MED15::ATF1-Rearranged Tumor: A Novel Cutaneous Tumor With Melanocytic Differentiation.

We recently described novel dermal tumors with melanocytic differentiation and morphologic and biological similarities to cutaneous clear cell sarcoma, including CRTC1::TRIM11 cutaneous tumor, and clear cell tumors with melanocytic differentiation and either ACTIN::MITF or MITF::CREM. Here, we describe a series of 3 patients presenting with tumors reminiscent of CRTC1::TRIM11 cutaneous tumor, found to demonstrate a novel MED15::ATF1 fusion. All 3 patients were children (5-16 years old). Primary excision of case 1 showed a circumscribed wedge-shaped silhouette with peripheral intercalation into collagen fibers and scattered lymphoid aggregates. All 3 tumors abutted the epidermis; one showed a junctional component. Tumors were highly cellular and comprised of monomorphic, oval-to-round epithelioid cells arranged in vague nests and short fascicles in variably fibrotic stroma. Mitotic rate was high (hotspot 6-12/mm2), without atypical mitoses. Necrosis was focally present in case 3. All cases showed strong, diffuse nuclear staining for SOX10 and MITF (2/2) but showed variable expression for S100 protein (1/3) and other melanocytic markers-Melan-A (focal in 2/3), HMB45 (focal in 1/3), and Pan-Melanoma (patchy in 1/1). Whole-exome RNA sequencing demonstrated a MED15::ATF1 fusion without any other notable alterations. Cases 1 and 2 were completely excised without recurrence (12 months). Case 3 developed a grossly apparent regional lymph node spread shortly after primary biopsy. The patient was treated with wide excision, radiation, cervical lymph node dissection (4/46 with >75% lymph node replacement), and neoadjuvant and adjuvant nivolumab (alive without disease at cycle 11). This series is presented to aid in future diagnosis of this novel dermal tumor with melanocytic differentiation and emphasize the potential for aggressive biologic behavior, which should be considered in patient management planning.

A critical re-evaluation of Mohs micrographic surgery for a facial basal cell carcinoma in older adults: Should we waive this treatment in certain patients?

BACKGROUND: Skin cancer incidences are increasing. Treatment for basal cell carcinomas (BCCs) can be questioned in certain patients. Treatment options are various, but Mohs micrographic surgery (MMS) has the highest cure rate. It is, however, time-consuming and results in high logistical burden and treatment costs for both patients and society. OBJECTIVES: This study critically re-evaluates MMS for facial BCCs in older adults. The main objective is to examine all clinical, tumour and patient characteristics in relation to safety and survival to detect a subgroup in which MMS was not the best choice. The overall aim is to identify characteristics that support clinical decision-making in daily practice. METHODS: Patients that received MMS between November 1998 and December 2012 were included. Only patients >75 years with a facial BCC were withheld for analysis. This is a retrospective cohort study, since evaluating the outcome of MMS in accordance with life expectancy is the main objective. Patient charts were evaluated towards comorbidities, complications and survival. RESULTS: This cohort comprises 207 patients. Median survival was 7.85 years. The age-adjusted Charlson comorbidity index (aCCI) was divided into low/medium scores (aCCI < 6) and high scores (aCCI ≥ 6). Median survival was 11.58 years in the low aCCI group and 3.60 years in the high aCCI group (p < 0.001). There was a very strong association between high aCCI and survival (HR, 6.25; 95% CI, 3.83-10.21). Other characteristics were not associated with survival. CONCLUSIONS: Clinicians should assess the aCCI in older patients presenting with a facial BCC before deciding if MMS is an eligible treatment option. High aCCI has shown to be an indicator for low median survival, even in MMS patients with usually high functional status. MMS should be waived as treatment in older patients with high aCCI scores in favour of other, less intensive and less expensive treatment options.

Fractional Carbon Dioxide Laser of Recent Surgical Scars in the Head and Neck Region: A Split-Scar, Evaluator-Blinded Study.

BACKGROUND: Postoperative scarring is a common cause of patient dissatisfaction. Several strategies have been developed to improve its clinical aspects. OBJECTIVE: To assess efficacy and safety of the 10,600 nm ablative fractional carbon dioxide (CO2) laser in the treatment of recent surgical scars in the head and neck region. METHODS AND MATERIALS: A prospective, randomized, single-blind intrapatient controlled study was conducted on 9 postoperative scars in the head and neck region. On half of the scar, 3 treatment sessions were performed. Physician/Patient Global Assessment (PhGA/PGA) and Patient and Observer Scar Assessment Scales (POSAS) were used to evaluate treatment efficacy. Safety was evaluated by registration of pain and adverse events. RESULTS: No statistically significant differences were noted in terms of PhGA or POSAS (observer). Patient Global Assessment (p = 0.058) and POSAS (patient) (p = 0.091) showed a trend toward better improvement of the treated half. Itch score (p = 0.046) and global end evaluation (patient) (p = 0.026) demonstrated a statistically significant difference in favor of the treated part. Adverse events were minor, and no long-term side effects were noted. CONCLUSION: The use of CO2 fractional laser is safe and is associated with high patient satisfaction. However, objective measurements could not confirm its efficacy in the treatment of recent surgical scars.

Total-Body Examination vs Lesion-Directed Skin Cancer Screening.

IMPORTANCE: Skin cancer is the most frequent cancer type. It remains unknown if and how screening programs can be organized in a cost-effective manner. OBJECTIVE: To compare the 2 screening strategies of systematic total-body examination (TBE) and lesion-directed screening (LDS), with a focus on the participation rate, detection rate, anxiety, and cost. DESIGN, SETTING, AND PARTICIPANTS: Population-based cross-sectional screenings by a team of 6 dermatologists were organized in 2 sociodemographically similar regions. The TBE was organized in a community of 9325 inhabitants 18 years and older (Wichelen, East Flanders, Belgium) during a 5-day screening (March 14-18, 2014). The LDS was organized in a sociodemographically comparable community (Nevele, East Flanders, Belgium) of 9484 adult inhabitants during a 4-day screening (April 22 and 25-27, 2014). The first population received a personal invitation for a standard TBE. In the second population, individuals were invited for an LDS if they had a lesion meeting 1 or more of the following criteria: ABCD rule (A, asymmetry; B, borders; C, colors; and D, differential structures), ugly duckling sign, new lesion lasting longer than 4 weeks, or red nonhealing lesions. MAIN OUTCOMES AND MEASURES: In total, 1982 individuals were screened, and 47 skin cancers (2.4%) were histologically confirmed, including 9 melanomas (0.5%), 37 basal cell carcinomas (1.9%), and 1 squamous cell carcinoma or Bowen disease (0.1%). RESULTS: The positive predictive value for all suspicious lesions was 56.6% (47 of 83). The participation rate was 17.9% (1668 of 9325) in the TBE group vs 3.3% (314 of 9484) in the LDS group (P < .01). The skin cancer detection rate per 100 participants did not differ significantly between the 2 groups, with rates of 2.3% (39 of 1668) in the TBE group vs 3.2% (8 of 248) in the LDS group (P = .40). The operational effectiveness per 100 invitees was 0.4% (39 of 9325) in the TBE group vs 0.1% (8 of 9484) in the LDS group (P < .01). In addition, LDS was 5.6 times less time consuming than TBE. Participants in the LDS group had significantly higher baseline anxiety levels compared with participants in the TBE group (3.7 vs 3.3 points on a visual analog scale, P < .01). In screenees without a suspicious lesion, anxiety levels significantly dropped after screening. CONCLUSIONS AND RELEVANCE: Total-body examination yielded a higher absolute number of skin cancers. Lesion-directed screening had a similar detection rate of 3.2% (8 of 248) but was 5.6 times less time consuming. When performed by dermatologists, LDS is an acceptable alternative screening method in health care systems with limited budgets or long waiting lists.

Xanthoma disseminatum: case report and mini-review of the literature.

Xanthoma disseminatum is a non-familial disorder of non-Langerhans cell origin or a class II histiocytosis with unknown etiology, with just over 100 cases reported in the literature. Because of the rarity of this disease, there is no established treatment. We studied clinical manifestations and different treatments of xanthoma disseminatum from a series of cases, including our own patient. We studied 15 articles on treatment of xanthoma disseminatum. Local treatment with cryotherapy, radiotherapy, surgery, and carbon dioxide lasers have been attempted with various results. Systemic medication with peroxisome proliferator-activated gamma receptors, statins, fenofibrate, chlorodeoxyadenosine, cyclophosphamide, doxycycline, and cyclosporine have also been reported, but none have proven particularly successful. Xanthoma disseminatum is usually benign and is often self-limiting. If the lesions are accessible to surgery, that is likely to give the best results. However, if the lesions are not accessible for surgical removal then carbon dioxide laser treatment may be considered. The choice of oral treatment should be made on the basis of the patient's condition, since none of them have proven particularly effective. Expectant management is justifiable as long as the lesions are limited to the skin.

Facial exercises for facial rejuvenation: a control group study.

OBJECTIVE: Facial exercises are a noninvasive alternative to medical approaches to facial rejuvenation. Logopedists could be involved in providing these exercises. Little research has been conducted, however, on the effectiveness of exercises for facial rejuvenation. This study assessed the effectiveness of 4 exercises purportedly reducing wrinkles and sagging of the facial skin. METHOD: A control group study was conducted with 18 participants, 9 of whom (the experimental group) underwent daily training for 7 weeks. Pictures taken before and after 7 weeks of 5 facial areas (forehead, nasolabial folds, area above the upper lip, jawline and area under the chin) were evaluated by a panel of laypersons. In addition, the participants of the experimental group evaluated their own pictures. Evaluation included the pairwise presentation of pictures before and after 7 weeks and scoring of the same pictures by means of visual analogue scales in a random presentation. RESULTS: Only one significant difference was found between the control and experimental group. In the experimental group, the picture after therapy of the upper lip was more frequently chosen to be the younger-looking one by the panel. CONCLUSION: It cannot be concluded that facial exercises are effective. More systematic research is needed.

Hypomelanoses in children.

Hypomelanosis of the skin is a frequently encountered problem in childhood, being totally innocent or representing the first sign of a multisystem disorder. Medical history, clinical examination, Wood's light investigation, histological analysis of the skin and a multidisciplinary consultation can contribute to a correct and early diagnosis of the different types of hypopigmentations. In the present paper, we present a systematic clinical approach to the differential diagnosis of those skin disorders.

Immune mediated mechanisms of melanocyte destruction: Paving the way for efficient immunotherapeutic strategies against melanoma.

Insights into immune reactions against benign and malignant melanocytes may help the development of more efficient immunotherapeutic treatments for melanoma. The interplay between an active systemic antitumor immunity and a responsive local tumor environment is crucial to achieve effective clinical responses. Increasing evidence confirms this strategy can lead to an adequate and durable immunosurveillance of melanocytes.

EGFR in melanoma: clinical significance and potential therapeutic target.

BACKGROUND: The role of epidermal growth factor receptor (EGFR) has been established in a range of neoplasms. In melanoma, data on EGFR protein expression are conflicting. Fluorescence in situ hybridization (FISH) analysis for EGFR gene expression in melanoma showed EGFR gene amplification to be linked with worse prognosis. Cetuximab has been shown to suppress the formation of metastasis in mice. METHODS: EGFR protein expression and gene copy number status were evaluated by means of immunohistochemistry and FISH in melanoma samples of patients with known clinicopathological data. Associations between EGFR expression and prognostic parameters were investigated. The effect of different cetuximab concentrations on the BLM melanoma cell line was evaluated by means of methyl tetrazolium (MTT), sulforhodamine B (SRB) and Matrigel invasion assays. RESULTS: EGFR protein expression was more frequently observed in patients with a positive sentinel lymph node. However, EGFR immunostaining has no predictive value. The presence of EGFR polysomy was associated with thicker tumors. Treatment of the BLM melanoma cell line with different concentrations of cetuximab reduced the invasive capacity of the cells, but did not alter cell viability or growth. CONCLUSION: EGFR appears to be involved in progression and metastasis of a subset of melanomas. Targeting EGFR could therefore represent a therapeutic option for these melanomas.

Scarf osteotomy for hallux valgus deformity: a prospective study with 8 years of clinical and radiologic follow-up.

BACKGROUND: Scarf midshaft metatarsal osteotomy has become increasingly popular as a treatment option for moderate-to-severe hallux valgus deformities because of its great versatility. Numerous studies on Scarf osteotomy have been published. However, no prospective studies were available until 2002. Since then, only short-term follow-up prospective studies have been published. We present the results of a prospective study of 21 patients treated by Scarf osteotomy for hallux valgus with follow-up of 8 years. METHODS: Between August 1, 1999, and October 31, 1999, 23 patients (23 feet) with moderate-to-severe hallux valgus deformity were included. Clinical (American Orthopaedic Foot and Ankle Society score) and radiologic (hallux valgus angle, first intermetatarsal angle, and sesamoid position) evaluations were performed preoperatively and 1 and 8 years postoperatively. RESULTS: Clinical evaluation showed a significant improvement in the mean forefoot score from 47 to 83 (of a possible 100) at 1 year (P < .001). Radiographic evaluation showed significant improvement in the hallux valgus angle (mean improvement, 19 degrees ; P < .001) and in the intermetatarsal angle (mean improvement, 6 degrees ; P < .001). These clinical and radiographic results were maintained at the final evaluation 8 years postoperatively. CONCLUSIONS: Scarf osteotomy tends to provide predictable and sustainable correction of moderate-to-severe hallux valgus deformities.

The role of RhoC in growth and metastatic capacity of melanoma.

BACKGROUND: RhoC overexpression in tumor cells promotes invasive and metastatic behavior. RhoC expression levels have been correlated with tumor progression and metastasis in multiple human cancers. In melanoma, RhoC is upregulated in highly metastatic tumors. Induced expression in melanoma cell lines resulted in invasion and metastasis, whereas inhibition of RhoC reversed the metastatic phenotype both in vitro and in vivo. METHODS: RhoC mRNA and protein expression in two human melanoma cell lines (DX3aza and MeWo) and pooled primary melanocytes were investigated by means of real-time quantitative polymerase chain reaction and western blotting. RhoC protein expression was evaluated in 123 primary cutaneous melanoma samples by the use of immunohistochemistry and correlated with known prognostic features. RESULTS: RhoC upregulation was observed in the highly metastatic DX3aza cell line, whereas in MeWo, only low expression levels could be detected. RhoC expression in primary cutaneous melanoma was strongly associated with thicker and ulcerated tumors. RhoC expression was associated with the presence of lymphatic metastases at the time of diagnosis and shorter disease-free and overall survival rates, without being an independent predictor. CONCLUSION: These results further support a role for RhoC in growth and metastasis of melanoma.

Clinical significance of the expression of c-Ski and SnoN, possible mediators in TGF-beta resistance, in primary cutaneous melanoma.

BACKGROUND: Loss of TGF-beta growth control is considered as a hallmark of several human neoplasms including melanoma. Resistance of cancer cells to TGF-beta has been linked to mutations in proteins involved in the TGF-beta pathway. In melanoma such mutations have not been observed. C-Ski and SnoN, two structurally and functionally highly homologous proteins, are known as negative regulators in the TGF-beta signaling pathway. C-Ski and SnoN expression levels and subcellular localization have been associated with clinicopathological parameters and tumour progression in several human malignancies. In melanoma cell lines, high c-Ski and SnoN expression levels have been described. OBJECTIVE: The objective of this study was to evaluate the clinical value of c-Ski and SnoN expression in primary cutaneous melanoma. METHODS: We evaluated c-Ski and SnoN expression by immunohistochemical staining in 120 primary melanomas. Possible associations between c-Ski and SnoN staining patterns and clinicopathological parameters were analyzed. RESULTS: Nuclear c-Ski expression was significantly associated with thicker and ulcerated tumours. The percentage of SnoN positivity was higher in ulcerated tumours and in the sentinel node positive group. CONCLUSION: These results suggest that c-Ski and SnoN, mediators in TGF-beta resistance, might be implicated in melanoma growth and progression.

The role of VEGF-C staining in predicting regional metastasis in melanoma.

Sentinel lymph node status is the most important prognostic factor in primary melanoma. The number of melanoma-associated lymphatic vessels has been associated with sentinel lymph node status and survival. Vascular endothelial growth factor-C (VEGF-C) is found to promote tumour-associated lymphatic vessel growth. In many human neoplasms, VEGF-C expression in neoplastic cells or tumour-associated macrophages (TAMs) has been linked to lymphatic dissemination of tumour cells. Recent studies have suggested a correlation between VEGF-C expression in primary melanoma and the presence of lymph node metastasis. We performed VEGF-C immunohistochemical staining on melanoma tissues of 113 patients with known sentinel lymph node status. We showed that both high VEGF-C expression in melanoma cells and TAMs are positively associated with the presence of a positive sentinel lymph node. No correlation with Breslow thickness, Clark invasion level or ulceration could be detected. VEGF-C expression in melanoma cells was predictive of a shorter overall and disease-free survival, without being an independent predictor of survival. Our results confirm that VEGF-C expression in primary cutaneous melanoma plays a role in the lymphatic spread of the tumour.

Knee arthrodesis with an intramedullary nail: a retrospective study.

A group of 19 patients who underwent knee arthrodesis with use of an intramedullary nail between 1996 and 2005, was studied. In the majority of patients knee arthrodesis was performed as a salvage procedure for the limb following an infected total knee arthroplasty. The outcome of the procedure was evaluated with radiographs, the SF-36 score and the Oxford 12-item knee score. The functional result of a successful arthrodesis was found to be comparable with that of a revised hinged total knee arthroplasty. Knee arthrodesis with an intramedullary nail allows weightbearing within 1 week and is accompanied by a high rate of pain relief. However, recurrence of infection is the most challenging problem.

Topical pimecrolimus in the treatment of vitiligo.

Although the treatment of vitiligo has improved during the last decade, therapy is still not satisfactory for many patients. Recently topical calcineurin inhibitors were introduced in the treatment of atopic dermatitis. Considering the autoimmune hypothesis of vitiligo pathogenesis, the use of these topical calcineurin inhibitors seems reasonable. Most clinical vitiligo trials have been performed with tacrolimus and show beneficial effects. Concerning the value of pimecrolimus in the treatment of vitiligo only few data are available. Therefore we performed an open pilot study in 26 patients to evaluate the efficacy and safety of 1% pimecrolimus in the treatment of vitiliginous lesions in the head and neck region. In 13 of 26 (50%) evaluated target lesions, repigmentation was noted after a 6 month treatment period with a median percentage of repigmentation of 72.9% (interquartile range: 30.5-98.3%). Duration of vitiligo and total affected body surface area tended to be inversely correlated with the success rate of treatment. Side effects were mainly limited to a burning sensation at the application site. Despite the promising results of topical immunomodulators in the treatment of vitiligo, prudence is in order, as long-term follow up studies are still lacking.