Statins and cancer prevention.

Randomized controlled trials for preventing cardiovascular disease indicated that statins had provocative and unexpected benefits for reducing colorectal cancer and melanoma. These findings have led to the intensive study of statins in cancer prevention, including recent, large population-based studies showing statin-associated reductions in overall, colorectal and prostate cancer. Understanding the complex cellular effects (for example, on angiogenesis and inflammation) and the underlying molecular mechanisms of statins (for example, 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase-dependent processes that involve geranylgeranylation of Rho proteins, and HMG-CoA-independent processes that involve lymphocyte-function-associated antigen 1) will advance the development of molecularly targeted agents for preventing cancer. This understanding might also help the development of drugs for other ageing-related diseases with interrelated molecular pathways.

Herpes folliculitis masquerading as cutaneous lymphoma.

Herpes virus infections presenting as folliculitis are uncommon. We describe a 48-year-old white man with a distant history of a childhood gastric lymphoma and renal cell carcinoma presenting with an itchy eruption. He was concerned about recurrence. A punch biopsy revealed interface dermatitis with a dense atypical superficial and deep perivascular and periadnexal lymphohistiocytic infiltrate with occasional eosinophils extending to the subcutis, with destruction of vessel walls. It was composed of predominantly CD3-positive lymphocytes with scattered CD56-positive cells and CD20-positive cells, concerning for lymphoma. A T-cell gene rearrangement study was negative. Deeper sections uncovered multinucleated giant keratinocytes in the follicular epithelium of 1 hair follicle, consistent with herpes folliculitis. Cutaneous herpes infections can exhibit several variable clinical and histopathological features. Knowledge of alternative presentations of herpes infections, histological clues to the presence of herpes infections, and careful clinicopathological correlation are necessary to differentiate herpes infections from cutaneous lymphomas and other inflammatory dermatoses.

Generation of transgene-free lung disease-specific human induced pluripotent stem cells using a single excisable lentiviral stem cell cassette.

The development of methods to achieve efficient reprogramming of human cells while avoiding the permanent presence of reprogramming transgenes represents a critical step toward the use of induced pluripotent stem cells (iPSC) for clinical purposes, such as disease modeling or reconstituting therapies. Although several methods exist for generating iPSC free of reprogramming transgenes from mouse cells or neonatal normal human tissues, a sufficiently efficient reprogramming system is still needed to achieve the widespread derivation of disease-specific iPSC from humans with inherited or degenerative diseases. Here, we report the use of a humanized version of a single lentiviral "stem cell cassette" vector to accomplish efficient reprogramming of normal or diseased skin fibroblasts obtained from humans of virtually any age. Simultaneous transfer of either three or four reprogramming factors into human target cells using this single vector allows derivation of human iPSC containing a single excisable viral integration that on removal generates human iPSC free of integrated transgenes. As a proof of principle, here we apply this strategy to generate >100 lung disease-specific iPSC lines from individuals with a variety of diseases affecting the epithelial, endothelial, or interstitial compartments of the lung, including cystic fibrosis, α-1 antitrypsin deficiency-related emphysema, scleroderma, and sickle-cell disease. Moreover, we demonstrate that human iPSC generated with this approach have the ability to robustly differentiate into definitive endoderm in vitro, the developmental precursor tissue of lung epithelia.

Sézary syndrome: immunopathogenesis, literature review of therapeutic options, and recommendations for therapy by the United States Cutaneous Lymphoma Consortium (USCLC).

Sézary syndrome (SS) has a poor prognosis and few guidelines for optimizing therapy. The US Cutaneous Lymphoma Consortium, to improve clinical care of patients with SS and encourage controlled clinical trials of promising treatments, undertook a review of the published literature on therapeutic options for SS. An overview of the immunopathogenesis and standardized review of potential current treatment options for SS including metabolism, mechanism of action, overall efficacy in mycosis fungoides and SS, and common or concerning adverse effects is first discussed. The specific efficacy of each treatment for SS, both as monotherapy and combination therapy, is then reported using standardized criteria for both SS and response to therapy with the type of study defined by a modification of the US Preventive Services guidelines for evidence-based medicine. Finally, guidelines for the treatment of SS and suggestions for adjuvant treatment are noted.

Dermatofibrosarcoma protuberans arising in the context of Shwachman-Diamond syndrome.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon malignant spindle-cell tumor usually presenting in adulthood. The epidemiology of DFSP has recently been reviewed, and there have been 152 reported cases of DFSP in patients below the age of sixteen. We present the case of a DFSP arising in a young patient with Shwachman-Diamond syndrome (SDS).

Enacting legislation to restrict youth access to tanning beds: a survey of advocates and sponsoring legislators.

BACKGROUND: Passing tanning bed legislation restricting underage use has remained challenging. OBJECTIVE: We sought to determine the resources required to pass tanning bed legislation restricting use to children and identify key barriers to its passage. METHODS: A total of 15 states sought to pass tanning bed legislation in 2006; in-depth surveys were completed with advocates in 10 states and legislators in 5 states. RESULTS: Advocates sought advice from the sponsoring legislator or legislators (n = 9), held discussions with other organizations (n = 8), and used a lobbyist (n = 5). The 3 major barriers were strong lobbying efforts by the tanning bed industry (n = 10), proceedings after the bill was filed (n = 5), and obtaining support from other organizations (n = 4). For legislators, the most significant barrier was making colleagues aware of the health effects of tanning bed use. LIMITATIONS: Five of 10 legislators and 10 of 15 advocates responded to the survey. CONCLUSION: Barriers to passage of tanning bed legislation can potentially be surmounted with advice to advocates and coordinated efforts by multiple organizations.

Anaplastic Kaposi's sarcoma: an uncommon histologic phenotype with an aggressive clinical course.

Anaplastic Kaposi sarcoma (KS) is an uncommon histologic phenotype of Kaposi's and one that is typically associated with a locally aggressive clinical course. We report a case of a 53-year-old human immunodeficiency virus-positive male, on highly active antiretroviral therapy 1 month prior to admission, who presented with fever, cough, respiratory distress, multiple skin lesions and cervical and inguinal lymphadenopathy not responding to multiple antibiotics. Microscopic examination of punch biopsies from the forehead and chest revealed a spindled cell neoplasm with marked cytologic atypia and scattered mitoses, features consistent with a diagnosis of anaplastic KS and confirmed by immunohistochemistry with HHV-8. Biopsy of an involved lymph node also revealed involvement by KS. Despite aggressive clinical treatment, the patient rapidly deteriorated and expired 1 week after the diagnosis of anaplastic KS was rendered. Our case underscores the aggressive clinical course of this uncommon histologic variant of KS and its recalcitrant clinical behavior.

Epidermotropic metastatic mucoepidermoid carcinoma.

Mucoepidermoid carcinoma (MEC), an invasive malignant neoplasm composed of mucus-secreting, epidermoid, and intermediate cells in varying proportions, is the commonest malignant salivary gland neoplasm in adults. Cutaneous metastases from the same, although not entirely common, has been previously reported but are typically confined to dermis. In this report, we present a case of MEC presenting as a cutaneous metastasis. A histologic feature unique to this case was epidermotropism, previously not noted in either metastatic or primary MEC.

Mycosis fungoides in Arab children and adolescents: a report of 36 patients from Kuwait.

Mycosis fungoides (MF) is rare in children and adolescents. This study was aimed to determine the clinicoepidemiologic features of juvenile onset (≤18 yrs) MF in Kuwait. Thirty-six children and adolescents (≤18 yrs) with MF registered in a referral photobiology unit for cutaneous lymphomas between July 1991 and June 2009 were included in this study. Children and adolescents were observed to constitute 16.6% of the total number of patients with MF, with 97% of patients of Arab ethnicity. The age-adjusted incidence rate of MF in children and adolescents among the total population was 0.29/100,000 persons/year. Among 36 Arab children and adolescents, boys outnumbered girls by 1.25:1. Mean and median age at onset of disease was 9 years, and age at diagnosis was 13 years. Patch stage disease was the most common clinical variant (75%) with 56% with pure hypopigmented MF-variant. The majority of patients (75%) had stage IB (TNM and B staging) disease. The study highlights a high prevalence and incidence of juvenile MF in Kuwait with a predominantly hypopigmented presentation.

Selection criteria for genetic assessment of patients with familial melanoma.

Approximately 5% to 10% of melanoma may be hereditary in nature, and about 2% of melanoma can be specifically attributed to pathogenic germline mutations in cyclin-dependent kinase inhibitor 2A (CDKN2A). To appropriately identify the small proportion of patients who benefit most from referral to a genetics specialist for consideration of genetic testing for CDKN2A, we have reviewed available published studies of CDKN2A mutation analysis in cohorts with invasive, cutaneous melanoma and found variability in the rate of CDKN2A mutations based on geography, ethnicity, and the type of study and eligibility criteria used. Except in regions of high melanoma incidence, such as Australia, we found higher rates of CDKN2A positivity in individuals with 3 or more primary invasive melanomas and/or families with at least one invasive melanoma and two or more other diagnoses of invasive melanoma and/or pancreatic cancer among first- or second-degree relatives on the same side of the family. The work summarized in this review should help identify individuals who are appropriate candidates for referral for genetic consultation and possible testing.

A case report of inflammatory nonscarring alopecia associated with the epidermal growth factor receptor inhibitor erlotinib.

Epidermal growth factor receptor inhibitors (EGFRIs) are new anticancer agents that act by inhibiting EGFR signaling transduction pathways, thus decreasing tumor growth. In more than 30 countries, EGFRIs are currently used in the treatment of a number of solid tumors, and other indications are being sought. In the United States, select EGFRIs have been approved in certain patients with non-small cell lung cancer, metastatic colorectal carcinoma, and advanced squamous cell carcinoma of the head and neck. Various cutaneous side effects of EGFRIs have been reported, including acneiform eruptions, chronic paronychia, xerosis, a seborrheic dermatitis-like eruption, changes in hair texture, and nonscarring alopecia. We present a 60-year-old woman with non-small cell lung cancer who developed a persistent generalized itchy eruption and progressive nonscarring alopecia shortly after initiation of erlotinib (Tarceva). Scalp biopsy showed near-equal number of anagen and catagen/telogen hair follicles, and a superficial and deep perivascular lymphoplasmocytic infiltration. These changes are typical of the nonscarring alopecia induced by EGFRIs. Because it is likely that EGFRIs will be increasingly used, dermatopathologists are likely to see more reactions from these agents. Familiarity with their side effects is essential to accurate diagnosis and effective patient management.

Screening, early detection, and trends for melanoma: current status (2000-2006) and future directions.

UNLABELLED: 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. LEARNING OBJECTIVE: 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.

Successful adjuvant treatment of recalcitrant mucous membrane pemphigoid with anti-CD20 antibody rituximab.

Rituximab is a humanized monoclonal antibody directed against CD20-positive B cells and originally developed for the treatment of non-Hodgkins lymphoma. We report a case of severe mucous membrane pemphigoid responsive to rituximab infusions. The clinical presentation, etiology, and management options for mucous membrane pemphigoid are also discussed.

Compliance with restrictions on sale of indoor tanning sessions to youth in Minnesota and Massachusetts.

BACKGROUND: Minnesota and Massachusetts require parental permission, for persons younger than 16 or 18 years of age, respectively, for indoor tanning. OBJECTIVES: This report examines business practices and characteristics associated with sales of indoor tanning to underage girls. METHODS: Fifteen-year-old girls tried to purchase an ultraviolet tanning session in 200 indoor tanning businesses in the Minneapolis-St Paul and Boston areas without parental consent. Business characteristics were recorded. Later, businesses were interviewed by telephone about their facilities and practices. RESULTS: Eighty-one percent of businesses sold a session to an underaged buyer on at least one of two tries. Illegal purchases did not differ by state. Businesses least likely to sell were larger, dedicated to indoor tanning, required employee certification, and had a minimum age of sale for their business. However, businesses in each of these categories still sold tanning sessions to underaged adolescents at 44% to 62% of the visits. Employees who requested parental consent or age identification almost never sold a session. LIMITATIONS: Businesses in Minnesota and Massachusetts only were included. CONCLUSION: Minnesota and Massachusetts laws specifying a minimum age of sale for indoor tanning are ineffective.

Sun care advertising in popular U.S. magazines.

PURPOSE: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Case reports: nodular vasculitis responsive to mycophenolate mofetil.

Mycophenolate mofetil is commonly used as a steroid-sparing agent effective in the management of erythema nodosum, idiopathic nodular panniculitis (Pfiefer-Weber-Christian disease), bullous pemphigoid, pemphigus vulgaris, and psoriasis. We report a case of nodular vasculitis responsive to mycophenolate mofetil. The clinical presentation, etiology, and management options for nodular vasculitis are discussed.

Chemoprevention of melanoma: an unexplored strategy.

The incidence and mortality of melanoma has continued to increase steeply-faster than most other preventable cancers in the United States. Current sun protection strategies have yet to reduce this increased incidence and mortality. Chemoprevention, defined as the use of natural or synthetic agents to delay, reverse, suppress, or prevent premalignant molecular or histologic lesions from progressing to invasive cancer, has become an important area in cancer research. Melanoma, with its associated risk factors and its known precursors or premalignant lesions, should lend itself well to chemoprevention. Prerequisites for this research should include determination of the molecular mechanisms of ultraviolet (UV) melanomagenesis; use of animal models to test candidate prevention agents; use of molecular and histologic markers as surrogate end point markers; collection of epidemiological, basic science, or in vitro data on potential chemoprevention candidate drugs; and selection of a high-risk patient population in which to carry out clinical chemoprevention trials. Preliminary data available in all these areas are reviewed. Possible mechanisms and molecular targets for the chemoprevention of UV-induced melanoma are discussed. This recent information should stimulate research in the chemoprevention of melanoma.

Cutaneous melanoma: pathogenesis and rationale for chemoprevention.

OBJECTIVE: To critically review aspects of melanoma pathogenesis that lend themselves to a chemoprevention strategy. To discuss potential candidate chemoprevention agents with an emphasis on the lipid lowering drugs, the statins, currently, the most promising agents. DATA SOURCES: A retrospective review of the literature. STUDY SELECTION: Studies included those relevant to melanoma pathogenesis, to the scientific rationale of chemoprevention, and pertinent epidemiologic, pre-clinical, and clinical studies. The referenced study designs and methodologies varied. DATA EXTRACTION AND SYNTHESIS: Data were extracted by two reviewers, and the main results are presented in a quantitative descriptive manner. CONCLUSION: Melanoma is a preventable disease by altering behavior (sun exposure) among at-risk individuals. There is also considerable evidence to suggest that melanoma development may be prevented or delayed by drugs of sufficiently low toxicity to make clinical trials of chemoprevention feasible and potentially successful. Among potential candidate agents, statins have compelling data for long-term safety and sufficient pre-clinical and clinical evidence for efficacy to justify their evaluation in well-designed trials in high-risk individuals, incorporating intermediate biologic endpoints.