Sook Jung Yun

Histomorphologic assessment and interobserver diagnostic reproducibility of atypical spitzoid melanocytic neoplasms with long-term follow-up

Predicting clinical behavior of atypical Spitz tumors remains problematic. In this study, we assessed interobserver agreement of diagnosis by 13 expert dermatopathologists for atypical Spitz tumors (n=75). We determined which histomorphologic features were most heavily weighted for their diagnostic significance by the experts and also which histomorphologic features had a statistically significant correlation with clinical outcome. There was a low interobserver agreement among the experts in categorizing lesions as malignant versus nonmalignant (&kgr;=0.30). The histomorphologic features that were given the most diagnostic significance by the experts were: consumption of the epidermis, atypical mitoses, high-grade cytologic atypia, and mitotic rate. Conversely, the histomorphologic features that most correlated with disease progression were: frequent mitoses, deep mitoses, asymmetry, high-grade cytologic atypia, and ulceration. The presence and/or pattern of pagetoid spread, consumption of the epidermis, and lymphoid aggregates demonstrated no association with clinical behavior. The results support the assertion that there is a lack of consensus in the assessment of atypical Spitz tumors by expert dermatopathologists. Importantly, many features used to distinguish conventional melanoma from nevi were not useful in predicting the behavior of atypical Spitz tumors. This study may provide some guidance regarding histologic assessment of these enigmatic tumors.

Clinical Evaluation of 168 Korean Patients with Rosacea: The Sun Exposure Correlates with the Erythematotelangiectatic Subtype

BACKGROUND Although rosacea is a chronic cutaneous inflammatory disorder thats commonly seen in adults, the etiology and pathogenesis of the illness remain unclear. A well established diagnostic classification and grading system may play a critical role in performing research and it would serve as a diagnostic reference in the clinical field. OBJECTIVE We sought to classify the patients with the new standard classification and grading system and we wanted determine the peculiar features and relationships of each subtype. We also analyzed the relationships between the degree of sun exposure and each subtype. METHODS We reviewed the medical records and clinical photos of 168 patients who were diagnosed with rosacea from 2002 to 2007 at our hospital. The standard classification and grading system suggested by the National Rosacea Society (NRS) Expert Committee was adopted to evaluate each patients subtype and the severity. RESULTS The male:female ratio was 1:2.29. The mean age at the time of diagnosis was 47.8 years. The mean duration of disease was 3.5 years. Sun exposure and hot baths/exercise were the two most common precipitating factors, while the majority of patients did not have any specific factor that relieved their symptoms. According to the NRS classification and grading system, the patients were classified into four subtypes. One hundred sixty two (96.4%) patients were diagnosed with the erythematotelangiectatic subtype irrespective of severity. Eighty five (50.6%) patients had the papulopustular subtype and 24 (14.3%) patients had ocular rosacea. Eight (4.8%) patients displayed mild phymatous change. The degree of sun exposure had significant correlation with the development and severity of the erythematotelangiectatic subtype (p<0.05), while it had no correlation with the papulopustular, ocular and phymatous subtypes. CONCLUSION Although the erythematotelangiectatic subtype was the most common subtype of rosacea, many patients also had other subtypes of rosacea simultaneously. Based on our results, we proved that ocular rosacea is an extension of the clinical spectrum of erythematotelangiectatic rosacea. In addition, the results of our study particularly suggest that sun exposure has a different influence on each subtype of rosacea.

A Clinicopathologic Analysis of 177 Acral Melanomas in Koreans Relevance of Spreading Pattern and Physical Stress

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.

Hair Loss Pattern due to Chemotherapy-Induced Anagen Effluvium: A Cross-Sectional Observation

Background: Anagen effluvium is a common side effect of chemotherapy, but few studies have examined its clinical characteristics. Objective: This study was aimed at evaluating the hair loss caused by chemotherapeutic agents. Methods: Sixty-four patients with anagen effluvium were evaluated in the study. Chemotherapeutic agents were classified into 5 different groups. The pattern of hair loss was analyzed when specific involvement of the hairline was obvious. Results: Forty-six (71.9%) of the 64 total patients maintained hairs along their hairline. Hairs were maintained with a total hairline in 20 (31.3%), frontal hairline in 13 (20.3%) and occipital hairline in 12 (18.8%) patients. Among the 20 males with patterned hair loss, the following hairlines were preserved: occipital in 10 (50%), total in 7 (35%) and frontal in 3 (15%). Among the 25 females with patterned hair loss, hairlines were preserved as total in 13 (52%), frontal in 10 (40%) and occipital in 2 (8%). However, no significant differences were detected in hair loss patterns according to age, associated symptoms, chemotherapeutic agent group or combination of chemotherapeutic agents. Conclusion: Our results suggest that anagen effluvium induced by chemotherapeutic agents represents patterned hair loss.

Serum Lactate Dehydrogenase Is a Novel Marker for the Evaluation of Disease Severity in the Early Stage of Toxic Epidermal Necrolysis

Objective: To evaluate serum lactate dehydrogenase (LDH) and its correlation with skin manifestations in patients with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Methods: Serum LDH levels were measured in 33 patients (17 SJS and 16 TEN), from initial hospital admission to remission stage. Results: The mean LDH level was 920.82 ± 655.50 U/l in TEN and 595.35 ± 182.03 U/l in SJS (normal range: 218–472). We arbitrarily divided these patients into 2 groups, the first were admitted within 3 days of onset (early stage) and the second after 4 days of onset (late stage). The ratio of early- to late-stage patients was 7:9 in TEN and 7:10 in SJS. The mean LDH level for 7 TEN patients in the early stage was 1,319.14 ± 843.10 U/l, which was significantly higher than that of the SJS group (686.71 ± 171.81 U/l; p = 0.024). In the late-stage patients, the mean levels of TEN and SJS patients were 611.0 ± 160.33 and 531.4 ± 167.89 U/l, respectively; these differences between TEN and SJS were not significant. Conclusion: Serum LDH levels can be used as a marker of disease severity in the early stage of TEN.

Expression of vanilloid receptor 1 in cultured fibroblast.

Abstract:  Although the vanilloid receptor 1 (VR1) was originally discovered on primary sensory neurons, its broad tissue expression in non‐neuronal cells has been reported on. Recently, VR1 expression was clearly demonstrated in a variety of cutaneous components, such as keratinocytes, glandular epithelium, mast cells and sebocytes, except for melanocytes and fibroblasts. However, we demonstrated the VR1 expression in the cultured human skin fibroblasts as follows. Previously cloned human VR1 primers that corresponded to the expected size of 680 bp by reverse transcriptase polymerase chain reaction were identified on the fibroblasts, the same as was noted for the positive control, the HaCaT cells. A positive immunoreactivity of the VR1 was observed both on fibroblasts and on HaCaT cells by Western blotting analysis. Fibroblasts treated with capsaicin, an agonist to the VR1, induced significant changes of the membrane current and the intracellular calcium level, and these changes were antagonized by capsazepin. Capsaicin treatment also showed a positive immunocytochemistry result. Our results suggest the existence of VR1 on fibroblasts; this receptor is likely to be influenced by ligand‐dependent activation.

Clinical characteristics and risk of melanoma development from giant congenital melanocytic naevi in Korea: a nationwide retrospective study.

Background  Giant congenital melanocytic naevi (GCMN) are known risk factors for the development of melanoma. However, melanoma risk among Asians is rarely evaluated.

High Lymphatic Vessel Density and Lymphatic Invasion Underlie the Adverse Prognostic Effect of Radial Growth Phase Regression in Melanoma

Regression in the radial growth phase (RGP) of primary cutaneous melanomas is common and has been shown to be an adverse prognostic factor. However, the underlying mechanism is unclear. We performed dual immunohistochemical staining of podoplanin and S-100 on paraffin tissues from 321 patients with vertical growth phase primary melanomas, who had 10 years or more of follow-up. Lymphatic vessel density (LD) and lymphatic invasion (LI) were quantified and documented. The time to first metastasis and melanoma-specific death (MSD) from the date of definite treatment were analyzed using univariate and multivariate Cox models. Among the 116 vertical growth phase melanomas that had regression in the adjacent RGP, 75 (23%) were classified as complete and 41 (13%) were classified as partial. LD was significantly higher (P<0.001) in the 75 lesions with complete regression (mean±SD, 23.7±12.3/mm2) compared with the 41 lesions with partial regression (15.5±7.1/mm2) and was lower in 155 areas of the adjacent normal dermis (7.3±3.5/mm2) and 69 areas of the distant normal dermis (5.5±2.6/mm2). Patients whose lesions had areas of complete regression with LI and either high or low LD or had no LI with high LD, had shorter time to first metastasis (hazard ratio=2.5, 3.8, and 2.5, respectively) and increased risk of melanoma-specific death (hazard ratio=3.1, 1.3 and 3.0, respectively) than those with no LI, and low LD or those without areas of complete regression. These data indicate that complete RGP regression is associated with significantly increased LD. In addition, the adverse prognostic effect of RGP regression is at least partially mediated through lymphangiogenesis and LI in this area.

Nrf2-dependent and Nrf2-independent induction of phase 2 detoxifying and antioxidant enzymes during keratinocyte differentiation

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 H2O2, 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.

Comparative study of the bactericidal effects of 5-aminolevulinic acid with blue and red light on Propionibacterium acnes.

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.