Awareness of sun exposure risks and photoprotection for preventing pigmentary disorders in Asian populations: Survey results from three Asian countries and expert panel recommendations.

BACKGROUND: In this article, we review and discuss the photoprotection behavior of Asians based on the literature, along with a subanalysis of an original online survey, and make recommendations to optimize photoprotection for Asian populations to prevent photoaging and pigmentary disorders. METHODS: An international panel of eight dermatologists from Asia (China, Korea, Japan, Singapore, Indonesia, and Vietnam) met to discuss sunscreen photoprotection for Asian patients. Additionally, a subanalysis of an online survey by 3000 respondents from three Asian countries (China, Indonesia, and Japan) investigated general public awareness and attitudes to sun exposure. RESULTS: A pre-meeting survey of the eight experts from Asia showed key concerns of Asian patients consulting dermatologists are pigmentary disorders, especially actinic/senile lentigo, post-inflammatory hyperpigmentation, melasma, vitiligo, and Hori's nevus. The survey subanalysis of participants from China, Indonesia, and Japan with predominantly Fitzpatrick skin types (FST) II to IV revealed that they are particularly concerned about sun exposure causing photoaging and pigmentary disorders. Most of the respondents indicated they have limited knowledge on sunlight radiation and appropriate sunscreen protection factors. Only 22%, 13%, and 3% for China, Indonesia, and Japan, respectively, systematically use multiple protective measures (using sunscreen, avoiding midday sun, staying in the shade, wearing a hat, protective clothing, and sunglasses) when exposed to the sun. CONCLUSIONS: Further education is needed for Asian populations on the importance of comprehensive daily photoprotection, including broad-spectrum sunscreen, with high UVA and visible light protection, to reduce and prevent photoaging and pigmentary disorders.

The role of dermocosmetics in the management of cancer-related skin toxicities: international expert consensus.

Skin toxicities are very common in patients undergoing cancer treatment and have been found to occur with all types of cancer therapeutic interventions (cytotoxic chemotherapy, targeted therapies, immunotherapy, and radiotherapy). Further, skin toxicities can lead to interruption or even discontinuation of anticancer treatment in some patients, translating to suboptimal outcomes. Dermocosmetics (or cosmeceuticals)-defined as skincare solutions incorporating dermatologically active ingredients (beyond vehicle effects) that directly improve symptoms of various skin conditions-are increasingly being used in cancer care to prevent and manage skin toxicities. The active ingredients in these products have a measurable biological action in skin; they typically improve skin integrity (barrier function/hydration and other factors) while relieving skin symptoms. The Association Francophone des Soins Oncologiques de Support (AFSOS) and Multinational Association of Supportive Care in Cancer (MASCC) partnered to select a multidisciplinary group of healthcare professionals involved in the management of patients with cancer and skin toxicities. The group reviewed existing literature and created a summary of recommendations for managing these toxicities through online meetings and communication. In this publication, the group (1) reviews new skin toxicities seen with oncology drugs and (2) evaluates the role of dermocosmetics in improving patient outcomes and minimizing cancer treatment interruptions. We provide general recommendations for initiation and selection of skin care in all oncology patients as well as recommendations for what factors should be considered when using dermocosmetics in specific types of skin toxicities.

Development of actinic lentigines due to multiple sub-erythemal exposure to UVA1 radiation in Asian skin.

The appearance of actinic lentigines mainly found on face, back of the hands, upper back and décolleté is associated with chronic sun exposure. However, there is no study looking at the role of long UVA specifically in the development of actinic lentigines. This study was conducted in 20 Japanese adult women exposed on the upper back area three times per week for 6 weeks to incremental sub-erythemal UVA1 doses (5 J/cm2 at weeks 1 and 2, 10 J/cm2 at weeks 3 and 4 and 15 J/cm2 at weeks 5 and 6). Clinical assessment, performed on day 0 (before any exposure), and on days 14, 28 and 42, included the evaluation of skin pigmentation (pigmented spots), chromametry of the pigmented skin lesions and measurement of dyschromy. The number of pigmented spots and uniformity of the skin's pigmentation were clearly increased in comparison with baseline, statistical significance of the difference (p < 0.05) being reached at D 28 and D 42 in both cases. In conclusion, repeated sub-erythemal UVA1 exposure induces the development of actinic lentigines. Thus, a suitable protection including long UVA coverage is also needed to prevent from the damages induced by low, sub-erythemal doses of UV exposure.

Sun exposure behaviours as a compromise to paradoxical injunctions: Insight from a worldwide survey.

BACKGROUND: Behavioural interventions can improve attitudes towards sun protection but the impact remains inconsistent worldwide. OBJECTIVE: To assess awareness of and attitudes towards the multiple facets of sun exposure and suggest ways to improve prevention from overexposure to the sun in all geographical zones and multiple skin types. METHODS: Online survey was conducted from 28 September to 18 October 2021. Study population was selected from the Ipsos online Panel (3,540,000 panellists), aged ≥18 years, from 17 countries around the five continents. Demographics, sun-exposure habits and practices, understanding of risks and information on phototypes were documented and analysed using descriptive statistics. RESULTS: Eighty-eight per cent of participants knew that sunlight can cause skin health problems (90% phototypes I-II, 82% phototypes V-VI, >90% in American and European countries, 72% in Asia and 85% in Africa). Eighty-five per cent used some form of protection against sunlight, predominantly: Seeking shade (77%), avoiding the midday sun (66%), facial application of sunscreen (60%) and wearing protective clothing (44%). The perception of sunlight itself is positive ('it gives energy' for 82%; 'tanned skin looks attractive' for 72%), although less in Asian countries and among individuals with dark skin phototypes. Eighty-three per cent reported having experienced sunburn, mainly in Australia, Canada, USA, Germany, France and Russia, and among individuals with dark skin phototypes. Only 12% systematically/often used all types of protection during exposure to the sun and 23% believed it is safe to go out in the sun with no protection when their skin is already tanned. From 13% (skin phototype I) to 26% (phototype VI) reported not using any form of protection against the sun. Knowledge and habits were significantly superior among people who are accustomed to seeing a dermatologist for a complete skin exam. CONCLUSIONS: Dermatologists could play a crucial role in relaying novel prevention messages, more finely tailored to specific risks, populations and areas of the world.

Expert recommendations on supportive skin care for non-surgical and surgical procedures.

A thorough knowledge of non-surgical procedures (laser, peelings, injections, threads) and surgical procedures (combined surgeries and skin grafts), including contraindications and potential risks and side effects, (e.g. infection, hypopigmentation, hyperpigmentation, and scarring) is essential to be able to reduce their incidence and ensure the patient receives the most benefit from the procedure. Individuals with darker skin and of high Fitzpatrick phototype are at higher risk of dyschromias, notably melasma and post-inflammatory hyperpigmentation, which may be treated using aesthetic procedures but may also arise as a complication of some procedures. A group of experts in cosmetic surgery and dermatology reviewed the published literature and discussed recommendations for optimizing outcomes with practical advice on supportive skincare before, during and after non-surgical or surgical procedures. A broad-spectrum sunscreen with a high sun protection factor against UVB and high protection against UVA, especially long UVA, is essential for all treatment modalities for the prevention and potential improvement of pigmentation disorders. Supportive skin care management to prepare, cleanse and protect the skin and post-procedure skin care with healing and anti-inflammatory ingredients are recommended to speed up regeneration and wound healing whilst minimizing scarring and downtime. Additionally, adjunctive skin care to procedures with antioxidant, anti-ageing and lightening properties may enhance skin benefits.

Topical formulation containing peptides and vitamin C in ampoules improves skin aging signs: Results of a large, international, observational study.

INTRODUCTION: Peptide-C ampoules (PC) contain peptides, 10% of vitamin C, hyaluronic acid, and Vichy volcanic mineralizing water. AIMS: To assess the effectiveness and tolerability of PC. PATIENTS AND METHODS: An observational study conducted in 9 countries in women ≥30 years old with signs of facial skin aging (grade >0 for forehead and/or crow's feet wrinkles and bothered by skin quality). Investigator assessments and subject questionnaires were performed at initial visit and Day 30 after application of PC twice daily for 28 days. Tolerance was assessed throughout the study. RESULTS: Effectiveness and safety were analyzed in 1382 and 1742 subjects, respectively. Most subjects (mean age 48.5 ± 8.6 years) had skin phototype II or III (91.7%) and dry or combination skin (63.9%). PC was used as a standalone care or prior to a planned procedure (70%), or after a procedure (30%). Between baseline and Day 30, 63% and 64% of all subjects (N = 1360) had an improvement in forehead wrinkles and crow's feet wrinkles, respectively. Skin hydration improved in 67.3% of subjects. According to investigator and subject assessments, skin quality, skin radiance, skin aging signs, wrinkles, complexion, and skin pores significantly improved by Day 30. Similar results were observed for subgroup analyses when PC was used as standalone skin care or after a procedure. Tolerance of PC was rated as good to very good by 97.7% of subjects. CONCLUSIONS: Peptide-C ampoules is effective in reducing visible signs of skin aging, and well tolerated, when used alone or as an adjunct to anti-aging procedures.

Long-Term Outcome of Neoadjuvant Tyrosine Kinase Inhibitors Followed by Complete Surgery in Locally Advanced Dermatofibrosarcoma Protuberans.

In locally advanced dermatofibrosarcoma protuberans (DFSP), imatinib mesylate has been described as an efficient neoadjuvant therapy. This retrospective study included patients with locally advanced DFSP who received neoadjuvant TKI (imatinib or pazopanib) from 2007 to 2017 at Saint Louis Hospital, Paris. The primary endpoint was the evaluation of the long-term status. A total of 27 patients were included, of whom nine had fibrosarcomatous transformation. The median duration of treatment was 7 months. The best response to TKI treatment before surgery, evaluated according to RECIST1.1 on MRI, consisted of complete/partial response (38.5%) or stability (46.2%). DFSP was surgically removed in 24 (89%) patients. A total of 23 patients (85%) were disease-free after 64.8 months of median follow-up (95% confidence interval 47.8; 109.3). One patient developed distant metastases 37 months after surgical tumor resection and finally died. Two patients (7%) did not get surgery because of metastatic progression during TKI treatment, and one patient refused surgery even though the tumor decreased by 30%. Treatment-related adverse events (AE) occurred in 23 patients (85%). Only four patients (imatinib: n = 3, pazopanib: n = 1) had grade ≥3 AE requiring temporary treatment disruption. Neoadjuvant TKI followed by complete surgery with micrographic analysis is an effective strategy for locally advanced and unresectable DFSP, with durable local recurrence disease-free survival.

Feasibility of daylight-mediated photodynamic therapy for actinic keratosis throughout the year in Central and South America: a meteorological study.

BACKGROUND: Daylight-mediated photodynamic therapy (DL-PDT) is an efficacious treatment option for thin actinic keratosis (AK) that offers advantages over conventional PDT in terms of tolerability, treatment duration, and cost. A clinical study conducted in Australia determined the mean irradiance during a 2-hour exposure to be 305.8 W/m(2) (range: 40-585 W/m(2) ). The protoporphyrin IX light dose is influenced by latitude, weather conditions, and time of year. A recent study of meteorological data concluded that DL-PDT can be performed effectively throughout the year in Australia. OBJECTIVES: Based on the same hypothesis and applying the same methodology, the present study investigated the suitability of daylight to perform DL-PDT in Central and South America. METHODS: Solar radiation and weather data were gathered and analyzed to assess daylight irradiance (light intensity) throughout a full year across 32 geographical locations in Central and South America. RESULTS: The minimum average daily solar irradiance reported was above 305.8 W/m(2) in all locations investigated throughout the year. Annual averages of daily irradiance ranged from 578 W/m(2) in Chihuahua, Mexico, to 321 W/m(2) in Puerto Montt, Chile. CONCLUSIONS: Daylight-mediated PDT for AK can be performed effectively throughout the year in Central and South America given that weather conditions permit a comfortable 2-hour direct exposure to daylight.

Treatment of face and scalp solar (actinic) keratosis with daylight-mediated photodynamic therapy is possible throughout the year in Australia: Evidence from a clinical and meteorological study.

BACKGROUND/OBJECTIVES: Solar (actinic) keratosis (AK) is an emergent concern worldwide and is associated with an increased risk of development of non-melanoma skin cancer, especially squamous cell carcinoma. Daylight-mediated photodynamic therapy (DL-PDT) using methyl aminolaevulinate cream has proved to be an effective, nearly painless, and more convenient alternative to conventional PDT for the treatment of AK. In a phase III, randomised, controlled trial performed in Australia, the mean irradiance (light intensity) received by patients during DL-PDT treatment, assessed via a spectroradiometer, was 305 W/m(2) (min. 40 to max. 585 W/m(2) ) with similar efficacy irrespective of intensity or dose. The objective of the present meteorological study was to assess the suitability of natural daylight to perform DL-PDT for the treatment of face and scalp AK during different periods of the year and different geographical locations and latitudes across Australia. METHODS: To determine daylight irradiance during a complete year in eight different geographical locations throughout Australia, we used meteorological software (Meteonorm, Meteotest, Bern, Switzerland), and available solar radiation and weather data from 1986-2005. RESULTS: The average daily irradiance remained within the levels (40-585 W/m(2) ) measured during the clinical DL-PDT study in Australia, throughout the year and in all geographical locations investigated (yearly average from Darwin 548 W/m(2) to Hobart 366 W/m(2) ). CONCLUSIONS: DL-PDT for the treatment of face and scalp AK in Australia can be performed effectively throughout the entire year as long as weather conditions permit daylight exposure and allow participants to remain under direct light for 2 h.

Ultrasound-guided core needle biopsy of superficial lymph nodes: an alternative to fine-needle aspiration cytology for the diagnosis of lymph node metastasis in cutaneous melanoma.

To investigate the diagnostic value of ultrasound-guided core needle biopsy (US-CNB) in suspected cases of lymph node metastasis from cutaneous melanoma. All patients with cutaneous melanoma followed in Saint-Louis Hospital between 2006 and 2010 who underwent US-CNB for suspicion of melanoma lymph node metastasis were reviewed retrospectively. Histopathological results of US-CNB samples were classified as melanoma, other malignancy, suspicious, inadequate, or benign. The diagnostic accuracy of US-CNB was assessed by comparison with two reference standards: histopathological examination of the radical lymph node dissection or, when this was not available, clinical and radiological follow-up. The data from 72 US-CNB were analyzed. Forty-four melanomas, 22 benign, three other malignancies, three inadequate samples, and no inconclusive specimens were diagnosed. Seventy-one US-CNB results were confirmed (98.6%). US-CNB achieved high sensitivity, specificity, and positive predictive value (respectively, 97.9, 100, and 100%). No adverse events were reported after the procedure. US-CNB provided a mean tissue volume of 16.7 mm per lymphadenopathy. US-CNB has diagnostic value similar to that of fine-needle aspiration cytology. It represents a reliable alternative method in melanoma lymph node metastasis to avoid surgery in patients who will not benefit from it. US-CNB provides relatively large samples of tissue suitable for comprehensive genomic analyses currently needed for research and personalized care of melanoma patients.

Description and outcome of a cohort of 8 patients with WHIM syndrome from the French Severe Chronic Neutropenia Registry.

BACKGROUND: WHIM syndrome (WS), a rare congenital neutropenia due to mutations of the CXCR4 chemokine receptor, is associated with Human Papillomavirus (HPV)-induced Warts, Hypogammaglobulinemia, bacterial Infections and Myelokathexis. The long term follow up of eight patients highlights the clinical heterogeneity of this disease as well as the main therapeutic approaches and remaining challenges in the light of the recent development of new CXCR4 inhibitors. OBJECTIVE: This study aims to describe the natural history of WS based on a French cohort of 8 patients. METHODS: We have reviewed the clinical, biological and immunological features of patients with WS enrolled into the French Severe Chronic Neutropenia Registry. RESULTS: We identified four pedigrees with WS comprised of eight patients and one foetus. Estimated incidence for WS was of 0.23 per million births. Median age at the last visit was 29 years. Three pedigrees encompassing seven patients and the fetus displayed autosomal dominant heterozygous mutations of the CXCR4 gene, while one patient presented a wild-type CXCR4 gene. Two subjects exhibited congenital conotruncal heart malformations. In addition to neutropenia and myelokathexis, all patients presented deep monocytopenia and lymphopenia. Seven patients presented repeated bacterial Ears Nose Throat as well as severe bacterial infections that were curable with antibiotics. Four patients with late onset prophylaxis developed chronic obstructive pulmonary disease (COPD). Two patients reported atypical mycobacteria infections which in one case may have been responsible for one patient's death due to liver failure at the age of 40.6 years. HPV-related disease manifested in five subjects and progressed as invasive vulvar carcinoma with a fatal course in one patient at the age of 39.5 years. In addition, two patients developed T cell lymphoma skin cancer and basal cell carcinoma at the age of 38 and 65 years. CONCLUSIONS: Continuous prophylactic anti-infective measures, when started in early childhood, seem to effectively prevent further bacterial infections and the consequent development of COPD. Long-term follow up is needed to evaluate the effect of early anti-HPV targeted prophylaxis on the development of skin and genital warts.

Pregnancy promotes melanoma metastasis through enhanced lymphangiogenesis.

The relationships of pregnancy and melanoma have been debatable. Our aim was to assess the influence of gestation on the course of melanoma in a classic murine model of tumor progression and in women. B16 mouse melanoma cells were injected in nonpregnant or pregnant mice on day 5 of gestation. Animals were evaluated for tumor progression, metastases, and survival. Tumor sections were analyzed for lymphatic and blood vessel number and relative surface and expression of angiogenic growth factors. Finally, primary melanomas from pregnant and nonpregnant women, matched for age and tumor thickness, were also considered. Tumor growth, metastasis, and mortality were increased in B16-injected pregnant mice. Tumors displayed an increase in intratumoral lymphangiogenesis during gestation. This increased lymphatic angiogenesis was not observed in normal skin during gestation, showing its specificity to the tumor. An analysis of melanoma from pregnant and matched nonpregnant women showed a similar increase in lymphatic vessels. Tumors from pregnant mice had increased expression of vascular endothelial growth factor A at the RNA and protein levels. The increased vascular endothelial growth factor A production by melanoma cells could be reproduced in culture using pregnant mouse serum. In conclusion, pregnancy results in increased lymphangiogenesis and subsequent metastasis. Caution should be applied in the management of patients with advanced-stage melanoma during gestation.

Imatinib mesylate as a preoperative therapy in dermatofibrosarcoma: results of a multicenter phase II study on 25 patients.

AIMS: The treatment of dermatofibrosarcoma protuberans (DFSP) involves wide local excision with frequent need for reconstructive surgery. A t(17;22) translocation resulting in COL1A1-PDGFB fusion is present in >95% of cases. Certain patient observations and a report on nine patients suggest that imatinib mesylate, targeting platelet-derived growth factor receptor beta, has clinical potential in DFSP. The primary aim of this phase II multicenter study was to define the percentage of clinical responders (Response Evaluation Criteria in Solid Tumors) to a 2-month preoperative daily administration of 600 mg of imatinib mesylate before wide local excision. The secondary aims were to determine tolerance, objective response from imaging results (ultrasound and magnetic resonance imaging), and pathologic responses observed in sequential tissue specimens. PATIENTS AND METHODS: A two-stage flexible design was used with interim analysis after the recruitment of six patients. Twenty-five adults suffering from primary or recurrent DFSP were included from July 2004 to May 2006. RESULTS: The COL1A1-PDGFB fusion gene was detected in 21 out of 25 patients following fluorescence in situ hybridization analysis (two cases were noninformative). A clinical response was achieved in nine (36%) patients (95% confidence interval, 18.9-57.5). The median relative tumoral decrease was 20.0% (range, -12.5 to 100). Apart from expected grade 1 or 2 side effects, we observed one grade 3 neutropenia, one grade 3 maculopapular rash, and one grade 4 transient transaminitis. CONCLUSION: Our results support the use of imatinib in a neoadjuvant setting in nonresectable DFSP, or when surgery is difficult or mutilating. These results will be useful for setting hypotheses in the evaluation of new drugs to treat primary or secondary resistance to imatinib.

Highly sensitive multivariable assay detection of melanocytic differentiation antigens and angiogenesis biomarkers in sentinel lymph nodes with melanoma micrometastases.

OBJECTIVES: To evaluate the prognostic value of melanocytic differentiation antigens and angiogenesis biomarkers in sentinel lymph nodes (SLNs) with melanoma micrometastases. DESIGN: Prognostic study of an inception cohort. SETTING: Academic research. Patients Between July 1, 1999, and July 31, 2002, all patients who had primary cutaneous or mucosal melanomas that have a Breslow depth of 1.5 mm or greater, ulceration, or Clark level IV or V, or had SLN biopsies. MAIN OUTCOME MEASURES: By the use of quantitative reverse transcription-polymerase chain reaction, the expression of the following was analyzed in SLNs: 2 melanocytic differentiation antigens (tyrosinase [P17646] and melanoma antigen recognized by T cells [MART-1; Q16655]) and genes involved in angiogenesis (VEGF [NM_001025366] and VEGFR2 [AF035121]), lymphangiogenesis (VEGFC [NM_005429], VEGFR3 [X68203], LYVE1 [NM_016164], and PROX1 [002763]), and invasion (uPA [NM_002658], PAI1 [NM_00602], and EMMPRIN [L10240]). Outcome measures were the association of these melanocytic differentiation antigens and angiogenesis biomarkers with clinicopathologic characteristics of patients, and an evaluation of the prognostic value for relapse-free survival and overall survival. RESULTS: Ninety-one patients were included, with a median follow-up period of 41 months. Micrometastases were present in 15% (14 of 91) of patients. Tyrosinase (P < .001), MART-1 (P < .001), vascular endothelial growth factor 121 (VEGF(121)) (P = .007), and PAI1 (P = .02) expression was significantly associated with micrometastasis. In univariate analysis, histologic findings and tyrosinase and MART-1 expression were significantly associated with relapse-free survival. Tyrosinase and MART-1 expression was associated with overall survival. A multiple Cox proportional hazards regression model identified negative histologic findings and tyrosinase expression that exceeded 27 copies/copy of TATA box-binding protein (third quartile) as significantly associated with an increased risk of relapse or death. CONCLUSIONS: Quantitative assessment of melanocytic differentiation antigens in SLNs, which has prognostic value, is more specific than qualitative assessment. Prognosis may be more effectively predicted by the combination of quantitative assessment of melanocytic differentiation antigens in SLNs with histologic assessment. A significant association was found between the presence of micrometastases and the expression of angiogenesis biomarkers.

Interest in an original methodology to define the optimal dosage of interferon-alpha-2a in metastatic melanoma patients.

Interferon-α-2a (IFNa) has proven antitumor activity in a variety of neoplastic diseases, but no clear modality of administration has been validated. The aim of our study was to estimate the optimal dose of continuous subcutaneous administration of IFNa in stage IV metastatic melanoma patients. An innovative dose-finding approach, combining phase I and phase II trials, was planned to evaluate the toxicity and efficacy of four dose levels of IFNa (3, 6, 9, and 12 MIU/day). Sixteen patients were enrolled in this study. Three patients were treated according to the dose-allocation rule with IFNa at 3 MIU/day, nine patients at 6 MIU/day, and four patients at 9 MIU/day. Dose-limiting toxicities were grade 3 in five patients (three at a dose level of 6 MIU/day and two at a dose level of 9 MIU/day). Four clinically relevant responses were obtained, one at dose level 3 MIU/day, one at a dose level of 6 MIU/day, and two at a dose level of 9 MIU/day. The three final responses, at dose levels of 6 and 9 MIU/day, were associated with a dose-limiting toxicity. A dose level of 6 MIU/day was well tolerated but did not reach the desired efficacy target of 20%, and a dose level of 9 MIU/day was estimated to be too toxic. This original dose-finding methodology made it possible to estimate the rate of toxicity and efficacy in a small sample of patients without toxicity associated with each dose level.

Fetal microchimeric cells participate in tumour angiogenesis in melanomas occurring during pregnancy.

Melanoma is a major malignancy in younger individuals that accounts for 8% of all neoplasias associated with gestation. During pregnancy, a small number of fetal cells enter the maternal circulation. These cells persist and then migrate to various maternal tissues where they may engraft and differentiate, particularly if there is organ damage, adopting the phenotype of the host organ. To understand the relationship between melanoma and pregnancy, we analyzed these tumors in both humans and mice. Fetal cells were detected in 63% of human primary melanomas versus 12% in nevi during pregnancy (P = 0.034) and in 57% of B16 melanomas in pregnant mice but never in normal skin (P = 0.000022). More than 50% of these fetal cells expressed the CD34, CD31, or von Willebrand factor endothelial cell markers. In addition, the Lyve-1 lymphatic antigen was expressed by more than 30% of fetal cells in mice. In conclusion, we show that melanomas during pregnancy frequently harbor fetal cells that have an endothelial phenotype. Further studies are needed to assess whether the fetal contribution to lymphangiogenesis may alter the prognosis of the maternal tumor.

Slow dynamic lymphoscintigraphy is not a reliable predictor of sentinel-node negativity in cutaneous melanoma.

We reviewed data from 160 consecutive patients (89 M/71 F; 53.5 [range, 9-88] years) who had under-gone lymphoscintigraphy and sentinel lymph node biopsy (SNB) in our hospital for histologically proven cutaneous malignant melanoma (CMM) (located on the upper limb: 33; lower limb: 57; trunk: 44; and head and neck: 26 patients), with a Breslow index > 1 mm and without clinical or radiologic evidence of metastatic spread. Colloidal (99m)Tc-rhenium sulfide (36-76 MBq) was injected intradermally in the four quadrants around the tumorectomy scar, followed by dynamic acquisition and static imaging. SN(s) were identified in 157 patients (overall identification rate, 98%). Fast (< 20 minutes), intermediate (20-30 minutes), or slow (> 30 minutes) lymphatic drainage was observed, respectively, in 122 (78%), 24 (15%), or 11 (7%) cases. Overall malignancy rate was 15%, respectively found in 19 (16%), 2 (8%), and 2 (18 %) patients with fast, intermediate, or slow drainage. No statistical difference between SN-positivity rates of patients with fast (19/122 = 16%) versus intermediate or slow drainage (4/35 = 11.4%) was observed (p = 0.69). Therefore, lymphoscintigraphic SN appearance time in CMM patients is unable both to predict SN metastasis and spare them from undergoing SN excision.

The contribution of large genomic deletions at the CDKN2A locus to the burden of familial melanoma.

Mutations in two genes encoding cell cycle regulatory proteins have been shown to cause familial cutaneous malignant melanoma (CMM). About 20% of melanoma-prone families bear a point mutation in the CDKN2A locus at 9p21, which encodes two unrelated proteins, p16(INK4a) and p14(ARF). Rare mutations in CDK4 have also been linked to the disease. Although the CDKN2A gene has been shown to be the major melanoma predisposing gene, there remains a significant proportion of melanoma kindreds linked to 9p21 in which germline mutations of CDKN2A have not been identified through direct exon sequencing. The purpose of this study was to assess the contribution of large rearrangements in CDKN2A to the disease in melanoma-prone families using multiplex ligation-dependent probe amplification. We examined 214 patients from independent pedigrees with at least two CMM cases. All had been tested for CDKN2A and CDK4 point mutation, and 47 were found positive. Among the remaining 167 negative patients, one carried a novel genomic deletion of CDKN2A exon 2. Overall, genomic deletions represented 2.1% of total mutations in this series (1 of 48), confirming that they explain a very small proportion of CMM susceptibility. In addition, we excluded a new gene on 9p21, KLHL9, as being a major CMM gene.