Two Cases of Angiosarcoma with Persistent Unilateral Eyelid Swelling.

Angiosarcoma is a widely known neoplasm with one of the poorest prognoses; however, such cases are rarely observed by the ophthalmologists in clinical practice. The tumor commonly develops on the face and scalp and may cause eyelid swelling. We present 2 such cases. Case 1 was an 82-year-old woman who presented with indulated swelling of the right eyelid that extended to the upper forehead. Biopsy revealed a poorly circumscribed tumor infiltrated throughout the dermis and fat tissue, exhibiting both angiomatous and solid patterns. Immunohistochemistry showed CD31(-) and D2-40/podoplanin(+), suggesting angiosarcoma. The patient had multiple lung metastases and died 14 months later. Case 2 was a 77-year-old man who presented with swelling of the left eyelid, and erythema on the left temporal skin developed ulcerated nodules. Biopsy showed proliferated tumor cells in a sheet form, extensively throughout the dermis. Angiosarcoma was preferred based on immunohistochemistry: CD31(+), CD34(+), and D2-40(-). The patient was treated with electron beam therapy and chemotherapy and died after 13 months. It would be difficult for an ophthalmologist to suspect such a rare neoplasm only from swelling of the eyelids. However, angiosarcoma should be considered if the swelling spreads steadily from a head rash with a nodule or ulcer nearby.

Efficacy of a novel phosphodiesterase inhibitor, E6005, in patients with atopic dermatitis: An investigator-blinded, vehicle-controlled study.

INTRODUCTION: Phosphodiesterase type 4 (PDE4) inhibition is a well-known anti-inflammatory mechanism. However, the clinical use of PDE4 inhibitors has been compromised by the occurrence of mechanism-associated adverse reactions, which often limit the maximum tolerated dose. To minimize systemic exposure, a topically active PDE4 inhibitor with low transdermal bioavailability could be clinically useful. The purpose of this study was to evaluate the efficacy of a novel topical PDE4 inhibitor, E6005, in patients with atopic dermatitis. METHODS: This randomized, investigator-blinded, vehicle-controlled, multiple ascending dose study included 40 adult male patients with atopic dermatitis, who were randomly assigned to 10 days of treatment with either E6005 ointment (0.01, 0.03, 0.1 or 0.2%) or vehicle ointment. RESULTS: Of 81 patients screened, 40 who had typical lesions on their posterior trunk were randomized into the study. One patient receiving 0.03% E6005 treatment discontinued because of acute gout and one receiving vehicle treatment discontinued because of progression of atopic dermatitis. The targeted lesion severity scores decreased in a concentration-dependent manner in patients treated with E6005. This drop was significant in the 0.2% E6005 ointment treatment group (mean percent change: -54.30%, p = 0.007). CONCLUSION: E6005 ointment showed anti-inflammatory efficacy in adult patients with atopic dermatitis.

Induction of cytotoxic T cells as a novel independent survival factor in malignant melanoma with percutaneous peptide immunization.

BACKGROUND: Malignant melanoma (MM) often shows multiple chemo-resistance, leading to poor prognosis of the patients. Therapeutic anti-cancer vaccination may be a feasible way to prolong the survival of patients. We have demonstrated that application of antigenic peptides via the tape-stripped, horny layer-removed skin, known as percutaneous peptide immunization (PPI), induces tumor cell-specific cytotoxic T lymphocytes (CTLs) in rodents and humans. OBJECTIVE: To evaluate clinical significance of PPI in advanced MM patients. METHODS: We performed PPI in 59 patients undergoing advanced MM with Melan-A, tyrosinase, MAGE-2, MAGE-3 and gp-100 peptides based on HLA typing in individuals. The induction of CTLs was assessed by the tetramer or pentamer flow cytometry in 35 patients. Patients showing positive CTL responses to all antigens were defined as complete responder (n=18), and those showing negative responses to at least one applied antigen were classified as incomplete responder (n=17). The primary endpoint of the study was overall survival (OS). For statistical analysis, log-rank test, univariate and multivariate Cox proportional hazard model were used. RESULTS: OS of the complete responders was longer than that of the incomplete responders (median survival time: 55.8 vs 20.3 months, log rank P=0.089). A hazard ratio for the complete responders relative to the incomplete responders was 0.23 (95% confidence interval: 0.06-0.93, P=0.039) in a multivariate Cox proportional hazard model. CONCLUSION: The induction of CTLs was a novel independent survival factor, and the induction of peptide-specific CTLs by PPI contributes to the prolonged survival and represents an impact on therapeutic approaches in MM. Unique trial number: UMIN000005706.

Skin wrinkling morphology changes suddenly in the early 30s.

BACKGROUND/PURPOSE: Does the morphology of wrinkles alter gradually with aging or suddenly at a certain age? On the basis of the theoretic wrinkle simulation of ideal skin, we have suggested that the wrinkle morphology suddenly changes from stratum corneum wrinkling to epidermis wrinkling; the former induces shallow fine furrows, and the latter induces deep prominent wrinkles. To examine the existence of drastic change in wrinkling morphology, we developed a new measurement system for facial skin wrinkling test. METHODS: The mechanical compression test of facial skin was carried out for 102 Japanese women aged 25-56 years. The test was performed on the right temple area skin, and the area of wrinkles induced by the compression was measured using a digital video camera. The rate of increase in wrinkle area during compression was defined as the skin wrinkling rate, and it was calculated for all subjects automatically by image processing. RESULTS: The test results showed that the skin wrinkling rate underwent a step increase at the age 33, which means that the wrinkling morphologies of young and old skins are completely different, and so it changes suddenly in the early 30s. CONCLUSION: A new skin measurement system was developed to validate our theory of wrinkle formation mechanism with aging. The results demonstrated the wrinkling morphology changes suddenly at early 30s.

[A case of polyarteritis nodosa successfully treated by rituximab].

A 47-year-old man was admitted to our hospital in January, 2006 because of a huge cutaneous ulcer in his lower limb. He was diagnosed with polyarteritis nodosa due to the cutaneous ulcer, mononeuritis multiplex, muscular pain, elevated serum CRP level and from histological findings of a skin biopsy. He was initially treated with 60 mg/day of prednisolone, followed by 1000 mg/day of intravenous cyclophosphamide (IVCY) therapy. In June, skin grafting to the cutaneous ulcer was carried out, although the graft did not survive. He revealed therapy-resistance to high dose corticosteroid and IVCY therapy, and so was treated with intravenous high dose immunoglobulin therapy. Serum CRP level then decreased and in October skin grafting was once again undertaken, this time the graft successfully survived. In December, serum CRP level increased again and cutaneous ulcer relapsed, thus he was treated with leukocyte apheresis therapy, although it was ineffective. In February 2007, he subsequently received rituximab (375 mg/m(2)/week x 3). Then, serum CRP level decreased rapidly, and cutaneous ulcer also improved. Recently the efficacy of rituximab against rheumatoid arthritis, systemic lupus erythematosus, polymyositis/dermatomyositis and ANCA-associated vasculitis has been recognized. This case suggests that rituximab is also effective against corticosteroid-resistant polyarteritis nodosa.

Excellent clinical results with a new preparation for chemical peeling in acne: 30% salicylic acid in polyethylene glycol vehicle.

BACKGROUND: Chemical peeling by salicylic acid in ethanol or another vehicle may be accompanied by stinging and burning followed by postinflammatory hyperpigmentation in the treated area, or salicylism. We have developed a new formulation: 30% salicylic acid in polyethylene glycol (SA-PEG). A topical application of SA-PEG remodels photodamaged skin in mice and humans, without systemic absorption. OBJECTIVE: The objective was to evaluate the safety and efficacy of SA-PEG for clinical use in the treatment of acne. MATERIALS AND METHODS: We evaluated the effects of the preparation histologically in mice and its safety and efficacy in 44 volunteers with normally aged skin and in 436 patients with acne. RESULTS: Histologic studies in animals showed no inflammatory changes in the skin following topical application of SA-PEG. Volunteers noted an improved skin texture. In the acne patients, the comedones and papules disappeared, resulting in an excellent outcome. There was a notable absence of stinging and burning, edema, bleeding, or crusting in the treated area. CONCLUSION: The SA-PEG preparation appeared to be safe and effective, with minimal associated inflammation or adverse effects, even in Asian patients who tend to develop hyperpigmentation or keloids. This preparation is thus ideal for chemical peeling.

Giant microcystic adnexal carcinoma of the scalp.

Microcystic adnexal carcinoma (MAC) is an uncommon, locally aggressive tumor. It typically involves the upper lip of middle-aged adults, and in rare instances the scalp. We report a Japanese woman with a giant MAC on the scalp. Physical examination revealed a 110 mm x 120 mm induration on her parietal region. Microscopically, the tumor showed both pilar and sweat gland differentiation. Resection included the cranium; for reconstruction we used a titan mesh allograft and covered it with a free latissimus dorsi muscle flap and a mesh skin graft. Ours is the first case of a MAC measuring more than 100 cm2 arising on the scalp of an individual in the third decade of life.

Introduction of tyramide signal amplification (TSA) to pre-embedding nanogold-silver staining at the electron microscopic level.

The tyramide signal amplification (TSA) technique has been shown to detect scarce tissue antigens in light and electron microscopy. In this study we applied the TSA technique at the electron microscopic level to pre-embedding immunocytochemistry. This protocol was compared to the non-amplified protocol. With the TSA protocol, the labeling of GM130, a cis-Golgi matrix protein, was tested in a cell line and found to be highly sensitive and more enhanced than that with the simple protocol. Moreover, the gold particles were well localized to the cis-side of the Golgi apparatus in both the TSA and the simple protocol.

Clinicopathologic differences between 22 cases of CD56-negative and CD56-positive subcutaneous panniculitis-like lymphoma in Japan.

CD56 is an important marker for prospecting clinicopathologic features of cytotoxic T-cell and natural killer (NK)/T-cell lymphomas. We examined 22 cases of subcutaneous panniculitis-like lymphoma and classified these into CD56-positive and CD56-negative groups. The 11 CD56-negative cases were mainly in the younger age group and had systemic subcutaneous nodules without ulceration. They exhibited subcutaneous invasion by medium-sized lymphoma cells, scattered erythrophagocytosis, patchy necrosis, and little tumor invasion in the superficial dermis. Their lymphoma cells had characteristics of CD3 epsilon-, CD8-, TcR beta F1-, T-cell intracellular antigen (TIA)1-, and granenzyme B-positive cytotoxic T cells and were negative for apoptosis-promoting proteins CD95 (Fas), Bax, CPP32 (caspase 3), and p53 (DO7). Ten patients were alive despite clinical signs of hemophagocytic syndrome and relapses in 7 cases. The 11 CD56-positive cases had systemic ulcerative skin tumors composed of pleomorphic lymphoma cells with massive necrosis and little erythrophagocytosis involving the subcutis and also often the whole dermis. Their tumor cells were positive for CD3 epsilon, TIA1, granenzyme B, CD95, CD95L (Fas ligand), Bax, and CPP32. Three cases were of the TcR beta F1-positive phenotype, 1 was of the TcR gamma/delta-positive T-cell phenotype, and 6 were of the TcR beta F1- and TcR gamma/delta-negative NK/T-cell phenotype. Six cases were p53 (DO7) positive. Seven cases had complications of liver dysfunction and cytopenia, and 8 died of disease. One CD56-negative case and 3 CD56-positive cases had nuclear signals of Epstein-Barr virus-encoded RNA in their lymphoma cells. The 2 groups had significantly (P <0.01) different prognoses by Kaplan-Meier and log-rank methods. Patients with CD56-negative and CD56-positive groups had statistically different clinicopathologic, immunohistologic, and functional findings and prognoses.

Clinicopathologic analysis of 22 cases of subcutaneous panniculitis-like CD56- or CD56+ lymphoma and review of 44 other reported cases.

In 22 histologic cases of subcutaneous panniculitis-like lymphoma, we studied the clinicopathologic differences between CD56- and CD56+ cases (11 each). CD56- cases had skin ulcers (1 [9%]); tumor invasion in the superficial dermis (1 [9%]); erythrophagocytosis (10 [91%]); and medium-sized (11 [100%]), CD8+ (10 [91%]), T-cell receptor (TcR)betaF1+ (10 [91%]), and CD95 (Fas)- tumor cells. CD56+ cases had skin ulcers (9 [82%]); tumor invasion in the superficial dermis (8 [73%]); erythrophagocytosis (1 [9%]); and pleomorphic large (10 [91%]), CD8+ (2/10 [20%]), TcRbetaF1 + (3/10 [30%]), and CD95 (Fas)+ (7/10 [70%]) tumor cells. These 7 factors were significantly different between groups (P < .01). Median survival rates were 96 and 12 months for the CD56- and CD56+ groups, respectively. Age younger than 40 years, no skin ulcers, no tumor invasion in the superficial dermis, and CD8+, TcRbetaF1 +, CD95 (Fas)-, and CD56- tumor cells were significantly better prognostic factors (P < .01). The CD56- and CD56+ groups showed different tumor cell characteristics, clinicopathologic findings, and prognosis. In the CD56+ group, 1 was gamma/delta T-cell phenotype, 3 were alpha/beta T-cell, and 6 were TcRbetaF1- and gamma/delta- NK/T-cell, and 3 NK/T-cell cases had nuclear signals of Epstein-Barr virus-encoded RNA. Cases of CD56+ T- and NK/T-cell lymphoma had similar clinicopathologic findings and prognosis.

Activation of bacterial ceramidase by anionic glycerophospholipids: possible involvement in ceramide hydrolysis on atopic skin by Pseudomonas ceramidase.

We have reported previously that the ceramidase from Pseudomonas aeruginosa AN17 isolated from a patient with atopic dermatitis requires detergents for hydrolysis of ceramide (Cer) [Okino, Tani, Imayama and Ito (1998) J. Biol. Chem. 273, 14368--14373]. In the present study, we report that some glycerophospholipids strongly activated the hydrolysis of Cer by Pseudomonas ceramidase in the absence of detergents. Among the glycerophospholipids tested, cardiolipin was most effective in stimulating hydrolysis of Cer followed by phosphatidic acid, phosphatidylethanolamine and phosphatidylglycerol, whereas phosphatidylcholine, lysophosphatidic acid and diacylglycerol were less effective. Interestingly, Staphylococcus aureus-derived lipids, which contain cardiolipin and phosphatidylglycerol as major lipid components, also strongly enhanced the hydrolysis of normal Cer, as well as the human skin-specific omega-hydroxyacyl Cer, by the enzyme in the absence of detergents. It was confirmed that several strains of P. aeruginosa, including AN17, secrete a significant amount of staphylolytic proteases to lyse S. aureus cells, resulting in the release of cardiolipin and phosphatidylglycerol. Since both P. aeruginosa and S. aureus are suspected of being present in microflora of atopic skin, we speculate that S. aureus-derived glycerophospholipids stimulate the hydrolysis of Cer in atopic skin by bacterial ceramidase.