Acral melanoma foot lesions. Part 2: clinical presentation,diagnosis, and management

Acral melanoma (AM) is a rare subtype of cutaneous malignant melanoma found on acral skin, primarily on the soles of the feet. Although rare, it is the most common subtype of melanoma found in patients of African or Asian ethnicity and has a poor prognosis, often because of the more advanced stage of presentation at diagnosis. In the second of this two‐part series, we review the clinical presentation, histopathology, diagnosis and management of AM. Clinically, AM presents as a variegated lesion with blue–black pigment and irregular borders on acral skin. A parallel‐ridge pattern is a very specific dermoscopic finding for AM. The differential diagnoses of AM include acral naevus, pyoderma gangrenosum, pyogenic granuloma, verrucous carcinoma and peripheral neuropathy‐induced foot ulcers. If there is a clinical suspicion of AM, an excisional biopsy should be taken. Once diagnosis is confirmed by histology, surgical excision is the standard treatment. Overall, dermoscopy and histopathology are key tools in the diagnosis of AM. A greater emphasis on melanoma screening and awareness is essential in minority populations to improve survival outcomes in AM.     

Acral lentiginous melanoma: conventional histology vs. three-dimensional histology

Background  Patients with acral lentiginous melanoma (ALM) seem to have a poor prognosis. ALMs represent 4–10% of cutaneous melanomas in white populations. Surgery is mostly based on conventional histological evaluation. With micrographic surgery, continuously spreading tumours can be excised with smaller excision margins for better cosmesis and function.
Objectives  Clinical parameters and surgical strategies influencing the prognosis of patients with ALM were evaluated.
Methods  Two hundred and forty-one patients (44% male, 56% female) with stage I/II ALM were recorded during 1980–2006. One hundred and thirty-three patients underwent complete histology of three-dimensional excision margins (3D histology) using the paraffin technique. Risk factors for disease-specific and recurrence-free survival were estimated.
Results  Patients were aged 26–87 years (median 63) with median tumour thickness of 2·0 mm. The median follow-up was 41 months. Multivariate analysis identified ulceration, conventional histology and tumour thickness as risk factors for recurrence-free and disease-specific survival. Using 3D histology, excision margins were significantly smaller (median 7 vs. 20 mm) without an increased risk of local recurrences. Patients with 3D histology had a 5-year survival of 81% compared with 63% with conventional histology. Retrospective analysis with immunohistological methods (anti-Melan-A) could improve the diagnostic specificity in detecting further melanocytic cell nests.
Conclusions  Clinical and surgical risk factors seem to have different influences on the outcome of ALM. 3D histology allows reduction of excision margins by two-thirds without an increased risk of local recurrences and with better prognosis. 3D immunohistology could be a valuable diagnostic tool to reduce the rate of local recurrences.     

Paediatric morphoea: a holistic review. Part 1: epidemiology,aetiopathogenesis and clinical classification

Morphoea, also known as localized scleroderma, is a debilitating fibrosing disorder of uncertain aetiology, affecting the skin and subcutaneous tissues. Paediatric-onset disease is not uncommon and is associated with frequent relapses. The disease has complex pathogenetic mechanisms and multiple clinical subtypes, and affects children of all ages. Recent research has focused on elucidating the disease pathophysiology and identifying measures of disease activity. We performed a literature search on PubMed, MEDLINE and Google Scholar, using keywords such as ‘pediatric morphea’, ‘juvenile localised scleroderma’ and ‘juvenile systemic sclerosis’. Relevant studies, including randomized trials, reviews of standard current guidelines and original research articles, were selected, and results were analysed before being summarized. In the first of this two-part review, we provide a bird’s-eye view of the current literature concerning the epidemiology, aetiopathogenesis and clinical classification of paediatric morphoea; in Part 2, we review the diagnosis, markers of disease activity, management and natural history.     

Lupus erythematosus. Part I: epidemiology,genetics and immunology

Lupus erythematosus (LE) is an important dermatologic autoimmune disease and in many aspects, including epidemiology, genetics, immunology, diagnostics and treatment, may be regarded as model for many other autoimmune diseases. Constant efforts in the past years have unraveled important new aspects of LE pathogenesis. Among these are the genetic associations with immunoregulatory signaling pathways such as TNF‐, NF‐κB‐, IL23/IL17‐ and interferon pathway as well as new insights into the relevance of the innate immune system. Here Toll‐like receptors and neutrophils play a central role. The knowledge about immune and autoimmune interactions in LE pathogenesis and the contributing cell types is steadily increasing and has led to new therapeutic approaches using antibodies directed against the B‐cell activating factor BLyS. In the first part of this review article, the current knowledge about epidemiology, genetics and immunology is summarized. A second article will deal with diagnostics, clinical picture and different treatment modalities.     

Reporting regression in primary cutaneous melanoma. Part 1: history,histological criteria and pathogenesis

Regression is an important histopathological parameter reported for the diagnosis of primary cutaneous melanoma. Histological regression is defined by The College of American Pathologists as the replacement of tumour cells by lymphocytic inflammation, with attenuation of the epidermis, and nonlaminated dermal fibrosis with inflammatory cells, melanophagocytosis and telangiectasia. Histological regression may be reported as absent versus present and, if present, as complete, partial or segmental. The stages of histological regression are early, intermediate and late, depending on the extent of histological inflammation and fibrosis. Regression occurs when the host’s immune system attacks primary melanocytic tumour cells via tumour‐infiltrating lymphocytes, resulting in fibrosis. The immunological mechanisms driving complete, partial and segmental regression may vary. In this first part of this two‐part review, we review the history, histological criteria and pathogenesis of regression in primary cutaneous melanoma, while in Part 2 we will review the effect of histological regression on prognosis, evaluation and management.     

Acral cutaneous melanoma in caucasians: clinical features, histopathology and prognosis in 112 patients

BACKGROUND: Acral lentiginous melanoma (ALM) is the fourth distinct variant of cutaneous melanoma. The histological diagnosis and prognosis of ALM are still controversial. OBJECTIVES: To review the features of a large series of patients with ALM, and confirm the validity of the histological criteria for this type of melanoma. METHODS: A collection of 2642 patients with cutaneous melanoma was recorded during the period 1986-97, among these 187 were located on acral sites. Histological specimens were reviewed in 112 acral melanomas; the following study is based on this subgroup. RESULTS: Histological examination revealed acral lentiginous melanomas predominantly in palmoplantar and subungual locations (60%), while superficial spreading melanomas (SSM) were found mainly on the dorsal aspects of hands and feet (30%). Nodular melanomas (NM) (9%) occurred in all acral sites. The histological re-examination confirmed the characteristics of ALM as described by Reed in 1976. With increasing tumour thickness nesting of tumour cells and upward migration to the cornified layer was similarly observed. The 5-year survival rate for patients with primary acral melanoma without recognizable metastasis was 82%. ALM differed significantly in survival from SSM (P = 0.001) and lentigo maligna melanoma (P < 0. 001), but survival rates were similar to NM (P = 0.9). CONCLUSIONS: ALM, as diagnosed by current histological criteria, occur on the palms, soles and subungual sites, and have a poor prognosis.     

Mycology – an update. Part 1: Dermatomycoses: Causative agents,epidemiology and pathogenesis

Dermatomycoses are caused most commonly by dermatophytes. The anthropophilic dermatophyte Trichophyton rubrum is still the most frequent causative agent worldwide. Keratinolytic enzymes, e.g. hydrolases and keratinases, are important virulence factors of T. rubrum. Recently, the cysteine dioxygenase was found as new virulence factor. Predisposing host factors play a similarly important role for the development of dermatophytosis of the skin and nails. Chronic venous insufficiency, diabetes mellitus, disorders of cellular immunity, and genetic predisposition should be considered as risk factors for onychomycosis. A new alarming trend is the increasing number of cases of onychomycosis – mostly due to T. rubrum – in infancy. In Germany, tinea capitis is mostly caused by zoophilic dermatophytes, in particular Microsporum canis. New zoophilic fungi, primarily Trichophyton species of Arthroderma benhamiae, should be taken into differential diagnostic considerations of tinea capitis, tinea faciei, and tinea corporis. Source of infection are small household pets, particularly rodents, like guinea pigs. Anthropophilic dermatophytes may be introduced by families which immigrate from Africa or Asia to Europe. The anthropophilic dermatophytes T. violaceum, T. tonsurans (infections occurring in fighting sports clubs as “tinea gladiatorum capitis et corporis”) and M. audouinii are causing outbreaks of small epidemics of tinea corporis and tinea capitis in kindergartens and schools. Superficial infections of the skin and mucous membranes due to yeasts are caused by Candida species. Also common are infections due to the lipophilic yeast fungus Malassezia. Today, within the genus Malassezia more than 10 different species are known. Malassezia globosa seems to play the crucial role in pityriasis versicolor. Molds (also designated non‐dermatophyte molds, NDM) are increasingly found as causative agents in onychomycosis. Besides Scopulariopsis brevicaulis, several species of Fusarium and Aspergillus are found.     

Systemic sclerosis – dermatological aspects. Part 1: Pathogenesis,epidemiology, clinical findings

Systemic sclerosis is a chronic inflammatory multiorgan disease belonging to the group of collagen‐vascular disorders. With a prevalence of 10/100,000 inhabitants it may be regarded a rather rare disease. Its etiology and pathogenesis have still not been elucidated in detail, especially with regard to the differential involvement of skin and the cause of the clinically heterogeneous disease courses. Various components of the vasculature, connective tissue as well as the immune system are involved in a yet unknown sequence and significance. Patients need to be cared for in an interdisciplinary fashion depending on the individual organ involvement. Apart from the skin, the heart, kidneys and lungs are mainly affected in addition to frequent gastrointestinal and musculoskeletal symptoms. Clinically two distinct subsets may be separated, acral (also termed limited) and diffuse scleroderma, which are characterized by anti‐centromere and anti‐Scl‐70/topoisomerase‐1 antibodies, respectively. Recent data demonstrate a poor prognosis even in limited disease when pulmonary arterial hypertension develops at an early stage. In diffuse disease sudden and rapid onset will result in a sclerosis of major internal organs and early death in many cases.     

What’s new in atopic eczema? An analysis of systematic reviews published in 2017. Part 2: epidemiology,aetiology and risk factors

This article forms part of a series of annual updates that summarizes the evidence base for atopic eczema (AE). It provides a summary of key findings from 28 systematic reviews that were published or indexed during 2017, and focuses on the epidemiology, aetiology and risk factors of AE. AE is the largest single contributor to morbidity associated with skin disease worldwide, once mortality has been excluded. There is a high prevalence of sleep disturbance in individuals with AE and they take more sick leave than controls. While there is a lack of skin bacterial diversity in patients with AE, there is a relative abundance of Staphylococcus aureus and Staphylococcus epidermidis. Compared with controls, affected individuals more often show an IgE response to S. aureus antigens and have higher serum interleukin‐31 levels. Early antibiotic exposure, environmental pollutants, maternal atopy and food allergy are associated with an increased risk of AE, and very preterm birth is associated with decreased risk. Patients with AE have a reduced risk of meningioma, but are more likely to develop attention‐deficit hyperactivity disorder compared with controls. Patients with eosinophilic oesophagitis are significantly more likely than unaffected individuals to have AE. There is no significant overall association between AE and allergic contact dermatitis (ACD), and in children referred for patch testing, ACD was more common in those without AE. Hand eczema is more prevalent in patients with AE. There is no association between AE and Type 2 diabetes, hypertension, stroke or myocardial infarction.     

Antigenic phenotype of pigment cell lesions: a study of melanoma, its precursor lesions and heterogeneity in metastatic melanoma

Expression of surface antigens on cells comprising malignant, dysplastic, and benign pigment cell lesions has been evaluated in situ using an avidin-biotin immunohistologic technique. We have demonstrated expression of HLA-DR, beta 2-microglobulin, and 2 melanoma-associated antigens (MAA) in a range of benign and malignant lesion, and have confirmed the close association of HLA-DR and MAA on malignant lesions. In addition, 5 subcutaneous lesions removed at the same time from one individual were evaluated. Clinical and histologic appearance differed among lesions although the antigenic patterns were similar.     

Keloid disease: Review with clinical atlas. Part I: Definitions,history, epidemiology,clinics and diagnosis

Keloids are chronic progressive dermal pseudo-tumors that can grow considerably in volume and surface area but do not invade other tissues. They are usually triggered by dermal injury or inflammation, but they are not scars in the normal sense of the word, since they enlarge and progress over decades. The phenomenon usually referred to as “hypertrophic scars” represents a kind of keloidal process that does not extend beyond the initial site of injury and spontaneously regresses in 12–24 months. The multiplication of keloids and hypertrophic scars in a single patient is known as keloid disease. Keloid disease is due to a familial predisposition (autosomal dominant) that preferentially affects people of non-European ancestry, especially those of sub-Saharan African descent. Keloid disease has a deep impact on quality of life, not only because of disfiguring lesions, but also because of the frequency of associated intense neurogenic pruritus and pain, as well as recurrent bouts of suppuration. Diagnosis relies primarily on a good knowledge of the clinical characteristics of keloids, thus warranting the inclusion of a clinical atlas in the first part of the review. The second part will deal with the pathology, pathophysiology and treatment of keloid disease.     

Reporting regression in primary cutaneous melanoma. Part 2: prognosis,evaluation and management

The effect of histological regression on patient prognosis for primary cutaneous melanoma is controversial. Some authors hypothesize that regression indicates a robust systemic immune response and may decrease risk of metastasis. Others argue that histological regression calls into question a T0 diagnosis because there may have been an invasive component of the melanoma that is no longer visible but is still active. The literature to date does not suggest that histological regression is associated with increased risk of positive sentinel lymph node status, metastasis or increased risk of mortality. Thus, the presence of histological regression should not change patient staging, evaluation or management. The criteria used for reporting regression have varied dramatically across studies, and standardized reporting is needed to foster evidence-based practices in the future.     

Infantile haemangioma: Part I. Pathophysiology,epidemiology, clinical features,life cycle and associated structural abnormalities

Infantile haemangioma (IH) is the most common tumour of infancy. Its typical natural history is characterized by an early rapid growth following birth and a slow spontaneous regression phase within a period of 3 to 7 years. The exact aetiopathogeny underlying IH is still to be fully understood, but the role of fetal hypoxic stress is strongly suggested as a triggering signal in epidemiological studies. IH are composed of a complex mixture of cells including multipotent stem cells, a majority of immature endothelial cells, pericytes, dendritic cells and in the late stage, adipocytes. Most of IH are nodular and are not associated with malformations. However, in some cases, IH referred to as segmental may be associated with developmental abnormalities such as PHACES and PELVIS/SACRAL syndromes.     

Acral lentiginous melanoma treated with topical imiquimod cream: possible cooperation between drug and tumour cells

An 85‐year‐old woman presented with a lesion on the sole of her right foot, which was histologically confirmed as acral lentiginous melanoma. Because of the large field involved and because the patient refused any invasive or painful treatment, topical treatment with imiquimod was commenced. At the 20‐month follow‐up, the patient was still continuing treatment with topical imiquimod, and no metastases to the lymph nodes or viscera were found, either clinically or in imaging studies. We believe that the success of the treatment cannot be explained only by the stimulation of the immune system induced by imiquimod. A possible explanation might be ‘tumour dormancy’, where a tumour grows very slowly because of a balance between the neoplasia and the immune (and nonimmune) mechanisms of tumour control. The use of imiquimod has so far allowed our patient to avoid surgery, and perturbation of the mechanisms of tumour regulation, such as local immunity and angiogenesis, has not taken place.