Early Diagnosis of Melanoma and Breast Cancer in Women: Influence of Body Image Perception.

The diagnosis of melanoma and breast cancer may impact many aspects of life with significant reductions in emotional functioning and quality of life. The aim of the study was to analyze the emotional traits of female patients with oncological in early-stage diagnosis, investigating predictors for psychological distress and analyzing body image perception. An observational study was conducted, A sample of 84 female cancer patients (age range 30-55 years) with melanoma (n = 42) and breast cancer diagnosis (n = 42). The examined emotional variables were psychological distress; depression, stress, and anxiety; metacognitions; and body self-perception. Findings showed higher psychological distress in breast cancer than in melanoma patients (p = 0.00), which was related to lower positive self-perception of body image (p = 0.03). Furthermore, psychological distress was negatively correlated with consequences of clinical treatment on body image, and low well-being affected the social interaction and well-being with own body. There was no significant difference between cancer staging and timing from diagnosis. Prevention and therapeutic psychological protocols might be adapted and tailored to the unmet needs of the patients in medical treatments to promote and enhance the Quality of Life in survivorship.

Intralesional Methotrexate for the Treatment of Advanced Keratinocytic Tumors: A Multi-Center Retrospective Study.

INTRODUCTION: Keratinocyte tumors (KT) are frequently observed. Surgery is the treatment gold standard. In some cases, a surgical approach might not be the best option. Radiotherapy (RT) and systemic treatments can frequently cause side effects or be contraindicated. Intralesional methotrexate (MTX) can be a conservative yet effective alternative. We decided to evaluate the effectiveness and safety of intralesional chemotherapy with MTX for the treatment of squamous cell carcinoma (SCC), keratoacanthoma (KA), and basal cell carcinoma (BCC). METHODS: All patients had a histologically confirmed diagnosis of BCC, SCC, or KA and no indication to surgery or RT. MTX was injected subcutaneously proceeding from the periphery of the lesion toward the center. Different protocols in terms of dose, frequency, and length of treatment were used to compare them. Treatment efficacy was evaluated in terms of tumor size reduction. Patients were divided into three groups: responders (improvement of more than 50%), partial responders (< 50%), and non-responders (no improvement or worsening). All data were analyzed using the chi-squared test (χ2). RESULTS: Thirty-five patients were included. Twenty-one patients suffered from SCC, 12 from KA, and 2 from BCC. KA showed a higher response rate than SCC and BCC. For AK, 92% of patients had a complete resolution; 8% were partial responders. For SCC, 47.6% of cases were responders and 14.3% partial responders, while 38% non-responders. All BCCs showed no improvement. A treatment protocol of weekly injections, performed for 4 to 6 weeks, was the most efficient. Doses of 25 mg/ml per session seemed to be most effective. About one third of our patients developed side effects with mild anemia being the most frequent. CONCLUSIONS: For selected cases, intralesional MTX can be a safe and effective option for the treatment of KT, especially in case of KA and, to a lesser extent, SCC.

Intra-patient Heterogeneity of BRAF and NRAS Molecular Alterations in Primary Melanoma and Metastases.

Mutations in MAPK signalling genes are driver events in melanoma, and have therapeutic relevance in the metastatic and adjuvant setting. This study evaluated the intra-patient heterogeneity of BRAF, NRAS and c-KIT mutational status between 30 primary melanomas and 39 related metastases, using molecular analysis and immunohistochemistry. BRAF mutations were identified in 46.7% of primary melanomas and 48.7% of metastases and NRAS mutations in 20% and 25.6%, respectively. Intra-patient heterogeneity was detected in 13.3% of patients for both BRAF and NRAS genes and was not associated with clinico-pathological characteristics of melanomas or metastases. High consistency was observed between immunostaining and molecular methods for BRAFV600E (k = 0.90; p < 0.001) and NRASQ61R (k = 0.87; p < 0.001). These findings demonstrate a relevant intra-patient heterogeneity between primary and metastatic lesions that is independent of clinical variables and methodological approach.

Telomeres and Telomerase in Cutaneous Squamous Cell Carcinoma.

The role of telomere biology and telomerase activation in skin cancers has been investigated in melanoma and basal cell carcinoma but limited evidence is available for cutaneous squamous cell carcinoma (cSCC). We will review the current knowledge on the role of telomere and telomerase pathway in cSCC pathogenesis. At the somatic level, both long and short telomere lengths have been described in cSCC. This telomere dichotomy is probably related to two different mechanisms of tumour initiation which determines two tumour subtypes. Telomere shortening is observed during the invasive progression from in situ forms of cSCC, such as Bowen's disease (BD) and actinic keratosis (AK), to invasive cSCC. At the germline level, controversial results have been reported on the association between constitutive telomere length and risk of cSCC. Approximately 75⁻85% of cSCC tumours are characterized by a high level of telomerase activity. Telomerase activation has been also reported in AKs and BD and in sun-damaged skin, thus supporting the hypothesis that UV modulates telomerase activity in the skin. Activating TERT promoter mutations have been identified in 32⁻70% of cSCCs, with the majority showing the UV-signature. No significant correlation was observed between TERT promoter mutations and cSCC clinico-pathological features. However, TERT promoter mutations have been recently suggested to be independent predictors of an adverse outcome. The attention on telomere biology and telomerase activity in cSCC is increasing for the potential implications in the development of effective tools for prognostic assessment and of therapeutic strategies in patients with cutaneous cSCC.

Familial Melanoma: Diagnostic and Management Implications.

BACKGROUND: An estimated 5%-10% of all cutaneous melanoma cases occur in families. This review describes susceptibility genes currently known to be involved in melanoma predisposition, genetic testing of familial melanoma patients, and management implications. RESULTS: CDKN2A is the major high-penetrance susceptibility gene with germline mutations identified in 20%-40% of melanoma families. A positive CDKN2A mutation status has been associated with a high number of affected family members, multiple primary melanomas, pancreatic cancer, and early age at melanoma onset. Mutations in the other melanoma predisposition genes-CDK4, BAP1, TERT, POT1, ACD, TERF2IP, and MITF-are rare, overall contributing to explain a further 10% of familial clustering of melanoma. The underlying genetic susceptibility remains indeed unexplained for half of melanoma families. Genetic testing for melanoma is currently recommended only for CDKN2A and CDK4, and, at this time, the role of multigene panel testing remains under debate. Individuals from melanoma families must receive genetic counseling to be informed about the inclusion criteria for genetic testing, the probability of an inconclusive result, the genetic risk for melanoma and other cancers, and the debatable role of medical management. They should be counseled focusing primarily on recommendations on appropriate lifestyle, encouraging skin self-examination, and regular dermatological screening. CONCLUSIONS: Genetic testing for high-penetrance melanoma susceptibility genes is recommended in melanoma families after selection of the appropriate candidates and adequate counseling of the patient. All patients and relatives from melanoma kindreds, irrespective of their mutation status, should be encouraged to adhere to a correct ultraviolet exposure, skin self-examination, and surveillance by physicians.

Clinical Outcomes of Patients with Advanced Cancer and Pre-Existing Autoimmune Diseases Treated with Anti-Programmed Death-1 Immunotherapy: A Real-World Transverse Study.

BACKGROUND: Patients with a history of autoimmune diseases (AIDs) have not usually been included in clinical trials with immune checkpoint inhibitors. MATERIALS AND METHODS: Consecutive patients with advanced cancer, treated with anti-programmed death-1 (PD-1) agents, were evaluated according to the presence of pre-existing AIDs. The incidence of immune-related adverse events (irAEs) and clinical outcomes were compared among subgroups. RESULTS: A total of 751 patients were enrolled; median age was 69 years. Primary tumors were as follows: non-small cell lung cancer, 492 (65.5%); melanoma, 159 (21.2%); kidney cancer, 94 (12.5%); and others, 6 (0.8%). Male/female ratio was 499/252. Eighty-five patients (11.3%) had pre-existing AIDs, further differentiated in clinically active (17.6%) and inactive (82.4%). Among patients with pre-existing AIDs, incidence of irAEs of any grade was significantly higher when compared with patients without AIDs (65.9% vs. 39.9%). At multivariate analysis, both inactive (p = .0005) and active pre-existing AIDs (p = .0162), female sex (p = .0004), and Eastern Cooperative Oncology Group Performance Status <2 (p = .0030) were significantly related to a higher incidence of irAEs of any grade. No significant differences were observed regarding grade 3/4 irAEs and objective response rate among subgroups. Pre-existing AIDs were not significantly related with progression-free survival and overall survival. CONCLUSION: This study quantifies the increased risk of developing irAEs in patients with pre-existing AIDs who had to be treated with anti-PD-1 immunotherapy. Nevertheless, the incidence of grade 3/4 irAEs is not significantly higher when compared with control population. The finding of a greater incidence of irAEs among female patients ranks among the "hot topics" in gender-related differences in immuno-oncology. IMPLICATIONS FOR PRACTICE: Patients with a history of autoimmune diseases (AIDs) have not usually been included in clinical trials with immune checkpoint inhibitors but are frequent in clinical practice. This study quantifies the increased risk of developing immune-related adverse events (irAEs) in patients with pre-existing AIDs who had to be treated with anti-programmed death-1 immunotherapy. Nevertheless, their toxicities are mild and the incidence of grade 3/4 irAEs is not significantly higher compared with those of controls. These results will help clinicians in everyday practice, improving their ability to offer a proper counselling to patients, in order to offer an immunotherapy treatment even to patients with pre-existing autoimmune disease.

Understanding the Molecular Genetics of Basal Cell Carcinoma.

Basal cell carcinoma (BCC) is the most common human cancer and represents a growing public health care problem. Several tumor suppressor genes and proto-oncogenes have been implicated in BCC pathogenesis, including the key components of the Hedgehog pathway, PTCH1 and SMO, the TP53 tumor suppressor, and members of the RAS proto-oncogene family. Aberrant activation of the Hedgehog pathway represents the molecular driver in basal cell carcinoma pathogenesis, with the majority of BCCs carrying somatic point mutations, mainly ultraviolet (UV)-induced, and/or copy-loss of heterozygosis in the PTCH1 gene. Recent advances in sequencing technology allowed genome-scale approaches to mutation discovery, identifying new genes and pathways potentially involved in BCC carcinogenesis. Mutational and functional analysis suggested PTPN14 and LATS1, both effectors of the Hippo-YAP pathway, and MYCN as new BCC-associated genes. In addition, emerging reports identified frequent non-coding mutations within the regulatory promoter sequences of the TERT and DPH3-OXNAD1 genes. Thus, it is clear that a more complex genetic network of cancer-associated genes than previously hypothesized is involved in BCC carcinogenesis, with a potential impact on the development of new molecular targeted therapies. This article reviews established knowledge and new hypotheses regarding the molecular genetics of BCC pathogenesis.