Genetics of melanocytic nevi Roh, Mi Ryung; Eliades, Philip; Gupta, Sameer ...
Pigment cell & melanoma research,
November 2015, Letnik:
28, Številka:
6
Journal Article
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Summary
Melanocytic nevi are a benign clonal proliferation of cells expressing the melanocytic phenotype, with heterogeneous clinical and molecular characteristics. In this review, we discuss the ...genetics of nevi by salient nevi subtypes: congenital melanocytic nevi, acquired melanocytic nevi, blue nevi, and Spitz nevi. While the molecular etiology of nevi has been less thoroughly studied than melanoma, it is clear that nevi and melanoma share common driver mutations. Acquired melanocytic nevi harbor oncogenic mutations in BRAF, which is the predominant oncogene associated with melanoma. Congenital melanocytic nevi and blue nevi frequently harbor NRAS mutations and GNAQ mutations, respectively, while Spitz and atypical Spitz tumors often exhibit HRAS and kinase rearrangements. These initial ‘driver’ mutations are thought to trigger the establishment of benign nevi. After this initial phase of the cell proliferation, a senescence program is executed, causing termination of nevi growth. Only upon the emergence of additional tumorigenic alterations, which may provide an escape from oncogene‐induced senescence, can malignant progression occur. Here, we review the current literature on the pathobiology and genetics of nevi in the hope that additional studies of nevi promise to inform our understanding of the transition from benign neoplasm to malignancy.
Background Extramammary Paget disease (EMPD) is a rare intraepithelial neoplasm of the skin characterized by ill-defined margins and high recurrence rates after wide local excision. Although Mohs ...micrographic surgery (MMS) has been proposed to decrease the rate of local recurrence, the efficacy of MMS for this condition has not yet been established. Objective We sought to assess the efficacy of MMS for the treatment of EMPD. Methods A comprehensive systematic review and individual patient data meta-analysis was performed including all available clinical studies and case reports with 5 or more subjects describing the use of MMS for EMPD. Results Eight studies were identified and included in the current review: 3 retrospective studies and 5 case series. In all, 81 patients with 90 cases of MMS were included from these 8 studies. The overall recurrence rate for EMPD after MMS was 12.2% correlating with an estimated 5-year tumor-free rate of 83.6% by using Kaplan-Meier curve analysis. The treatment of EMPD with MMS resulted in significantly lower recurrence rates than wide local excision in this meta-analysis of 3 observational studies with comparators (odds ratio 0.20; 95% confidence interval 0.05-0.81). Limitations Limitations include lack of controlled trials, small sample sizes in the included studies, and publication bias. Conclusion The current evidence supports the efficacy of MMS in the treatment of EMPD. Further controlled clinical trials are needed.
Background
Although focus has recently been directed toward the early treatment of surgical scars, the optimal time at which to initiate treatment with fractional laser and its effect on scar ...remodeling remains controversial.
Objectives
To assess the safety and efficacy of treating surgical scars using an ablative carbon dioxide (CO2) fractional laser during the early postoperative period.
Materials and Methods
We performed a prospective, split‐scar, evaluator‐blinded study on 16 postoperative scars of 15 patients. Patients began treatment 3 weeks after surgery and were treated in two sessions of CO2 fractional laser therapy on half of the scar at 2‐week intervals. All patients were followed for 3 months after the final treatment session.
Results
Three months after the last treatment, a greater decrease in Vancouver Scar Scale score was noted in the treated half of the scars, especially in terms of texture and thickness. Patients also expressed a significantly greater degree of satisfaction with the treated side as assessed using a subjective 4‐point scale. Only one patient experienced any adverse effect, which was the development of hypertrophy, on the treated and untreated side of the scar.
Conclusion
CO2 fractional laser is an effective treatment modality for surgical scars in the early postoperative period.
Background Melanoma of unknown primary (MUP) is a condition of metastatic melanoma without a primary lesion. Objective We sought to identify the prognosis of MUP compared with melanoma of known ...primary (MKP). Methods We searched for observational studies containing at least 10 patients with MUP from MEDLINE and EMBASE from inception to December 22, 2012. The outcomes of interest were overall and disease-free survival; meta-analyses of hazard ratio stratified by stage using a random effects model were performed. In addition, second systematic review identified risk factors influencing the survival of patients with MUP. Results Eighteen studies including 2084 patients with MUP and 5894 with MKP were included. MUP had a better overall survival compared with MKP in stage III (15 studies; hazard ratio 0.83, 95% confidence interval 0.73-0.96, P = .010) and stage IV (6 studies; hazard ratio 0.85, 95% confidence interval 0.75-0.96, P = .008). Secondly, 22 studies including 3312 patients with MUP were reviewed, and increased stage and old age were the risk factors in patients with MUP. Limitations Diverse observational studies were reviewed, and selection and reporting biases are possible. Conclusions The current meta-analyses suggest better survival outcomes in patients with MUP than those in patients with MKP with the same corresponding tumor stage.
Acral melanoma commonly occurs in areas that are not exposed to much sunlight, such as the sole of the foot. Little is known about risk factors and mutational processes of plantar acral melanoma. ...Nuclear envelope rupture during interphase contributes to genome instability in cancer. Here, we show that the nuclear and micronuclear membranes of melanoma cells are frequently ruptured by macroscopic mechanical stress on the plantar surface due to weight-bearing activities. The marginal region of plantar melanoma nodules exhibits increased nuclear morphological abnormalities and collagen accumulations, and is more susceptible to mechanical stress than the tumor center. An increase in DNA damage coincides with nuclear membrane rupture in the tumor margin. Nuclear envelope integrity is compromised by the mechanosensitive transcriptional cofactor YAP activated in the tumor margin. Our results suggest a mutagenesis mechanism in melanoma and explain why plantar acral melanoma is frequent at higher mechanical stress points.
Surgical scars are crucial cosmetic problem, especially when in exposed areas such as the anterior neck following thyroidectomy.
To evaluate the impact of post-thyroidectomy scars on quality of life ...(QoL) of thyroid cancer patients and identify the relationship between scar characteristics and QoL.
Patients with post-thyroidectomy scars on the neck were recruited. QoL was measured using the Dermatology Life Quality Index (DLQI). Scar characteristics were graded according to Vancouver scar scale (VSS) score.
Ninety-seven patients completed a battery of questions at the time of enrollment. Post-thyroidectomy scars were classified according to morphology as linear flat scars, linear bulging scars, hypertrophic scars or adhesive scars. There were 32 patients (33.0%), 9 patients (9.3%), 41 patients (42.3%) and 15 patients (15.5%), respectively, in each group. The mean total DLQI score was 9.02. Domain 2 (daily activities, 2.87 points), which includes questions about clothing, was the most greatly impacted among patients. The total DLQI scores of patients who have experienced scar-related symptoms were significantly higher than those of patients without symptoms (p<0.05). The VSS scores were 3.09 for linear flat scars, 6.89 for linear bulging scars, 6.29 for hypertrophic scars and 5.60 for adhesive scars. However, the DLQI scores did not significantly differ among scar types or VSS scores.
Post-thyroidectomy scars on the neck affect the QoL of thyroid cancer patients regardless of scar type. Therefore, clinicians should pay attention to the psychological effects of scars on patients and take care to minimize post-thyroidectomy scar.
Background Although determining the recurrence of cutaneous squamous cell carcinoma (cSCC) is important, currently suggested systems and single biomarkers have limited power for predicting ...recurrence. Objective In this study, combinations of clinical factors and biomarkers were adapted into a nomogram to construct a powerful risk prediction model. Methods The study included 145 cSCC patients treated with Mohs micrographic surgery. Clinical factors were reviewed, and immunohistochemistry was performed using tumor tissue samples. A nomogram was constructed by combining meaningful clinical factors and protein markers. Results Among the various factors, four clinical factors (tumor size, organ transplantation history, poor differentiation, and invasion into subcutaneous fat) and two biomarkers (Axin2 and p53) were selected and combined into a nomogram. The concordance index (C-index) of the nomogram for predicting recurrence was 0.809, which was higher than that for the American Joint Committee on Cancer (AJCC) 7th, AJCC 8th, Brigham and Women's Hospital, and Breuninger staging systems in the patient data set. Conclusion A nomogram model that included both clinical factors and biomarkers was much more powerful than previous systems for predicting cSCC recurrence. Keywords: Cutaneous squamous cell carcinoma, Clinical risk factors, Biomarkers, Combined risk factors, Nomogram, Prognosis
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective:
Mucosal melanoma is an aggressive malignancy with a poor response to conventional therapies. The efficacy of radiotherapy (RT), especially combined with immune checkpoint inhibitors ...(ICIs), for this rare melanoma subtype remains unknown. We investigated the reciprocal effect of RT and ICI on mucosal melanoma patients.
Materials and Methods:
We identified 23 patients with 31 tumors who were treated with RT between July 2008 and February 2017. All patients received RT for primary or metastatic gross tumor mass with a median dose of 4 Gy per fraction (range 1.8–12 Gy). Eleven patients (14 lesions) were treated with RT alone, whereas 12 (17 lesions) were administered pembrolizumab combined with RT (ICI+RT group). The local control (LC) and adverse event (AE) rates were compared between the groups. Eight patients with metastatic mucosal melanoma treated with ICI alone during the same study period were included as a comparison group.
Results:
The median follow-up period was 17.4 (range 3.7–95.2) months. The target lesion control rate at 1-year was significantly higher in the ICI+RT group than in the RT-alone group or ICI-alone group (94.1% vs. 57.1% vs. 25%;
P
< 0.05). No abscopal effect was observed in our cohort. Treatment-related AEs were not significantly increased in the combined treatment group compared with the RT-alone group (
P
> 0.05). No grade ≥3 AEs occurred in the ICI+RT group.
Conclusions:
Besides RT acting as an immune adjuvant, ICI might have a radiosensitizing effect and may increase LC without severe toxicity. We have initiated a phase II study to determine the effects of RT in patients with melanoma undergoing anti-PD1 (NCT04017897).
Restoring the apical triangle (AT) to maintain the symmetry of the face after Mohs micrographic surgery can be challenging. We have applied secondary intention (SI) after partial closure in cases ...with large defects.
To compare the cosmetic results between immediate closure (IC) and SI.
We retrospectively reviewed 24 patients (IC group: n = 15, SI group: n = 9). To evaluate the symmetry, the comparative ratio (CR; area of the AT of the involved side/area of the normal contralateral side) was calculated.
The defects were significantly larger in the SI group than in the IC group (588.89 ± 346.53 mm
2
vs. 252.87 ± 196.52 mm
2
, p < .01). While there was no statistically significant difference in average CR, the standard deviation was higher in the SI group (0.95 ± 0.08 vs. 0.93 ± 0.31, p = .3359), indicating the difficulty in predicting the results of SI healing. The average visual analog scale score evaluated by two dermatologists was higher in the IC group, albeit without a significant difference (8.23 ± 0.96 vs. 7.78 ± 1.52, p = .5267).
SI after partial closure can be an option for large defects in the AT area.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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