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Background: Although other primary systemic cancers in patients with melanoma have been studied, there have been few focusing on acral melanomas., Objectives: We assessed other primary systemic cancers in patients with acral and nonacral melanomas., Methods: We analyzed other primary cancers in 452 patients with melanoma from 1994 to 2013. Metachronous cancers were defined as those given a diagnosis more than 2 months after diagnosis of melanoma. The others were considered prechronous or synchronous cancers., Results: Among 51 cases of other primary cancers, gastrointestinal cancer (35.3%, n = 18/51) was the most common, followed by thyroid (17.6%), lung (11.8%), and breast (5.9%). Those were more prevalent in the acral melanoma group (12.8%, n = 31/243) compared with the nonacral melanoma group (9.6%, n = 20/209). Of 23 cases of metachronous cancer, the risk was the highest in bone marrow, followed by oral cavity, bladder, colon, lung, and thyroid. Among 28 cases of prechronous or synchronous cancers, gastrointestinal tract (35.7%, n = 10/28) was the most common site, followed by thyroid (17.9%), breast (10.7%), and lung (7.1%)., Limitations: The study is limited by a small number of patients., Conclusion: Careful follow-up and imaging studies are necessary for early detection of other primary cancers and metastatic lesions in patients with melanoma., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Caveolin-1 (Cav-1) is one of the key molecules to modulate collagen metabolism in the skin. This study aimed to unravel the relationship between Cav-1 and collagen levels in the aged skin, and also to evaluate a new role of anti-Cav-1 agent as a collagen-modulating agent. A negative correlation between Cav-1 and collagen I (COL I) was detected in chronologically aged skin of humans and mice, which was further confirmed by Cav-1 knock-down or knock-out experiments. Next, we tested whether methyl-β-cyclodextrin (MβCD) as a chemical Cav-1 inhibitor could be developed as a collagen-modulating agent in the skin. Testing different conditions of MβCD injection via the intra-dermal route revealed that 2.5% MβCD administered twice per week for two months showed a potent COL I-up-regulating activity, leading to the increase of skin thickness (P < 0.05) without adverse reactions such as skin fibrosis. In human dermal fibroblasts, MβCD treatment induced up-regulated COL I and down-regulated Cav-1, supporting the results of mouse experiments. Collectively, MβCD has a COL I-enhancing activity in chronologically-aged skin, where Cav-1 acts as a brake in COL I expression, suggesting its potential role for an anti-aging agent.

Importance: The pathogenesis of acral melanoma remains unclear, even though trauma may be a predisposing factor. A study about the association of long-term physical stress with the incidence and spreading patterns through detailed anatomic mapping may be important to understand the unique features of acral melanoma., Objectives: To analyze the epidemiologic and clinicopathologic characteristics of acral melanoma and evaluate how long-term physical stress or pressure strength influences acral melanoma based on the analysis of differences in incidence, prognosis of the distinct site (weight or non-weight-bearing portion of sole, volar, or subungual location), and the spreading pattern of melanoma on the soles., Design, Setting, and Patients: Cross-sectional, retrospective study of 177 Korean patients with acral melanoma from January 1, 1994, through October 31, 2012., Main Outcomes and Measures: Anatomic mapping and histopathologic examination of acral melanoma. RESULTS The male to female ratio was 1:1.03, and the mean age at first admission was 55.3 years. Acral lentiginous melanoma was the most common histopathologic subtype (85.9%), followed by nodular melanoma (12.8%). There was a high incidence of acral melanoma at more physically stressed sites, such as the center of the heels and inner forefoot. In addition, a peculiar spreading pattern with the long axis of melanoma, typically along naturally occurring creases due to long-term pressure on the soles, was often observed. The prognostic index and survival rate showed no significant difference between volar and subungual locations or between weight and non-weight-bearing portions of the soles., Conclusions and Relevance: Clinicopathologic characteristics of acral melanoma diagnosed at an advanced stage and resulting in a low survival rate are not significantly different between Koreans and other Asians. Interestingly, based on our study, long-term physical stress or pressure strength can influence the incidence and spreading pattern of acral melanoma in a particular manner. Acral melanoma occurs on more physically stressed sites with the long axis along natural creases on the sole. A further prospective investigation, especially of in situ lesions, regarding location-based differences in incidence, progress, and survival is necessary to better understand the pathophysiologic characteristics of acral melanoma.

Background: Amelanotic acral melanoma (AAM) is very rare and difficult to diagnose both clinically and pathologically. Complete-type AAM shows no black to brown pigmentation in the lesion, whereas incomplete-type AAM shows focal or subtle pigmentation. AAM has been the subject of few investigations., Objectives: We analyzed the clinicopathological features, BRAF mutations, and KIT aberrations in 35 Korean AAM cases., Methods: We included 28 cases of complete-type and 7 cases of incomplete-type AAM., Results: In all, 26 AAMs (45.7%) were located on the feet of patients, 21 of which (82.9%) showed ulceration. Sixteen cases developed in subungual areas. Nodular melanoma was the most common histopathological subtype (63.6%). The most frequent cell types affected were epithelioid and spindled. HMB-45 staining was strongly positive in 66.7% of AAMs; 4 (12.1%) were negative for HMB-45, and 3 of these were complete-type AAMs. Of 33 total patients, BRAF mutations were detected in 2 AAM cases, and KIT aberrations were present in 11 cases (33.3%). Four cases (12.1%), all of which were complete-type AAMs, had KIT mutations. KIT aberrations were weakly correlated with c-kit staining. Twenty patients were TNM stage I or II, and mean survival was 30.14 ± 4.54 months., Limitations: The study is limited by the small number of patients., Conclusion: Physicians should be aware of rare and hard-to-diagnose AAMs. We expect that tyrosine kinase inhibitors would be effective for KIT-mutated patients with complete-type AAMs., (Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Cutaneous metastatic carcinoma of the nose is a rare presentation associated with lung cancer. We report here 3 cases of cutaneous metastatic carcinoma of the nose that originated from lung cancer. Two men, age 61 and 76 years, with lung cancers were referred for evaluation of a tumour on the tip of the nose. The third patient, a 57-year-old man, had developed a rosacea-like tumour on the tip of the nose; although he had no history of internal cancer, whole-body positron-emission tomography-computed tomography revealed a primary lung cancer. Skin biopsies of all 3 cases showed metastatic squamous cell carcinoma, and all primary lung cancers were squamous cell carcinomas. Only 3 patients are described here, and further reports are needed to substantiate this interesting phenomenon. When an elderly patient presents to dermatology with a tumour on the nose with or without known internal cancer, it is necessary to approach the diagnosis with caution.

As antioxidant enzymes can be actively modulated during keratinocyte (KC) differentiation, this study was aimed to evaluate the modulation of a group of phase 2 detoxifying and antioxidant enzymes (phase 2 enzymes) during KC differentiation. In postconfluence-induced differentiation model of KC, heme oxygenase-1 (HO-1), NADP(H):quinone oxidoreductase-1 (NQO-1), and glutathione S-transferase pi (GSTpi) were up-regulated at a transcriptional level. In Western blot analysis, the phase 2 enzymes were up-regulated by H(2)O(2), but down-regulated by N-acetyl cysteine, indicating the active role of reactive oxygen species for their expression during KC differentiation. When a redox-sensitive NF-E2 related factor-2 (Nrf2), a key transcriptional factor for phase 2 enzymes, was knocked down by small interfering RNA transfection in differentiated KCs, only NQO-1 was down-regulated in both mRNA and protein levels. In human skin, expression levels of the phase 2 enzymes were up-regulated in the differentiated KC in the normal epidermis and keratotic foci in squamous cell carcinoma, further supporting the differentiation-dependent expression of phase 2 enzymes in vivo. This study demonstrates that a group of phase 2 enzymes are modulated during KC differentiation via either Nrf2-dependent (NQO-1) or Nrf2-independent (HO-1 and GSTpi) ways.

Propionibacterium acnes naturally produces endogenous porphyrins that are composed of coproporphyrin III (CPIII) and protoporphyrin IX (PpIX). Red light alone and photodynamic therapy (PDT) improve acne vulgaris clinically, but there remains a paucity of quantitative data that directly examine the bactericidal effects that result from PDT on P. acnes itself in vitro. The purpose of this study was to measure the difference of bactericidal effects of 5-aminolevulinic acid (ALA)-PDT with red and blue light on P. acnes. P. acnes were cultured under anaerobic conditions and divided into two groups (ALA-treated group and control group), and were then illuminated with blue (415 nm) and red (635 nm) lights using a light-emitting diode (LED). The cultured P. acnes were killed with both blue and red LED light illumination. The efficacy increased with larger doses of light and a greater number of consecutive illuminations. We demonstrated that red light phototherapy was less effective for the eradication of P. acnes than blue light phototherapy without the addition of ALA. However, pretreatment with ALA could enhance markedly the efficacy of red light phototherapy., (© 2010 Japanese Dermatological Association.)

We describe a 74-year-old man presenting with a 10-year history of an asymptomatic, skin-colored hard plaque on his left cheek. Microscopy revealed well-demarcated tumor with peripheral palisading and peritumoral clefting in the dermis. The tumor included many plasmacytoid cells with cytoplasmic hyaline inclusions and eccentric nuclei. Electron microscopic examination showed that hyaline inclusions consisted of aggregates of filaments. Immunoperoxidase staining showed diffuse cytoplasmic expression of 34bE12, smooth muscle actin, calponin and p63. We diagnosed the patient with basal cell carcinoma (BCC) with myoepithelial differentiation and treated him with excision. Eight months postoperatively, the patient remained well with no recurrence. This distinct variant of BCC with myoepithelial differentiation, showing cytoplasmic hyaline inclusions and eccentric nuclei, has previously been confusingly termed 'signet-ring cell BCC'. However, these plasmacytoid cells differ from signet-ring cells with vacuolated cytoplasm. To avoid confusion, we suggest the designation 'BCC with myoepithelial differentiation'., (Copyright © 2010 John Wiley & Sons A/S.)

The pigment synthesizing melanoma, so-called animal type melanoma, is a rare variant of melanoma that is characterized by prominent melanin production and an unpredictable prognosis. Congenital onset of this melanoma is exceedingly rare. A 2-month-old Korean girl had a black nodule and a satellite black macule on the scalp which were noticed at birth. She received a surgical resection 3 months later because of rapidly growing lesions and the histopathologic features of a pigment synthesizing melanoma. Two months later, she returned with cervical area swelling, and the excised multiple lymph nodes showed metastatic malignant melanoma. The exact origin and pathogenesis of congenital pigment synthesizing melanoma is different from the more common forms of melanoma and remains poorly understood., (Copyright (c) 2009 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

We report a 68-year-old Korean man presenting with asymptomatic erythematous polycyclic annular firm plaques on his back that spread to the right shoulder. Histopathologic examination showed dense, diffuse infiltrates involving the entire dermis, consisting of atypical lymphocytes with many centrocytes and a few centroblasts. Spindle-shaped cells with elongated, twisted nuclei containing dispersed chromatin were also seen. Immunohistochemical analysis showed that all of the cells were strongly positive for CD20, CD21, CD79a and CD45, while they were negative for CD3, CD5, CD10, CD23, CD35, CD43, CD45RO and CD68. The spindle cells were also negative for smooth-muscle actin, desmin, S-100 and CD34. They consistently expressed nuclear bcl-6, but did not express bcl-2, multiple myeloma-1 and p16. We diagnosed him with primary cutaneous spindle cell B-cell lymphoma (PCSBCL) and treated him with six cycles of cyclophosphamide, adriamycin, vincristine, prednisone and rituximab (R-CHOP) chemotherapy; his skin lesions disappeared completely. Immunohistochemical profiles suggest that PCSBCL is a variant of primary cutaneous follicle center lymphoma.

Although non-scarring diffuse hair loss has been frequently observed in systemic lupus erythematosus (SLE) patients, the pattern of hair loss with regard to its frequency in SLE has been rarely studied. The aim of this cross-sectional study was to evaluate the hair loss patterns in SLE during the course of disease. We evaluated 122 SLE patients (age range, 13-71 years; mean age, 32.7 +/- 10.6; female : male ratio, 12.6:1), by conducting interviews about hair loss patterns before and after a diagnosis of SLE using a questionnaire format. History taking and physical examinations were done at the time of interview, and photographs were taken to discriminate the active LE-specific scarring hair loss from the LE-nonspecific diffuse hair loss. Frequency and correlation analysis were performed on the data from the interviews and photographs for determining their relation with the SLE Disease Activity Index (SLEDAI). We found that 104 patients experienced at least one hair loss event before or during the course of SLE. Eighteen patients experienced patch alopecia, including eight who experienced this malady both before and after the diagnosis; thus, the overall prevalence of patch alopecia was 14.8% (18/122). Eighty-six patients experienced hair loss after diagnosis, of which non-scarring diffuse hair loss was the most common pattern (65.1%, 56/86) followed by non-scarring patch alopecia (15.1%, 13/86). The interview survey failed to identify a statistically significant relationship between the hair loss pattern and the SLEDAI. Our results suggest that non-scarring patch alopecia is also an important pattern in SLE that should be included in the differential diagnosis of alopecia areata and confirmed by histopathological examination.

Drug rash with eosinophilia and systemic symptoms (DRESS) is characterized by fever, rash and internal organ involvement after exposure to certain drugs. Most of the aromatic anticonvulsants, such as phenytoin, phenobarbital, and carbamazepine, can induce DRESS. Cross-sensitivity between not only the aromatic anticonvulsants, but also the aromatic and non-aromatic anticonvulsants, is possible. We report here a case of a Korean woman who had previously tolerated valproate, but developed DRESS due to valproate after carbamazepine intake, which indicates cross-sensitivity. Her skin lesions displayed diffuse oedematous patches on the entire body associated with tense bullae on her arms and legs. Circulating auto-antibody to 190-kDa antigen was detected in the patient's serum by indirect immunofluorescence and immunoblotting, which might contribute to a pathogenic role in DRESS.

Peroxiredoxins (Prxs) are expressed in the epidermis, and the accentuated expression of the Prx I and Prx II isotypes (Prx I/II) in the suprabasal layers suggests the potential role of Prx I/II in epidermal differentiation. To evaluate the novel function of Prx I/II, we checked the modulation of Prx I/II in differentiating keratinocytes. To induce differentiation in vitro, normal human epidermal keratinocytes (NHEK) were cultured for up to 10 days after the confluent state (post-confluency). In Western blot analysis, the marked induction of Prx I was observed from the second day, but the marked induction of Prx II was observed later from the sixth day of post-confluency, when loricrin and transglutaminase 1 were induced (sixth day of post-confluency). When NHEK cells were treated with INF-gamma and TGF-beta1, Prx I/II were up-regulated by INF-gamma, but Prx I/II were down-regulated by TGF-beta1. In summary, Prx I and Prx II are induced at the early and late stage of differentiation of NHEK cells, respectively.