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Background/objective Acral and cutaneous melanomas are usually difficult to accurately diagnose in the early stage, owing to the similarity in clinical manifestations and morphology with those of dysplastic nevus (DN). In this study, we aimed to evaluate the diagnostic value of four-color fluorescence in-situ hybridization (FISH) probes specific to the RREB1,CCND1,and MYB genes, and centromere of chromosome 6, in distinguishing DN and melanoma. Methods Fifty one DN and 58 melanoma cases were collected and tested with four-color FISH. Histological features were reviewed and concordant morphologic diagnosis by three pathologists was considered the golden criterion. Results Fifty DN and 59 melanoma cases, with 37 melanomas in situ and 22 melanomas in Clark level 2, were confirmed finally; among them, 42 (71.2%) cases were acral. A comparison of clinicopathological features between the two entities showed that several features were considerably more frequently observed in the melanoma group, including more mitotic figures, stratum corneum pigmentation, lymphocyte infiltration, cell atypia, successive or pagetoid melanocyte growth pattern in the epidermis, larger tumor size, and older age at diagnosis. FISH was positive in 3 (6.0%) DN and 56 (94.9%) melanoma cases according to Gerami’s criteria. In distinguishing the two groups, the sensitivity of the four-color FISH was 94.9% and specificity was 94.0%.We found that CCND1 gain was the most sensitive, either in Gerami’s or Gaiser’s criteria. Further analysis showed that CCND1gain was more obvious in the acral group of melanoma. Conclusions We conclude that the four-color FISH test was highly sensitive and specific in distinguishing early-stage acral and cutaneous melanomas from dysplastic nevus in Chinese population, and the most sensitive criterion was the gain of CCND1.

COVID-19-Associated cutaneous manifestations are one of the most important and relatively common extra-respiratory presentations of SARS-COV-2 infection. The exact identification and classification of these lesions can facilitate the accurate diagnosis and treatment. There are several case reports and small case series which describe cutaneous lesions in hands and feet. Currently, there is no scoping review about acral skin manifestations associated with COVID-19. This paper covers the COVID-related acral skin manifestations in ten entities including acral papulo-vesicular eruption, acral urticarial lesion, acral non-inflammatory purpura and necrosis, acro-ischemia associated COVID-19, acral vasculitis, chilblain-like lesion (COVID Toe), acral erythema multiform (EM) like lesion, hand and foot skin lesions associated with multisystem inflammatory syndrome in children (MISC), acral peeling conditions and red half-moon nail sign. Future studies should focus on exact investigation of etiologies of these lesions including role of immune senescence, environment, gender, immunogenetics and relation of these lesion with major organ involvements. This article is protected by copyright. All rights reserved.

Verrucous xanthoma is a benign histiocytic lesion of macrophage derivation. We describe a woman with a non-mucosal verruciform xanthoma located on her right thumb and review the features of patients with verruciform acral-associated xanthoma. A 69-year-old woman presented with a lesion on her right thumb of eight years duration that had been previously treated with liquid nitrogen cryotherapy without resolution. An initial biopsy was consistent with the surface of a callous. A second biopsy demonstrated a verruciform xanthoma. The patient elected to apply lactic acid 12% twice daily and pare the lesion with a pumice stone once weekly; this resulted in flattening of the xanthoma-associated hyperkeratosis. Acral verruciform xanthoma has, albeit rarely, been described on the hands and feet of individuals. Including the patient in this report, six individuals have been reported with verrucous xanthoma on the hands and 12 individuals have been reported with a verrucous xanthoma on the feet. Verruciform xanthoma most commonly occurs on the oral mucosa. Genital lesions are also a frequent site. Acral-distributed verruciform xanthoma is rare; we propose that a verruciform xanthoma that occurs on acral sites be referred to as a verruciform acral-associated (Vacas) xanthoma.

Pemphigus vulgaris is an autoimmune disorder with many clinical variants. In this report, we present a 57-year-old female patient who presented with unilateral acral erosions, pustulations, and crusts, which was diagnosed as localized pemphigus vulgaris, which is a very rare variant of pemphigus.

Background The incidence of melanoma among those of an Asian ethnicity is lower than in Caucasians; few large-scale Asian studies that include follow-up data have been reported. Objectives To investigate the clinical characteristics of Japanese patients with melanoma and to evaluate the prognostic factors. Methods Detailed patient information was collected from the database of Japanese Melanoma Study Group of the Japanese Skin Cancer Society. The American Joint Committee on Cancer seventh Edition system was used for TNM classification. The Kaplan-Meier method and Cox proportional hazards model were used to estimate the impact of clinical and histological parameters on disease-specific survival in patients with invasive melanoma. Results In total, 4594 patients were included in this analysis. The most common clinical type was acral lentiginous melanoma (40.4%) followed by superficial spreading melanoma (20.5%), nodular melanoma (10.0%), mucosal melanoma (9.5%), and lentigo maligna melanoma (8.1%). The 5-year disease-specific survival for each stage was as follows: IA = 98.0%, IB = 93.9%, IIA = 94.8%, IIB = 82.4%, IIC = 71.8%, IIIA = 75.0%, IIIB = 61.3%, IIIC = 41.7%, and IV = 17.7%. Although multivariate analysis showed that clinical classifications were not associated with survival across all stages, acral type was an independent poor prognostic factor in stage IIIA. Conclusions Our study revealed the characteristics of melanoma in the Japanese population. The 5-year disease-specific survival of each stage showed a similar trend to that of Caucasians. While clinical classification was not associated with survival in any stages, acral type was associated with poor survival in stage IIIA. Our result might indicate the aggressiveness of acral type in certain populations.

Introduction Melanoma is considered a rare cancer among Asians with a wide range of mucocutaneous manifestations. Failure to recognize a lesion as melanoma at first presentation might delay surgery aimed at complete resection. Acral melanoma has been related with the highest rate of misdiagnosis (~30%) causing further delayed diagnosis. Reliability of patient’ history taking in melanoma has not yet been systematically reported. Presented cases Two patients visited our oncology clinic with pigmented lesions in their soles. A 66-year-old man disclosed it appeared since a year ago after accidently hitting a stone while farming. Physical examination showed a black-brown irregular 100 × 80 mm lesion covering the distal third of the right sole with ulceration in the central lesion. The second patient was a geriatric woman with a black-purple 25 × 27 mm lesion with slight protrusion and ulceration in the central, irregular border, and partial hyperkeratosis. She explained the lesion emerged two years ago after she accidently stepped on a nail. Both patients were then diagnosed with acral melanomas and were treated with wide-excision, closure with skin grafting, and inguinal dissection. Discussion Both patients reported history of traumas in lesions later confirmed as acral melanomas. Although history taking can provide up to 80% of the information for accurate diagnosis, in ambivalent cases, careful anamnesis, clinical examination, and biopsy are required to confirm diagnosis of acral melanoma. Early disease identification to establish definitive diagnosis of cancer is generally associated with better clinical outcomes. In suspected cases, vigilance toward misleading information in history taking is required., Highlights • Acral melanoma is associated with higher rates of misdiagnosis than other melanoma subtypes. • Elderly patients often have chronic podiatric lesions associated with history of trauma. • Caution concerning misleading information during history taking is required to avoid delayed diagnosis of melanoma. • Biopsy is warranted for all undetermined skin lesions including unresolved wounds after standard treatment.

Pityriasis rosea (PR) is a common, selflimited inflammatory skin condition, usually affects the trunk and proximal extremities. A variety of atypical manifestations of PR have been recognized ranging from the difference in the morphology, distribution, and course. Herein, the rare form of acral PR in an adult has been illustrated as the 29- year-old Thai female who presented with generalized erythematous papules and plaques with peripheral collarette scales on the trunk and extremities, prominently on the hands and feet.[...]

The coronavirus 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had enormous health, economic, and social consequences. The clinical spectrum of cutaneous manifestations observed in patients with COVID-19 is both heterogeneous and complex. To date, reports have identified 5 main categories: acral lesions, vesicular rashes, urticarial rashes, maculopapular rashes, and livedoid and necrotic lesions. However, these will probably be modified as new information comes to light. Cutaneous manifestations associated with COVID-19 probably reflect the activation of pathogenic pathways by the virus or a response to inflammatory processes, vascular or systemic complications, or even treatments. Familiarity with the cutaneous manifestations of COVID-19 may enable early diagnosis or help guide prognosis.

Chilblain‐like acral lesions have been identified in some coronavirus disease 2019 (COVID‐19) patients. It has been suggested that these pseudo‐chilblains could be a specific marker of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. Most patients with these lesions have had negative polymerase chain reactions (PCRs), but some authors believe serology tests are likely to give positive results. We designed a prospective study including all patients with pseudo‐chilblains treated in outpatient department in April and May 2020 and then performed SARS‐CoV‐2 PCR and serology tests on all available patients. We evaluated 59 patients, of whom 17 had undergone PCR before the study period, all with negative results. For the present study, we performed 20 additional PCRs, serology tests in 25 patients, and a parvovirus B19 antibody test in 15 patients. All results were negative. Our findings counter the hypothesis that serology is likely to reveal SARS‐CoV‐2 infection in patients with pseudo‐chilblains. One hypothesis for our negative results is that the time period between symptom onset and antibody production is longer in these patients; another is that the lesions are caused by behavioral changes during lockdown rather than SARS‐CoV‐2 infection. We nevertheless maintain that COVID‐19 should be ruled out in people presenting with chilblain‐like lesions.

Recently, young COVID‐19 patients have presented with erythematous and purpuric acral lesions similar to chilblains1–3. Despite the scarcity of published cases, this topic has attracted significant mass media attention.4 Dermatologists have noted that more people than would be expected at this time of year are seeking medical attention for these chilblain‐like lesions. Some have suggested that people presenting with this manifestation should be tested and isolated2. Determining the accuracy of this association is therefore crucial. To establish the real prevalence of COVID‐19 in patients with acral skin lesions, we firstly evaluated all the cases of acral lesions presented in dermatology and paediatrics departments and family doctors’ offices in an eastern Spanish region over a three‐week period. Then we prospectively performed a SARS‐CoV‐2 PCR on nasopharyngeal aspirates taken from all available patients to determine whether their cutaneous manifestations were predictive of a positive result. To put our findings into context, we reviewed all the articles published before May 2020 concerning COVID‐19 patients with cutaneous lesions. We evaluated 58 patients, whose characteristics are summarized in Table 1. In most cases, lesions were chilblain‐like. Fifteen patients had already been tested, and only one had a positive result: an 85‐year‐old man admitted for severe Covid‐19 pneumonia. He had an ulcer on a toe that was finally determined to be vascular in nature. We performed prospective PCR testing in 24 patients. All test results were negative. In total, then, PCR was negative in 38 patients and positive in a single patient whose lesion was very unlikely to be due to COVID‐19. Our bibliography search returned 97 articles and we found 2 more through cross‐references. Nine of these articles dealt with acral lesions specifically. Their results are summarized in Table 2. Data published in the literature are heterogeneous, as are the methods employed to collect them. The first papers looked at cutaneous manifestations in patients with confirmed SARS‐CoV‐2 infection.5–8 This approach cannot reveal whether this dermatologic manifestation is a specific marker of SARS‐CoV‐2 infection, since patients without COVID‐19 are not included. The other approach, which we have followed, is to analyse all patients with acral lesions. This can be done retrospectively, reporting on patients in the sample who have already been tested, or prospectively, performing the test on all available patients, regardless of whether they have symptoms. The retrospective method has a significant risk of confounding bias: due to the scarcity of COVID‐19 tests8, they are usually reserved for patients with COVID‐19‐related symptoms, who are obviously more likely to test positive. All previous studies including only patients with cutaneous acral lesions (summarized in table 2) have been retrospective, and only a minority of patients were tested. In total, 12 out of at least 49 tested patients were positive (24.5%). Combined with our results, they total 13 positives out of 88 tests (14.8%). There are two possible explanations for the high proportion of negative results: I) A high number of false negatives. II) The lesions are not related to SARS‐CoV‐2 infection. The low prevalence of an infected contact in our sample, after three weeks of strict confinement in Spain, makes the possibility of being infected in our cohort less likely. The diffusion of this entity by the mass media may have caused patients who would not normally consult to do so.9 . Other possible explanations include a concomitant parvovirus B19 outbreak10 or trauma‐induced lesions. Our study suggests that acral skin lesions are not a specific marker of SARS‐CoV‐2 infection. Although larger prospective studies are needed, current evidence indicates that acral skin lesions should not be regarded as a sign of COVID‐19 in otherwise asymptomatic patients.

Cellular digital fibroma is a benign fibrous lesion that typically occurred on either a finger or a toe. Cellular digital fibroma was introduced as a distinctive cluster of differentiation 34 (CD34)-positive lesion in July 2005. Cellular digital fibroma has been described in 20 patients: 12 men and 8 women. The patients ranged in age from 27 to 83 years old (median, 52 years old) at diagnosis. The tumor had been present from 2 months to 2 years (median, 11 months) prior to seeking medical attention. The cellular digital fibroma was usually slowly growing and asymptomatic; there has been no prior history of trauma at the tumor site. The lesion typically presented as either an erythematous or a flesh-colored, solitary papule of 5 mm or smaller. It frequently occurred on either the dorsal, lateral or ventral side of a digit. Yet, some of the lesions were located on the nail fold of the digit. Cellular digital fibroma shows a prominent cellular proliferation of spindle-shaped fibroblasts, without any atypia or mitoses, that extends from the papillary into the upper reticular dermis; diffuse and strongly positive CD34 staining is present throughout the entire tumor. There is no erosion by the tumor of the bony phalanx. Other acral tumors, such as superficial acral fibromyxoma (which also has diffuse strongly positive CD34 staining) and acquired digital fibrokeratoma (which is either CD34-negative or only focal CD34 positive), are in the clinical and pathologic differential diagnosis of cellular digital fibroma. Conservative complete excision is the treatment of cellular digital fibroma; however, even for tumors that have only been partially removed during biopsy, recurrence has not been observed. In conclusion, cellular digital fibroma is a unique CD34-positive acral lesion of the distal fingers and toes whose diagnosis requires correlation of the clinical morphology and the pathologic features of the tumor.

Cutaneous vascular malformations (CVM) represent a spectrum of human diseases identified at birth or in paediatric patients and classified according to the type of vessel affected. Confusing classification in human medicine has led to misdiagnoses and frequent nomenclature revision. Cutaneous lymphatic malformations (CLM) are reported sporadically in humans.To describe the clinicopathological findings of superficial dermal cutaneous lymphatic malformations (SDCLM) in two cats.Two unrelated adult domestic short hair cats.The two cats were evaluated clinically and with a dermoscope for recurrent swelling and presence of vesicles oozing serosanguineous fluid affecting the right and left hind foot, respectively, since birth. Skin biopsy specimens were collected for histopathological and immunohistochemical evaluation and electron microscopy.A CVM was suspected based on the age of onset, clinical signs, results of diagnostic imaging and histopathological findings. Dermoscopy was used to describe the alterations of the skin surface. The involvement of the lymphatic vessels was confirmed using immunohistochemical findings and electron microscopy.To the best of the authors' knowledge, this is the first description of the clinical, dermoscopic, histopathological and ultrastructural characteristics of SDCLM in cats resembling the human counterpart. SDCLMs are rare conditions and appropriate histopathological and immunohistochemical confirmation is required to avoid misdiagnosis and mistreatment.Les malformations vasculaires cutanées (CVM) représentent un spectre de maladies humaines identifiées à la naissance ou chez les enfants et sont classés selon le type de vaisseaux atteints. Une classification trouble en médecine humaine a mené à des erreurs de diagnostic et de fréquentes révisions de nomenclature. Les malformations lymphatiques cutanées (CLM) sont rapportées de façon sporadique chez l'homme.Décrire les données clinicopathologiques des malformations lymphatiques cutanées dermiques superficielles (SDCLM) chez deux chats.Deux chats européens adultes non apparentés. MÉTHODES: Les deux chats ont été évalués cliniquement et avec un dermoscope pour écoulement cutané récidivant et la présence de vésicules séro-sanguinolentes localisées sur les extrémités postérieures respectivement, droite et gauche, depuis la naissance. Des biopsies cutanées ont été prélevées pour histopathologie, immunohistochimie et microscopie électronique. RÉSULTATS: Une CVM a été suspectée sur l’âge d'apparition des lésions, les lésions cliniques, les résultats d'imagerie et d'histopathologie. La dermoscopie a été utilisée pour décrire les altérations de la surface cutanée. L'invasion des vaisseaux lymphatiques a été confirmée par immunohistochimie et microcopie électronique.A la connaissance des auteurs, ceci est la première description des caractéristiques cliniques, dermoscopiques, histopathologiques et ultra structuraux de SDCLM chez les chats ressemblants à l’équivalent de l'homme. Les SDCLMs sont des atteintes rares et une confirmation histopathologique et immunohistochimique est nécessaire pour éviter une erreur de diagnostic et un traitement inadapté.INTRODUCCIÓN: las malformaciones vasculares cutáneas (CVM) representan un espectro de enfermedades humanas identificadas al nacer o en pacientes pediátricos y clasificadas según el tipo de vaso afectado. La clasificación confusa en medicina humana ha llevado a diagnósticos erróneos y una revisión frecuente de la nomenclatura. Las malformaciones linfáticas cutáneas (CLM) se reportan esporádicamente en humanos. OBJETIVO: describir los hallazgos clinicopatológicos de malformaciones linfáticas cutáneas superficiales (SDCLM) en dos gatos. ANIMALES: dos gatos domésticos adultos de pelo corto no relacionados. MÉTODOS: los dos gatos fueron evaluados clínicamente y con un dermatoscopio debido a la presencia de inflamación recurrente y la formación de vesículas que exudaban líquido serosanguinolento y que afectaban desde el nacimiento a extremidades posteriores derecha e izquierda, respectivamente. Se recogieron muestras de biopsia de piel para evaluación histopatológica e inmunohistoquímica y microscopía electrónica. RESULTADOS: se sospechaba una CVM en función de la edad de inicio y los signos clínicos, los resultados de pruebas de imagen y los hallazgos histopatológicos. La dermatoscopia se utilizó para describir las alteraciones de la superficie de la piel. La afectación de los vasos linfáticos se confirmó mediante hallazgos inmunohistoquímicos y microscopía electrónica. CONCLUSIÓN E IMPORTANCIA CLÍNICA: a entender de los autores, esta es la primera descripción de las características clínicas, dermatoscópicas, histopatológicas y ultraestructurales de SDCLM en gatos que tienen similitud a casos similares en medicina humana. Los SDCLM son condiciones poco frecuentes y se requiere una confirmación histopatológica e inmunohistoquímica adecuada para evitar diagnósticos erróneos y tratamiento inadecuado.Kutane Blutgefäßmissbildungen (CVM) repräsentieren ein Spektrum an Erkrankungen des Menschen, die bei der Geburt oder bei Pädiatriepatienten identifiziert und nach dem betroffenen Blutgefäßtyp eingeteilt werden. Eine verwirrende Einteilung in der Humanmedizin hat zu falschen Diagnosen und häufiger Revision der Nomenklatur geführt. Beim Menschen werden kutane lymphatische Missbildungen (CLM) sporadisch beschrieben.Eine Beschreibung der klinisch-pathologischen Befunde der oberflächlichen dermalen lymphatischen Malformationen (SDCLM) bei zwei Katzen.Zwei nicht verwandte erwachsene europäische Kurzhaarkatzen.Die zwei Katzen wurden klinisch sowie mit einem Dermoskop auf wiederkehrende Schwellungen und das Auftreten von Bläschen, die serosanguinöse Flüssigkeit absonderten und seit der Geburt den rechten bzw den linken Hinterfuß betrafen, evaluiert. Die Dermoskopie wurde eingesetzt, um die Veränderungen der Hautoberfläche zu beschreiben. Die Beteiligung von lymphatischen Gefäßen wurde mittels immunhistochemischer Befunde und Elektronenmikroskopie bestätigt.Nach bestem Wissen der Autoren handelt es sich hierbei um die erste Beschreibung der klinischen, dermoskopischen, histopathologischen und ultrastrukturellen Charakteristika von SDCLM bei Katzen, welche dem humanen Pendant entspricht. SDCLMs sind seltene Erkrankungen, bei denen eine entsprechende histopathologische und immunhistochemische Bestätigung nötig ist, um eine falsche Diagnose und eine falsche Behandlung zu verhindern.背景: 皮膚血管奇形(CVM)は、出生時または小児患者で特定され、罹患血管の種類に応じて分類される人医療領域を示した疾患である。人医学分類がの混乱が誤診を招き、頻繁な命名法の改訂が行われている。人では皮膚リンパ管奇形(CLM)が散発的に報告されている。 目的: 本研究の目的は、2匹の猫における真皮浅層皮膚リンパ奇形(SDCLM)の臨床病理学的所見を説明することであった。 供試動物: 遺伝的に無関係な2匹のドメスティックショートヘア、成猫。 方法: 2匹の猫を臨床的に評価し、出生時からそれぞれ罹患した下右後肢および左後肢の再発性腫脹および滲出性漿液性小水胞の存在についてダーモスコープで評価した。組織病理学的および免疫組織化学的評価および電子顕微鏡検査のため、皮膚生検サンプルを収集した。 結果: 発症年齢、臨床徴候、画像診断の結果および組織病理学的所見に基づいて、CVMが疑われた。皮膚表面の変化を記述するため、ダーモスコピーを使用した。リンパ管の関与は、免疫組織化学的所見および電子顕微鏡を使用して確認された。 結論と臨床的重要性: 著者の知る限りでは、本症例は人に相当する猫のSDCLMの臨床的、皮膚鏡検査、組織病理学的および超微細構造的特徴の最初の記述である。 SDCLMはまれな疾患であり、誤診や誤治療を避けるために適切な組織病理学的および免疫組織化学的確認が必要である。.背景: 皮肤血管畸形(CVM)是人类在出生或童年时罹患的一类疾病,需要根据发病血管的类型进行分类。人医的分类混乱常导致误诊和频繁的命名修订。皮肤淋巴管畸形(CLM)在人医中鲜有报道。 目的: 报告2只猫真皮浅层皮肤淋巴管畸形(SDCLM)的临床病理表现。 动物: 两只不相关的成年家养短毛猫。 方法: 对两只猫进行临床评价,并在出生后用皮肤镜分别评价是否出现复发性肿胀,以及右后足和左后足是否存在囊泡渗出浆液血性液体。收集皮肤活检样本,进行组织病理学和免疫组化评估及电镜观察。 结果: 根据发病年龄、临床体征、诊断性影像学结果和组织病理学结果,怀疑为CVM。皮肤镜用于描述皮肤表面的变化。免疫组化结果和电镜证实了淋巴管发病。 结论和临床重要性: 据作者所知,这是首次发现与人类相似的猫SDCLM,并报告了其临床、皮肤镜、组织病理学和超微结构特征。SDCLM 是罕见疾病,需要适当的组织病理学和免疫组化证实,以避免误诊和误治。.As malformações vasculares cutâneas (CVM) representam um espectro de doenças humanas identificadas ao nascimento ou em pacientes pediátricos e são classificadas de acordo com o tipo de vaso afetado. A classificação confusa em medicina humana levou a diagnósticos errôneos e frequente revisão de nomenclatura. Malformações cutâneas linfáticas (CLM) são relatadas esporadicamente em humanos.Descrever os achados clinicopatológicos de malformações cutâneo linfáticas dérmicas (SDCLM) em dois gatos.Dois gatos domésticos de pelo curto adultos. MÉTODOS: Os dois gatos foram avaliados clinicamente e com um dermatoscópio por inchaço recorrente e presença de vesículas drenando fluido serossanguinolento afetando a pata direita e esquerda, respectivamente, desde o nascimento. Amostras de biópsia cutânea foram coletadas para avaliação histopatológica e imunohistoquímica e microscopia eletrônica.Suspeitou-se de CVM baseado na idade de surgimento, sinais clínicos, resultados de diagnóstico por imagem e achados histopatológicos. A dermatoscopia foi utilizada para descrever as alterações na superfície da pele. O envolvimento dos vasos linfáticos foi confirmado utilizando os achados de imunohistoquímica e microscopia eletrônica. CONCLUSÃO E IMPORTÂNCIA CLÍNICA: De acordo com os conhecimentos do autor, esta é a primeira descrição das características clínicas, dermatoscópicas, histopatológicas e ultraestruturais da SDCLM em gatos correlata à forma humana. SDCLMs são doenças raras e a confirmação histopatológica e imunohistoquímica é necessária para evitar erros de diagnóstico e tratamento.

Aim The aim of the study was to evaluate the efficacy and safety of nivolumab combined with ipilimumab in treatment-naive Japanese patients with advanced melanoma. Methods In this multicentre, single-arm study, treatment-naive Japanese patients with unresectable stage III/IV or recurrent melanoma received nivolumab (1 mg/kg) plus ipilimumab (3 mg/kg) every 3 weeks for four doses, followed by biweekly doses of nivolumab (3 mg/kg). The primary end-point was centrally assessed objective response rate (ORR). Secondary end-points included overall survival (OS), progression-free survival (PFS), disease control rate and safety. Results The subtypes of the thirty patients enrolled were: 12, mucosal; eight, non-acral cutaneous; seven, acral; two, uveal and one, unknown primary melanoma. The ORR was 43.3% (95% confidence interval [CI]: 25.5, 62.6) with central and local assessment. The centrally and locally assessed disease control rate (95% CI) were 73.3% (54.1, 87.7) and 86.7% (69.3, 96.2), respectively. At the median follow-up period of 14.1 months (range 5.2–27.7), median OS and centrally assessed PFS were not reached. OS (95% CI) at 6, 12, 18 and 24 months was 93.3% (75.9, 98.3), 83.3% (64.5, 92.7), 72.9% (50.0, 86.5) and 65.6% (40.4, 82.2), respectively. Treatment-related adverse events (AEs) occurred in all patients. Grade III–IV and serious AEs occurred, mostly during the combination phase, in 23 (76.7%) and 20 (66.7%) patients, respectively. No treatment-related deaths occurred. Conclusions This study confirmed the efficacy and safety of nivolumab plus ipilimumab in treatment-naive Japanese patients with advanced melanoma including rare subtypes. Incidence rates for grade III–IV AEs were high but manageable with appropriate medical attention and treatment. Trial registration JapicCTI-152869.

Background The tumor microenvironment including immune surveillance affects malignant melanoma (MM) behavior. Nuclear factor κB (NF-κB) stimulates the transcription of various genes in the nucleus and plays a role in the inflammatory process and in tumorigenesis. CD8+ T cells have cytotoxic properties important in the elimination of tumors. However, inhibitory receptors on the cell surface will bind to programmed death-ligand 1 (PD-L1), causing CD8+ T cells to lose their ability to initiate an immune response. This study analyzed the association of NF-κB and PD-L1 expression levels and CD8+ T-cell counts with depth of invasion of acral MM, which may be a predictor of aggressiveness related to an increased risk of metastasis. Methods A retrospective cross-sectional study was conducted in the Department of Anatomical Pathology, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin Hospital using 96 cases of acral melanoma. Immunohistochemical staining was performed on paraffin blocks using anti–NF-κB, –PD-L1, and -CD8 antibodies and invasion depth was measured using dotSlide-imaging software. Results The study showed significant associations between the individual expression of NF-κB and PD-L1 and CD8+ T-cell number, with MM invasion depth. NF-κB was found to be a confounding variable of CD8+ T-cell number (p < .05), but not for PD-L1 expression (p = .154). Through multivariate analysis it was found that NF-κB had the greatest association with the depth of invasion (p < .001), whereas PD-L1 was unrelated to the depth of invasion because it depends on the number of CD8+ T cells (p = .870). Conclusions NF-κB plays a major role in acral MM invasion, by decreasing the number of CD8+ T cells in acral MM.

Psoriasis is resistant to treatment and it shows frequent relapse; systemic treatment is often associated with toxicities, and long-term safety data are lacking for most of the newer drugs like biologics. Moreover, some body areas such as hands, feet, intertriginous areas, scalp, and nails are even more resistant. Frequently, systemic treatments are necessary considering the higher psychological impact on the patient. There is a lack of agreement on the best therapeutic modalities in the management of psoriasis involving difficult-to-treat locations. At present, there are no Indian guidelines for these conditions. Available literature has been reviewed extensively on the treatment of psoriasis involving difficult-to-treat locations; level of evidence has been evaluated as per the Oxford Centre for Evidence-Based Medicine 2011 guideline, and therapeutic suggestions have been developed. Best care has been employed to consider socioeconomic, cultural, genetic, and ethnic factors to prepare a therapeutic suggestion that is appropriate and logical to be used among Indian population and people of similar ethnic and socioeconomic background.

Background Nivolumab has been widely studied in non-acral cutaneous melanoma; however, limited data are available in other melanoma subtypes. We report outcomes by melanoma subtype in patients who received nivolumab after progression on prior ipilimumab. Patients and methods CheckMate 172 was a phase II, single-arm, open-label, multicentre study that evaluated nivolumab in patients with advanced melanoma who progressed on or after ipilimumab. Patients received 3 mg/kg of nivolumab, every 2 weeks for up to 2 years. The primary end-point was incidence of grade ≥3, treatment-related select adverse events (AEs). Results Among 1008 treated patients, we report data on patients with non-acral cutaneous melanoma (n = 723 [71.7%]), ocular melanoma (n = 103 [10.2%]), mucosal melanoma (n = 63 [6.3%]), acral cutaneous melanoma (n = 55 [5.5%]) and other melanoma subtypes (n = 64 [6.3%]). There were no meaningful differences in the incidence of grade ≥3, treatment-related select AEs among melanoma subtypes or compared with the total population. No new safety signals emerged. At a minimum follow-up of 18 months, median overall survival was 25.3 months for non-acral cutaneous melanoma and 25.8 months for acral cutaneous melanoma, with 18-month overall survival rates of 57.5% and 59.0%, respectively. Median overall survival was 12.6 months for ocular melanoma and 11.5 months for mucosal melanoma, with 18-month overall survival rates of 34.8% and 31.5%, respectively. Conclusions The safety profile of nivolumab after ipilimumab is similar across melanoma subtypes. Compared with non-acral cutaneous melanoma, patients with acral cutaneous melanoma had similar survival outcomes, whereas those with ocular and mucosal melanoma had lower median overall survival. ClinicalTrials.gov ID : NCT02156804 .

Opinion statement Melanoma has several clinically and pathologically distinguishable subtypes, which also differ genetically. Mutation patterns vary among different melanoma subtypes, and efficacy of immune-checkpoint inhibitors differs depending on the subtype of melanoma. In spite of the recent revolution of systemic therapies for advanced melanoma, access to innovative agents is still restricted in many countries. This review article aimed to describe the epidemiology and current status of systemic therapies for melanoma in Japan, where melanoma is rare, but access to innovative agents is available. Acral and mucosal melanomas, which are common in Asian populations, predominantly occur in sun-protected areas and share several biological features. Both the melanomas harbor KIT mutation in approximately 15% of the cases; BRAF or NRAS mutation is found in approximately 10–15% of acral melanoma, but these mutations are less frequent in mucosal melanoma. Combined use of BRAF and MEK inhibitors is one of the standards of care for patients with advanced BRAF-mutant melanoma. In patients with melanoma harboring KIT mutation in exon 11 or 13, KIT inhibitors can be a treatment option; however, none of them have been approved in Japan. Immune-checkpoint inhibitors are expected to be less effective against acral and mucosal melanomas because their somatic mutation burden is lower than those in non-acral cutaneous melanomas. A recently completed phase II trial of nivolumab and ipilimumab combination therapy in 30 Japanese patients with melanoma, including seven with acral and 12 with mucosal melanoma, demonstrated an objective response rate of 43%. Regarding oncolytic viruses, canerpaturev (C-REV, also known as HF10) and talimogene laherparepvec (T-VEC) are currently under review in early phase trials. In the adjuvant setting, dabrafenib plus trametinb combination, nivolumab monotherapy, and pembrolizumab monotherapy were approved in July, August, and December 2018 in Japan, respectively. However, most of the adjuvant phase III trials excluded patients with mucosal melanoma. A phase III trial of adjuvant therapy with locoregional interferon (IFN)-β versus surgery alone is ongoing in Japan (JCOG1309, J-FERON), in which IFN-β is injected directly into the site of the primary tumor postoperatively, so that it would be drained through the untreated lymphatic route to the regional node basin. After the recent approval of these new agents, the JCOG1309 trial will be revised to focus on patients with stage II disease. In conclusion, acral and mucosal melanomas have been treated based on the available medical evidence for the treatment of non-acral cutaneous melanomas. Considering the differences in genetic backgrounds and therapeutic efficacy of immunotherapy, specialized therapeutic strategies for these subtypes of melanoma should be established in the future.

Pityriasis versicolor is a superficial mycosis affecting the skin. It is caused by malassezia species of fungi. Common sites of involvement are chest, neck and shoulders. We report a rare case of pityriasis versicolor affecting both arms and dorsum of both hands but sparing the commonly involved sites and masquerading vitiligo.

El sarcoma fibroblastico mixoinflamatorio es un tumor maligno de bajo grado de partes blandas, generalmente localizado en extremidades y que afecta a sujetos de mediana edad. Clinicamente, la lesion es infiltrativa, indolora y de curso evolutivo lento. Se presenta un caso que afecta la mano, haciendo una extensa revision de la bibliografia, con especial atencion a su diagnostico y tratamiento. Acral myxoinflammatory fibroblastic sarcoma is a rare low-grade malignant soft tissue tumor, usually observed in the extremities of middle-aged patients. Clinically, the lesion is infiltrating, pain-free and a slow progression. A case involving the hand is presented, doing an extensive review of the literatura, with particular attention to diagnosis and treatment.

Pantoea agglomerans is a rare Gram-negative bacterium most often implicated in plant diseases and opportunistic organ system infections in immunocompromised humans. Because P. agglomerans uncommonly causes skin infections and presents with nonspecific clinical and histological findings, dermatologic diagnosis may be delayed. Our patient had a unique skin eruption that persisted after multiple treatment regimens and was finally diagnosed as P. agglomerans cutaneous infection. It is important for clinicians to consider this uncommon skin infection in their differential diagnosis of erythematous papules and vesicles with systemic symptoms. Diagnosis is via bacterial culture as histology is usually nonspecific and may not offer a conclusive diagnosis. Risk factors that may be clues to this infection include the occupation of farming, recent hospitalization, immunosuppression, and skin compromise in the form of open wounds.

An 86-year old woman presented to our clinic with a partial black streaklike pigmentation on her right thumb nail, which extended from the distal toward the proximal nail plate. At first glance, a subungual hematoma was considered. However, turning the hand around revealed a large, irregular brown pigmentation on the glabrous skin of the thumb, which reached under the free edge of the nail (Fig 1).

Objectives Malignant melanoma is the eighth most commonly diagnosed malignancy in Nova Scotia, Canada. The incidence of and death from malignant melanoma are increasing, despite surgical resection of lesions. The risk for local recurrence after treatment is 3.2%. Our aim was to determine the characteristics of malignant melanoma and the risk for relapse in an industrial region of Nova Scotia. Methods We performed a retrospective analysis of the records of 90% of all melanoma patients in 1999–2010 in Cape Breton, Nova Scotia (N = 100). Data were derived from the patients’ medical records kept at the Cape Breton District Health Authority. Results Of the 100 cases of malignant melanoma, 57 were in men and 43 were in women. Treatment consisted of local excision for 91 patients, therapeutic lymph node dissection for 5 and no treatment for 2. Relapses occurred in 16 patients (10 men, 6 women) between 2003 and 2010. Eleven of the 16 patients with relapses (69%) were alive at 1 year, four (25%) at 2 years and three (19%)] at 5 years. The majority, 80/100, of patients are still alive without malignant melanoma, while two patients are alive but with malignant melanoma. Of the 18 patients who died, eight died from malignant melanoma. Conclusions We obtained a better 5-year survival rate (82%) than that reported in the literature (73%). In Cape Breton, more men than women have malignant melanoma and are more likely to have local recurrence. The long-term survival rate after relapse was poor.

Introduction Melanoma is the most deadly type of skin cancer with 75% of all skin cancer deaths within the US attributed to it. Risk factors for melanoma include ultraviolet exposure, genetic predisposition, and phenotypic characteristics (eg, fair skin and blond hair). Whites have a 27-fold higher incidence of melanoma than African-Americans (AA), but the 5-year survival is 17.8% lower for AA than Whites. It is reported continuously that AA have more advanced melanomas at diagnosis, and overall lower survival rates. This minority melanoma paradox is not well understood or studied. Objective To explore further, the possible explanations for the difference in melanoma severity and survival in AA within the US. Methods Qualitative review of the literature. Results Lack of minority-targeted public education campaigns, low self-risk perception, low self-skin examinations, intrinsic virulence, vitamin D differences, and physician mistrust may play a role in the melanoma survival disparity among AA. Conclusion Increases in public awareness of melanoma risk among AA through physician and media-guided education, higher index of suspicion among individuals and physicians, and policy changes can help to improve early detection and close the melanoma disparity gap in the future.

Background The role of the phosphatidylinositol-3 kinase signaling pathway in the development of acral melanoma has recently gained evidence. Phosphatase and tensin homologue (PTEN), one of the key molecules in the pathway, acts as a tumor suppressor through either an Akt-dependent or Akt-independent pathway. Akt accelerates degradation of p53. Objective We assessed the expression of PTEN, phospho-Akt (p-Akt), and p53 by immunohistochemistry in benign acral nevi, acral dysplastic nevi, and acral melanomas in the radial growth phase and with a vertical growth component. Methods Ten specimens in each group were included. Paraffin-embedded specimens were immunostained with antibodies for PTEN, p-Akt, and p53. We scored both the staining intensity and the proportion of positive cells. The final score was calculated by multiplying the intensity score by the proportion score. Results All specimens of benign acral nevi except one showed some degree of PTEN-negative cells. The numbers of p-Akt and p53-positive cells were higher in acral dysplastic nevi and melanoma than in benign nevi. P-Akt scores were 1.7, 1.8, 2.6, and 4.4, and p53 scores were 2.0, 2.1, 3.8, and 4.1 in each group. PTEN and p-Akt scores in advanced acral melanoma were higher than in the other neoplasms. Conclusion The expression of PTEN was decreased and the expression of p-Akt was increased in acral melanoma, especially in advanced cases. The PTEN-induced pathway appears to affect the late stage of melanomagenesis. Altered expression of p-Akt is thought to be due to secondary changes following the loss of PTEN.

Acral melanoma is the most frequent subtype in the Asian and Mexican mestizo populations. Dermoscopy is a noninvasive diagnostic technique that helps the differential diagnosis of pigmented skin lesions on acral volar skin. We, herein, present a case of acral congenital melanocytic nevus with a parallel ridge dermoscopic pattern. Since the parallel ridge pattern in a melanocytic lesion of the acral skin is classically ascribed to melanoma, the present case can be definitely labeled as "atypical" and worth of being elucidated in its histopathological correlates.

The etiology and pathogenesis of lentiginous acral melanomas are poorly understood. Recent studies have postulated that DNA repair mechanisms and cell growth pathways are involved in the development of melanoma, particularly changes in the MAPK pathways (RAS, BRAF, MEK 1/2, and ERK 1/2). The aim of this study is to assess the status of the MAP kinase pathways in the pathogenesis of acral melanomas. The authors examined the components of the RAS–RAF–MEK–ERK cascades by immunohistochemistry in a series of 16 primary acral melanomas by tissue microarray. The expression of MAP kinase cascade proteins changed in most cases. The authors observed that 57.14% of cases were BRAF positive and that 61.53%, 71.42%, and 71.42% of cases were positive for MEK2, ERK1, and ERK2, respectively; RAS was not expressed in 92.31%, and all cases were negative for MEK1. The absence of RAS and positivity for MEK2, ERK1, and ERK2 were most seen in invasive cases with high thickness. These aspects of the MAPK pathway require further examination in acral melanomas between different populations. Nevertheless, the results highlight significant alterations in the MAP kinase cascades that are related to histological indicators of prognosis in primary acral melanomas.

Background: Infantile hemangiomas (IH) on the extremities have not been systematically studied. Objective: We sought to describe the clinical characteristics and distribution patterns of IH affecting acral surfaces and to explore the relationship among these patterns, limb development, and IH pathogenesis. Methods: This was a retrospective multicenter cohort study. Photographic archives from 4 tertiary pediatric dermatology referral centers were searched for patients with IH larger than 1 cm and involving 1 or more digit. Hemangioma location, distribution, and morphologic subtype were recorded. Medical records were reviewed for demographic and clinical data. Results: In all, 73 patients were identified. The most common IH pattern resembled that of a "biker glove" (73%), followed by localized IH on the distal digits (14%), segmental IH extending over the distal digits (8%), and intermediate patterns (5%). Overall, 63% of acral IH were segmental, 26% indeterminate, and 11% localized. Five patients had associated structural anomalies. Complications were noted in 33% of cases. Limitations: Limitations were retrospective study design; selection bias based on recall and photography; documentation and follow-up were not standardized across institutions; and treatment information may not reflect current approaches. Conclusion: Acral IH display specific patterns and are associated with a relatively high risk of ulceration.

Indian children often present with atypical forms of pityriasis rosea (PR). We describe a female infant with acrally located eruptions consistent with a clinical diagnosis of PR. This is an extremely rare presentation of the disease.

Pityriasis versicolor is a superficial fungal infection of the skin caused by the yeast of the genus Malassezia and presents as hypo or hyper pigmented scaly macules. The most commonly affected sites include upper trunk, upper arms, neck and the abdomen. Lesions confined to the acral parts like hands and feet have rarely been reported. In this article the author reports a 40 year old male who presented with multiple hypo pigmented scaly macules confined to the acral parts (hands and wrist). The acral variant of pityriasis versicolor is considered to be a very rare clinical entity which prompted the author to report this case.

Bowen's disease commonly presents as a solitary asymptomatic plaque involving head and neck region or lower limbs. We present a case of a sixty seven-year-old man with an itchy, oozy, crusted solitary plaque on the right ring finger of eighteen months duration with histopathology consistent with Bowen's disease. The lesion was initially treated with topical 5% imiquimod but due to relapse and inadequate response to a second course, complete surgical excision followed by full thickness skin grafting was done. Recurrence after about 6 months in the form of a small papule adjacent to the initial site was also treated with excision. This report highlights the potential of Bowen's disease to mimic more common dermatoses and a high index of suspicion, supported by histopathology, is required to diagnose and treat it without delay, which in turn may require a multimodality approach. We also reviewed the current literature on the same.

Acral lentiginous melanoma (ALM) is the most common type of melanoma in dark skinned peoples and Asians. The mean age of ALM ranges from 55 to 68 years. We report a case of ALM in a 60-year-old male patient presented with growth over palmer surface of left thumb since 2 years. The prognosis of invasive acral melanoma is poor, but future studies are needed to know more about the clinical outcome of this malignancy.

Acanthosis nigricans (AN) is a dermatosis characterized by velvety, papillomatous, brownish-black, hyperkeratotic plaques, typically on the intertriginous surfaces and neck. The majority (80%) of AN occurs idiopathically or in benign conditions such as endocrinopathies like diabetes mellitus, polycystic ovary syndrome; metabolic syndrome and/or heritable disease. Malignancy-associated AN is rare. AN may rarely be associated with autoimmune diseases including systemic lupus erythematosus, due to antibodies to the insulin receptor, so-called type B insulin resistance. Here we report a case of AN in a case of diffuse progressive systemic sclerosis without evidence of insulin resistance.

Superficial angiomyxomas (SA) are clinically variable, infrequent, benign skin lesions. They are usually located on the trunk, but can also appear on the lower limbs, head, and neck. The present case, hence, is unusual, because the lesion developed on the toe. They are diagnosed histologically, and are characterized by being poorly delimited tumors with the presence of interstitial myxoid material and scanty cellularity. We discuss the clinical and histological features of digital SA as well as a brief outline of other myxoid lesions.

Hansen's disease is a chronic granulomatous disease caused by Mycobacterium leprae, an acid-fast bacillus that lives in the cytoplasm of macrophages and Schwann cells. Commonly affected areas include the peripheral nervous system, skin, upper respiratory tract, eyes, and testes. Patients may show no signs of the disease for up to 20 years after infection. The disease may present along a spectrum of clinical manifestations ranging from lepromatous leprosy to tuberculoid leprosy.1 The peripheral nervous system is often affected first, as patients present with numbness and paresthesia but no visible lesions. Cutaneous lesions are variable in presentation, depending on which pole of disease the patient has, but may include papules, nodules, and plaques. Lesions are typically hypopigmented, erythematous, or copper colored, and they may be associated with reduction or complete loss of sensation and anhidrosis.2 Hansen's disease rarely presents with verrucous lesions. This case report presents an unusual filiform verrucous presentation of Hansen's disease on the plantar aspect of the feet in a patient with lepromatous leprosy.

Background Malignant acrospiroma is a rare tumor of the eccrine sweat glands accounting for around 6% of all malignant eccrine tumors. Typically, it presents as large ulcerated nodules, and diagnosis can be challenging as it has great overlap with its benign counterpart. Case presentation We herein report a case of acral malignant acrospiroma, initially treated with surgical excision and adjuvant radiotherapy. After metastatic disease was confirmed, subject received multiple lines of chemo- as well as targeted therapy. Genomic testing was also done using next generation sequencing. Conclusion To the best of our knowledge, this is the first case of acral malignant acrospiroma with reported next generation sequencing results.