Susan Swetter, M.D.

View details for DOI 10.1002/cncr.28289

View details for Web of Science ID 000326418500019

View details for DOI 10.2217/fon.13.112

View details for PubMedID 23731359

Abstract

IMPORTANCE Spitz nevi are benign melanocytic proliferations that can sometimes be clinically and histopathologically difficult to distinguish from melanoma. Agminated Spitz nevi have been reported to arise spontaneously, in association with an underlying nevus spilus, or after radiation or chemotherapy. However, to our knowledge, the genetic mechanism for this eruption has not been described. OBSERVATIONS We report a case of agminated Spitz nevi arising in a nevus spilus and use exome sequencing to identify a clonal activating point mutation in HRAS (GenBank 3265) (c.37G→C) in the Spitz nevi and underlying nevus spilus. We also identify a secondary copy number increase involving HRAS on chromosome 11p, which occurs during the development of the Spitz nevi. CONCLUSIONS AND RELEVANCE Our results reveal an activating HRAS mutation in a nevus spilus that predisposes to the formation of Spitz nevi. In addition, we demonstrate a copy number increase in HRAS as a "second hit" during the formation of agminated Spitz nevi, which suggests that both multiple Spitz nevi and solitary Spitz nevi may arise through similar molecular pathways. In addition, we describe a unique investigative approach for the discovery of genetic alterations in Spitz nevi.

View details for DOI 10.1001/jamadermatol.2013.4745

View details for PubMedID 23884457

Abstract

IMPORTANCE Worse survival among patients with melanoma has been demonstrated in middle-aged and older men compared with women, but few studies have explored survival differences by sex in adolescents and young adults, in whom melanoma is the third most common cancer. Focusing on sex disparities in survival among younger individuals may provide further evidence of biological rather than behavioral factors that affect melanoma outcome. OBJECTIVE To determine whether long-term survival varies between white male and female adolescents and young adults with melanoma (15 to 39 years of age at diagnosis) in the United States. DESIGN, SETTING, AND PARTICIPANTS Population-based cohort with a mean follow-up of 7.5 years of 26 107 non-Hispanic white adolescents and young adults with primary invasive melanoma of the skin diagnosed from January 1, 1989, through December 31, 2009, and reported to the Surveillance, Epidemiology, and End Results network of cancer registries. MAIN OUTCOME AND MEASURE Melanoma-specific survival. RESULTS There were 1561 melanoma-specific deaths in the study population. Although adolescent and young adult males accounted for fewer overall melanoma cases (39.8%) than females, they comprised 63.6% of melanoma-specific deaths. Adolescent and young adult males were 55% more likely to die of melanoma than age-matched females after adjustment for tumor thickness, histologic subtype, presence and extent of metastasis, and anatomical location (hazard ratio, 1.55; 95% CI, 1.39-1.73). Males were also more likely to die within each age range assessed (eg, 15-24, 25-29, 30-34, and 35-39 years), and even those with thin melanomas (≤1.00 mm) were twice as likely to die as age-matched females (hazard ratio, 1.95; 95% CI, 1.57-2.42). Adjustment for health insurance and socioeconomic status in a subanalysis did not significantly alter these results. CONCLUSIONS AND RELEVANCE Male sex is associated with worse survival among white adolescents and young adults with melanoma after controlling for thickness and other prognostic factors. Continued public health efforts are necessary to raise awareness of the outcome of melanoma in young men. Further investigation of possible biological mechanisms that account for these sex differences is merited.

View details for DOI 10.1001/jamadermatol.2013.4408

View details for Web of Science ID 000323721400005

View details for PubMedID 23804160

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with decreased risk of gastric, colorectal, and breast cancer. However, the impact of NSAIDs on the risk of melanoma has been inconsistent. The authors evaluated the association between NSAID use and cutaneous melanoma risk in the Women's Health Initiative (WHI) Observational Study (OS).At study entry, use of aspirin (acetylsalicylic acid [ASA]) and nonaspirin NSAIDs was assessed among 59,806 postmenopausal Caucasian women ages 50 to 79 years. Cox proportional hazards models were constructed after adjusting for participant skin type, sun exposure history, and medical indications for NSAID use among other confounders.During a median follow-up of 12 years, 548 incident melanomas were confirmed by medical review. Women who used ASA had a 21% lower risk of melanoma (hazard ratio, 0.79; 95% confidence interval, 0.63-0.98) relative to nonusers. Increased duration of ASA use (<1 year, 1-4 years, and ? 5 years) was associated with an 11% lower risk of melanoma for each categorical increase (Ptrend = .01), and women with ? 5 years of use had a 30% lower melanoma risk (hazard ratio, 0.70; 95% confidence interval, 0.55-0.94). In contrast, use of non-ASA NSAIDs and acetaminophen were not associated with melanoma risk.Postmenopausal women who used ASA had a significantly lower risk of melanoma, and longer duration of ASA use was associated with greater protection. Although this study was limited by the observational design and self-report of NSAID use, the findings suggest that ASA may have a chemopreventive effect against the development of melanoma and warrant further clinical investigation.

View details for DOI 10.1002/cncr.27817

View details for Web of Science ID 000317618700016

View details for PubMedID 23483536

Abstract

The NCCN Guidelines for Melanoma provide multidisciplinary recommendations on the clinical management of patients with melanoma. This NCCN Guidelines Insights report highlights notable recent updates. Foremost of these is the exciting addition of the novel agents ipilimumab and vemurafenib for treatment of advanced melanoma. The NCCN panel also included imatinib as a treatment for KIT-mutated tumors and pegylated interferon alfa-2b as an option for adjuvant therapy. Also important are revisions to the initial stratification of early-stage lesions based on the risk of sentinel lymph node metastases, and revised recommendations on the use of sentinel lymph node biopsy for low-risk groups. Finally, the NCCN panel reached clinical consensus on clarifying the role of imaging in the workup of patients with melanoma.

View details for Web of Science ID 000317543800007

View details for PubMedID 23584343

Abstract

Reduced melanoma risk has been reported with regular use of nonsteroidal anti-inflammatory drugs (NSAIDs). However, the ability of NSAIDs to reach melanocytes in vivo and modulate key biomarkers in preneoplastic lesions such as atypical nevi has not been evaluated.This randomized, double-blind, placebo-controlled trial of sulindac was conducted in individuals with atypical nevi (AN) to determine bioavailability of sulindac and metabolites in nevi and effect on apoptosis and vascular endothelial growth factor A (VEGFA) expression in AN. Fifty subjects with AN ≥ 4 mm in size and 1 benign nevus (BN) were randomized to sulindac (150 mg twice a day) or placebo for 8 weeks. Two AN were randomized for baseline excision, and 2 AN and BN were excised after intervention.Postintervention sulindac, sulindac sulfone, and sulindac sulfide concentrations were 0.31 ± 0.36, 1.56 ± 1.35, and 2.25 ± 2.24 μg/mL in plasma, and 0.51 ± 1.05, 1.38 ± 2.86, and 0.12 ± 0.12 μg/g in BN, respectively. Sulindac intervention did not significantly change VEGFA expression but did increase expression of the apoptotic marker cleaved caspase-3 in AN (increase of 3 ± 33 in sulindac vs decrease of 25 ± 45 in the placebo arm, P = .0056), although significance was attenuated (P = .1103) after adjusting for baseline expression.Eight weeks of sulindac intervention resulted in high concentrations of sulindac sulfone, a proapoptotic metabolite, in BN but did not effectively modulate VEGFA and cleaved caspase-3 expression. Study limitations included limited exposure time to sulindac and the need to optimize a panel of biomarkers for NSAID intervention studies.

View details for DOI 10.1002/cncr.27540

View details for Web of Science ID 000311306000017

Abstract

Melanoma is a relatively immunogenic tumor, in which infiltration of melanoma cells by T lymphocytes is associated with a better clinical prognosis. We hypothesized that radiation-induced cell death may provide additional stimulation of an anti-tumor immune response in the setting of anti-CTLA-4 treatment.In a pilot melanoma patient, we prospectively tested this hypothesis. We treated the patient with two cycles of ipilimumab, followed by stereotactic ablative radiotherapy to two of seven hepatic metastases, and two additional cycles of ipilimumab.Subsequent positron emission tomography-computed tomography scan indicated that all metastases, including unirradiated liver lesions and an unirradiated axillary lesion, had completely resolved, consistent with a complete response by RECIST.The use of radiotherapy in combination with targeted immunotherapy as a noninvasive in vivo tumor vaccine strategy appears to be a promising method of enhancing the induction of systemic immune responses and anti-tumor effect.

View details for DOI 10.1593/tlo.12280

View details for Web of Science ID 000313359800002

View details for PubMedID 23323154

Abstract

Controversy has emerged over the past decades regarding the value and impact of melanoma screening to detect early stage disease for improved prognosis. Those questioning the benefits of prevention efforts base their arguments on the absence of prospective, randomized studies demonstrating decreased melanoma mortality to justify the cost associated with screening and educational campaigns. For those in favor of melanoma screening, the lack of proven survival benefit is not a justification to abandon this approach, but rather a reflection of the lack of resources necessary to conduct a long-term trial. In 2009, the US Preventive Services Task Force (USPSTF)report did not recommend routine primary care screening for the general population given the absence of evidence. However, since the USPSTF report, a series of new studies are available, which support the potential benefit of screening and have the potential to significantly impact current policies regarding skin cancer screening, particularly for melanoma.

View details for DOI 10.1007/s11912-012-0256-6

View details for Web of Science ID 000308286700013

View details for PubMedID 22907282

Abstract

Low socioeconomic status (SES) is associated with more advanced melanoma at diagnosis and decreased survival. Exploring the pathways linking lower SES and thicker melanoma will help guide public and professional strategies to reduce deaths.The authors surveyed 566 newly diagnosed patients at Stanford University Medical Center, Veterans Affairs Palo Alto Health Care System, and University of Michigan. SES was assessed by education level (high school/general education degree or less [HS], associate/technical school degree, or ?college graduate). All data was obtained by self-report among patients within three months of their diagnosis.HS-educated individuals were significantly more likely than college graduates to believe that melanoma was not very serious (odds ratio [OR], 2.90; 95% confidence interval [CI], 1.79-4.71) and were less likely to know the asymmetry, borders (irregular), color (variegated), and diameter (>6 mm) (ABCD) melanoma rule or the difference between melanoma and ordinary skin growths (OR, 0.34 [95% CI, 0.23-0.52] and 0.26 [95% CI, 0.16-0.41] respectively). Physicians were less likely to have ever told HS-educated versus college-educated individuals they were at risk for skin cancer (OR, 0.46; 95% CI, 0.31-0.71) or instructed them on how to examine their skin for signs of melanoma (OR, 0.40; 95% CI, 0.25-0.63). HS-educated individuals were less likely to have received a physician skin examination within the year before diagnosis (OR, 0.54; 95% CI, 0.37-0.80).Decreased melanoma risk perception and knowledge among low-SES individuals and decreased physician communication regarding skin examinations of these individuals may be key components of the consistently observed socioeconomic gradient in mortality. The current findings suggest the need to raise melanoma awareness among lower-SES patients and to increase physician awareness of socioeconomic disparities in clinical communication and care.

View details for DOI 10.1002/cncr.26706

View details for Web of Science ID 000307116900019

View details for PubMedID 22179775

Abstract

Reduced melanoma mortality should result from an improved understanding of modifiable factors related to early detection. The authors of this report surveyed newly diagnosed patients to identify differences in prediagnosis behavioral and medical care factors associated with thinner versus thicker melanoma.In total, 566 adults with invasive melanoma completed questionnaires within 3 months of diagnosis on demographics, health care access, skin self-examination (SSE), and physician skin examination (PSE) practices in the year before diagnosis. SSE was measured by us e of a melanoma picture aid and routine examination of some/all body sites versus none. Patient-reported partial or full-body PSE also was assessed. Melanoma thickness was dichotomized at 1 mm.Patient ranged in age from 18 years to 99 years, and 61% were men. The median tumor thickness was 1.25 mm, and 321 tumors (57%) were >1 mm thick. Thinner tumors (≤1 mm) were associated with age ≤60 years (P = .0002), women (P = .0127), higher education level (P = .0122), and physician discovery (P ≤ .0001). Patients who used a melanoma picture aid and performed routine SSE were more likely to have thinner tumors than those who did not (odds ratio [OR], 2.66; 95% confidence interval [CI], 1.48-4.80). Full-body PSE was associated with thinner tumors (OR, 2.51; 95% CI, 1.62-3.87), largely because of the effect of PSE in men aged >60 years (OR, 4.09 95% CI, 1.88-8.89).SSE and PSE were identified as complementary early detection strategies, particularly in men aged >60 years, in whom both partial and full-body PSE were associated with thinner tumors. Given the high rates of physician access, PSE may be a more practical approach for successful early detection in this subgroup with highest mortality.

View details for DOI 10.1002/cncr.26707

View details for PubMedID 22179848

View details for DOI 10.1200/JCO.2011.41.3849

View details for Web of Science ID 000305413200007

View details for PubMedID 22547593

View details for DOI 10.1038/jid.2012.3

View details for Web of Science ID 000302856200008

View details for PubMedID 22336950

View details for DOI 10.1111/j.1365-2133.2012.10911.x

View details for Web of Science ID 000304661600004

View details for PubMedID 22524396

View details for Web of Science ID 000301222300009

View details for Web of Science ID 000299653900030

View details for PubMedID 22250251

Abstract

The incidence of primary cutaneous melanoma has been increasing dramatically for several decades. Melanoma accounts for the majority of skin cancer-related deaths, but treatment is nearly always curative with early detection of disease. In this update of the guidelines of care, we will discuss the treatment of patients with primary cutaneous melanoma. We will discuss biopsy techniques of a lesion clinically suspicious for melanoma and offer recommendations for the histopathologic interpretation of cutaneous melanoma. We will offer recommendations for the use of laboratory and imaging tests in the initial workup of patients with newly diagnosed melanoma and for follow-up of asymptomatic patients. With regard to treatment of primary cutaneous melanoma, we will provide recommendations for surgical margins and briefly discuss nonsurgical treatments. Finally, we will discuss the value and limitations of sentinel lymph node biopsy and offer recommendations for its use in patients with primary cutaneous melanoma.

View details for DOI 10.1016/j.jaad.2011.04.031

View details for Web of Science ID 000296268000014

View details for PubMedID 21868127

Abstract

Incidence and mortality rates of melanoma throughout most of the developed world have increased in the past 25 years. We propose that reduction of deaths from melanoma can be best enhanced by strong collaborations between experts in dermatology, primary care, oncology, cancer education and health systems research, epidemiologists, and behavioral scientists, among others. Public and professional educational campaigns should be guided by an understanding of 3 underlying but overlapping roots: epidemiology and preventable mortality (an understanding of who is most likely to be given the diagnosis of thick or late-stage melanoma), biology (an investigation of tumor types that are relatively common but potentially most lethal), and sociology (an analysis of the changes needed in social structures to improve access to those most in need of early detection programs). We review these major concepts, concentrating on the key risk factors for advanced melanoma.

View details for DOI 10.1016/j.jaad.2011.05.045

View details for Web of Science ID 000296268100011

View details for PubMedID 22018072

Abstract

During the past 3 decades in the United States, melanoma incidence among non-Hispanic white girls and women aged 15 to 39 years has more than doubled. To better understand which specific subpopulations of girls and women experienced this increase and thereby to target public health interventions, we assessed the relationship between melanoma incidence and small-area level measures of socioeconomic status (SES) and UV radiation (UV-R) exposure.Longitudinal study of California Cancer Registry, US Census, and National Oceanic and Atmospheric Administration data from pericensal periods January 1, 1988, through December 31, 1992, and January 1, 1998, through December 31, 2002.State of California.A total of 3800 non-Hispanic white girls and women aged 15 to 39 years, in whom 3842 melanomas were diagnosed.Incidence rates per 100 000 person-years and rate ratios according to SES quintiles and UV-R exposure tertiles.Whereas melanoma rates increased over time for all SES categories, only changes among the highest 3 categories achieved statistical significance. UV radiation was significantly and positively associated with melanoma incidence only among adolescent girls and young women in the 2 highest quintiles ranked by SES, which suggests that SES is not a proxy for UV-R exposure. Those living in neighborhoods with the highest SES and UV-R categories had 80.0% higher rates of melanoma than those in neighborhoods in the lowest categories (rate ratio, 1.80; 95% confidence interval, 1.13-3.01).Understanding the ways that SES and UV-R exposure work together to influence melanoma incidence is important for planning effective prevention and educational efforts. Interventions should target adolescent girls and young women living in high SES and high UV-R neighborhoods because they have experienced a significantly greater increase in disease burden.

View details for DOI 10.1001/archdermatol.2011.44

View details for Web of Science ID 000292840700003

View details for PubMedID 21422322

Abstract

The incidence patterns and socioeconomic distribution of cutaneous melanoma among Hispanics are poorly understood.The authors obtained population-based incidence data for all Hispanic and non-Hispanic white (NHW) patients who were diagnosed with invasive cutaneous melanoma from 1988 to 2007 in California. By using a neighborhood-level measure of socioeconomic status (SES), the variables investigated included incidence, thickness at diagnosis, histologic subtype, anatomic site, and the relative risk (RR) for thicker (>2 mm) versus thinner (? 2 mm) tumors at diagnosis for groups categorized by SES.Age-adjusted melanoma incidence rates per million were higher in NHWs (P < .0001), and tumor thickness at diagnosis was greater in Hispanics (P < .0001). Sixty-one percent of melanomas in NHWs occurred in the High SES group. Among Hispanics, only 35% occurred in the High SES group; and 22% occurred in the Low SES group. Lower SES was associated with thicker tumors (P < .0001); this association was stronger in Hispanics. The RR of thicker tumors versus thinner tumors (? 2 mm) in the Low SES group versus the High SES group was 1.48 (95% confidence interval [CI], 1.37-1.61) for NHW men and 2.18 (95% CI, 1.73-2.74) for Hispanic men. Patients with lower SES had less of the superficial spreading melanoma subtype (especially among Hispanic men) and more of the nodular melanoma subtype. Leg/hip melanomas were associated with higher SES in NHW men but with lower SES in Hispanic men.The socioeconomic distribution of melanoma incidence and tumor thickness differed substantially between Hispanic and NHW Californians, particularly among men. Melanoma prevention efforts targeted to lower SES Hispanics and increased physician awareness of melanoma patterns among Hispanics are needed.

View details for DOI 10.1002/cncr.25355

View details for Web of Science ID 000285368300021

View details for PubMedID 20737564

Abstract

Melanoma incidence has been correlated strongly and positively with both socioeconomic status (SES) and lower latitude and other measures of ambient UV radiation (UVR). However, because high-SES populations may be colocated in areas of high UVR, we assessed their joint influences on melanoma occurrence to better target subpopulations for melanoma education and screening.We obtained from the California Cancer Registry information regarding 23,564 incident cases of invasive cutaneous melanoma among non-Hispanic white residents between January 1, 1998, and December 31, 2002. We geocoded each case based on residence at diagnosis and linked previously tested neighborhood measures of SES and average annual UVR to calculate age-adjusted incidence rates, rate ratios, and the corresponding 95% confidence intervals. Poisson regression was used to calculate multivariately adjusted rate ratios.UVR was significantly and positively associated with melanoma incidence only among persons living in the top 40% of California neighborhoods ranked by SES. People in neighborhoods of the highest SES and UVR categories had 60% higher rates of melanoma than those from neighborhoods in the lowest categories (rate ratio, 1.60; 95% confidence interval, 1.02-2.51).Our findings indicate that UVR and SES interact to influence melanoma occurrence and suggest that socioeconomic gradients in melanoma incidence are not explained entirely by UVR.Cancer prevention and early detection educational efforts should be targeted to high-SES groups in areas of high UVR exposure. Contextual measures of both SES and UVR should be considered important determinants of melanoma occurrence in future studies.

View details for DOI 10.1158/1055-9965.EPI-10-0692

View details for Web of Science ID 000283991600005

View details for PubMedID 20978173

Abstract

Pediatric melanoma is difficult to study because of its rarity, possible biological differences in preadolescents compared with adolescents, and challenges of differentiating true melanoma from atypical spitzoid neoplasms. Indeterminant lesions are sometimes designated as melanocytic tumors of uncertain malignant potential (MelTUMPs). We performed a retrospective, single-institution review of melanomas, MelTUMPs and Spitz nevi with atypical features (SNAFs) in patients at 21 years of age and younger from 1995 to 2008. We identified 13 patients with melanoma, seven with MelTUMPs, and five with SNAFs. The median age for melanoma patients was 17 years, 10 for MelTUMPs, and six for SNAFs. Of the 13 melanoma patients, only four were younger than 15 years, while six were adolescents, and three were young adults. Nine melanoma patients (69%) were female. The most common histologic subtype was superficial spreading. The median depth for melanomas was 1.2 mm, and 3.4 mm for MelTUMPs. Microscopic regional nodal involvement detected on elective or sentinel lymph node (SLN) dissection was present in 2/10 (20%) of primary melanomas and 2/6 (33%) of Mel-TUMPs. Complete lymphadenectomy was performed on four melanoma patients, with three positive cases. Patient outcome through March 31, 2009 revealed no in-transit or visceral metastasis in patients with MelTUMPs or SNAFs. One SLN-positive patient (8%) with melanoma developed recurrent lymph node and liver metastasis and died 15 months after primary diagnosis. Our data highlight the rarity, female predominance, and significant rate of SLN positivity of pediatric melanoma. The high rate of MelTUMPs with regional nodal disease reinforces the need for close follow-up.

View details for DOI 10.1111/j.1525-1470.2009.01078.x

View details for Web of Science ID 000278037100005

View details for PubMedID 20403119

Abstract

Understanding risk patterns for developing a second primary malignancy (SPM) after cutaneous melanoma (CM) has implications for both research and clinical practice, including cancer screening.We sought to describe incidence patterns of SPMs occurring after CM.We calculated incidence rates and relative risks for the development of 65 different SPMs occurring in 16,591 CM survivors during 1.3 million person-years of observation in the Surveillance, Epidemiology, and End Results program data from 1973 to 2003.Compared with the general population, CM survivors had a 32% higher risk of developing any SPM and demonstrated significantly elevated risks for 13 cancers: melanoma of the skin (standardized incidence ratio [SIR] 8.99), soft tissue (SIR 2.80), melanoma of the eye and orbit (SIR 2.64), nonepithelial skin (SIR 2.31), salivary gland (SIR 2.18), bone and joint (SIR 1.70), thyroid (SIR 1.90), kidney (SIR 1.29), chronic lymphocytic leukemia (SIR 1.29), brain and nervous system (SIR 1.31), non-Hodgkin lymphoma (SIR 1.25), prostate (SIR 1.13), and female breast (SIR 1.07). Risks of second primary melanoma of the skin, melanoma of the eye and orbit, and cancers of the prostate, soft tissue, salivary gland, and bone and joint were elevated throughout the study period, implying no surveillance bias.Possible underreporting of CM incidence in cancer registries is a limitation. In addition, the lack of individual-level data in cancer registry data precludes detailed examination of coincident risk factors.Risks of particular SPMs after CM may be explained by surveillance bias or shared risk factors. However, these probably do not explain the increased risks observed for prostate, soft tissue, salivary gland, and bone and joint cancers years after CM diagnosis. Further investigation into genetic or environmental commonalities between CM and these cancers is warranted.

View details for DOI 10.1016/j.jaad.2009.07.039

View details for Web of Science ID 000277190100004

View details for PubMedID 20223559

Abstract

Reported recurrence rates for transected nonmelanoma skin cancer (NMSC) vary widely, and few studies have addressed recurrence of tumors followed clinically or treated with nonsurgical modalities.Retrospective review of dermatopathology records from January 1999 to January 2005 was conducted to identify biopsies or excision specimens with histologically transected basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) which were not subsequently excised. Patient and tumor characteristics associated with recurrence were analyzed in a subgroup of patients with predominantly 'low-risk' and/or minimally transected NMSCs. Prospective follow up was performed through March 31, 2008. Data was analyzed with Chi-square and Fishers exact tests and multivariate logistic regression.Of 376 transected NMSCs, 27 (7.2%) recurred, including 20 (9%) of 223 BCCs and 7 (4.6%) SCCs in situ of 153 SCCs. The overall recurrence rate of the 124 minimally transected NMSCs was even lower (5.6%). Multivariate logistic regression identified three significant predictors of recurrence: tumor location on the head and neck (p = 0.041), tumor size (p = 0.00741) and superficial subtype of BCC (p = .035).Although surgical excision of NMSC remains the standard of care, observation or nonsurgical treatment may be acceptable in many cases of incompletely excised low-risk or minimally transected NMSCs.

View details for DOI 10.1111/j.1600-0560.2009.01340.x

View details for Web of Science ID 000272165500010

View details for PubMedID 19615009

Abstract

Although skin self-examination (SSE) may increase rates of early melanoma detection, the efficacy of different SSE practices has not been thoroughly studied. We examined associations between SSE practices and tumor thickness in patients with recently diagnosed melanoma.321 melanoma patients at three hospitals completed questionnaires on demographics and SSE practices. Patient-reported SSE was measured by routine examination of 13 specific body areas, frequency of mole examination, and use of a melanoma picture aid to assist with SSE. Histologic diagnoses and Breslow depth were confirmed by dermatopathologists. Regression analyses were used to calculate ratios of geometric mean tumor thickness and odds ratios for having thicker versus thinner tumors for different SSE behaviors.Rates of SSE varied considerably by SSE item. Patients routinely examining at least some of their skin had thinner melanomas [adjusted geometric mean tumor ratio, 0.73; 95% confidence interval (95% CI), 0.50-0.94]. Frequency of mole examination did not predict tumor thickness. Using a melanoma picture as a SSE aid was strongly associated with reduced tumor thickness (adjusted ratio, 0.75; 95% CI, 0.66-0.85 for ever versus never use). A composite measure of thoroughness of SSE was the best predictor of thickness (adjusted ratio, 0.58; 95% CI, 0.36-0.75) for high versus low thoroughness.SSE was associated with decreased tumor thickness by most measures. However, the diverse rates of SSE practices and the distinct associations between these practices and melanoma thickness suggest a complexity in SSE that should be addressed in future studies. SSE should be evaluated by more than one measure.

View details for DOI 10.1158/1055-9965.EPI-09-0310

View details for Web of Science ID 000271562600031

View details for PubMedID 19861521

View details for DOI 10.1016/j.jaad.2009.03.016

View details for Web of Science ID 000270258300015

Abstract

It is controversial whether worldwide increases in melanoma incidence represent a true epidemic. Dramatic increases in incidence in the setting of relatively stable mortality trends have also been attributed to expanded skin screening and detection of biologically indolent tumors with low metastatic potential. To better understand how melanoma incidence trends varied by severity at diagnosis and factors relevant to screening access, we assessed recent United States incidence and mortality trends by histologic type, tumor thickness, and area-level socioeconomic status (SES). We obtained population-based data regarding diagnoses of invasive melanoma among non-Hispanic whites from nearly 291 million person-years of observation by the Surveillance Epidemiology and End Results (SEER) program (1992-2004). Age-adjusted incidence and mortality rates were calculated for SEER and a subset (California) for which small-area SES measure was available. Overall, melanoma incidence increased at 3.1% (P<0.001) per year. Statistically significant rises occurred for tumors of all histologic subtypes and thicknesses, including those >4 mm. Melanoma incidence rates doubled in all SES groups over a 10-year period whereas melanoma mortality rates did not increase significantly. We conclude that screening-associated diagnosis of thinner melanomas cannot explain the increasing rates of thicker melanomas among low SES populations with poorer access to screening.

View details for DOI 10.1038/jid.2008.423

View details for Web of Science ID 000267270300013

View details for PubMedID 19131946

Abstract

Sentinel lymph node (SLN) metastasis is a major determinant for staging, prognostication and clinical management of patients with cutaneous melanoma. However, the role of lymphatic vs. vascular invasion (VI) for SLN spread remains unclear.We compared the frequency of lymphatic invasion (LI) vs. VI in melanoma sections from 94 patients with a mean three-year clinical follow up using immunostains for the lymphatic endothelial markers D2-40 (podoplanin) and LYVE-1 and the panvascular marker CD31.LI occurred more frequently than VI (16 vs. 3%, respectively, p = 0.001) and correlated with higher American Joint Committee on Cancer stage at diagnosis (p = 0.0004). In a univariate analysis, LI was strongly associated with SLN metastasis (p = 0.008), independent of tumor thickness. In a multivariate analysis, LI was not a significant risk factor for SLN metastasis. The presence of intratumoral lymphatics (ITLs) was associated with distant metastasis, whereas VI was rare and did not correlate with SLN or distant metastasis. A combination of LI and ITL had higher positive and negative predictive values for the risk of developing SLN metastasis compared with routine histology and VI.Detection of LI in the primary tumor may aid in identifying melanoma patients with the propensity to develop SLN metastasis.

View details for DOI 10.1111/j.1600-0560.2008.01166.x

View details for Web of Science ID 000266490200008

View details for PubMedID 19032379

Abstract

Immune dysfunction develops in patients with many cancer types and may contribute to tumor progression and failure of immunotherapy. Mechanisms underlying cancer-associated immune dysfunction are not fully understood. Efficient IFN signaling is critical to lymphocyte function; animals rendered deficient in IFN signaling develop cancer at higher rates. We hypothesized that altered IFN signaling may be a key mechanism of immune dysfunction common to cancer. To address this, we assessed the functional responses to IFN in peripheral blood lymphocytes from patients with 3 major cancers: breast cancer, melanoma, and gastrointestinal cancer. Type-I IFN (IFN-alpha)-induced signaling was reduced in T cells and B cells from all 3 cancer-patient groups compared to healthy controls. Type-II IFN (IFN-gamma)-induced signaling was reduced in B cells from all 3 cancer patient groups, but not in T cells or natural killer cells. Impaired-IFN signaling was equally evident in stage II, III, and IV breast cancer patients, and downstream functional defects in T cell activation were identified. Taken together, these findings indicate that defects in lymphocyte IFN signaling arise in patients with breast cancer, melanoma, and gastrointestinal cancer, and these defects may represent a common cancer-associated mechanism of immune dysfunction.

View details for DOI 10.1073/pnas.0901329106

View details for Web of Science ID 000266580500043

View details for PubMedID 19451644

Abstract

To determine factors associated with physician discovery of early melanoma in middle-aged and older men.Survey.Three institutional melanoma clinics.A total of 227 male participants (aged > or =40 years) with invasive melanoma who completed surveys within 3 months of diagnosis. Intervention Survey.Factors associated with physician-detected thin melanoma.Patients with physician-detected melanoma were older, 57% were 65 years or older compared with 34% for other-detected (odds ratio [OR], 2.57; 95% confidence interval [CI], 1.19-5.55) and 42% for patient-detected melanoma (P = .07). Physician-detected melanoma in the oldest patients (aged > or =65 years) had tumor thickness equal to that of self-detected melanoma or melanoma detected by other means in younger patients. Back lesions composed 46% of all physician-detected melanoma, 57% of those detected by other means, and 16% of self-detected lesions (physician- vs self-detected: OR, 4.25; 95% CI, 1.96-9.23). Ninety-two percent of all physician-detected back-of-the-body melanomas were smaller than 2 mm compared with 63% of self-detected lesions (P = .004) and 76% of lesions detected by other means (P = .07).Skin screenings of at-risk middle-aged and older American men can be integrated into the routine physical examination, with particular emphasis on hard-to-see areas, such as the back of the body. "Watch your back" professional education campaigns should be promoted by skin cancer advocacy organizations.

View details for Web of Science ID 000265411100005

View details for PubMedID 19380662

View details for Web of Science ID 000265411100022

View details for PubMedID 19380679

Abstract

To identify factors related to the detection of melanoma and to determine those that differ between thinner vs thicker tumors in middle-aged and older men.Survey.Three institutional melanoma clinics.Men 40 years or older who had newly diagnosed invasive melanoma.Differences in melanoma awareness, skin examination practices, discovery patterns, and social/medical care factors relative to tumor thickness.Two hundred twenty-seven men completed surveys within 3 months of melanoma diagnosis; 57 (25.1%) had thicker tumors (>2.00 mm). Thicker tumors were associated with nodular histologic features (43.9%), a lack of atypical nevi, having less than a high school education, and patient vs physician (dermatologist or nondermatologist) detection. Knowledge of melanoma (P = .007), attention to skin cancer detection information (P = .02), an interest in health topics (P = .003), and knowing the importance of physician skin examination (P = .05) were more common in those with thin tumors. Tumor thickness did not correlate with age, anatomic location, marital/cohabitation status, prior skin cancer, or sun sensitivity. Overall patient awareness of melanoma warning signs, skin self-examination practices, and Internet use were poor (<20%, <50%, and <14%, respectively).Physician discovery, the patient's higher level of education and detection-promoting awareness and attitudes, and the presence of clinically atypical nevi were related to thinner melanomas. Innovative outreach strategies and novel educational campaigns incorporating these factors, coupled with sharper messages regarding the importance of physician screening, are needed to improve early detection in middle-aged and older men.

View details for Web of Science ID 000265411100004

View details for PubMedID 19380661

Abstract

Worldwide, the incidence of thick melanoma has not declined, and the nodular melanoma (NM) subtype accounts for nearly 40% of newly diagnosed thick melanoma. To assess differences between patients with thin (or=2.01 mm) nodular melanoma, the authors evaluated factors such as demographics, melanoma detection patterns, tumor visibility, and physician screening for NM alone and compared clinical presentation and anatomic location of NM with superficial spreading melanoma (SSM).The authors used data from a large population-based study of Queensland (Australia) residents diagnosed with melanoma. Queensland residents aged 20 to 75 years with histologically confirmed first primary invasive cutaneous melanoma were eligible for the study, and all questionnaires were conducted by telephone (response rate, 77.9%).During this 4-year period, 369 patients with nodular melanoma were interviewed, of whom 56.7% were diagnosed with tumors 2.00 mm).Awareness of factors related to earlier detection of potentially fatal nodular melanomas, including the benefits of a physician examination, should be useful in enhancing public and professional education strategies. Particular awareness of clinical warning signs associated with thin nodular melanoma should allow for more prompt diagnosis and treatment of this subtype.

View details for DOI 10.1002/cncr.24162

View details for Web of Science ID 000264148300022

View details for PubMedID 19189368

View details for Web of Science ID 000270264600004

View details for PubMedID 19401060

View details for Web of Science ID 000260536400016

View details for PubMedID 18976405

View details for DOI 10.1016/j.jaad.2008.08.007

View details for Web of Science ID 000261141600026

View details for PubMedID 19022107

Abstract

Insurance status and SES are associated with the stage of melanoma at diagnosis. However, the influence of Medicaid enrollment on melanoma stage has not been studied in detail. This study examined the effect of Medicaid enrollment status and duration on melanoma stage at diagnosis in a large, multi-ethnic California population.California Cancer Registry records were linked with statewide Medicaid enrollment files to identify 4558 men and women diagnosed with invasive cutaneous and metastatic melanoma during 1998-1999. Multivariate logistic regression was used to evaluate the association between prediagnosis Medicaid enrollment status and late-stage diagnosis and tumor depth at diagnosis.Late-stage disease was diagnosed in 27% of Medicaid and 9% of non-Medicaid melanoma patients. Those enrolled in Medicaid at diagnosis and those enrolled intermittently during the year prior to diagnosis had significantly greater covariate-adjusted odds of late-stage cancer than those not enrolled in Medicaid (OR 13.64, 95% CI=4.43, 41.98, and OR 2.77, 95% CI=1.28, 5.99, respectively). Participants continuously enrolled during the previous year were not at increased odds for late-stage disease. An increased likelihood of late-stage melanoma was also associated with low SES (p<0.05) and non-Hispanic black race/ethnicity (p<0.10) after covariate adjustment.Men and women intermittently enrolled in Medicaid or not enrolled until the month of diagnosis had a significantly increased likelihood of late-stage melanoma. Greater education and outreach, particularly in low-SES areas, are needed to improve melanoma awareness and access to screening.

View details for DOI 10.1016/j.amepre.2008.03.026

View details for Web of Science ID 000256996900002

View details for PubMedID 18482824

Abstract

To provide an updated and expanded analysis of clinical outcome and immunohistochemical (IHC) findings unique to primary dermal melanoma (PDM) that may be used to differentiate this entity from primary nodular melanoma (PNM) and cutaneous metastatic melanoma (MM).Cohort analysis and extensive IHC panel comparing PDM with PNM and cutaneous MM.Melanoma clinics and pathology departments of academic and VA medical centers.Thirteen patients with a solitary dermal or subcutaneous nodule of histologically proven melanoma, prospectively followed through April 30, 2007.Clinical, pathologic, and IHC assessment of patients diagnosed as having PDM.Long-term clinical outcome and determination of unique clinical and IHC features in the study cohort compared with other melanoma subtypes.Histologically, there was no evidence of an overlying in situ component, ulceration, or regression, and there was no associated nevus in any cases. Clinical history and findings from workup, including imaging studies, skin examination, and sentinel lymph node biopsy, were negative for evidence of melanoma elsewhere. The mean Breslow depth was 9.6 mm. Two patients developed satellite or in-transit recurrences, 1 developed pulmonary metastasis, and another died of liver metastases. Overall, the cohort showed a 92% melanoma-specific survival rate at a mean duration of follow-up of 44 months. The IHC findings showed that PDM exhibited lower levels of staining for the antigens p53 (P = .02), Ki-67 (Mib-1) (P = .002), cyclin D1 (P = .001), and podoplanin (recognized by D2-40 antibody) lymphovascular staining (P <.001) compared with MM and PNM. All other markers were comparable.Patients with PDM have remarkably prolonged survival compared with patients with MM or PNM of similar thickness. Preliminary results suggest that PDM may be characterized by lower levels of p53, Ki-67, cyclin D1, and D2-40 compared with histologically similar MM and PNM.

View details for Web of Science ID 000252439200006

View details for PubMedID 18209168

Abstract

In the past 5 years, there have been notable strides toward the earlier recognition and discovery of melanoma, including new technologies to complement and augment the clinical examination and new insights to help clinicians recognize early melanoma. However, incidence and mortality rates throughout most of the developed world have risen over the past 25 years, while education and screening, potentially the best means for reducing the disease, continue to be severely underutilized. Much progress needs to be made to reach middle-aged and older men and persons of lower socioeconomic status who suffer a disproportionate burden of death from melanoma. Worldwide melanoma control must also be a priority, and comprehensive educational and screening programs should be directed to Northern Ireland and a number of Eastern European nations, whose 5-year survival rates range between 53% and 60%, mirroring those of the United States and Australia more than 40 years ago.After completing this learning activity, participants should be aware of the most recent melanoma epidemiologic data, both in the United States and internationally; worldwide early detection and screening programs; clinical strategies to recognize and improve the detection of early melanoma; the latest technologies for early detection of melanoma; and public and professional education programs designed to enhance early detection.

View details for DOI 10.1016/j.jaad.2007.06.032

View details for Web of Science ID 000249695600001

View details for PubMedID 17870429

Abstract

Digital dermoscopy systems employ computer-based algorithms to quantitate features of pigmented skin lesions (PSLs) and provide an assessment of malignancy risk. We evaluated interobserver concordance of PSL malignancy risk between a pigmented lesion specialist and an artificial neural network (ANN)-based automated digital dermoscopy system. While digital dermoscopy provides a reliable means of image capture, storage, and comparison of PSLs over time, the ANN algorithm requires further training and validation before the malignancy risk assessment feature can be widely used in clinical practice.

View details for DOI 10.1016/j.jaad.2006.08.033

View details for Web of Science ID 000244612700009

View details for PubMedID 17109995

Abstract

To compare the effect of differing health care delivery models, specifically, gatekeeper (GK) vs direct access (DA) routes, on melanoma outcome as measured by tumor thickness and cancer stage at diagnosis.Retrospective medical record review of patients previously diagnosed as having cutaneous melanoma who were referred to a university-based clinic from January 1, 1996, through December 31, 2000.Stanford Pigmented Lesion and Cutaneous Melanoma Clinic, Stanford, Calif. Patients Two hundred thirty-four patients with primary melanoma stratified according to health care access route (GK or DA).Differences in Breslow thickness, American Joint Committee on Cancer stage, histologic features, patient delay in seeking medical attention, and physician delay in diagnosis (time between initial physician visit and diagnostic biopsy procedure).Of 234 patients, 168 (72%) were referred through the DA route and 66 (28%) through the GK route. A significant association was found between physician delay and access route; patients in the DA group underwent biopsy sooner (< or =3 months vs >3 months) than those in the GK group (P<.001). No significant difference was observed in stage at diagnosis (predominantly stage IA), proportion of nodular melanoma (DA 4% vs GK 2%), patient delay, or median tumor thickness between DA and GK routes (0.42 mm vs 0.50 mm, respectively). A trend toward a greater proportion of histologically ulcerated melanoma was observed in the DA group compared with the GK group (12% vs 5%, respectively; P = .06).This pilot study demonstrated no difference in outcome between GK and DA routes as measured by melanoma thickness and stage, although patients in the DA group underwent diagnostic biopsy sooner than those in the GK group. The potential effect of health care models on melanoma outcomes merits further study.

View details for Web of Science ID 000243509100004

View details for PubMedID 17224539

Abstract

From 1973 through 2002, melanoma mortality rates have risen steeply in middle-aged and older men. Men's higher mortality rate from melanoma is hardly an isolated example of the ways in which men's health lags behind women's health. Given the significantly higher melanoma mortality rates of men compared with women, there is now a need for a melanoma education program targeted to middle-aged and older men and their closest contacts, including spouses, significant others, and health care professionals.In this article, we discuss the theoretical and practical foundations for such a program. Then, taking into account factors such as socioeconomic status, health literacy, and residence, we present suggestions for creating such a campaign.Planners for a new educational campaign must understand the target audience's motivations for and perceived barriers to behavioral change. Future studies should examine what motivates certain men to conduct skin self-examinations, ask their physicians about melanoma, and attend melanoma screenings, whereas other men with similar risk factors are less prevention conscious. Issues of health literacy and understandability of our messages must be further explored.

View details for DOI 10.2310/7750.2006.00066

View details for Web of Science ID 000248050200001

View details for PubMedID 17241595

Abstract

To determine the effect of facial skin resurfacing for treatment of actinic keratoses (AKs) and prophylaxis against new primary basal and squamous cell carcinomas in individuals with previous nonmelanoma skin cancer (NMSC) or severe photodamage.Randomized, prospective 5-year trial.Dermatology and otolaryngology clinics of a Veterans Affairs hospital.Thirty-four patients with a history of facial or scalp AKs or basal or squamous cell carcinoma were enrolled. Five of 7 eligible patients who declined study-related treatment were used as controls. Twenty-seven patients were randomized to 3 treatment arms; 3 patients were discontinued from the study.Carbon dioxide laser resurfacing, 30% trichloroacetic acid peel, or 5% fluorouracil cream applied twice daily for 3 weeks.Reduction in the number of AKs was measured 3 months after treatment. The incidence of new NMSC in treated areas was assessed between January 1, 2001, and June 30, 2005. Times from baseline to diagnosis of first skin cancer were compared between the treatment and control groups.Treatment with fluorouracil, trichloroacetic acid, or carbon dioxide laser resulted in an 83% to 92% reduction in AKs (P< or =.03), a lower incidence of NMSC compared with the control group (P<.001), and a trend toward longer time to development of new skin cancer compared with the control group (P=.07). However, no significant differences were noted among the treatment groups.All 3 modalities demonstrated benefit for AK reduction and skin cancer prophylaxis compared with controls and warrant further study in a larger trial.

View details for Web of Science ID 000239762700003

View details for PubMedID 16924046

View details for Web of Science ID 000238948500018

Abstract

Neither the prevalence of sunless tanner use nor its impact on sunburning and tanning bed use has been evaluated in the United States.We surveyed young adults in greater Boston to measure use of artificial tanning products, as well as recent history of sunburns and tanning bed use.In July 2004, 448 individuals 18 to 30 years of age completed a brief questionnaire at universities, shopping venues, and parks.Twenty-two percent of respondents used sunless tanning lotions in the preceding 12 months, and another 22% had not used them but would consider doing so in the coming year. Sunless tanning users were more likely to be female, younger, and more likely to report being severe burners. Both users and potential users were more likely to have sunburned during the summer and to have used tanning beds than those who neither used nor intended to use sunless tanning lotions, even after controlling for skin type.The study was based on a non-randomly selected sample in one city and was cross-sectional in nature.Our study raises the possibility that sunless tanning products do not decrease rates of sunburning or use of tanning beds. While safe alternatives to ultraviolet exposure are desirable, the potential risks of widely endorsing artificial tanning products must be considered.

View details for DOI 10.1016/j.jaad.2006.01.014

View details for Web of Science ID 000237908900014

View details for PubMedID 16713463

Abstract

We assessed the placement of magazine advertising for sun care products to lay the groundwork for broader promotion to more diverse and high-risk demographic groups.We reviewed 579 issues of 24 magazines published between the months of May and September from 1997 to 2002. We conducted a cover-to-cover review of top-selling magazines for men, women, teens, parents, travelers, and outdoor recreation users. We determined if there were any advertisements for the following sun care products: sun tanning lotions containing sun protection factor (SPF), sunless tanners without SPF, sunscreen with SPF, moisturizers with SPF, or cosmetics with SPF (which include sunless tanners containing SPF.Sun care products, including sunscreens, were advertised primarily in women's magazines (77%). Nearly two thirds of all sun care products advertised were either for cosmetics (38%) or moisturizers (26%) containing SPF, followed by ads for sunscreen sold as a stand-alone product (19%). None of the ads contained all of the recommendations for safe use of sunscreen: a minimum SPF of 15, both UVA and UVB protection, reapplication instructions, and an adequate application coverage of 2 milligrams per square centimeter.Magazine advertising to men, travelers, outdoor recreation users, and parents/families (totaling a circulation of 41 million readers) during this six-year period were far fewer than those for women, despite high rates of excessive sun exposure in these groups.

View details for Web of Science ID 000237487100008

View details for PubMedID 16706006

View details for Web of Science ID 000236854700014

View details for PubMedID 16618872

View details for DOI 10.1016/j.jaad.2005.06.002

View details for Web of Science ID 000232898000046

View details for PubMedID 16243168

Abstract

Worldwide, lentigo maligna melanoma (LMM) comprises 4%-15% of cutaneous melanoma and occurs less commonly than superficial spreading or nodular subtypes. We assessed the incidence of melanoma subtypes in regional and national Surveillance, Epidemiology, and End Results (SEER) cancer registry data from 1990 to 2000. Because 30%-50% of SEER data were not classified by histogenetic type, we compared the observed SEER trends with an age-matched population of 1024 cases from Stanford University Medical Center (SUMC) (1995-2000). SEER data revealed lentigo maligna (LM) as the most prevalent in situ subtype (79%-83%), and that LMM has been increasing at a higher rate compared with other subtypes and to all invasive melanoma combined for patients aged 45-64 and > or =65 y. The SUMC data demonstrated LM and LMM as the only subtypes increasing in incidence over the study period. In both groups, LM comprised > or =75% of in situ melanoma and LMM > or =27% of invasive melanoma in men 65 y and older. Regional and national SEER data suggest an increasing incidence of LM and LMM, particularly in men > or =age 65. An increased incidence of LM subtypes should direct melanoma screening to heavily sun-exposed sites, where these subtypes predominate.

View details for DOI 10.1111/j.0022-202X.2005.23852.x

View details for Web of Science ID 000232556700011

View details for PubMedID 16185266

Abstract

To review sentinel lymph node (SLN) data from Stanford University Medical Center from January 1, 1997, to January 1, 2004, including rates of SLN positivity according to 2002 American Joint Committee on Cancer (AJCC) tumor classification, relation to other clinical and pathologic prognostic factors, and rates and sites of melanoma recurrence.Retrospective case series.Stanford University Medical Center and Stanford melanoma clinics.A total of 274 consecutive patients with primary melanoma who underwent SLN biopsy (SLNB) between January 1, 1997, and January 1, 2004, or who were referred to the Stanford melanoma clinics after SLNB and were followed up through March 2005.All patients underwent standard wide local excision of their primary tumors and SLNB with intradermal injection of isosulfan blue dye and/or technetium sulfur colloid.Rates of SLN positivity per 2002 AJCC tumor classification, relation to other clinical and pathologic prognostic factors, and rates and sites of melanoma recurrence in node-negative and node-positive patients.Positive SLNs were detected in 39 (15%) of 260 cases, including 0 (0%) of 45 for cutaneous melanomas 1.0 mm thick or less (T1), 21 (18%) of 115 for melanomas 1.01 to 2.0 mm thick (T2), 12 (19%) of 64 for melanomas 2.01 to 4.0 mm thick (T3), and 5 (16%) of 32 for melanomas thicker than 4.0 mm (T4). Median Breslow depths were 1.89 mm for SLN-positive biopsy specimens and 1.50 mm for SLN-negative biopsy specimens (P = .07). The recurrence rate was 46% among SLN-positive patients, with a median time to recurrence of 8 months. Bivariate analysis revealed SLN positivity to be associated with AJCC tumor classification (P = .02), location on the trunk (P = .03), and presence of ulceration (P = .03). By multivariate logistic regression, ulceration (P = .01) was predictive of SLN positivity, whereas SLN status (P< .001), ulceration (P = .02), and location (P = .03) were predictive of recurrent disease.Data from the past 8 years confirm the accuracy and prognostic value of SLNB in cutaneous melanoma and the low rate of regional nodal recurrence for SLN-negative patients.

View details for Web of Science ID 000231072100011

View details for PubMedID 16103331

Abstract

Lentigo maligna (LM) can histologically simulate dysplastic nevus (DN). Partial biopsy of LM may lead to misdiagnosis.One hundred and fourteen cases of LM and LM melanoma (LMM) were diagnosed at the Veterans Affairs Palo Alto Health Care System (1993-2002). Biopsy and excision specimens for 68 in situ and 28 invasive melanomas were classified as having predominant classical LM features, predominant DN-like morphology, or a mixed pattern.Biopsy specimens demonstrated a predominant classical pattern in 38% (25/65) LM and 36% (10/28) LMM, predominant DN-like features in 43% (28/65) LM and 25% (7/28) LMM, and mixed pattern in 15% (10/65) LM and 29% (8/28) LMM. Most LM and LMM biopsies were partial. Significant DN-like features were present in 51% LM and 57% LMM excision specimens. Median age was 72 years for LM and 73 years for LMM, mean lesion diameters were 1.3 and 1.7 cm for LM and LMM, respectively, and 85% of LM and 75% of LMM cases were located on heavily sun-exposed sites.Misdiagnosis of LM or LMM as DN could have devastating results. Large pigmented lesions on sun-damaged skin in elderly individuals should warrant consideration of LM/LMM diagnosis, even in the setting of DN-like features histologically. Excisional biopsy may help to avoid misdiagnosis.

View details for Web of Science ID 000229637200003

View details for PubMedID 15953373

Abstract

Melanoma accounts for the majority of skin cancer deaths worldwide and has dramatically increased in incidence over the past half-century. Despite recent trends showing improved survival, and stabilization of incidence rates in younger Americans, melanoma incidence and mortality continue to rise unabated in older individuals, particularly in men over age 65. Efforts at early clinical detection of melanoma in older individuals should take into account the differences in melanoma subtypes in older individuals, potentially reduced access to medical specialists in this population, as well as comorbidities that may affect ability to undergo treatment for advanced disease. Secondary melanoma prevention should be focused on targeted education to older men and their spouses for early detection and reduction of mortality in this extremely high-risk group.

View details for Web of Science ID 000238211600017

View details for PubMedID 15471201

Abstract

Sebaceous carcinoma is a rare, aggressive neoplasm that arises from the adnexal epithelium of sebaceous glands and is commonly associated with Muir-Torre syndrome.The metastatic potential of extraocular sebaceous carcinoma warrants a thorough evaluation to establish the extent of disease.We describe a 55-year-old man who presented with an asymptomatic abdominal wall mass 3 years after definitive diagnosis of Muir-Torre syndrome.A biopsy of the surgical specimen revealed sebaceous carcinoma.Dermatologists are crucial to the early recognition and diagnosis of extraocular sebaceous carcinoma. In our patient with documented Muir-Torre syndrome, continued surveillance allowed for prompt recognition and treatment of this associated cutaneous malignancy.

View details for Web of Science ID 000220940700025

View details for PubMedID 15099333

View details for Web of Science ID 000220118300013

View details for PubMedID 15023783

View details for DOI 10.1016/j.jaad.2003.07.027

View details for Web of Science ID 000220080500026

View details for PubMedID 14988697

View details for Web of Science ID 000188877100024

View details for PubMedID 14967808

Abstract

The term primary dermal melanoma has been used to describe a subtype of melanoma confined to the dermis and/or subcutaneous fat that histologically simulates metastasis but is associated with an unexpectedly prolonged survival. We report 7 cases of primary dermal melanoma diagnosed from 1998 to 2002 with no identifiable junctional or epidermal component or nevoid precursor. Histopathologic and immunohistochemical features were compared with known cases of cutaneous metastasis and nodular melanoma in an attempt to differentiate this entity from clinical and pathologic mimics.Seven patients had a single dermal and/or subcutaneous focus of melanoma. Metastatic staging workup findings were negative, including results from sentinel node and imaging studies. Mean Breslow depth was 7.0 mm, and mean maximum tumor diameter was 6.2 mm. The study cohort showed 100% survival at mean follow-up of 41 months (range, 10-64 months). Immunohistochemical analysis with S100, HMB-45, Ki-67, CD34, and p75 antibodies showed no significant staining patterns compared with metastatic and nodular melanomas.Primary dermal melanoma appears to be a distinct subtype of melanoma based on the excellent prognosis associated with this case series and others. Additional research focusing on cause, appropriate staging, and outcome of previously identified solitary dermal metastasis is warranted to further delineate this entity.

View details for Web of Science ID 000188060200013

View details for PubMedID 14732666

View details for Web of Science ID 000185517700010

View details for DOI 10.1067/mjd.2003.284

View details for Web of Science ID 000182977200018

View details for PubMedID 12734509

Abstract

Issues regarding appropriate management of stage I to III melanoma are addressed. Accurate surgical staging is critical to identifying patients who can benefit from therapeutic lymph node dissection and adjuvant therapy. Patients with primary tumors > or = 1 mm thick are appropriate candidates for sentinel lymph node biopsy, and node-positive patients benefit from therapeutic lymphadenectomy. Although the overall survival benefit of high-dose interferon has been questioned, the weight of evidence supports the use of adjuvant therapy in patients with stage IIB and III disease.

View details for DOI 10.1002/jso.10216

View details for Web of Science ID 000181294400013

View details for PubMedID 12619066

Abstract

Early recognition and treatment of thin cutaneous melanoma have contributed to a decreased case-fatality rate over the past 60 years. The only known preventive measure for melanoma is sun protection in childhood, which directly affects the number of melanocytic nevi developing as an adult. Additional melanoma risk factors, clinical features, and malignant potential of precursor lesions are discussed. The four major clinicopathologic subtypes of melanoma are described, with recommendations for appropriate biopsy techniques for suspected melanoma. Nationwide skin cancer screenings by dermatologists and greater public awareness of the warning signs of melanoma have enhanced detection of early melanoma, and promoted chances for cure.

View details for Web of Science ID 000181917900005

View details for PubMedID 12691451

Abstract

Wound healing following a partial biopsy of basal cell (BCC) and squamous cell carcinomas (SCC) may induce tumor regression.Nonmelanoma skin cancer (NMSC) biopsy and re-excision specimens from 1994 to 2001 were reviewed for histologic evidence of scar vs. presence of residual tumor in excision specimens. Regressed and non-regressed tumors were analyzed to assess the influence of anatomic location, biopsy technique (punch vs. shave), histologic subtype of BCC or SCC, time interval between biopsy and excision, and patient age.Nine hundred and ten excisions were performed for transected BCC or SCC, 217 (24%) of which showed scar with no residual tumor. Logistic regression analysis revealed significant differences in the regressed vs. non-regressed subsets. SCCs were more likely to regress than BCCs (40% vs. 20%, respectively, p < 0.00001). Independent of the NMSC type, tumors regressed more often following shave rather than punch biopsy (34% vs. 15%, respectively, p < 0.00001), as did tumors on the trunk and extremities compared with head and neck cases (31% vs. 21%, respectively, p < 0.01).In our series, 24% of NMSCs transected on the initial biopsy showed no residual tumor in the excision specimens, implying that some event in the interval between biopsy and excision may lead to the eradication of residual tumor. The exact mechanism is unclear, but wound healing likely plays an important role.

View details for Web of Science ID 000181633300008

View details for PubMedID 12641794

Abstract

Skin cancer screening in populations at increased risk may be more useful than mass screening. We assessed the effectiveness of screening a targeted population in the Veterans Affairs Palo Alto Health Care System (VAPAHCS) for skin cancer/precancer detection and follow-up.We studied the demographics, presumptive diagnoses, and outcome of 374 participants in free screening clinics conducted over a 3-year period in multiple northern California sites. The number of attendees with presumptive actinic keratosis (AK), basal cell carcinoma (BCC), squamous cell carcinoma (SCC), dysplastic nevus (DN), and melanoma was noted.Three hundred sixty-two males and 12 females were screened (mean age 63.4 years); 74% were Caucasian. Two hundred three individuals (54%) had a positive screen including 139 (52%) with presumptive AK, 41 (11%) with BCC, 9 (2%) with SCC, and 14 (4%) with DN versus potential melanoma. One hundred one (50%) of referred individuals were subsequently evaluated by VAPAHCS dermatologists. Biopsy was performed in 34/36 cases (94%), with a positive predictive value of 62% in patients with suspected BCC, 43% for SCC, 37.5% for DN and 12.5% for melanoma.Targeting a predominantly elderly Caucasian population with minimal to no prior dermatologic care yielded high rates of detection for precancers, skin cancer, and atypical nevi, and resulted in an increased percentage of pathologically confirmed nonmelanoma skin cancer, particularly BCC, compared to prior screening studies and population-based cancer registries.

View details for DOI 10.1016/S0091-7435(02)00027-0

View details for Web of Science ID 000181261700005

View details for PubMedID 12590991

Abstract

Whole-body positron emission tomography (PET) provides diagnostic information not currently available with traditional imaging and may improve the accuracy of staging melanoma patients.A retrospective cohort review was performed of 104 patients with primary or recurrent melanoma who underwent PET to determine sensitivity/specificity for metastatic detection compared with body computed tomography (CT). One hundred fifty-seven PET and 70 CT scans were analyzed, with a median patient follow-up of 24 months. Metastases were confirmed with positive histology (87.5%) or documented disease progression (12.5%). Fifty-three patients prospectively underwent consecutive studies within a mean 3-week interval for direct comparative analysis.PET demonstrated 84% sensitivity (95% confidence interval [CI],.78 to.89) and 97% specificity (95% CI,.91 to.99), whereas CT showed 58% sensitivity (95% CI,.49 to.66) and 70% specificity (95% CI,.51 to.84). Exclusion of areas not evaluated on CT (head, neck/supraclavicular, extremities) increased CT sensitivity to 69% (95% CI,.59 to.77). Sixty-six consecutive PET and CT scans were performed with 81% and 57% of metastases detected, respectively.PET is more sensitive and specific than CT for detection of melanoma metastasis and should be considered the primary staging study for recurrent disease. PET shows greater ability to detect soft tissue, small-bowel, and lymph node metastasis that do not meet criteria designated as abnormal by CT. PET is superior to CT even when sites not routinely evaluated by CT are excluded from comparative analysis.

View details for Web of Science ID 000177327500008

View details for PubMedID 12167578

Abstract

Interstitial mycosis fungoides (IMF) is a rare variant of mycosis fungoides that resembles the interstitial form of granuloma annulare and inflammatory morphea. IMF has received little attention in the literature.Clinical, histological, immunophenotypical, and genotypical findings of five cases of IMF were reviewed. The histological and immunophenotypical findings were compared with those of eight cases of interstitial granuloma annulare and six cases of inflammatory morphea.Five patients with IMF presented with non-indurated, erythematous macules; ill-defined erythematous plaques with slight scale; and nodules on the trunk and proximal limbs. Two of five patients had a prior diagnosis of mycosis fungoides. Skin biopsies revealed a striking dermal interstitial infiltrate of lymphocytes with rare histiocytes that resembled the interstitial form of granuloma annulare or inflammatory morphea. Epidermotropic lymphocytes were present at least focally in all cases. A band-like lymphocytic infiltrate was observed in two of five cases. In contrast, many plasma cells and histiocytes were observed in cases of inflammatory morphea and interstitial granuloma annulare, respectively. With Movat-pentachrome stains, increased dermal mucin deposition was observed in two of five IMF cases, in all cases of interstitial granuloma annulare, and in one of six cases of inflammatory morphea. There was focal loss of elastic fibers in all cases of inflammatory morphea. Immunohistochemical studies of IMF highlighted a dominant population of T cells (CD3+) in the dermis and epidermis. In contrast, moderate numbers of B cells (CD20+) were admixed with T cells and plasma cells in inflammatory morphea. Almost equal numbers of histiocytes (CD68+) and T cells comprised the infiltrate of interstitial granuloma annulare. In two of five IMF cases, a clonal T-cell population was detected by PCR T-cell gamma gene rearrangement analysis.Mycosis fungoides occasionally presents as an interstitial lymphocytic infiltrate that mimics granuloma annulare and inflammatory morphea. Hematoxylin & eosin (H&E) findings alone can sometimes distinguish the three disorders. Immunophenotyping and genotyping may be helpful in difficult cases.

View details for Web of Science ID 000175587800002

View details for PubMedID 11972709

Abstract

To convene a multidisciplinary panel of dermatologists, surgical oncologists, and medical oncologists to formally review available data on the sentinel lymph node (SLN) biopsy procedure and high-dose adjuvant interferon alfa-2b therapy for patients with melanoma and to rate the "appropriateness," "inappropriateness," or "uncertainty" of the procedure and therapy to guide clinical decision making in practice.The panel comprised 13 specialists (4 dermatologists, 4 oncologists, and 5 surgeons) from geographically diverse areas who practiced in community-based settings (n = 8) and academic institutions (n = 5). Participants were chosen based on recommendations from the relevant specialty organizations.A formal literature review was conducted by investigators at Protocare Sciences Inc, Santa Monica, Calif, on the risks and benefits of performing an SLN biopsy in patients with stage I or II melanoma and adjuvant interferon alfa-2b therapy in patients with stage II or III disease. The MEDLINE database was searched from 1966 through July 2000, and supplemental information was obtained from various cancer societies and cancer research groups. Panel participants were queried on additional sources of relevant information. Unpublished, presented data were included in abstract form on 1 recently closed clinical trial.The RAND/UCLA Appropriateness Method was used to review and rate multiple clinical scenarios for the use of SLN biopsy and interferon alfa-2b therapy. The consensus method did not force agreement.The panel rated 104 clinical scenarios and concluded that the SLN biopsy procedure was appropriate for primary melanomas deeper than 1.0 mm and for tumors 1 mm or less when histologic ulceration was present and/or classified as Clark level 4 or higher. The SLN biopsy was deemed inappropriate for nonulcerated Clark level 2 or 3 melanomas 0.75 mm or less in depth and uncertain in tumors 0.76 to 1.0 mm deep unless they were ulcerated or Clark level 4 or higher. Interferon alfa-2b therapy was deemed appropriate for patients with regional nodal and/or in-transit metastasis and for node-negative patients with primary melanomas deeper than 4 mm. The panel considered the use of interferon alfa-2b therapy uncertain in patients with ulcerated intermediate primary tumors (2.01-4.0 mm in depth) and inappropriate for node-negative patients with nonulcerated tumors less than 4.0 mm deep. Specialty-specific ratings were conducted as well.

View details for Web of Science ID 000170942600011

View details for PubMedID 11559220

Abstract

We identified circulating CD8+ T-cell populations specific for the tumor-associated antigens (TAAs) MART-1 (27-35) or tyrosinase (368-376) in six of eleven patients with metastatic melanoma using peptide/HLA-A*0201 tetramers. These TAA-specific populations were of two phenotypically distinct types: one, typical for memory/effector T cells; the other, a previously undescribed phenotype expressing both naive and effector cell markers. This latter type represented more than 2% of the total CD8+ T cells in one patient, permitting detailed phenotypic and functional analysis. Although these cells have many of the hallmarks of effector T cells, they were functionally unresponsive, unable to directly lyse melanoma target cells or produce cytokines in response to mitogens. In contrast, CD8+ T cells from the same patient were able to lyse EBV-pulsed target cells and showed robust allogeneic responses. Thus, the clonally expanded TAA-specific population seems to have been selectively rendered anergic in vivo. Peptide stimulation of the TAA-specific T-cell populations in other patients failed to induce substantial upregulation of CD69 expression, indicating that these cells may also have functional defects, leading to blunted activation responses. These data demonstrate that systemic TAA-specific T-cell responses can develop de novo in cancer patients, but that antigen-specific unresponsiveness may explain why such cells are unable to control tumor growth.

View details for Web of Science ID 000080823300037

View details for PubMedID 10371507

Abstract

Hereditary ochronosis, or alkaptonuria, results from deficiency of homogentisic acid oxidase. It is an autosomal recessive condition found in geographically isolated populations. The excess homogentisic acid deposits in collagenous structures, leading to unusual pigmentation of the skin overlying cartilaginous structures, but on occasion pigment is also seen in the sclera, in sweat after oxidation, and classically, in urine when left standing at room temperature. This case report highlights the pathogenesis and expression of this rare disorder.

View details for Web of Science ID 000080885500009

View details for PubMedID 10388955

Abstract

Over 200 basal cell carcinomas (BCCs) are biopsied and subsequently excised each year at the Veterans Affairs Palo Alto Health Care System (VAPAHCS). A focal infiltrative pattern developed in the region of the biopsy scar in the re-excision specimens of 20 cases out of approximately 400 BCCs (< 5%) examined histopathologically over a 2-year period. The patient population included predominantly male, elderly Caucasians (mean age 71), and all tumors fulfilled clinical and histologic criteria for nodular BCC at the time of initial punch or shave biopsy. No patient showed recurrence of tumor following simple re-excision with 2-3 mm surgical margins, with a mean follow up of 25.4 months after excisional surgery. These neoplasms had a more benign clinical course, possibly related to scar formation in healing sites of previously biopsied nodular BCC, rather than true aggressive-growth BCC. The authors conclude that a focal infiltrative pattern in a re-excision specimen may occur histologically as a scar-induced pattern which mimics an aggressive-growth BCC, but does not appear to have the same prognosis. We believe this is an important histologic observation, as recognition of biopsy scar changes in an excisional specimen of BCC may help to distinguish it from true aggressive-growth BCC.

View details for Web of Science ID 000076432400004

View details for PubMedID 9826167

Abstract

A 34-year-old healthy woman presented with a 15-month history of persistent, nonhealing vulvar ulcerations due to herpes simplex virus (HSV) type 2. Extensive dermatologic workup and serial skin biopsies failed to reveal an underlying vulvar dermatosis or autoimmune bullous disorder. Virologic studies revealed resistance to acyclovir in vitro due to deficiency in thymidine kinase activity. Serum antibody to human immunodeficiency virus was negative on two occasions, separated by 1 year. Immunologic evaluation showed normal HSV-specific proliferative and CD8 cytotoxic T lymphocyte responses as well as normal NK cell function. Vulvar lesions failed to heal in association with trials of topical trifluorothymidine and oral valacyclovir but resolved completely with the application of 1% foscarnet cream. No recurrence of HSV has been observed in 24 months of follow-up to date.

View details for Web of Science ID 000072159900004

View details for PubMedID 9498430

View details for Web of Science ID A1997WH06700026

View details for PubMedID 9041849

Abstract

We have noted a high frequency of aggressive-growth basal cell carcinomas (BCCS) in our patient population. Subtypes observed with increased frequency include morpheaform, infiltrative, and micronodular.Our purpose was to examine the frequency of histologic subtypes of all BCCs seen in the dermatology clinics in the Veterans Affairs Palo Alto Health Care System in an 18-month period.We reviewed 432 consecutive primary BCC biopsy specimens taken from 252 patients.Aggressive-growth BCC was observed in 20.7% of biopsy specimens, including 13.4% morpheaform, 5.7% infiltrative, and 1.6% micronodular subtypes. The mean age of the patient population was 70 years, with a standard deviation of 9.1 years.Our observed percentage of aggressive-growth BCC is substantially higher than in most other large studies. A high frequency of aggressive-growth BCC coupled with the increasing incidence of nonmelanoma skin cancer may have significant implications for future health care resource allocation.

View details for Web of Science ID A1996VY37700005

View details for PubMedID 8959949

Abstract

Early recognition and treatment of thin cutaneous melanomas (stages Ia and Ib) have contributed to a decreased case-fatality rate during the past several decades. The only known preventable risk factor for melanoma is sun protection in childhood, which directly affects the number of melanocytic nevi developing in an adult. Additional risk factors, clinical features, and the malignant potential of precursor lesions are discussed. The four major clinicopathologic subtypes of melanoma are described with recommendations for appropriate biopsy techniques for suspected melanoma. Nationwide skin cancer screenings by dermatologists and greater public awareness of the warning signs of melanoma have enhanced detection of early melanoma and have promoted chances for a cure.

View details for Web of Science ID A1996WA77200006

View details for PubMedID 8977551

View details for Web of Science ID A1996VY37700031

View details for PubMedID 8959975

View details for Web of Science ID A1996TT73200011

View details for PubMedID 8850041

Abstract

Scleredema is a rare connective disease which must be differentiated from scleroderma in childhood. Scleredema is characterized by thickening of the dermis of the neck, head, and upper trunk. We report a case of scleredema in an 8-year-old boy with coincident streptococcal colonization. The patient report demonstrates many of the common features of scleredema, including an associated streptococcal infection, a relatively benign presentation of illness, and the characteristic mucopolysaccharide intradermal staining on skin biopsy. The literature on scleredema is reviewed, focusing on the disease course, differential diagnosis, and an overview of the proposed three subgroups of scleredema. The association of scleredema to a prior streptococcal infection is explored, and a proposed autoimmune pathophysiology of the disease, as it relates to streptococcal infection, is presented.

View details for Web of Science ID A1994PM02600006

View details for PubMedID 7813140

Abstract

A 30-year-old immunocompromised man with known pulmonary Mycobacterium chelonae colonization developed a systemic infection with cutaneous manifestations. The eruption consisted of multiple, nontender, subcutaneous nodules on the extremities. A diagnosis of disseminated M. chelonae was made on the basis of recovery of M. chelonae subspecies abscessus from blood and bronchoalveolar lavage fluid and histologic evidence of acid-fast bacilli in a skin biopsy specimen. We believe this is the first reported case of disseminated M. chelonae infection in an immunocompromised host in whom a primary source of the infection was identified.

View details for Web of Science ID A1993KL57000020

View details for PubMedID 8436657