PD-1 and PD-L1 expression in Kaposi sarcoma: A comparative study according to the pathological stage and clinical characteristics.

BACKGROUND: Kaposi sarcoma (KS) is a mesenchymal tumor with distinct histopathological features according to stage of progression. Programmed death-1 (PD-1) and its ligand PD-L1 play major roles in the immune escape strategy of tumors. OBJECTIVES: This study evaluated expression of PD-1 and PD-L1 in various stages of KS and investigated associations between their expression and clinical characteristics. METHODS: Fifty cases with histopathologically diagnosed KS were classified as early or late stage. These specimens were stained with anti-PD-1 and anti-PD-L1 antibodies. The extent of expression in the intratumoral and peritumoral areas was judged by two dermatopathologists. RESULTS: PD-1 and PD-L1 were expressed in 72.2% (13/18) and 11.1% (2/18) of early-stage cases, respectively, compared with 43.8% (14/32) and 28.1% (9/32) of late-stage cases, respectively. At the late stage, PD-1 expression was significantly higher in the peritumoral area than in the intratumoral area (P = 0.001). PD-1 expression in the intratumoral area was significantly higher at the early stage than at the late stage (P = 0.013). PD-L1 expression in the peritumoral area was significantly higher at the late stage than at the early stage (P = 0.038). CONCLUSIONS: The pattern of PD-1 and PD-L1 expression differs according to the stage of KS, but is unaffected by clinical variables.

Inflammatory features and rete ridge patterns of facial solar lentigo may guide laser treatment.

Relatively little is known about the clinicopathological characteristics of solar lentigo (SL), rendering the choice of laser treatment a clinical challenge. This study compared the clinicohistopathological characteristics of patients with SL on the face with and without conspicuous inflammation. The medical records were evaluated to determine the clinical and histopathological characteristics. Based on the degree of histopathologically observed inflammation, the patients were divided into two groups, those with inflammatory and noninflammatory SL. The demographic characteristics of patients in the inflammatory (n = 62, 62.6%) and noninflammatory groups (n = 37, 37.4%) did not differ significantly. Lesion duration was shorter, and the proportion of patients whose lesions changed within 6 months was higher in the inflammatory than in the noninflammatory group. The mean longest lesion diameter was greater in the inflammatory than in the noninflammatory group. Histopathologically, epidermis was thicker in the inflammatory than in the noninflammatory group. The grade of basal hyperpigmentation was higher in the noninflammatory group, whereas telangiectasia was more frequent in the inflammatory group. The treatment response rate was lower in the inflammatory (7/21, 33.3%) than in the noninflammatory group (8/10, 80.0%). Optimal laser treatment strategies may differ in these two groups.

A case of cutaneous extranodal natural killer/T-cell lymphoma clinically and histopathologically mimicking interface dermatitis.

Extranodal natural killer/T-cell lymphoma (ENKTL) is a rare but aggressive cancer characterised by angiocentric and angiodestructive infiltration by NK-cells, or cytotoxic T-cell types. Histopathologically, ENKTL shows a multinodular or diffuse infiltration localised to vascular structures, resulting in angiodestruction and necrosis. We present a patient with an initially suspected diagnosis of benign interface dermatitis with a differential diagnosis of mycosis fungoides that was later found to be an aggressive extranodal natural killer/T-cell lymphoma of a nasal type and with a dismal prognosis.

Cutaneous angioimmunoblastic T-cell lymphoma: Epstein-Barr virus positivity and its effects on clinicopathologic features.

BACKGROUND: Epstein-Barr virus (EBV) positivity frequently presents in patients with nodal angioimmunoblastic T-cell lymphoma (AITL). However, the presence of EBV in skin lesions and its clinicopathologic significance have not been evaluated. OBJECTIVE: To analyze the clinical and histopathologic features of cutaneous AITL and evaluate EBV positivity in skin tissue and its effects on clinicopathologic features of AITL. METHODS: Clinicopathologic variables in patients with cutaneous AITL were analyzed and compared depending on EBV in situ hybridization status in skin lesions by using patients' medical records. RESULTS: Of the 86 patients with AITL, 42 had a cutaneous presentation. In situ hybridizations positive for EBV were noted in 19 of 42 patients with cutaneous AITL. EBV positivity was more common in papular and nodular skin lesions than other cutaneous morphologies, such as nonspecific rash or purpuric patches. An EBV-positive in situ hybridization was associated with a pattern of dense, superficial and deep infiltrates of pleomorphic, large-sized, atypical lymphocytes. EBV positivity in skin lesions was an independent negative prognostic factor in patients with AITL. LIMITATIONS: Retrospective study at a single institution. CONCLUSION: EBV-positive cutaneous AITL is associated with distinctive clinicopathologic features.

Expression of lymphocyte-activating gene 3 and T-cell immunoreceptor with immunoglobulin and ITIM domains in cutaneous melanoma and their correlation with programmed cell death 1 expression in tumor-infiltrating lymphocytes.

BACKGROUND: Lymphocyte-activating gene 3 (LAG-3) and T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif (TIGIT) domains are emerging checkpoint proteins. OBJECTIVE: We evaluated LAG-3 and TIGIT protein expression patterns, correlated these patterns with programmed cell death 1 (PD-1) protein expression, and determined their effects on clinicopathologic characteristics and biologic responses in melanoma. METHODS: Diagnostic tissue from 124 patients with melanoma were evaluated for LAG-3, TIGIT, and PD-1 expression by immunohistochemistry. Clinicopathologic features and survival were analyzed according to the expression of LAG-3, TIGIT, and PD-1. RESULTS: LAG-3 and TIGIT expression on tumor-infiltrating lymphocytes were significantly correlated with that of PD-1 and was also significantly associated with negative prognostic factors: deeper Breslow thickness, lymph node involvement, and advanced stage of disease. However, PD-1 expression was not associated with clinicopathologic variables of prognostic significance. High expression of either LAG-3 or TIGIT was associated with worse survival. Subgroup analysis on the basis of Breslow thickness showed that both LAG-3 and TIGIT have prognostic significance regardless of tumor thickness. High expression of PD-1 was not predictive of survival. LIMITATIONS: Retrospective study in a single institution and possibility of type 1 error. CONCLUSION: Expression of LAG-3 and TIGIT represents an independent unfavorable prognostic factor in cutaneous melanoma.

Anti-aging and hydration efficacy of a cross-linked hyaluronic acid microstructure patch.

This study evaluated the safety and efficacy of biodegradable microstructure patches composed of cross-linked hyaluronic acid (CLHA). A primary skin irritation test showed that the CLHA patches were not an irritant, whereas a clinical study showed that application of single CLHA patches significantly improved skin hydration at the periorbital region for 3 days and at the nasolabial fold for 6 days. Patch application also improved superficial wrinkles at the periorbital region for 3 days and at the nasolabial fold for 1 day. The absence of side effects indicated that application of these CLHA microstructure patches is both safe and convenient for moisturization and anti-wrinkle effects.

A case of recurrent pigmented macules in Laugier-Hunziker syndrome treated using a Q-switched Nd-YAG laser.

Laugier-hunziker syndrome (LHS) is a sporadic and acquired melanotic pigmentation of lips and oral mucosa which is not associated with gastrointestinal hamartomas in contrast to Peutz-Jeghers syndrome. Treatment using Q-switched neodymium: yttrium-aluminum-garnet (QS-ND:YAG) laser, Q-switched alexandrite laser and, cryotherapy have been reported. However, to the best of our knowledge, there is no report regarding long-term follow-up for recurrence. Herein we report the clinical features and the treatment of recurrent pigmented lesions in LHS patients. A patient diagnosed with LHS seven years ago presented with recurrent labial macules. She had undergone QS-ND:YAG laser 7 years ago and the labial macules have been gone several years. A physical examination revealed the macules were mainly on new locations and the spots on the site where the laser was previously done rarely recur. The untreated pigmented macules on gum were maintained in the same shape for seven years. Recurrent lesions of the lips and previously untreated macules on the gums were successfully treated again with the QS-ND:YAG laser as done in 7 years ago. Our case shows a long-term clinical course of laser-treated labial macules in LHS and treatment response of recurred lesions.

Characterization and Prognostic Significance of Cutaneous Adverse Events to Anti-Programmed Cell Death-1 Therapy.

BACKGROUND: Anti-programmed cell death-1 (PD-1) immunotherapy using antibodies such as nivolumab or pembrolizumab has shown promise for treating various types of cancer. In this study, we reviewed the frequency and spectrum of cutaneous adverse events (AEs) caused by PD-1 antibodies and their possible correlation with treatment response. METHODS: We reviewed records of all patients from a single institution treated with either nivolumab or pembrolizumab from August 1, 2014 to April 1, 2017. RESULTS: Of 211 patients included in the study, 134 (63.5%) were treated with nivolumab and 77 (36.5%) with pembrolizumab. Thirty-five patients (16.4%) developed cutaneous AEs. Cutaneous AEs were significantly associated with longer treatment cycles (P = 0.001). The prevalence of cutaneous AEs did not differ between nivolumab (17.2%) and pembrolizumab (15.6%). Patient age, gender, baseline Eastern Cooperative Oncology Group scale and underlying malignancy were not associated with development of cutaneous AEs. Median time until onset of cutaneous AEs was 50.0 days (range, 1-378 days). Anti-PD-1 therapy was tolerable in most of patients with grade 1 (65.2%) and grade 2 (23.9%) cutaneous AEs. Pruritus (32.6%) and eczema (21.7%) were the most commonly reported cutaneous AEs. In lung cancer patients, cutaneous AEs were not associated with better treatment outcomes after adjusting for the number of treatment cycles. CONCLUSION: Both pembrolizumab and nivolumab exhibited tolerable cutaneous safety profiles in a variety of cancer patients undergoing anti-PD-1 therapy. Cutaneous AEs of anti-PD-1 therapy were not associated with antibody type, underlying malignancy, patient characteristics, or improved response.

Improvement in abdominal and flank contouring by a novel adipocyte-selective non-contact radiofrequency device.

BACKGROUND: The demand for undergoing subcutaneous fat reduction has been gradually increasing, and there are many methods and devices for performing non-surgical and non-invasive fat reduction, such as high-intensity focused ultrasound, cryolipolysis, radiofrequency (RF) devices, and lasers. OBJECTIVES: This study evaluated the efficacy and safety of a novel adipocyte-selective non-contact RF device for improving abdominal contouring in Asian subjects. METHODS: Twenty-four Asian subjects with abundant subcutaneous abdominal and love handle fat tissues were enrolled in this prospective clinical study. They received six 45-min weekly treatments with an RF field device over the abdominal and love handle regions. The body mass index and abdominal circumference were measured at baseline and at 4 and 8 weeks post the last treatment. The thickness of the abdomen and depth of subcutaneous abdominal fat tissue were respectively assessed using calipers and abdominal ultrasonography. A subset of 15 subjects was selected by randomization for fat volume measurement via abdominal CT. For safety evaluation, serum lipid, and liver-related blood tests were performed at baseline and at the sixth treatment session. Subjects rated their heat perception level using a four point scale and their pain score using an 11-point visual analog scale during RF treatment. RESULTS: Twenty-four subjects (21 females and 3 males) completed this study with an 8-week follow-up. The average decreases in abdominal circumference at 4 and 8 weeks post treatment were 3.48 ± 2.11 cm (P < 0.001) and 5.12 ± 0.47 cm (P < 0.001), respectively. The average decreases in abdominal fat thickness at 4 and 8 weeks treatment were 0.27 ± 0.61 cm (P = 0.041) and 0.47 ± 0.60 cm (P = 0.001), respectively. The average decreases in subcutaneous fat tissue depth at 4 and 8 weeks post treatment were 0.16 ± 0.43 cm (P = 0.091) and 0.34 ± 0.39 cm (P < 0.001), respectively. However, there was no significant change in the subcutaneous fat tissue volume. The mean heat perception level was 2.24, and the mean pain score was 0.74. No serious adverse effects were observed during treatment and the follow-up periods, and there were no clinically significant changes in lipid or liver-related levels. CONCLUSIONS: The adipocyte-selective non-contact RF field device appears to be effective and safe for improving abdominal contouring. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc.

Cutaneous Extranodal Natural Killer/T-Cell Lymphomas Histopathologically Mimicking Benign Inflammatory Disease.

Few studies have evaluated the histopathological features of cutaneous extranodal NK/T-cell lymphoma (ENKTL). The authors' study aims to describe cases of cutaneous ENKTL that histopathologically mimic benign inflammatory dermatosis. The authors searched the database of Asan Medical Center to identify cases of cutaneous ENKTL that were confirmed by skin biopsy between January 1998 and December 2014. The authors included cases that were initially diagnosed as benign inflammatory disorders on the histopathological examination, but finally diagnosed as cutaneous ENKTL on further evaluation. This study included 10 cases of cutaneous ENKTL. Six cases demonstrated nonspecific perivascular cellular infiltration, 2 cases demonstrated lupus erythematosus-like histological features, 1 case demonstrated psoriasiform lichenoid reaction, and 1 case demonstrated vasculitis-like features on histopathological examination. All cases were positive for CD56 and Epstein-Barr virus in situ hybridization. Perivascular infiltrations throughout the superficial and deep dermis with vasculopathy and panniculitic infiltration were common histopathological findings. The clinical features included 7 cases of erythematous to purpuric patches, 2 cases of facial swelling, and 1 case of cellulitis-like swelling. In conclusion, cutaneous ENKTL can histopathologically mimic benign inflammatory dermatosis. Cutaneous ENKTL should be suspected when histopathology shows perivascular dermal infiltration with vasculopathy and panniculitic cellular infiltration.

Nomalike Necrotizing Stomatitis in a Child with Crohn's Disease.

Noma is an opportunistic infection characterized by devastating gangrenous stomatitis leading to severe tissue destruction that predominantly affects malnourished children in sub-Saharan Africa. Only a few cases have been reported in immunocompromised patients from developed countries. We present an unusual case of nomalike necrotizing stomatitis in a previously healthy child with Crohn's disease in Korea.

Cutaneous anaplastic large-cell lymphoma (ALCL): A comparative clinical feature and survival outcome analysis of 52 cases according to primary tumor site.

BACKGROUND: Cutaneous anaplastic large-cell lymphoma (ALCL) is primary extranodal or secondary to nodal disease. OBJECTIVE: We sought to analyze clinical features and survival outcomes by primary tumor site in patients with cutaneous ALCL. METHODS: Clinical features, survival outcomes, and prognostic factors of 52 patients with primary or secondary cutaneous ALCL to primary nodal disease were retrospectively evaluated using medical records. RESULTS: Although skin lesion characteristics did not significantly differ between groups, the head and neck location was more common in primary cutaneous ALCL, whereas cutaneous lesion extent was greater in secondary cutaneous ALCL. Skin lesion extent in primary cutaneous ALCL was indicative of extracutaneous dissemination development and skin lesion relapse. Neither anaplastic lymphoma kinase expression nor clinical stage affected skin lesion characteristics in secondary cutaneous ALCL. Patients with primary rather than secondary cutaneous ALCL demonstrated better survival outcomes. The skin lesion extent and location on the leg were associated with the tendency toward a poorer prognosis in primary cutaneous ALCL. The secondary cutaneous ALCL prognosis was not influenced by skin lesion characteristics. LIMITATIONS: This was a retrospective study in a single institution. CONCLUSION: Survival outcomes and prognostic factors in cutaneous ALCL differed by primary tumor site.

Comparative histopathologic analysis of cutaneous extranodal natural killer/T-cell lymphomas according to their clinical morphology.

BACKGROUND: Few studies have evaluated the histopathologic features of cutaneous extranodal natural killer (NK)/T-cell lymphoma (ENKTL), and the histopathologic spectrum of this disease according to its clinical morphology remains unclear. OBJECTIVE: This study investigated the differences in pathologic findings of cutaneous ENKTL depending on clinical morphology. METHODS: A total of 41 cases of cutaneous ENKTL were included. Skin lesions were classified according to clinical morphology as: (i) nodular lesions, (ii) cellulitis or abscess-like swellings and (iii) erythematous to purpuric patches. Histopathologic variables were compared between groups. RESULTS: Perivascular infiltration of tumor cells and vasculopathy in the dermis and subcutaneous layer were common microscopic findings irrespective of clinical morphology. Erythematous to purpuric patches were mainly composed of small-sized tumor cells, whereas medium- to large-tumor cells were predominant in lesions of other clinical morphologies. The density of tumor cell infiltration was significantly higher in cellulitis or abscess-like lesions or nodular lesions compared with erythematous to purpuric patches. A panniculitis-like pattern and angiocentricity were less common in patch lesions than in cellulitis-like swelling and nodular lesions. CONCLUSION: There is a histopathologic spectrum of cutaneous ENKTL that is dependent on the clinical morphology.

Relative Frequency, Clinical Features, and Survival Outcomes of 395 Patients with Cutaneous Lymphoma in Korea: A Subgroup Analysis per 10-year Period.

Long-term changes in the relative frequency of cutaneous lymphoma (CL) have not been investigated in Asian populations. The aim of this study was to investigate the relative frequency, clinical characteristics, and survival outcomes of CL in Korean patients, and to evaluate the changes in relative frequency of CL over a 20-year period. The present retrospective cohort study included 395 patients, of whom 289 had primary CL and 106 secondary CL, seen at a tertiary referral hospital in Seoul, Korea. Primary CL included T-/NK-cell linage lymphoma (CTCL, 85.1%) and B-cell lineage lymphoma (CBCL, 14.9%). The relative frequency of CBCL increased over time, as shown by a decrease in the CTCL/CBCL ratio from 10.3 in 1994 to 2003 to 4.5 in 2004 to 2013. CTCL was more commonly associated with multiple and extensive skin lesions than CBCL. Extranodal NK/T-cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma were commonly associated with extensive skin lesions. The 5-year overall survival rate for all patients with primary CL was 81%.

Secondary Cutaneous Diffuse Large B-cell Lymphoma has a Higher International Prognostic Index Score and Worse Prognosis Than Diffuse Large B-cell Lymphoma, Leg Type.

Diffuse large B-cell lymphoma (DLBCL) can be separated into 2 groups: nodal and extranodal disease. The aim of this study was to analyse the clinical features of skin lesions and survival outcomes of cutaneous DLBCL according to the primary tumour site. A total of 44 patients with cutaneous DLBCL were classified as primary cutaneous DLBCL, leg type or cutaneous DLBCL secondary to primary disease. Although skin lesion characteristics did not differ significantly between groups, extensive cutaneous lesions were more often observed in secondary cutaneous DLBCL compared with DLBCL, leg type. Secondary cutaneous DLBCL was more commonly associated with an advanced stage and higher International Prognostic Index score than DLBCL, leg type. DLBCL, leg type demonstrated a better survival outcome than secondary cutaneous DLBCL. The multiplicity of skin lesions and time-point of cutaneous involvement were associated with prognosis in secondary cutaneous DLBCL. Survival outcomes and prognostic factors differ depending on the primary tumour site of cutaneous DLBCL.

Histopathological Analysis of 226 Patients With Rosacea According to Rosacea Subtype and Severity.

BACKGROUND: The histopathological features of rosacea have not been described in detail. OBJECTIVE: To evaluate the histopathological features of rosacea according to clinical characteristics such as subtype and severity. METHODS: We retrospectively analyzed histopathological findings in 226 patients with rosacea, which included 52 patients with the erythematotelangiectatic rosacea (ETR) and 174 patients with the papulopustular rosacea (PPR) subtype. The frequency of each histopathological finding was compared between subtypes. Histopathological features were also compared according to the severity, through subgroup analysis within each subtype group. RESULTS: Perivascular and perifollicular lymphohistiocytic infiltration were common dermal findings in both subtype groups, but the intensity of dermal inflammatory infiltration was higher in PPR than in ETR. Follicular spongiosis and exocytosis of inflammatory cells into hair follicles were noted in both subtypes; but these findings were significantly more common in the PPR subtype. Vascular changes (telangiectasia and proliferation) and solar elastosis were common histopathological findings in both subtypes, with no difference in frequency between subtype groups. Demodex mites were identified in about 40% of patients, and the frequency of demodex mites did not differ between subtype groups. The intensity of perifollicular inflammation and the presence of follicular inflammatory reactions were dependent on the severity of rosacea in both subtype groups. CONCLUSIONS: The intensity of inflammatory reactions, especially perifollicular infiltration, was higher in PPR patients than in ETR patients. Rosacea has a spectrum of histopathological features that are related to clinical progression between rosacea subtypes.

A multicenter, randomized, open-label pilot trial assessing the efficacy and safety of etanercept 50 mg twice weekly followed by etanercept 25 mg twice weekly, the combination of etanercept 25 mg twice weekly and acitretin, and acitretin alone in patients with moderate to severe psoriasis.

BACKGROUND: Etanercept, a soluble tumor necrosis factor receptor, and acitretin have been shown to be effective in treating psoriasis. Acitretin is widely used in Korea. However, the combination of etanercept plus acitretin has not been evaluated among Korean patients with psoriasis. The objective of this study was to investigate the efficacy and safety of combination therapy with etanercept and acitretin in patients with moderate to severe plaque psoriasis. METHODS: Sixty patients with psoriasis were randomized to receive etanercept 50 mg twice weekly (BIW) for 12 weeks followed by etanercept 25 mg BIW for 12 weeks (ETN-ETN); etanercept 25 mg BIW plus acitretin 10 mg twice daily (BID) for 24 weeks (ETN-ACT); or acitretin 10 mg BID for 24 weeks (ACT). The primary efficacy measurement was the proportion of patients achieving 75 % improvement in Psoriasis Area and Severity Index (PASI 75) at week 24. Secondary end points included 50 % improvement in PASI (PASI 50) at week 24 and clear/almost-clear by Physician Global Assessment (PGA) at each visit through week 24. RESULTS: The proportions of patients achieving PASI 75, PASI 50, and PGA clear/almost-clear at week 24 in the ETN-ETN (52.4, 71.4, and 52.4 %, respectively) and ETN-ACT groups (57.9, 84.2, and 52.6 %, respectively) were higher than in the ACT group (22.2, 44.4, and 16.7 %, respectively). The incidence of adverse events was similar across all arms. This was an open-label study with a small number of patients. CONCLUSION: In Korean patients with moderate to severe plaque psoriasis, etanercept alone or in combination with acitretin was more effective than acitretin. All treatments were well tolerated throughout the study. TRIAL REGISTRATION: This study was registered on July 7, 2009 at ClinicalTrials.gov, NCT00936065 .

Histological and molecular analysis of the long-pulse 1,064-nm Nd:YAG laser irradiation on the ultraviolet-damaged skin of hairless mice: In association with pulse duration change.

BACKGROUND: Nonablative lasers have been widely used to improve photodamaged skin, although the mechanism underlying dermal collagen remodeling remains unclear. OBJECTIVE: To investigate the effects and the molecular mechanisms of long-pulse neodymium-doped yttrium aluminum garnet (Nd:YAG) laser irradiation on dermal collagen remodeling in association with different pulse durations. MATERIAL AND METHODS: Five hairless mice were pretreated with ultraviolet B irradiation for 8 weeks. The dorsal quadrant of each mouse was then irradiated twice at 1-week intervals at a pulse duration of 1 ms, 12 ms, or 50 ms, and a constant fluence of 20 J/cm(2). The levels of dermal collagen, mRNAs of procollagens, matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs), and various growth factors were analyzed after 4 weeks. RESULTS: Long-pulse Nd:YAG treatment increased the dermal collagen level. A substantial increase in the level of procollagens, MMPs, TIMPs, and various growth factors was also observed irrespective of pulse duration, with a trend toward maximal increase at a pulse duration of 12 ms. CONCLUSION: Long-pulse 1,064-nm Nd:YAG laser irradiation promotes wound-healing process, which is characterized by the induction of growth factor expression and subsequent increase in MMPs and TIMPs, followed by matrix remodeling as confirmed by new procollagen production.

The Effect of MCP-1/CCR2 on the Proliferation and Senescence of Epidermal Constituent Cells in Solar Lentigo.

Solar lentigo (SL) is a representative photoaging skin disorder. Alteration of the main epidermal constituent cells-keratinocytes and melanocytes-in relation to the photoaged dermal environment or chemokine/cytokine network is suggested as its pathogenesis. Among these, we focused on monocyte chemoattractant protein-1 (MCP-1), as it is known to be associated with tissue aging. For the first time, we report that the MCP-1 receptor, CCR2, is expressed in normal human melanocytes. In SL tissue, there was an increase of CCR2+Melan A+ melanocytes with positivity to Rb protein compared to peri-lesional normal skin. MCP-1 induced the proliferation of normal human melanocytes without a significant change in the melanin content. MCP-1 treatment in normal human keratinocytes showed an increase in senescence-associated ß-galactosidase staining and p53 and p21 protein expressions. In summary, MCP-1 may participate in the development of SL by affecting epidermal constituent cells, for example, by inducing melanocyte proliferation and keratinocyte senescence.