New insights into associated co-morbidities in patients with cutaneous T-cell lymphoma (mycosis fungoides).

Studies of associated cancer in patients with mycosis fungoides (MF) have focused primarily on secondary cancers in North American and European populations. This study investigated the association between MF and malignancies, anxiety and depression in the Israeli population. Data on Israeli patients with MF and age- and gender-matched controls were collected from a database of population- based cohort (683 patients; 1,700 controls) and an institution- based cohort (343 patients; 846 controls) and analysed by univariate and multivariate methods. MF was significantly associated with Hodgkin's lymphoma in both cohorts (multivariate odds ratio (OR) 7.83, univariate OR ∞, respectively); acute leukaemia (multivariate OR 10.1, first cohort) and lung cancer (multivariate OR 10.15, second cohort). MF was significantly associated with anxiety and depression (multivariate OR 1.59, OR 1.51, respectively in first cohort). The current study provides support to the associations between MF and other cancers: Hodgkin's lymphoma, acute leukaemia and lung cancer. The study also emphasizes the association between MF and anxiety and depression.

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.

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.

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.

Sun protection and sunbathing practices among at-risk family members of patients with melanoma.

BACKGROUND: Despite the increased level of familial risk, research indicates that family members of patients with melanoma engage in relatively low levels of sun protection and high levels of sun exposure. The goal of this study was to evaluate a broad range of demographic, medical, psychological, knowledge, and social influence correlates of sun protection and sunbathing practices among first-degree relatives (FDRs) of melanoma patients and to determine if correlates of sun protection and sunbathing were unique. METHODS: We evaluated correlates of sun protection and sunbathing among FDRs of melanoma patients who were at increased disease risk due to low compliance with sun protection and skin surveillance behaviors. Participants (N = 545) completed a phone survey. RESULTS: FDRs who reported higher sun protection had a higher education level, lower benefits of sunbathing, greater sunscreen self-efficacy, greater concerns about photo-aging and greater sun protection norms. FDRs who reported higher sunbathing were younger, more likely to be female, endorsed fewer sunscreen barriers, perceived more benefits of sunbathing, had lower image norms for tanness, and endorsed higher sunbathing norms. CONCLUSION: Interventions for family members at risk for melanoma might benefit from improving sun protection self-efficacy, reducing perceived sunbathing benefits, and targeting normative influences to sunbathe.

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.

Cutaneous precursor B-cell lymphoblastic lymphoma in 2 adult patients: clinicopathologic and molecular cytogenetic studies with a review of the literature.

BACKGROUND: Precursor B-cell lymphoblastic lymphoma (B-LBL) is an uncommon high-grade neoplasm of immature B cells. In contrast to the more common lymphoblastic lymphoma of T-cell lineage, B-LBL can be an extranodal disease, with a propensity to involve skin and bone. Most reported cases of B-LBL in the skin, a rarity in adults, are manifestations of existing systemic disease. OBSERVATIONS: We report 2 unusual cases of primary cutaneous B-LBL in adults. Fluorescence in situ hybridization studies, not previously reported in primary cutaneous B-LBL to our knowledge, demonstrated rearrangement of the MLL gene in one patient and possible hyperdiploidy in the other, both reported in precursor acute lymphoblastic leukemia. CONCLUSIONS: Review of the literature identified 13 reported cases of B-LBL occurring primarily in the skin, in addition to our 2 cases. Precursor B-cell lymphoblastic lymphoma is more common in children and in young adults, with a tropism for the head and neck region. Histologically, B-LBL must be differentiated from other high-grade lymphoid tumors and small "blue round cell" tumors. Because of the common absence of mature B-cell markers in immunohistochemical studies and the frequent expression of CD99, B-LBL may present a diagnostic challenge. Although there is a suggestion in a limited number of patients that abbreviated therapy may provide long-term disease control, the risk of relapse remains significant, particularly if a patient's condition is misdiagnosed and the patient is treated as having mature B-cell lymphoma. In the absence of prospective studies for this population, patients with B-LBL are treated currently with intensive acute lymphoblastic leukemia regimens.

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.