Langerhans cell sarcoma with lineage infidelity/plasticity: a diagnostic challenge and insight into the pathobiology of the disease.

Langerhans cell sarcoma is a very rare and aggressive tumor of Langerhans cell lineage, for which aberrant expression of T-cell-related antigens has not yet been reported in a primary skin tumor. The authors describe the first known case of a primary cutaneous Langerhans cell sarcoma with lineage infidelity and use comparative genomic hybridization to investigate the genetic composition of the tumor and detect DNA copy number alterations throughout its entire genome. The case involves a 62-year-old woman who presented with an irregular nodule on the forehead surrounded by smaller lesions in its vicinity. The clinical impression was melanoma with satellitosis. The biopsy specimen showed an epidermotropic tumor with moderate-to-marked cellular pleomorphism and significantly increased mitotic rate but no necrosis. The immunoprofile of the lesion was remarkable, as next to common Langerhans cell markers: Langerin, CD1a, S100, and CD4; it also exhibited an aberrant T-cell phenotype with the expression of CD2, CD3, and CD43. In addition, fascin and CD30 were also expressed, further exaggerating potential diagnostic pitfalls. Langerhans cell lineage was confirmed by the demonstration of characteristic Birbeck granules on electron microscopy. Whole genome analysis for copy number changes and loss of heterozygosity showed a complex karyotype with variable hyperdiploidy and numerous allelic imbalances. Significant findings included a homozygous deletion at 9p21 involving the CDKN2A and loss of heterozygosity at 17p involving TP53 gene, coupled with a TP53 missense mutation. Despite reexcision and multiagent systemic chemotherapy, the patient died of metastasis 2 years after diagnosis. This case is an outstanding example of lineage infidelity in a hematologic malignancy and the utilization of comparative genomic hybridization in characterizing its genetic abnormalities.

Hemorrhagic acneiform lesions in a teenager as the initial presentation of granulomatosis with polyangiitis.

A 19-year-old girl presented with hemorrhagic acneiform lesions on the face for several months that was unresponsive to conventional acne treatment. A biopsy revealed a noninfectious suppurative granulomatous dermatitis with hemorrhage, possibly representing a ruptured folliculitis. A second biopsy revealed chronic granulomatous dermal inflammation and hemorrhage with foreign body giant cells non-infectious by stains. No vasculitis was noted in either biopsy. Later in her course she developed a severe sinusitis and eventually presented with severe fevers, rapid weight loss, sinusitis, and cough. Further workup produced the diagnosis of granulomatosis with polyangiitis (Wegener's granulomatosis). She rapidly improved with intravenous steroids and rituximab. To date, acneiform lesions have only been reported in young adult patients and may represent a clinical manifestation of granulomatosis with polyangiitis unique to this age group, as illustrated in our patient.

Pityriasis Lichenoides-Like Mycosis Fungoides: A Case Report.

A rare subtype of mycosis fungoides (MF) known as pityriasis lichenoides-like mycosis fungoides (PL-like MF) manifests as recurrent crops of erythematous scaly papules with the histological findings of MF. We report a 64-year-old male with recurrent crops of psoriasiform papules with mild scales on his trunk and extremities. Skin biopsy results were consistent with CD8+ cutaneous T-cell lymphoma (CTCL). Our patient had clinical features of pityriasis lichenoides and histological findings consistent with CD8+ MF. A differential diagnosis of PL, lymphomatoid papulosis (LyP), and PL-like MF was considered. Counseling patients with CD8+ cutaneous T-cell lymphoma can be challenging, as there is an aggressive variant named primary cutaneous aggressive epidermotropic CD8+ CTCL. However, with the ability to recognize PL-like MF, a rare indolent type of CD8+ CTCL, physicians can counsel patients appropriately.

Open label study to evaluate the efficacy of re-treatment with etanercept in patients with psoriasis.

BACKGROUND: Etanercept has been used to treat chronic plaque psoriasis. Previously reported data demonstrated that some patients experienced secondary failure and frequently rotational-switch therapy is used. The re-treatment with etanercept as part of the rotational therapy could be considered as another safe and efficient therapeutic approach. OBJECTIVE: To evaluate the efficacy of the re-treatment with etanercept in patients with a history of etanercept use with good response and secondary loss of efficacy. METHODS: This is an open label prospective study involving 20 patients with moderate to severe plaque psoriasis, who had been initially treated with etanercept and were re-treated after a variable interval with 50 mg BIW for 12 weeks. RESULTS: At week 12 of etanercept re-treatment, 13 of 20 patients (65%) achieved a PGA score of 2 or less and 40% (8 of 20), achieved a PGA score of 0 to 1. Etanercept was well tolerated and no serious adverse events were reported. LIMITATIONS: Our study involved a small number of patients. Failure of etanercept was establish by patient's history. However we were able to correlate such failure from our medical records in 17 patients. CONCLUSIONS: Re-treatment with etanercept, after secondary loss of efficacy should be considered in patients with psoriasis if satisfactory therapy cannot be achieved with other therapeutic regimens.

Histopathologic analysis of dermal lymphatic alterations in chronic venous insufficiency ulcers using D2-40.

BACKGROUND: Chronic venous insufficiency (CVI) ulcers represent a major medical problem worldwide. Current theories concerning the pathogenesis of CVI ulcers focus on abnormalities in the blood vascular system. Other abnormalities, such as chronic leg edema, may also play pathogenic roles in CVI ulcer development and further understanding of such alterations may lead to better treatments. OBJECTIVE: To gain insight into lymphatic abnormalities occurring in CVI, we compared dermal lymphatics in histologic sections from CVI ulcers and normal controls. METHODS: We compared global and architectural features of dermal lymphatics in D2-40-stained histologic sections from CVI ulcer tissue and from normal controls. D2-40 recognizes podoplanin, a transmembrane glycoprotein that is constitutively expressed in lymphatic endothelial cells, allowing us to distinguish dermal blood vessels from lymphatic vessels. RESULTS: Our analyses reveal that CVI ulcer specimens have more dermal lymphatic vessels per unit area than controls (5.71 vs 4.08 per mm(2), respectively; P = .0281); a higher percentage of lymphatic vessels with collapsed lumina compared with controls (30.5% vs 8.1%, respectively; P < .0001); and a higher percentage of competent lymphatic vessels displaying open inter-endothelial junctions compared with controls (5.7% vs 2.9%, respectively; P < .0369). LIMITATIONS: Our study is limited by its retrospective nature and relatively small sample size. CONCLUSIONS: Lymphatic vessels in CVI ulcer specimens display global and architectural differences compared with lymphatic vessels in control specimens. These findings further implicate lymphatic dysfunction in the pathogenesis of CVI ulcers and allow for the formulation of a hypothesis concerning lymphatic changes that may be tested in future studies.

Cutaneous fusariosis developing in a post-irradiation site.

Cutaneous fusariosis is an opportunistic mycosis in immunocompromised patients. We present a novel variation of an immunocompromised patient who developed fusariosis in a previously irradiated site. Irradiation led to atrophy, contraction, fibrosis, barrier disruption, and an altered dermal environment in which the infection developed. Significantly, this is the first case report of fusariosis in a previously irradiated site of an immunocompromised patient. Treatment included debridement and voriconazole.

Etanercept: an evolving role in psoriasis and psoriatic arthritis.

Tumor necrosis factor alpha (TNFalpha) plays a key pathophysiological role in psoriasis and psoriatic arthritis (PsA). Recent interest has thus focused on the clinical potential of TNFalpha antagonists (e.g. etanercept) in these settings. In psoriasis, several large pooled analyses and well-designed clinical trials documented the significant clinical efficacy and generally favorable tolerability of etanercept for up to 96 weeks. Similarly, in PsA, a large phase III trial showed that, etanercept significantly reduced arthritic symptoms and inhibited radiographic disease progression; sustained clinical benefit was again evident for up to 2 years. Etanercept is at the forefront of psoriatic disease management, and continued evolution and evaluation of the compound - for example, in detailed comparative studies and economic analyses - is likely to confirm a key role for etanercept in the treatment of psoriasis and PsA.

Use of tissue-engineered skin to study in vitro biofilm development.

BACKGROUND: Biofilms are aggregations of microorganisms that have been identified as potential pathogens in the chronicity of nonhealing wounds. OBJECTIVE To develop an in vitro wound model to study biofilms using Graftskin, a tissue-engineered skin equivalent. MATERIALS AND METHODS: Graftskin constructs were divided into sections, and wounds were created on each section. Bacterial suspensions with a concentration of 10(6) CFU/mL were prepared from cultures of pathogenic isolates of Pseudomonas aeruginosa and Staphylococcus aureus. A 25-microL aliquot of each suspension was deposited in the center of wounds created on the Graftskin. Sections were incubated at various time points, and a biopsy was then taken from the wounded and inoculated area. Sections were visualized with light (hematoxylin and eosin) and epifluorescent microscopy (calcofluor white and ethidium bromide). RESULTS Biofilm was observed on the wound model. Biofilm formation was dependent on time of Graftskin exposure to the bacteria. Biofilm was visualized in the S. aureus group at an earlier time point than in the P. aeruginosa group. CONCLUSIONS: We demonstrated biofilm formation in vitro using a wound model. This model may provide a basis on which future studies may explore therapeutic modalities to prevent and eradicate pathogenic bacterial biofilm. The authors have indicated no significant interest with commercial supporters.

A rare case of a cutaneous squamomelanocytic tumor: revisiting the histogenesis of combined neoplasms.

We describe what we believe to be the seventh report of a combined tumor with histologic features of both malignant melanoma and a squamous cell carcinoma, a squamomelanocytic tumor. An 82-year-old woman presented with a nondescript, skin-colored, firm papule on her nose. Histology showed 2 different neoplastic cell proliferations: atypical squamoid cells and irregularly shaped nests of atypical pigmented epithelioid cells (melanocytes) arranged in small to large nests at the dermal-epidermal junction and within the epidermis. Both components were closely admixed and restricted to the epidermis. Immunohistochemistry showed diffuse cytoplasmic reactivity for pancytokeratin in all areas supporting the histopathologic features of a squamous cell carcinoma. S-100 and melanoma antigen recognized by T cells 1 did not stain these areas and showed strong selective positivity for the atypical melanocytic component. A true malignant proliferation of 2 distinct cell phenotypes due to close paracrine interactions is our favored interpretation because of the intimate admixture, distinct immunohistochemical pattern, and unique histologic features. Perhaps, chronic sun damage (facial location and advanced age) and reduced immunity (history of other malignancies, particularly recent history of a basal cell carcinoma) played a complementary role for the development of the squamomelanocytic tumor.

Microscopic and physiologic evidence for biofilm-associated wound colonization in vivo.

A biofilm is a collection of microbial cells that are attached to a surface and embedded in a self-produced extrapolymeric substance. The understanding of the biofilm phenotype is important in the understanding of bacteria in vitro but it has been difficult to translate biofilm science to the clinical setting. More recently, preliminary criteria for defining biofilm associated diseases have been proposed and the purpose of this study was to create a biofilm-associated wound model based on these criteria. Using a porcine model, partial thickness wounds were inoculated with a wound isolate Staphylococcus aureus strain. Wounds were then treated with either one of two topical antimicrobial agents (mupriocin cream or triple antibiotic ointment) within 15 minutes to represent planktonic bacteria or 48 hours after initial inoculation to represent biofilm-associated wound infection. Using light microscopy, scanning electron microscopy and epifluorescence microscopy, we were able to observe biofilm-like structures in wounds after 48 hours of inoculation and occlusion. The in vivo antimicrobial assay was used to demonstrate that both mupirocin cream and the triple antibiotic ointment were effective in reducing planktonic S. aureus but had reduced efficacy against biofilm-embedded S. aureus. Our results demonstrated that S. aureus form firmly attached microcolonies and colonies of bacteria encased in an extracellular matrix on the surface of the wounds. These biofilm-like communities also demonstrated increased antimicrobial resistance when compared with their planktonic phenotype in vivo. The structural and physiological results support the hypothesis that bacterial biofilms play a role in wound colonization and infection.

A pilot study to determine the safety and efficacy of monochromatic excimer light in the treatment of vitiligo.

BACKGROUND AND OBJECTIVE: According to a European pilot study, the 308-nanometer (nm) Excilite mu (DEKA, Florence, Italy) system may be a promising tool for patients with vitiligo by offering targeted phototherapy, a rapid onset of repigmentation, and few adverse effects. The objective of this study was to evaluate the clinical efficacy and safety of the 308-nm Excilite mu in the treatment of vitiligo. METHODS AND LIMITATIONS: Ten patients with stable vitiligo were exposed to 10 weeks of targeted phototherapy with the Excilite mu device, followed by 5 weeks of observation. Skin types 1 and 2 were not included in the cohort, and Wood's light examination was not documented. RESULTS: At 2 weeks, repigmentation was observed in 60% of the subjects, according to patient assessment, and 50% of the subjects, according to the treating physician and independent observer assessments. All patients maintained the repigmentation during the 5-week, follow-up period. CONCLUSION: The 308-nm Excilite mu is a safe and fast-acting therapeutic option in patients with stable vitiligo and skin types 3 through 6.

CD4+/CD56+ Hematodermic neoplasm (plasmacytoid dendritic cell tumor).

A 60-year-old male presented with multiple, purplish-red, nodules and plaques. After a complete work-up, he was diagnosed with CD4+/CD56+ hematodermic neoplasm. We review the clinical, pathological, and immunohistochemical features of this disease. CD4+/CD56+ hematodermic neoplasm, which is also known as blastic natural killer-cell lymphoma, is a rare, aggressive neoplasm with a strong predilection for skin involvement.

Foreign body granuloma formation secondary to silicone injection.

Injectable silicone has been used extensively over the last 40 years for soft tissue augmentation. Although considered biologically inert, this material has been implicated in a variety of adverse reactions including granulomas, disfiguring nodules, and lymphedema, sometimes with latent periods of decades. Often these complications are a result of the use of industrial grade products injected by unlicensed or unskilled practitioners. Here we report a case of foreign body granuloma in the thigh secondary to silicone injection in the buttocks. Initially the patient did not disclose a cosmetic contouring procedure administered by a nonprofessional nine months earlier, making diagnosis difficult. We remind clinicians to include foreign body granulomas in the differential diagnosis of apparent cellulitis and to question patients about the use of injectable fillers.

Topical oxygen emulsion: a novel wound therapy.

OBJECTIVE: To investigate the use of a topical oxygen emulsion (TOE), consisting of a supersaturated oxygen suspension using perfluorocarbon components, on second-degree burns and partial-thickness wounds. DESIGN: Oxygen is a required substance for various aspects of wound repair, and increased oxygen tension in a wound has been shown to stimulate phagocytosis and to reduce the incidence of wound infection. Second-degree burns and partial-thickness wounds were created on the backs of specific pathogen-free pigs. Wounds were then randomly assigned to 1 of the following treatment groups: TOE, TOE vehicle, or air-exposed control. MAIN OUTCOME MEASURE: Wounds were assessed for complete epithelialization using a salt-split technique. RESULTS: The TOE was able to significantly (P = .001) enhance the rate of epithelialization compared with both vehicle and untreated control. These data suggest that topical oxygen may be beneficial for acute and burn wounds. CONCLUSIONS: The results obtained from this double-blind, control, in vivo study demonstrate that TOE can significantly enhance the rate of epithelialization of partial-thickness excisional wounds and second-degree burns. These findings could have considerable clinical implications for patients with surgical and burn wounds by providing functional skin at an earlier date to act as a barrier against environmental factors, such as bacteria invasion. Other types of wounds may also benefit from this therapy (eg, chronic wounds and surgical incisions). Additional studies, including clinical studies, are warranted.

Subacute annular generalized pustular psoriasis treated with etanercept and cyclosporine combination.

We present a case of a 36-year-old man with a 20-year history of stable plaque psoriasis admitted to our inpatient dermatology unit with subacute annular pustular psoriasis. Two weeks prior to admission the patient's dermatologist discontinued the use of 5 lbs (2.3 kg) of triamcinolone 0.1% cream, which the patient had been applying to his skin weekly over the last 8 years. The patient subsequently developed generalized erythematous annular and irregularly shaped, well-defined plaques and confluent pustules. Approximately 80% of his total body surface area was involved, sparing the face and the genitals. Initial therapy included cyclosporine 300 mg twice daily, topical hydrocortisone 1% ointment to affected areas, acetaminophen/oxycodone 10/325 mg every 4 hours for pain as needed, and subcutaneous etanercept 50 mg twice weekly. The patient was discharged on day 7 with significant improvement of skin lesions. On discharge the cyclosporine was increased to 400 mg twice daily. The patient continued etanercept 50 mg twice weekly. One month after discharge the patient was clear with only postinflammatory changes.

The incidence of recurrent herpes simplex and herpes zoster infection during treatment with arsenic trioxide.

We report the incidence of varicella zoster virus (VZV) and herpes simplex virus (HSV) infection in patients with multiple myeloma and colon cancer who were treated with arsenic trioxide for their disease. In this report, we discuss the effects of arsenic on immune system, and suggest arsenic compounds as a possible predisposing factor for viral reactivation in these patients.