Topical chemotherapy in cutaneous T-cell lymphoma: positive results of a randomized, controlled, multicenter trial testing the efficacy and safety of a novel mechlorethamine, 0.02%, gel in mycosis fungoides.

OBJECTIVE: To evaluate the efficacy and safety of a novel mechlorethamine hydrochloride, 0.02%, gel in mycosis fungoides. DESIGN Randomized, controlled, observer-blinded, multicenter trial comparing mechlorethamine, 0.02%, gel with mechlorethamine, 0.02%, compounded ointment. Mechlorethamine was applied once daily for up to 12 months. Tumor response and adverse events were assessed every month between months 1 and 6 and every 2 months between months 7 and 12. Serum drug levels were evaluated in a subset of patients. SETTING: Academic medical or cancer centers. PATIENTS: In total, 260 patients with stage IA to IIA mycosis fungoides who had not used topical mechlorethamine within 2 years and were naive to prior use of topical carmustine therapy. MAIN OUTCOME MEASURES: Response rates of all the patients based on a primary clinical end point (Composite Assessment of Index Lesion Severity) and secondary clinical end points (Modified Severity-Weighted Assessment Tool and time-to-response analyses). RESULTS: Response rates for mechlorethamine gel vs ointment were 58.5% vs 47.7% by the Composite Assessment of Index Lesion Severity and 46.9% vs 46.2% by the Modified Severity-Weighted Assessment Tool. By the Composite Assessment of Index Lesion Severity, the ratio of gel response rate to ointment response rate was 1.23 (95% CI, 0.97-1.55), which met the prespecified criterion for noninferiority. Time-to-response analyses demonstrated superiority of mechlorethamine gel to ointment (P< .01). No drug-related serious adverse events were seen. Approximately 20.3% of enrolled patients in the gel treatment arm and 17.3% of enrolled patients in the ointment treatment arm withdrew because of drug-related skin irritation. No systemic absorption of the study medication was detected. CONCLUSION: The use of a novel mechlorethamine, 0.02%, gel in the treatment of patients with mycosis fungoides is effective and safe. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT00168064.

Process and outcomes of a skin protection intervention for young adults.

Efforts to reduce skin cancer risk behaviors using appearance-oriented interventions (e.g. ultraviolet (UV) light photos showing skin damage) or motivational interviewing (MI) have shown promise in recent trials. In the study a randomized 2 (UV photo versus no UV photo) x 2 (MI versus no MI) factorial design with longitudinal follow up was used. Results showed that progression in stage of change (SOC) was significantly more likely in the photo than the education condition. Treatment credibility as rated by participants and counselor perceived positive therapeutic alliance predicted SOC progression. There was also preliminary evidence for differential intervention effectiveness by baseline SOC. The implications are discussed.

A retrospective analysis of the Dermatology Foundation's Career Development Award Program.

BACKGROUND: To provide research support that develops and retains leaders, educators, and investigators in dermatology and cutaneous biology, the Dermatology Foundation (DF) has designed and implemented a comprehensive Career Development Award (CDA) Program. OBJECTIVE: To assess the impact of the DF's 3-year CDA, a comprehensive survey of recipients who received this mechanism of support between 1990 and 2007 was performed. METHODS: Of 196 individuals receiving a DF CDA, 181 were identified and asked to complete a comprehensive questionnaire concerning their career status, employment history, professional rank, and record of independent research funding (private foundation, federal, other). A personal assessment of the impact of this funding on these individuals' career trajectory was also requested. RESULTS: Eighty percent of 181 CDA recipients identified currently hold full- or part-time positions in academic medicine. The faculty rank of 112 survey respondents included 46 assistant professors (41%), 41 associate professors (37%), 18 professors (16%), and 7 division or departmental chairs (6%). Of respondents, 84% reported that they have received subsequent independent research funding; 95 of these individuals (86%) have received funding from a federal agency (235 federal grants awarded to date with funding >$318M). LIMITATIONS: The study was retrospective and self-reported; some awardees did not respond to the survey. CONCLUSIONS: The DF's CDA Program has succeeded in supporting the early career development of talented investigators, educators, and leaders; fostered the promotion and retention of these individuals in academic medicine; and nucleated numerous investigative careers that have successfully acquired independent research funding.

Skin surveillance intentions among family members of patients with melanoma.

BACKGROUND: First-degree relatives of individuals diagnosed with melanoma are at increased disease risk. However, many first-degree relatives do not receive a periodic total cutaneous examination from a health care provider or engage in regular skin self-examination. The goal of this study was to identify correlates of total cutaneous examination and skin self-examination intentions among first-degree relatives of melanoma patients, thus providing insight on factors that should be targeted in future intervention research. METHODS: The participants were 545 first-degree relatives of melanoma patients at increased disease risk due to their risk factor profile and lack of skin surveillance behaviors. Participants completed a telephone survey regarding their total cutaneous examination and skin self-examination intentions and potential correlates, including demographics, medical factors, psychological factors, knowledge, and social influence factors. RESULTS: Intentions to receive a total cutaneous examination were higher among first-degree relatives with more education, those perceiving higher benefits and lower barriers to an examination, and those reporting greater physician and family support. Intentions to receive a skin self-examination were higher among those with higher benefits and lower barriers to self-examination, and higher family support. CONCLUSIONS: Interventions to promote skin surveillance behaviors among first-degree relatives of melanoma patients should highlight the benefits of early detection of melanoma, address barriers to receipt of total cutaneous examination and engagement in skin self-examination, and promote support from physicians and family members.

Clinical end points and response criteria in mycosis fungoides and Sézary syndrome: a consensus statement of the International Society for Cutaneous Lymphomas, the United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer.

Mycosis fungoides (MF) and Sézary syndrome (SS), the major forms of cutaneous T-cell lymphoma, have unique characteristics that distinguish them from other types of non-Hodgkin's lymphomas. Clinical trials in MF/SS have suffered from a lack of standardization in evaluation, staging, assessment, end points, and response criteria. Recently defined criteria for the diagnosis of early MF, guidelines for initial evaluation, and revised staging and classification criteria for MF and SS now offer the potential for uniform staging of patients enrolled in clinical trials for MF/SS. This article presents consensus recommendations for the general conduct of clinical trials of patients with MF/SS as well as methods for standardized assessment of potential disease manifestations in skin, lymph nodes, blood, and visceral organs, and definition of end points and response criteria. These guidelines should facilitate collaboration among investigators and collation of data from sponsor-generated or investigator-initiated clinical trials involving patients with MF or SS.

Beliefs and intentions for skin protection and UV exposure in young adults.

OBJECTIVE: To evaluate Fishbein's integrative model in predicting young adults' skin protection, sun exposure, and indoor tanning intentions. METHODS: Two hundred twelve participants completed an online survey. RESULTS: Damage distress, self-efficacy, and perceived control accounted for 34% of the variance in skin protection intentions. Outcome beliefs and low self-efficacy for sun avoidance accounted for 25% of the variance in sun exposure intentions. Perceived damage, outcome evaluation, norms, and indoor tanning prototype accounted for 32% of the variance in indoor tanning intentions. CONCLUSIONS: Future research should investigate whether these variables predict exposure and protection behaviors and whether intervening can reduce young adults' skin cancer risk behaviors.

Tailored versus generic interventions for skin cancer risk reduction for family members of melanoma patients.

BACKGROUND: Improving strategies for risk reduction among family members of patients with melanoma may reduce their risk for melanoma. OBJECTIVE: To evaluate the effects of two behavioral interventions designed to improve the frequency of total cutaneous skin examination by a health provider (TCE), skin self-examination (SSE), and sun protection among first degree relatives of patients with melanoma; and to evaluate whether increased intentions, increased benefits, decreased barriers, and improved sunscreen self-efficacy mediated the effects of the tailored intervention, as compared with the generic intervention on TCE, SSE, or sun protection. METHODS: Four hundred forty-three family members (56 parents, 248 siblings, 239 children) who were nonadherent with these practices were randomly assigned to either a generic (N = 218) or a tailored intervention (N = 225) which included 3 print mailings and 1 telephone session. Participants completed measures of TCE, SSE, and sun protections at baseline, 6 months, and 1 year, and measures of intentions, benefits, barriers, and self-efficacy at baseline and 6 months. RESULTS: Those enrolled in the tailored intervention had almost a twofold increased probability of having a TCE ( p < .0001). Treatment effects in favor of the tailored intervention were also noted for sun protection habits ( p < .02). Increases in TCE intentions mediated the tailored intervention's effects on TCE. Increases in sun protection intentions mediated effects of the tailored intervention's effect on sun protection. CONCLUSIONS: Tailored interventions may improve risk reduction practices among family members of patients with melanoma.

Cytoskeleton alterations in melanoma: aberrant expression of cortactin, an actin-binding adapter protein, correlates with melanocytic tumor progression.

Cortactin is a multidomain actin-binding protein important for the functions of cytoskeleton by regulating cortical actin dynamics. It is involved in a diverse array of basic cellular functions. Tumorigenesis and tumor progression involves alterations in actin cytoskeleton proteins. We sought to study the role of cortactin in melanocytic tumor progression using immunohistochemistry on human tissues. The results reveal quantitative differences between benign and malignant lesions. Significantly higher cortactin expression is found in melanomas than in nevi (P<0.0001), with levels greater in metastatic than in invasive melanomas (P<0.05). Qualitatively, tumor tissues often show aberrant cortactin localization at the cell periphery, corresponding to its colocalization with filamentous actin in cell cortex of cultured melanoma cells. This suggests an additional level of protein dysregulation. Furthermore, in patients with metastatic disease, high-level cortactin expression correlates with poor disease-specific survival. Our data, in conjunction with outcome data on several other types of human cancers and experimental data from melanoma cell lines, supports a potential role of aberrant cortactin expression in melanoma tumor progression and a rational for targeting key elements of actin-signaling pathway for developmental therapeutics in melanomas.

A new central scaffold for metastasis: parsing HEF1/Cas-L/NEDD9.

Greater understanding of metastasis is required to improve cancer treatment outcomes. Recently, changes in expression of the scaffold protein HEF1/CAS-L/NEDD9 were found to be a potent prometastatic stimulus in melanoma and other cancers. Mechanistic studies suggest diverse cellular roles of HEF1 and highlight its importance in the response to extracellular cues that drive invasion and metastasis. As a metastatic "hub" for signaling in cancer, HEF1 may provide a useful target for drug discovery efforts.

Clinicopathologic correlation of cutaneous metastases: experience from a cancer center.

OBJECTIVE: To analyze the clinical, histopathologic, and immunohistochemical characteristics of skin metastases. DESIGN: Retrospective analysis (January 1, 1990, to December 31, 2005). SETTING: Comprehensive cancer center. PATIENTS: Fifty-one patients (21 men and 30 women) with biopsy-proven skin metastases and correlative clinical data. INTERVENTIONS: Four dermatopathologists reviewed a random mixture of metastases and primary skin tumors. Immunohistochemical studies for 12 markers were performed on the metastases, with skin adnexal tumors as controls. MAIN OUTCOME MEASURES: Clinical characteristics of cutaneous lesions, clinical outcomes, histologic features, and immunohistochemical markers. RESULTS: Eighty-six percent (43 of 50) of the patients had known stage IV cancer, and skin metastasis was the presenting sign in 12% (6 of 50). In 45% (21 of 47) of the biopsies, the lesions were not suspected of being metastases owing to unusual clinical presentations. Seventy-six percent of the patients died of disease (median survival, 5 months). On pathologic review, many metastases from adenocarcinomas were either recognized or suspected, but the primary site was not easily identified based on histologic findings alone. Metastases from small cell carcinomas and sarcomas were histologically misinterpreted as primary skin tumors. Immunohistochemical analysis using a panel including p63, B72.3, calretinin, and CK5/6 differentiated metastatic carcinoma from primary skin adnexal tumors. CONCLUSIONS: Cutaneous metastases can have variable clinical appearances and can mimic benign skin lesions. They are usually seen in patients with advanced disease, but they can be the presenting lesion. Although many metastatic adenocarcinomas can be recognized based on histologic findings alone, immunohistochemical analysis is an important diagnostic adjunct in some cases.

A new nail in the CTCL coffin.

The impact of immunotherapy on the natural progression of cutaneous T-cell lymphoma (CTCL), particularly the mycosis fungoides and Sézary syndrome variants, has been based on our evolving understanding of the disease's immunobiology.

Granuloma annulare with a mycosis fungoides-like distribution and palisaded granulomas of CD68-positive histiocytes.

We describe 3 unusual cases of granuloma annulare with multiple macular lesions in a distribution that simulated mycosis fungoides in patients with no associated underlying diseases. Repeated biopsies showed typical well-formed palisading granulomas and no evidence of an atypical lymphocytic infiltrate. There was no vasculitis, neutrophilic, eosinophilic, or interstitial infiltrate. The patients had no associated underlying diseases. Most of the histiocytes in the palisading granulomas were strongly positive for CD68. The lymphocytes were a minor component of the granulomatous inflammation and were predominantly CD8(+) T-cells. The findings in these cases add to the spectrum of previously defined granulomatous eruptions of the skin.

Cutaneous metastases from genitourinary malignancies.

OBJECTIVES: To review the world literature for reports of cutaneous metastases from primary genitourinary malignancies and compare them with our experience during a 10-year period. Cutaneous metastases from primary visceral malignancies are uncommon manifestations of advanced disease. Among patients with urologic malignancies, the incidence and appearance of cutaneous metastases are not well established and recognition is poor among practicing urologists. METHODS: A Medline search and manual bibliographic review was performed to identify peer-reviewed reports pertaining to cutaneous metastases from all visceral malignancies. A comparative review of all pertinent cases arising from primary urologic malignancies was performed. A comprehensive search of our institution's tumor registry was performed to identify all analytic cases of urologic malignancy diagnosed, treated, and followed up between 1990 and 2000. Clinical and pathologic data were collated. RESULTS: We identified 2,369 reported cases of cutaneous metastases arising from 81,618 primary solid visceral malignancies, for an overall incidence of 2.9%. Dermatologic spread from primary urologic malignancies of the kidney, bladder, prostate, or testes was noted in 116 (1.3%) of 10,417. The incidence of cutaneous metastases from the kidney, bladder, prostate, and testes was 3.4%, 0.84%, 0.36%, and 0.4%, respectively. Overall, 436 cases of cutaneous metastases from urologic organs were identified in the English-language literature. We identified nine additional cases of pathologically confirmed cutaneous metastatic urologic tumors at our institution in the past 10 years. The most common presentation was an infiltrated plaque or nodules. Most cases displayed clinical features that mimicked common skin disorders. The median disease-specific survival was less than 6 months from the presentation of cutaneous metastasis. CONCLUSIONS: Cutaneous metastases from urologic tumors are uncommon and occur in 1% of patients with advanced disease. Urologic skin metastases are most common from renal tumors, followed by those of the bladder and then prostate. Their clinical appearance may mimic other common dermatologic disorders affecting patients with advanced malignancies. Definitive diagnosis requires an index of suspicion and skin biopsy. Cutaneous metastases from urologic malignancies are associated with a poor prognosis.