14 years after radiotherapy for breast carcinoma. Given the risk of post-radiation secondary primaries in breast cancer patients, long-term surveillance is necessary, with particular attention being paid to skin changes in the irradiation field. Radiation-induced morphea is a rare complication in which immunological abnormalities may stimulate malignant transformation. Long-term studies are required to clarify the pathogenesis of these rare associations.

Discrepant alterations in main candidate genes among multiple primary melanomas

BackgroundAlterations in key-regulator genes of disease pathogenesis (BRAF, cKIT, CyclinD1) have been evaluated in patients with multiple primary melanoma (MPM).MethodsOne hundred twelve MPM patients (96 cases with two primary melanomas, 15 with three, and 1 with four) were included into the study. Paired synchronous/asynchronous MPM tissues (N = 229) were analyzed for BRAF mutations and cKIT/CyclynD1 gene amplifications.ResultsBRAF mutations were identified in 109/229 (48%) primary melanomas, whereas cKIT and CyclinD1 amplifications were observed in 10/216 (5%) and 29/214 (14%) tumor tissues, respectively. While frequency rates of BRAF mutations were quite identical across the different MPM lesions, a significant increase of cKIT (p < 0.001) and CyclinD1 (p = 0.002) amplification rates was observed between first and subsequent primary melanomas. Among the 107 patients with paired melanoma samples, 53 (49.5%) presented consistent alteration patterns between first and subsequent primary tumors. About one third (40/122; 32.8%) of subsequent melanomas presented a discrepant pattern of BRAF mutations as compared to incident primary tumors.ConclusionsThe low consistency in somatic mutation patterns among MPM lesions from same patients provides further evidence that melanomagenesis is heterogeneous and different cell types may be involved. This may have implications in clinical practice due to the difficulties in molecularly classifying patients with discrepant primary melanomas.

Is skin self-examination for cutaneous melanoma detection still adequate? A retrospective study.

Objective: The aim of this retrospective study was to analyze the relationship between detection pattern, tumor thickness, patient demographics, and personal and family history of melanoma in the era of noninvasive diagnosis. Methods: All patients with primary cutaneous melanoma who presented to the Department of Dermatology at the University of Florence between January 2000 and November 2010 were interviewed at the time of their final histopathological diagnoses of melanoma as part of their clinical record. The treating physician specifically questioned all patients about who had first detected or suspected the lesion that resulted in the histological diagnosis of melanoma. Results: A total of 802 melanoma patients were analyzed. The spouse found approximately 16% of the melanomas, and a similar percentage was discovered by the general practitioner. The largest group of melanomas (36%) was discovered during regular annual skin examinations by dermatologists, while another large group (33%) were discovered by the patients themselves. The data that emerged from our study is that self-detection was associated with a greater probability of having a thick melanoma and, therefore, a poor prognosis (odds ratio 1.56). Conclusions: Because the current mortality of melanoma is still stable, we are convinced that a new message should be introduced to encourage high-risk patients to have an annual skin examination as a rule.