Gyong Moon Kim

The efficacy of 308-nm excimer laser/light (EL) and topical agent combination therapy versus EL monotherapy for vitiligo: A systematic review and meta-analysis of randomized controlled trials (RCTs)

BACKGROUND Combination therapies of excimer laser/light (EL) and various topical agents are widely used in the treatment of vitiligo. OBJECTIVE We sought to compare the efficacy of EL and topical agent combination therapy versus EL monotherapy for vitiligo. METHODS Manual searches of reference lists and computerized searches of the MEDLINE, EMBASE, and Cochrane library (from inception through December 15, 2014) were conducted to identify randomized controlled trials that assessed the efficacy of EL alone or in combination with topical agents for vitiligo. The primary outcome was treatment success (≥75% repigmentation), and the secondary outcome was treatment failure (<25% repigmentation); meta-analyses were performed when possible. RESULTS We analyzed 8 randomized controlled trials comprising a total of 425 patches/patients. The combination of EL and topical calcineurin inhibitors (4 studies: relative risk 1.93, 95% confidence interval 1.28-2.91; number needed to treat 4.5, 95% confidence interval 2.9-10) was superior to EL monotherapy for vitiligo. There was insufficient evidence to support beneficial effects of topical vitamin-D3 analogs (3 studies) and corticosteroids (1 study). LIMITATIONS These findings are based on small numbers of randomized controlled trials and heterogeneities among included studies are another limitation. CONCLUSION Topical calcineurin inhibitors in conjunction with EL are more effective compared with EL monotherapy.

Phototherapy for Vitiligo: A Systematic Review and Meta-analysis

Importance References to the expected treatment response to phototherapy would be helpful in the management of vitiligo because phototherapy requires long treatment durations over several months. Objective To estimate the treatment response of vitiligo to phototherapy. Data Sources A comprehensive database search of MEDLINE, EMBASE, and the Cochrane library from inception to January 26, 2016, was performed for all prospective studies. The main keywords used were vitiligo, phototherapy, psoralen, PUVA, ultraviolet, NBUVB, and narrowband. Study Selection All prospective studies reporting phototherapy outcome for at least 10 participants with generalized vitiligo were included. Of 319 studies initially identified, the full texts of 141 studies were assessed for eligibility, and 35 were finally included in the analysis. Of these, 29 studies included 1201 patients undergoing narrowband UV-B (NBUVB) phototherapy, and 9 included 227 patients undergoing psoralen–UV-A (PUVA) phototherapy. Data Extraction and Synthesis Two reviewers independently extracted the following data: study design, number and characteristics of the participants, phototherapy protocol, and rate of repigmentation based on the quartile scale. Single-arm meta-analyses were performed for the NBUVB and PUVA groups. Sample size–weighted means were calculated using a random-effects model for the repigmentation rates of the included studies. Main Outcomes and Measures The primary outcomes were at least mild (≥25%), at least moderate (≥50%), and marked (≥75%) responses on a quartile scale. Response rates were calculated as the number of participants who showed the corresponding repigmentation divided by the number of all participants enrolled in the individual studies. Results The meta-analysis included 35 unique studies (1428 unique patients). For NBUVB phototherapy, an at least mild response occurred in 62.1% (95% CI, 46.9%-77.3%) of 130 patients in 3 studies at 3 months, 74.2% (95% CI, 68.5%-79.8%) of 232 patients in 11 studies at 6 months, and 75.0% (95% CI, 60.9%-89.2%) of 512 patients in 8 studies at 12 months. A marked response was achieved in 13.0% (95% CI, 2.1%-23.9%) of 106 patients in 2 studies at 3 months, 19.2% (95% CI, 11.4%-27.0%) of 266 patients in 13 studies at 6 months, and 35.7% (95% CI, 21.5%-49.9%) of 540 patients in 9 studies at 12 months. For PUVA phototherapy, an at least mild response occurred in 51.4% (95% CI, 28.1%-74.7%) of 103 patients in 4 studies at 6 months and 61.6% (95% CI, 20.2%-100%) of 72 patients in 3 studies at 12 months. In the subgroup analyses, marked responses were achieved on the face and neck in 44.2% (95% CI, 24.2%-64.2%), on the trunk in 26.1% (95% CI, 8.7%-43.5%), on the extremities in 17.3% (95% CI, 8.2%-26.5%), and on the hands and feet in none after at least 6 months of NBUVB phototherapy. Conclusions and Relevance Long-duration phototherapy should be encouraged to enhance the treatment response in vitiligo. The greatest response is anticipated on the face and neck.

Characteristics of primary cutaneous lymphoma according to WHO‐EORTC classification in Korea

Background. Primary cutaneous lymphoma (PCL) is an extranodal non‐Hodgkin lymphoma with primary involvement of the skin. Epidemiological data on PCLs according to the World Health Organization/European Organization for Research and Treatment of Cancer classification (WHO‐EORTC) has not been investigated in Korea to date.

Successful treatment of Bowen's disease with ingenol mebutate 0.05% gel

1 Morgan MB, Lima-Maribona J, Miller RA, Kilpatrick T, Tannenbaum M. Pigmented squamous cell carcinoma of the skin: morphologic and immunohistochemical study of five cases. J Cutan Pathol 2000; 27: 381–386. 2 Satter EK. Pigmented squamous cell carcinoma. Am J Dermatopathol 2007; 29: 486–489. 3 Fraga-Braghiroli N, Stephens A, Oliviero M, Rabinovitz H, Scope A. Small brown circles: an important diagnostic clue for pigmented squamous cell carcinoma. J Am Acad Dermatol 2013; 69: e161–e163. 4 Zalaudek I, Citarella L, Soyer HP, Hofmann-Wellenhof R, Argenziano G. Dermoscopy features of pigmented squamous cell carcinoma: a case report. Dermatol Surg 2004; 30: 539–540. 5 Chung E, Marchetti MA, Pulitzer MP, Marghoob AA. Streaks in pigmented squamous cell carcinoma in situ. J Am Acad Dermatol 2015; 72: S64–S65.

Dermoscopic features of actinic keratosis and follow up with dermoscopy: A pilot study

Actinic keratosis (AK) is a common precursor of sun‐related squamous cell carcinoma. AK is difficult to be differentiated from other malignancies with the naked eyes. Dermoscopic features of AK were previously described in some studies, but not extensively investigated. We investigated the dermoscopic features of AK in Asians and assessed dermoscopy as a post‐treatment monitoring tool of AK. We retrospectively examined 34 AK lesions which had been diagnosed by histology. The changes of dermoscopic features and histopathological findings were assessed in all these lesions before and after treatment. Before treatment, 18 lesions were pigmented and 16 lesions were non‐pigmented AK dermoscopically. The frequent dermoscopic features of AK were keratin/scales (79.4%), red pseudonetwork (73.5%), targetoid‐like appearance (55.9%), rosette sign (38.2%) and absent fissures/ridges, crypts and milia‐like cysts. All the lesions had been treated with either photodynamic therapy, cryotherapy or 5% imiquimod cream. After treatment, dermoscopic features of 33 AK lesions were decreased or disappeared, and skin biopsies confirmed that atypical keratinocytes disappeared. One lesion showed accentuated and new dermoscopic features after treatment, and skin biopsy also showed progressing squamous cell carcinoma. In conclusion, scales, red pseudonetwork, targetoid‐like appearance and rosette sign were common dermoscopic findings of AK in Asians. In most cases, the treatment response correlated with the changes in dermoscopic features. These findings suggest that dermoscopy is a useful tool to monitor AK.

A case of metastatic squamous cell carcinoma arising from actinic cheilitis.

Actinic keratosis (AK) is a common, sun-induced, pre-malignant lesion with a strong likelihood of progressing to a malignancy. The reported risk of AK progressing to squamous cell carcinoma (SCC) varies from less than 1% to 20%. Clinically, induration, pain, large size, marked hyperkeratosis, ulceration, bleeding, rapid growth, and recurrence or persistence may be markers of AK progression into SCC. The risk of SCC metastasizing ranges between 0.5% and 3%. However, SCC of the lip arising from actinic cheilitis is more prone to metastasis than cutaneous SCC, with rates of the former varying between 3% and 20%. Here we report a typical case of SCC from actinic cheilitis with metastasis to the lymph nodes during a 4-year follow-up period. To exclude SCC, we emphasize the need for regular follow-up and prompt evaluation, including careful pathologic examination for actinic cheilitis.

Notch Intracellular Domain Expression in Various Skin Fibroproliferative Diseases

Background The effects of the Notch signaling pathway in fibroproliferative skin diseases have not been fully elucidated. Objective The aim of this study was to investigate the expression of activated Notch signaling molecules in various skin fibroproliferative diseases. Methods Immunohistochemical analysis of Notch intracellular domain (NICD) expression in keloid, hypertrophic scar, morphea, dermatofibroma, and normal control skin specimens was performed, and the clinical characteristics of patients with various skin fibroproliferative diseases were analyzed. Results NICD was highly expressed in fibroblasts of keloids and moderately to highly expressed in hypertrophic scars and dermatofibromas, whereas low or no expression was detected in the fibroblasts of normal skin specimens and morpheas. NICD was constitutively expressed in keratinocytes, endothelial cells, and immune cells in normal skin specimens. Conclusion NICD was significantly expressed in human fibroproliferative skin disorders, especially keloids, suggesting that an activated Notch signaling pathway is involved in the pathogenesis of skin fibrosis.

Carcinoma erysipeloides from adenocarcinoma of the lung.

Dear Editor: Lung cancer usually metastasizes the brain, bone, liver, adrenal gland, kidneys, and gastrointestitnal tract1. Lung cancer is the first cancer of cutaneous metastasis found in men and is second to breast cancer for women2. Adenocarcinomas have been estimated to account from 3.1% to 45.0% for cutaneous lung metastases1,3. Some adenocarcinomas to the skin from the lung show well-formed, glandular structures, which are similar to gastrointestinal metastatic adenocarcinomas2. A 67-year-old woman was referred for a pruritic, erythematous plaque on the neck for two months. The lesion was a solitary, indurated, nontender plaque (Fig. 1). A workup with weight loss and epigastric pains included a computed tomography (CT) of the chest and abdomen was performed 4 months prior to the presentation of the neck mass. The chest CT showed a enhancing mass lesion which probably indicated lung cancer. In addition, the abdomen CT and endoscopic retrograde cholangiopancreatography which were performed at that time also revealed a gall bladder (GB) carcinoma and cholangiocarcinoma. The patient subsequently received a stent insertion into the common bile duct (CBD) due to distal duct obstructions. Further workups, including a full body and brain positron emission tomography-computed tomography, demonstrated an intense and localized fluorodeoxyglucose (FDG) uptake which suggested primary lung cancer. The GB carcinoma and cholangiocarcinoma also showed. The brain and neck including thyroid displayed no definite abnormal metabolisms. The patient denied further treatments. After 4 months, she visited our outpatient clinic because of a skin lesion in the neck. The biopsy specimen showed well-circumscribed tumor nodules in the lymphatic vessel. The tumor was composed of pleomorphic cells with eosinophilic cytoplasm and mitotic figures. Rare gland formation was being noted (Fig. 2A). The tumor was stained positively for carcinoembryonic antigen, cytokeratin, and thyroid transcription factor 1 (TTF-1) (Fig. 2B) but negatively for desmin. The fact indicated that the mass in the left lung should be a lung cancer. Therefore, the carcinoma erysipeloid lesion lies in its potential as a diagnostic marker for internal malignancy even though the lung biopsy was not performed. Fig. 1 A solitary, irregular-shaped, erythematous plaque on the neck. Fig. 2 (A) Well-circumscribed tumor nodules in the lymphatic vessel (HE inset ×200). (B) Thyroid transcription factor-1 (TTF-1)-positive cells (TTF-1, original magnification ×40; inset ×200). ... Carcinoma erysipeloides is an uncommon form of cutaneous metastasis. Carcinoma erysipeloides is clinically characterized as a sharply defined, erysipelas-like, erythematous plaque associated with skin metastasis. These metastases suggest inflammatory skin changes due to the direct spread of tumor cells via dermal lymphatic vessels. Although carcinoma erysipeloides is usually caused by breast carcinoma, it is also associated with other malignancies, including adenocarcinoma of the pancreas, rectum, ovary, and parotid gland4. However, carcinoma erysipeloides in a female patient originated from adenocarcinoma of the lung has been observed very rarely. Cutaneous metastases are infrequently presented at the time of the cancer at the initial diagnosis. Several studies have demonstrated the utility of CK7, CK20 and TTF-1 when identifying the origin of tumors5. In the case of adenocarcinoma, immunohistochemistry is also quite useful. Nuclear expression of TTF-1 is a characteristic of both primary lung cancer and thyroid cancer. We suggest that adenocarcinoma of the lung should be taken into consideration as a possible cause of inflammatory cutaneous metastasis.

Myopericytoma of the facial cheek.

Dear Editor: A 44-year-old woman presented with a painful, solitary nodule on her right cheek. She noticed the flesh-colored nodule several years prior, and the nodule expanded slowly in size. There was no history of trauma. The patients past medical history and family history were unremarkable. Upon physical examination, a 0.5×0.7 cm-sized, skin-colored, firm nodule on the right cheek was seen (Fig. 1). The biopsy specimen revealed a concentric perivascular proliferation of blank, spindle-shaped myoid-appearing cells (Fig. 2A, B). Immunohistochemical stain showed diffuse immunoreactivity on smooth muscle actin and was negative for desmin (Fig. 2C, D). The CD34 stain highlighted only the endothelium of the vessel, but the perivascular concentric myoid tumor cells were not immunoreactive (Fig. 2E). From the clinicopathological findings, the diagnosis of myopericytoma (MPC) was made. Fig. 1 A 0.5×0.7 cm sized, skin-colored, subcutaneous nodule of the right cheek. Fig. 2 (A) Uncapsulated neoplasm situated in the subcutis (H&E, scanning view). (B) Proliferation of bland round to ovoid cells arranged in a concentric perivascular pattern and many thin-walled branching staghorn vessels (H&E, ×200). ... MPC is a rare, recently delineated tumor that originates from the perivascular myoid cells1. It was described by Granter et al.2 in 1998 and newly entered into a subgroup of perivascular tumors in the World Health Organization classification of soft tissue tumors3. MPCs are well-circumscribed and composed of a mixture of solid cellular areas intermixed with variable numbers of vascular channels. The latter are often elongated and display prominent branching, resulting in a stag-horn appearance. The cells in the solid areas are round, or short and spindle shaped with eosinophilic cytoplasm and vesicular nuclei. The presence of concentric layers of tumor cells around vascular channels resulting in a typical onion ring appearance is a hall mark of this tumor2. However, MPC tumors exhibits a broad spectrum of growth patterns: solid classic, hemangiopericytoma-like, angioleiomyoma-like, hypocellular fibroma-like, solitary fibrous tumor-like, glomus tumor-like, cellular immature, intravascular and malignant subtypes. The present case was classified as angioleiomyoma-like pattern. By immunohistochemistry, the neoplastic cells characteristically express muscle-specific actin, smooth muscle actin and h-caldesmon, and are negative for CD34 and desmin4. The differential diagnosis includes myofibroma/myofibromatosis, angioleiomyoma, or glomus tumors. Myofibroma/myofibromatosis shows a distinct biphasic pattern consisting of fascicles of spindle cells and immature appearing zones2. Although perivascular concentric growth pattern has been observed in a subset of angioleiomyoma, this is not the predominant histopathologic feature, and angioleiomyomas show positive reaction for desmin in the smooth muscle bundles. In contrast, MPC is usually negative or only focally positive for desmin5. Glomus tumors can be distinguished by tumor cells showing more abundant eosinophilic cytoplasm and distinct cell borders. In addition, glomus tumors lack the concentric orientations of tumor cells around vessels characteristic of MPC4. MPCs typically arise in subcutaneous tissue as single or multiple nodules on the extremities of adults, with only rare cases of multicentricity. MPC presents as a benign, slow-growing nodule, and may occasionally be painful. Tumors rarely exceed 2 cm in size. A rare malignant transformation has been reported as well5. Most MPCs do not recur following excision4. Our patient decided to leave her lesion untreated. Involvement of the face in MPC cases is previously undescribed in the Korean dermatologic literature. Presentation of this case of MPC on the cheek will aid others in recognizing this very rare entity.

A case of post-injury angiokeratoma circumscriptum of the chest.

Angiokeratomas represent vascular lesions and are histologically characterized by superficial vascular ectasia and overlying acanthosis and/or hyperkeratosis. Angiokeratomas can be classified into five types, with angiokeratoma circumscriptum representing the least common of the five types. Angiokeratoma circumscriptum presents at birth and frequently occurs unilaterally on the leg. Herein, we report a rare case of long term angiokeratoma circumscriptum (twelve years) on the right chest, discovered following the excision of a lipoma from the same area.