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Mucocutaneous squamous cell carcinoma (SCC) may rarely exhibit intracellular mucin production. Extracellular mucin production is an even rarer finding in SCC that is not well documented in the literature. Here, we report six cases of primary cutaneous and mucocutaneous SCC with prominent extracellular stromal mucin deposition and an epithelial spindle cell component. We propose the term 'yxoid spindle cell SCC' (MSC SCC) to describe the histologic characteristics of these six cases. We also propose a set of histologic and immunohistochemical findings for distinguishing MSC SCC from primary cutaneous and metastatic spindle cell neoplasms including other sarcomatoid carcinomas, myxoid sarcomas and the spindle cell variant of atypical fibroxanthoma (AFX). The criteria can also help discern MSC SCC from spindle cell melanomas, which may rarely show a prominent myxoid stroma. Given the small numbers of cases reported to date, the presence of prominent myxoid stroma in primary cutaneous spindle cell SCC has unknown prognostic significance at this time.

Furuncular myiasis caused by Cordylobia anthropophaga larvae is commonly seen in Africa but rarely is diagnosed in travelers returning from the sub-Saharan region. We report 2 cases of furuncular myiasis due to Cordylobia species in adolescent American travelers returning from Senegal.

Effective antimicrobials are critical in controlling one of the most common conditions encountered in medicine, namely, skin and skin structure infections. Unfortunately, the identification of appropriate and novel antimicrobials is continually challenged by the emergence of antimicrobial resistance among bacteria, fungi, and parasites. This work will focus on describing novel antibacterials and antifungals approved by the United States Food and Drug Administration in the past 4 years.

Background: A new approach to prevent disease recurrence in high-risk melanoma patients involves immunization with gp100 and tyrosinase peptides. This is the first study to examine the effects of such treatments on nevi. Design: We studied biopsies of ‘clinically atypical’ nevi from 10 patients before and after peptide vaccination. All had a cutaneous melanoma measuring at least 1.5 mm in depth, satellite metastases, or at least one positive lymph node. We performed immunohistochemical stains for CD3, CD4, CD8, MHC-I, MHC-II, CD1a, HMB-45, MART-1, tyrosinase, bcl-2, p53, and Ki-67 (mib-1). Results: Immunohistochemistry showed no differences in staining due to vaccination in either the immunologic or melanocytic markers. However, there was a significant increase in both p53 and bcl-2 staining, and a trend toward decreased Ki-67 staining, in the nevi post-treatment. Discussion: The primary goal of peptide vaccinations with gp100 and tyrosinase is to activate melanoma-specific T cells in order to prevent melanoma recurrence. Nevi were studied in order to assess the effects on benign melanocytes. No significant changes in lymphocytes, langerhans cells, expression of MHC antigens, or melanocytic markers were found. The increase in p53 and bcl-2 raises the possibility that vaccination with melanocytic antigens stimulates a response in benign melanocytes.

Kaposi sarcoma–associated herpesvirus (KSHV) infects endothelial cells within KS tumors, and these cells express the KSHV latent-cycle gene k-cyclin (kCYC) as well as vascular endothelial growth factor receptor 3 (VEGFR-3), a marker for lymphatic endothelium. To further understand KSHV-mediated pathogenesis, we generated transgenic mice expressing kCYC under the control of the VEGFR-3 promoter. kCYC mRNA and functional protein expression within tissue correlated with VEGFR-3 expression and were most abundantly detected within lung tissue. Clinically, most transgenic mice died within 6 months of age secondary to progressive accumulation of chylous pleural fluid. In skin, edema was detected by magnetic resonance imaging and mice demonstrated persistent erythema of the ears following trauma. Histologically, erythematous skin showed extravasation of erythrocytes and accumulation of erythrocytes within lymphatic lumens. In addition, lymphatic drainage of injected contrast dyes was markedly impaired in transgenic mice. Karyomegaly, a feature observed in kCYC-expressing cells in vitro, was detected in many tissues, and selectively occurred within lymphatic endothelial cells expressing kCYC mRNA by in situ hybridization. In summary, kCYC expression within VEGFR-3+ cells of mice causes marked impairment of lymphatic function. kCYC may contribute to the development of certain clinical and histologic features of KS, including localized edema and retention of extravasated erythrocytes within KS tumors.

Tumor spindle cells in all clinical types of Kaposi's sarcoma (KS) are infected with Kaposi's sarcoma-associated herpesvirus (KSHV). Although KSHV contains more than 80 genes, only a few are expressed in tumor spindle cells, including latency-associated nuclear antigen ( LANA ) and k-cyclin ( kCYC ). To assess the oncogenic potential of LANA and kCYC , primary human umbilical vein endothelial cells (HUVEC) and murine NIH 3T3 cells were stably transduced by using recombinant retroviruses expressing these genes or the known viral oncogene simian virus 40 large T antigen ( LTAg ). Interestingly, LANA -transduced HUVEC proliferated faster and demonstrated a greatly prolonged life span (mean ± standard deviation, 38.3 ± 11.0 passages) than untransduced cells and vector-transduced cells (kCYC -transduced HUVEC did not proliferate faster or live longer than control cells. LANA - and kCYC -transduced HUVEC, but not LTAg -transduced HUVEC, retained the ability to form normal vessel-like structures in an in vitro model of angiogenesis. In cellular assays of transformation, LANA - and kCYC -transduced NIH 3T3 cells demonstrated minimal or no anchorage-independent growth in soft agar and no tumorigenicity when injected into nude mice, unlike LTAg -transduced NIH 3T3 cells. Lastly, gene expression profiling revealed down-regulation, or silencing, of a number of genes within LANA -transduced HUVEC. Taken together, these results suggest that KSHV LANA is capable of inducing prolonged life span, but not transformation, in primary human cells. These findings may explain why LANA -expressing spindle cells proliferate within KS tumors, yet most often do not demonstrate biologic characteristics of transformation or true malignant conversion.

The plexiform spindle cell nevus (PLXSCN) is a distinct melanocytic lesion that often provokes concern for melanoma. We describe the features of 119 typical PLXSCNs and 9 atypical/high-grade lesions. Histologically, all cases had a fascicular plexiform architecture and were composed of predominately spindled cells. The 6 atypical plexiform spindle cell tumors (PLXSCTs) exhibited features such as greater mitotic activity, increased cellularity/nodular confluence, and more concerning cytological atypia. Three high-grade tumors (perhaps evolving plexiform spindle cell melanomas) had additional alarming clinical or histologic characteristics, such as patient age greater than 40 years, greater degree of cellularity, higher degree of cytological atypia, mitotic rate greater than 3/mm(2), regional lymph node metastases, and greater than 1 positive sentinel lymph node. Follow-up data were available for 18 typical PLXSCNs: all patients were without tumor recurrence or death in a mean follow-up period of 3.9 years (range, 1 month to 10 years). One atypical PLXSCT and 3 high-grade lesions had follow-up information: the atypical PLXSCT had sentinel lymph node involvement, and the patient was alive without recurrent disease at 1-year follow-up; 2 of the 3 high-grade lesions were positive for lymph node involvement, and all 3 patients were alive with 2-, 4-, and 0.8-year follow-up periods. All PLXSCTs should be completely excised with clear margins, and high-grade or potentially malignant lesions may require management as melanoma.

As previously recognized by various authors, "cutaneous ciliated cyst" is a confusing term. Typically, the term refers to rare cystic lesions, commonly found on the lower limbs of women in their reproductive years. To date, 40 cases diagnosed as "cutaneous ciliated cyst" have been reported in the literature. Histologically, the cysts are composed of a simple layer of ciliated columnar cells along with nonciliated columnar cells, cuboidal cells, and round "peg-like" cells, resembling fallopian tube epithelium. This histology has been described in cysts found in males and females and in locations other than the lower limbs. Controversy has thus arisen over the etiology of these lesions, with some believing that the cysts arise from heterotopic Mullerian rests and others advocating for ciliated metaplasia of eccrine glands. We herein describe the first case of cutaneous ciliated cyst of Mullerian origin occurring on the dorsal thumb of a 16-year-old female. A review of literature shows that 2 groups of cysts are covered under the umbrella term "cutaneous ciliated cysts." We thus propose the abandonment of the confusing term "cutaneous ciliated cyst" and the adoption of "cutaneous Mullerian cysts" for estrogen receptor/progesterone receptor-positive lesions resembling simple fallopian tube epithelium and "Cutaneous ciliated eccrine cyst" for estrogen receptor/progesterone receptor-negative lesions usually occurring in males, which are immunohistochemically compatible with an eccrine origin.

A significant proportion of patients seen by dermatologists have skin disease complicated by a psychiatric condition. These conditions often give rise to social, legal, and ethical concerns which impede the proper treatment of these patients, commonly involving the prescription of anti-psychotics for non-psychotic indications. This paper clarifies the social, legal, and ethical matters which frustrate the treatment and recovery of patients from their complex psycho-dermatologic disease. Specifically, this paper addresses the ethical and legal issues associated with prescribing anti-psychotics for non-psychotic indications. The presented data shows that the internationally prevalent medical practice of prescribing anti-psychotics for non-psychotic indications is not only ethical and legal, but also an essential treatment modality in the field of dermatology.

1Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA Antibodies against desmoglein proteins account for intraepidermal immunobullous disorders in the pemphigus family of diseases. Antibodies against desmoglein 3 are responsible for the blisters seen in patients with pemphigus vulgaris, whereas antibodies against desmoglein 1 lead to the more superficial separation seen in pemphigus foliaceus. Similar in both clinical and histologic features to pemphigus foliaceus (PF), an endemic form of the disease, fogo selvagem (FS) is found in high prevalence in certain regions of Brazil (Diaz et al., 1989). The endemic nature of the condition is thought to be precipitated by an immune response to an environmental antigen(s), currently not yet identified. This unique epidemiologic phenomenon provides researchers with an opportunity to study the differences between endemic and sporadic forms of this disease. In this issue of the Journal, Diaz et al. (2008) studied early immunologic responses among patients with FS to determine whether the IgM response differs from that seen in patients with the sporadic disease. In a comprehensive assessment of immune responses, they evaluated sera from patients with FS in rural endemic and urban areas of Brazil, patients with PF in the United States and Japan, and control subjects in these locations. Detection of desmoglein 1 IgM varied, with the highest levels (58%) in FS patients in endemic regions and control subjects (>50%) from the same areas. The desmoglein 1 IgM response was considerably lower (12–18%) in FS patients from urban areas of Brazil and still lower in patients from the United States (10%) and Japan (0%). Less variability was found in IgG responses in patients, with markedly lower responses in control subjects, apart from control subjects from rural areas of Brazil. The investigators hypothesize that an environmental agent responsible for the development of FS may cause an early IgM response that predates clinical disease. Through the following questions we will examine this paper in greater detail. For brief answers please refer to http:// network.nature.com/group/jidclub.

1Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA UV light is a major risk factor for skin cancer development (Essen and Klar, 2006). The mechanisms by which UV leads to cancer formation are complex and appear not to be limited solely to UV-induced DNA damage. UV induces immune suppression, which is associated with increased skin cancer formation, as evidenced by the increased cancer risk in immunosuppressed transplant patients (Bergstresser, 1983; Ulrich and Stockfleth, 2007). Therefore, protection against UV-induced immune suppression may have clinical benefits. In this issue, Damian et al. (2008) explore the potential role of topical nicotinamide in preventing UV immunosuppression in humans, based on animal models to prevent UV-induced immune suppression. Using volunteers with a positive Mantoux test (purified protein derivative positive from Bacille Calmette-Guerin vaccination), the authors studied the ability of topical nicotinamide to prevent UVB immune suppression and the mechanisms by which this occurred. They found that when nicotinamide was applied either before or after UV exposure (simulating normal sunlight exposure), the typically encountered immune suppression was reduced. Additionally, men were more sensitive to UV-light-induced immune suppression, which the investigators concluded may account, in part, for the greater incidence of skin cancer and skin cancer mortality in men. Nicotinamide did not work as a sunscreen but rather, as suggested by microarray analysis, as a mechanism that may include alterations in complement, energy metabolism, and apoptosis. Through the following questions we will delve into this paper in greater detail. For brief answers, please refer to http://network.nature.com/group/jidclub.