The Effect of Imiquimod on Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Malignant Melanoma Cell Invasion

BACKGROUND: A number of reports have been published regarding the use of imiquimod for the treatment of melanoma in situ and metastatic melanoma. Essential steps in the process of melanoma invasion and metastasis include degradation of basement membranes and remodeling of the extracellular matrix by proteolytic enzymes, including matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). OBJECTIVE: To evaluate the antiinvasive effect of imiquimod in human malignant melanoma cell lines, SK-MEL-2 and SK-MEL-24, in vitro, and to investigate imiquimod-induced changes in the expression of MMPs and TIMPs. METHODS: Invasiveness of melanoma cell lines following imiquimod treatment was evaluated by invasion assays. In order to investigate the mechanism of the anti-invasive effect of imiquimod, mRNA and protein levels of MMP-2, -9, membrane type 1 (MT1)-MMP, TIMP-1, and -2 were assessed by real-time reverse transcription-polymerase chain reaction, gelatin zymography, and western blotting. RESULTS: Imiquimod treatment decreased in vitro viability of melanoma cells in a concentration-dependent manner. Imiquimod also elicited a concentration-dependent suppression of invasion in both melanoma cell lines. A concentration-dependent decrease in MMP-2 and MT1-MMP protein levels and a concentration-dependent increase in TIMP-1 and -2 protein levels by imiquimod was observed in both melanoma cell lines. However, expression of MMP-9 protein was increased in SK-MEL-2 but decreased in SK-MEL-24 with increasing imiquimod concentrations. Imiquimod elicited alterations in MMPs and TIMPs mRNA levels that parallel the observed changes in protein levels. CONCLUSION: Imiquimod may elicit an anti-invasive effect on human melanoma cells by regulating MMPs and TIMPs.

A Case of Pseudolymphoma Syndrome Induced by Vancomycin / 대한피부과학회지

We report here on a case of a patient who experienced fever, skin eruption and lymphadenopathy 1 month after the beginning of vancomycin treatment. Generalized mild pruritic erythematous pin-head to rice-grain sized confluent scaly papules and plaques appeared on the whole body. Skin biopy showed the characteristic findings of pseudolymphoma mimicking mycosis fungoides. The skin lesions and general symptoms improved after discontinuation of vancomycin and starting steroid therapy. The patient was diagnosed with pseudolymphoma syndrome due to vancomycin. Pseudolymphoma syndrome shows clinical features that are different from those of usual drug eruptions, and the histologic findings are similar to mycosis fungoides. Thus, a thorough understanding of the clinical and histologic features of this entity may aid making a diagnosis, establishing treatment plans and determining the prognosis.

The Inhibitory Effect of Phytoclear-EL1 on Melanogenesis

BACKGROUND: Phytoclear-EL1, an extract from Euphorbia lathyris seeds, has a whitening effect due to inhibition of tyrosinase activity. OBJECTIVE: The purpose of this study was to investigate the inhibitory effect of phytoclear-EL1 on melanogenesis. METHODS: Cultured B-16 melanoma cells and 30 human volunteers were used for in vitro and in vivo studies, respectively. Phytoclear-EL1 was added to the cultured B-16 melanoma cells, and applied to UVB-induced hyperpigmented lesions of human volunteers twice daily for 7 weeks. Changes in the number of B-16 melanoma cells, as well as changes in morphology, melanin content, and tyrosinase activity, were measured and then compared with the normal control and the 10(-3)M arbutin groups. Also, the effect of phytoclear-EL1 on UVB-induced hyperpigmented lesions was examined through subjective and objective measurements. RESULTS: In the in vitro study (p<0.05), the number, melanin content, and tyrosinase activity of cultured B-16 melanoma cells were decreased in the 5microgram/ml phytoclear-EL1 group compared to the control group. On objective assessment with a chromameter, the 0.2% phytoclear-EL1 group had a larger difference in the mean L values before and 7 weeks after applying phytoclear-EL1 as compared to the other groups. On subjective assessment by both the researchers and subjects 7 weeks after applying experimental materials, the 0.2% phytoclear-EL1 group and positive control (3% arbutin) had higher scores than the placebo groups. These results demonstrated that phytoclear-EL1 in vivo and in vitro had an inhibitory effect on melanogenesis. CONCLUSION: Phytoclear-EL1 may be a candidate extract in the control of hyperpigmentary disorders.

A Case of Primary Cutaneous Anaplastic Large Cell Lymphoma Mimmicking Keratoacanthoma / 대한피부과학회지

Pseudoepitheliomatous hyperplasia with a massive neutrophil infiltrate associated with primary cutaneous anaplastic large cell lymphoma has been rarely reported. Herein we report on a 33-year-old man who presented with multiple asymptomatic erythematous walnut-sized rapidly growing tumors on the axilla, trunk and left inguinal area for 1 month. The histopathologic features showed a keratoacanthoma-like epithelial hyperplasia in the epidermis and several large atypical lymphoid cells with nuclear plemorphism and abundant cytoplasm in the dermis. The atypical cells were obscured by a rich infiltrate of neutrophils and some eosionophils. Immunohistochemical studies confirmed the majority of the large anaplastic cells in the dermis were CD30+ cells. In addition, the expressions of anaplastic lymphoma kinase (ALK) and epithelial membrane antigen (EMA) were negative. There was no evidence of extracutaneous involvement. The patient was diagnosed with primary cutaneous anaplastic large cell lymphoma (ALCL) and he was treated with low dose methotrexate (15 mg/week). We think that this case was challenging both clinically and histologically.

The Clinical Behavior, Histopathologic Observation and Follow-up of Bowenoid Papulosis / 대한피부과학회지

BACKGROUND: Bowenoid papulosis occurs primarily on the genitalia of young adults and this is characterized by multiple, apparently benign maculopapular lesions. Bowenoid papulosis shows the histopathological findings of a squamous cell carcinoma in situ, but it follows a largely benign clinical course. If it is misdiagnosed as malignant tumor, unnecessary excessive therapy may be performed. Therefore, exact recognition of this entity is important. OBJECTIVE: The purpose of this study is to examine the clinical and histopathologic features and outcomes of Bowenoid papulosis. METHODS: Twelve patients who had been diagnosed with Bowenoid papulosis between June 1996 and September 2007 were reviewed clinicopathologically. RESULTS: The mean age of the patients was 34.8 years (range: 23~57 years), and the mean duration of Bowenoid papulosis until presentation was 6.3 months (range: 5~48 months). Nine patients were males and 3 patients were females. Eleven patients (92%) had multiple lesions. The average size of the individual lesions was 1.4x0.6 cm in diameter. The colors of the papules were red to black. Seven of 9 male patients had lesions on the penile shaft, with 6 of those occurring at the proximal shaft. The other 2 male patients had lesions on the scrotum and perianal area, respectively. Three female patients had lesions on the labium major, labium major and clitoris, and perianal area respectively. Nine patients (75%) presented without symptom and 3 (25%) presented with mild pruritus. The histopathologic features were as follows: a rete ridge of approximately equal length and breadth throughout the entire lesion (100%), skipped areas of normal keratinocytes between zones of atypical keratinocytes (100%). necrotic keratinocytes (92%), parakeratosis (83%), mitotic figures (83%), vacuolated cells resembling owl's eyes (83%), multinucleated cells (67%), residual changes of typical condyloma acuminatum (17%), involvement of acrotrichia (100%) and involvement of acrosyringia (100%). Eleven patients were effectively treated with surgical excision (8 patients), CO2 laser (2 patients), diphenylcyclopropenone (DPCP) and immunotherapy (1 patient) and 1 patient underwent biopsy only. We followed 12 patients for an average 78.1 months (from 24 to 137 months). During this period, no recurrence or malignant transformation was observed. CONCLUSION: Bowenoid papulosis shows a form of squmaous cell carcinoma in situ for its histopathology, but it hardly ever progresses to squmaous cell carcinoma. On our long term follow-up, there was no malignant transformation. Thus, excessive treatment of Bowenoid papulosis by amputation of the external genitalia is not necessary. Therefore, a through understanding of the clinical and histopathologic features of this entity is necessary for making the diagnosis, the treatment planning and determining the prognosis.

High Dose UVA-1 Phototherapy for Morphea / 대한피부과학회지

Morphea is a rare, sclerotic connective tissue disorder and is thought to be caused by a decreased collagenase activity. Numerous treatment modalities have been tried, such as infiltration with glucocorticosteroid, D-penicillamine, antimalarial agents and cyclosporine. However, all have shown only limited success. We report a case of a 21 year- old female with localized scleroderma, who showed a marked improvement after localized therapy with high dose UVA-1.

A Case of Lichen Planus Limited to the Soles / 대한피부과학회지

Palmoplantar lichen planus is a rare, localized variant of the disease that may create difficulty in diagnosis if it is present as an isolated finding. As palmoplantar lichen planus do not usually have the classically clinical features of lichen planus, a biopsy is very useful. Histopathologic findings are identical to classic lichen planus. According to literature, similar lichen planus may be found elsewhere on the body in palmoplantar lichen planus. We report a case of lichen planus limited to the soles in a 50 year-old female, who presents with erythematous hyperkeratotic crusted pruritic plaques on both soles.

A Case of Granulocyte Colony-stimulating Factor InducedVasculitis with Atypical Myeloid Cells / 대한피부과학회지

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor (HGF) with many applications in cancer therapy. Many cutaneous adverse reactions associated with G-CSF have been reported in recent years, including injection site reactions, pyoderma gangrenosum, Sweet's syndrome, cutaneous leukocytoclastic vasculitis, and widespread folliculitis. We report a case of vasculitis with atypical myeloid cell induced by G-CSF on the lower extremities