The use of cisplatin electrochemotherapy in nonmelanoma skin cancers: A single-center study.

Electrochemotherapy (ECT) is a well-known nonconventional skin cancer ablative method that was shown to be safe and effective for treating both locoregional disease spreading and disseminated cutaneous and subcutaneous lesions from different types of cancer. The most common medications used are bleomycin and cisplatin. In the last years many studies were performed on ECT, lead it to be a valid therapeutic option in many international guidelines. Nevertheless, there are still no clear indications regarding timing of its use. The main aim of this study was first to assess the safety and effectiveness of intralesional cisplatin ECT for treating different types of nonmelanoma skin cancer in a group of eligible patients. The second endpoint was to assess patients' tolerability and symptoms improvement through the treatment. A single-center prospective study was performed. Patients with squamous cell carcinoma, basal cell carcinoma, or skin metastases were selected during 1 month. The ideal setting was the presence of two or three lesions with a maximum diameter of 2 cm. Both primary, recurrent, and metastatic lesions were included. Before and 8 weeks after treatment, all patients were evaluated to assess the number, measurement, and anatomical site of skin lesions using photography and metric notation. The medical device for membrane electroporation was the CLINIPORATOR EPS02 model. The cisplatin concentration was at least 1 mg/mL. The dose for each single lesion was calculated based on its volume, as is the standard procedure for ECT. Local or systemic adverse events and changes in symptoms were evaluated with a questionnaire based on a visual analog scale that was administrated before and after ECT. Eight patients with a total of 18 lesions underwent the procedure (six men and two women). Four out of eight (50%) patients had a complete response to the treatment. However, all eight patients had an overall tumor response (100%), experiencing an improvement in symptoms including less pain and bleeding from the tumor. Our study clearly show that ECT with intralesional cisplatin is a valuable and safety procedure for nonmelanoma skin cancer and cutaneous tumor metastasis. ECT with cisplatin was able to achieve a good local disease control leading to complete response in an half of cases. The results were stable after 1 year of follow-up. The outer ear area displayed a really good response, due to both ear's anatomical configuration and intralesional cisplatin pharmacological characteristics.

A clinical, pathological and immunohistochemical series of 9 cases of primary cutaneous apocrine carcinomas of the head and neck.

BACKGROUND/OBJECTIVES: Primary cutaneous apocrine carcinoma is a rare malignant adnexal skin tumour that can recur locally, spread to regional lymph nodes and metastatize to visceral organs. Wide dissemination and death from disease are much less common. The axilla is the most common site of presentation. It is infrequently reported in the head and neck region. METHODS: All cases diagnosed as primary cutaneous apocrine carcinoma of the head and neck were retrospectively collected from the archives of the Division of Pathological Anatomy, University of Florence from 1996 to 2016. There was no history or clinical evidence of breast cancer. Clinical data and follow-up were collected by the clinicians. RESULTS: Nine cases were found, with a mean age of 76 years, ranging in size between 0.3 and 3.5 cm. Clinically, they were frequently mistaken for basal cell carcinomas. Histopathologically, all the tumours showed decapitation secretion, a tubular, solid or mixed (tubulo-papillary and solid-tubular) growth pattern and were predominantly classified as grade 2 tumours. GCDFP-15 and hormone receptors were variably expressed. HER2 and podoplanin were negative in all cases. In one case, spreading to regional lymph nodes was observed. No cases were associated with death due to the disease. CONCLUSION: As immunohistochemical analysis lacks specificity in distinguishing primary cutaneous apocrine carcinoma from a cutaneous metastasis of breast carcinoma, detailed clinical history, breast examination, adequate treatment and follow-up are necessary to confirm a diagnosis of primary cutaneous apocrine carcinoma.

Appearance of cutaneous melanoma and subcutaneous metastases in metastatic gastric carcinoma undergoing chemotherapy with oral 5-fluorouracil prodrug.

Metastatic skin lesions of gastric cancers usually appear as nonspecific, firm, and hyperpigmented nodules. However, they occasionally present as unusual skin manifestations that mimic other skin disorders. We describe a case of multiple cutaneous metastases from gastric cancer resembling sebaceous cysts with a synchronous melanoma, in a patient after fluoropyrimidine-based systemic chemotherapy. Melanoma occurring as a second cancer has been recognized in patients having undergone previous chemotherapy or radiation for another cancer. We can assume that the capecitabine-based chemotherapy may have played a role in the development of the melanocytic neoplasm. Our observation adds extra evidence to the link between fluoropyrimidine-based immunosuppression and the induction of melanocytes' proliferation and transformation. For these reasons, it is advisable to require dermatological checkups for patients undergoing chemotherapy treatments in order to identify suspicious melanocytic lesions as soon as possible.

Fluorescence-advanced videodermatoscopy: A promising and potential technique for the in vivo evaluation of vitiligo.

Fluorescence advanced videodermatoscopy (FAV) has been proposed recently to be a new, noninvasive method for in vivo skin examination at high magnification. The working principle underlying FAV relates to the ability of endogenous molecules to absorb specific wavelengths and emit fluorescence. Herein we report our experience with FAV in the study of active, non-segmental vitiligo treated with narrowband UVB. Our findings indicate that FAV has the potential for application in the clinical follow-up, disease prognosis, and therapeutic monitoring of vitiligo.

Clinical and Dermoscopic Features of Lichenoid Keratosis: A Retrospective Case Study.

BACKGROUND: Lichenoid keratosis is a benign cutaneous lesion exhibiting many clinical faces and different dermoscopic features. OBJECTIVE: This study aims to determine the pattern of different clinical subtypes of lichenoid keratosis and to establish whether there is any correlation between the clinical variants of lichenoid keratosis and their dermoscopic appearance. METHODS: We retrospectively analyzed the medical records and clinical database of patients who had received a histological diagnosis of lichenoid keratosis. Based on the literature review and the clinical-dermoscopic features of lichenoid keratosis, we divided the lesions into 6 clinical subtypes to evaluate potential correlations between clinical and dermoscopic features in all subtypes. RESULTS: Fifty-one lesions were included in this clinical study. Preoperatively, only 1.9% of cases were clinically diagnosed as lichenoid keratosis, and the most common misdiagnosis was basal cell carcinoma (52.9%). We identified 6 subtypes of lichenoid keratosis and their corresponding dermoscopic features and clues. CONCLUSION: Since lichenoid keratosis has no pathognomonic dermoscopic clues and it is commonly misdiagnosed as malignant skin neoplasms, such as basal cell carcinoma and melanoma, improving the knowledge of both clinical and dermoscopic variability of lichenoid keratosis may help dermatologists to reduce unnecessary surgery and to reduce health care spending.

Pattern of HPV infection in basal cell carcinoma and in perilesional skin biopsies from immunocompetent patients.

BACKGROUND: The association between human papillomavirus (HPV) infection and non-melanoma skin cancers (NMSCs) such as squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) is not yet fully understood. We analysed the prevalence and spectrum of cutaneous beta-HPV types and mucosal/genital HPV types in paired biopsies (tumour and corresponding perilesional skin) obtained from 50 BCC immunocompetent patients. A small group of SCC patients (n=9) was also included. We also evaluated some previously postulated risk factors for HPV infection in NMSC patients. RESULTS: All biopsies were negative for mucosal/genital HPV types. Overall, beta-HPV DNA was detected more often in SCC compared to BCC patients (78% vs 55% of total samples). The frequency of infection increased with the patient's age [OR=4.88 (95% CI 1.29-18.39)]. There was no significant correlation between beta-HPV positivity and sex, skin type and UV exposure. The prevalence of beta-HPV species 1 types was significantly higher than those belonging to other beta-HPV species in biopsies from BCC (p=0.022) but not from SCC subjects (p=0.091). There was no significant difference in the overall prevalence of beta-HPV infection and the number of viral types between tumour lesions and perilesional skin. BCC samples were significantly more likely to be infected with beta-HPV species 1 types compared to perilesional skin (p=0.036) and showed a higher frequency of mixed infections (p=0.028). CONCLUSIONS: These findings demonstrate that beta-HPV types belonging to species 1 are the most common HPV types detected in the skin of BCC patients. Moreover beta-1-HPV types and mixed infections are significantly more frequent in tumour samples than in healthy perilesional skin. Our results suggest that beta-1-HPVs as well as co-infection with more than one viral type could be important in NMSC and in particular in BCC.Further studies aimed to compare the biological activity of viral types in tumours and in healthy skin (viral replication and expression, interference of infection with cellular functions) are necessary to understand the role of HPV infection in skin cancer.

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.

Epidemiology of melanoma: is it still epidemic? What is the role of the sun, sunbeds, Vit D, betablocks, and others?

The incidence of cutaneous malignant melanoma is continuously increasing worldwide, but only minimal changes in mortality have been observed. This phenomenon has brought into question whether this increased incidence reflects a true or apparent melanoma epidemic. The most recent data suggest that this epidemiological trend may be explained by the existence of a certain degree of melanoma overdiagnosis, especially of thin lesions, which probably would never progress to advanced disease if left untreated. However, acute sun exposure and widespread use of sunbeds may also justify the increase in melanoma incidence. Recently, both vitamin D and beta-blocker use seem to play a beneficial role in melanoma progression.

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.

Polymorphisms of estrogen receptors: risk factors for invasive melanoma - a prospective study.

Cross-sectional studies have reported associations between a number of polymorphisms in the estrogen receptor alpha (ERα) gene and the body mass index, hypertension, coronary flow reserve, coronary atherosclerosis, and osteoporosis. There are currently no data examining the genetic polymorphisms of the ERα and estrogen receptor beta (ERß) genes in melanoma patients. The aims of this study were to investigate the associations of genetic polymorphisms of the ERα and ERß genes with melanoma risk. The study group consisted of consecutive patients who visited the Department of Dermatology of the University of Florence between March 2005 and July 2007 for surgical excision of melanoma. In our study, homozygosity for the wild-type alleles showed different results at the PvuII, XbaI, and AluI restriction sites. Only the AluI site showed a lower proportion of the A allele in the melanoma group compared to the control group; the P and X alleles were lower in the control group than in the melanoma group. The distribution of wild-type alleles is important because these alleles have a protective role in the expression of altered proteins, which involves the ERs in our case. Because of the phenotypic prevalence of the wild-type allele, the heterozygotes did not express the polymorphism. The homozygosity of the polymorphic-type alleles shows that a alleles are more frequent in the case group than in the control group, with proportions of 43.8 and 39.5%, respectively. These results suggest that a polymorphism at the AluIrestriction site correlates with a higher proportion of melanoma. Thus, the polymorphism of ERß could ascribe to a higher susceptibility to melanoma.

An Ear with Multiple Vascular Lesions: Does Dermoscopy Offer Any Hints?

Cutaneous lesions of vascular origin are normally easily diagnosed, both clinically and dermoscopically. However, Kaposi's sarcoma can trigger difficulties in making a correct preoperative diagnosis. Although dermoscopic pictures are not pathognomonic for diagnosing Kaposi's sarcoma, dermoscopic analysis could be a useful complement to a differential diagnosis of nodular pigmented cutaneous lesions. Here, we discuss two clinical cases and analyze the primary dermoscopic features of Kaposi's sarcoma, evaluating the potential utility of this method for differential diagnosis.

Contrast-enhanced ultrasound: a filter role in AJCC stage I/II melanoma patients.

One of the most significant advances in melanoma staging is sentinel lymph node biopsy (SLNB). It is a surgical technique to detect occult nonpalpable micrometastases in regional lymph nodes. Recently, contrast-enhanced ultrasound (CEUS) was introduced as a noninvasive procedure, in spite of SLNB, for the detection of SLNs in patients with cutaneous melanoma. The main purpose of this study was to evaluate the diagnostic accuracy of CEUS in the diagnostic workup of patients with melanoma in comparison with the final histology of SLNs detected through preoperative lymphoscintigraphy. Fifteen patients with cutaneous melanoma underwent prompt excisional biopsy with narrow margins in order to avoid impairment of the melanoma lymphatic basin and were referred for SLNB according to routine indications between January and February 2009. In our study CEUS showed, albeit based on a small patient sample, a negative predictive value of 100%, that means that all negative results were confirmed by negative SLN histopathological examination; all ultrasonographically negative lymph nodes corresponded to nonmetastatic sentinel nodes.

Unusual presentation of tuberculosis in an infliximab-treated patient--which is the correct TB screening before starting a biologic?

Infliximab is an anti-TNFalpha chimeric monoclonal antibody, commonly used in the treatment of moderate to severe psoriasis. TNFalpha is a pro-inflammatory cytokine which play a key role in host defense from infections by intracellular bacteria, such as Listeria monocytogenes, Histoplasma Capsulatum and especially Mycobacterium Tuberculosis. Infliximab therapy increases the risk of tuberculosis due mainly to the reactivation of latent TB infection (LTBI) and, therefore, it is mandatory to screen patients for LTBI prior to starting a treatment with anti-TNFalpha agents. We report the case of a psoriatic patient, who, despite a negative screening for infection by M. tuberculosis including both tuberculin skin test (TST) and chest X-ray, developed after 4 months of infliximab treatment, a severe pulmonary, lymphnodal and intestinal tuberculosis during infliximab treatment.

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.