Epidermal Nevus Research Articles

Somatic Variants of KRT1/KRT10 Identified by Next-generation Sequencing in Patients with Epidermal Nevi.

Abstract is missing (Short communication)

Identifying Genetic Mutations in Vascular Anomalies Using a Sequencing Panel for Childhood Cancers: A Pilot Study

Introduction: Genetic mutations have been identified in the pathogenesis of vascular anomalies. Due to overlaps in genetic variants causing vascular anomalies and cancer, we used a next-generation sequencing panel for genomic profiling of childhood cancers to detect somatic mutations in children with vascular anomalies. We aim to review the utility of an oncology panel for the molecular diagnosis of vascular anomalies. Methods: Nine patients with histologically confirmed vascular anomalies were included. DNA was extracted from formalin-fixed paraffin-embedded tissue specimens obtained from affected tissue following diagnostic punch biopsies of the skin and core biopsies of the vascular malformation or tumor during sclerotherapy or surgical excision. Molecular analysis of the tissue samples was performed using AmpliSeq for Childhood Cancer DNA Assay Panel. Results: Two patients had antenatally detected vascular anomalies. The median age at diagnosis for the remaining patients was 7.0 years (IQR, 0.6–10.0 years). Seven were diagnosed with vascular malformations, while 2 had vascular tumors. Pathological somatic mutations were identified in 4 patients, leading to a diagnostic yield of 44.4%. Two different PIK3CA mutations were identified in 3 cases: 1 in a case of macrocystic lymphatic malformation, the other in a case of Congenital Lipomatous Overgrowth, Vascular malformations, Epidermal nevus, Spinal/Skeletal anomalies syndrome and Klippel–Trenaunay syndrome. BRAF mutation was identified in a patient with a veno-lymphatic malformation. Conclusion: An oncology next-generation sequencing panel can be used for genetic profiling of vascular anomalies. However, a more customized and sensitive panel may be of better diagnostic yield, as detection of somatic mutations in vascular anomalies is challenging due to tissue mosaicism, low-abundant genetic variants, and specimen limitations.

An Individualistic Homoeopathic Approach in a Case of Infected Epidermal Naevus—A Case Report

AbstractNaevi are circumscribed developmental defects or the lack of one or more components of the skin that manifest as overgrowths or hamartomas derived from embryonic ectoderm. The majority of naevi are present at birth or appear soon after birth. Naevi can be infected by various organisms, particularly by Staphylococcus, without other systemic involvement, similar to the skin. A 30-year-old male patient presented with an infected, painful congenital epidermal naevus on the anterior side of his right thigh. He experienced severe itching, burning, and sudden blister formation. After treatment, the infection completely resolved, leaving the naevus without any complications. Possible causal attribution of these changes was determined using the Modified Naranjo Criteria (score: 8 out of 13). No recurrence of further infection was reported in the next year, demonstrating the positive curative role of individualized homeopathic treatment in a case of infected epidermal naevus.

Case report: segmental form of Hailey-Hailey disease

The article presents a clinical case of a rare segmental form of familial benign chronic pemphigus with a positive family history. Patient S., born in 2014, complained of unilateral eruptions in the area of the left retroauricular fold, left axilla, inguinal fold and labia majora on the left, plantar surface of the left foot. Eruptions were represented by erythematous foci, single blisters with serous contents, erosions, crusts. For the entire period, the patient was observed with the following diagnoses: microbial eczema, Sneddon-Wilkinson Disease, Inflammatory Linear Verrucose Epidermal Nevus. Due to the long-term relapsing course and ineffective therapy, additional examination methods were carried out – histological and genetic studies. Only after genetic testing, in which a heterozygous mutation of the ATP2C1 gene was revealed, and geneticist’s consultation, the final diagnosis was established – Hailey-Hailey Disease.It is known, that the segmental form is formed as a result of mosaicism, which can be of two types. The term "mosaicism" refers to the presence in an organism of two or more genetically heterogeneous cell populations formed from a genetically homogeneous zygote. The formation of type 1 mosaicism is based on a de novo postzygotic mutation at an early stage of embryogenesis. In turn, type 2 mosaicism develops as a result of a postzygotic mutation against the background of an already existing prezygotic mutation. Determining the type of mosaicism by genetic testing will make it possible to assess the prognosis of the disease and the chance of transmitting this disease to offspring.

Nevus Unius Lateris (NUL) in a Theree-Year-Old Child Treated by Tretinoin 0.025%, Desoxymethasone 0.25%, and Urea 20% Cream

Background: Linear verrucous epidermal nevus is the most frequent variant of the epidermal nevus classification. Linear verrucous epidermal nevus is characterized by the proliferation of epithelium arranged in a configuration that follows Blaschko's line. Nevus unius lateris (NUL) is a variant of the verrucous epidermal nevus, which has a unilateral distribution of lesions. Lesions are usually found at birth or in the first year of life as brown to grey verrucous papules or papillomatous plaques. The management of NUL is challenging as the results are varied and there is a high risk of recurrence. Purpose: to report a case of NUL and its management, especially in children. Case: A 3-year-old girl presented with brownish spots and multiple small lumps on the left buttock that have extended to the left leg since she was 9-days-old. On dermatologic examination, there were numerous hyperpigmented verrucous papules and plaques along the Blaschko line over the affected area. In this case, the diagnosis of NUL, is based on clinical symptoms and dermoscopy examination showed multiple large brown oval or round structures with hyperpigmented brown border. The patient was treated with combination topical therapy of tretinoin 0.025%, corticosteroid desoxymethasone 0.25%, and urea 20% cream, and the lesion improved within four weeks. Discussion: Epidermal nevus is often cosmetically disturbing. The treatment is still challenging and various, including surgical and non-surgical, but none is ideal and could potentially recur over months or years. dst.

Extensive, Adolescent-Onset Inflammatory Linear Verrucous Epidermal Nevus – Treated Successfully with Oral Retinoids

Extensive, Adolescent-Onset Inflammatory Linear Verrucous Epidermal Nevus – Treated Successfully with Oral Retinoids

PA33 Mosaic KRAS mutation associated with epidermal naevus and somatic limb overgrowth

PA33 Mosaic <i>KRAS</i> mutation associated with epidermal naevus and somatic limb overgrowth

Unilateral focal palmoplantar keratoderma associated with a postzygotic variant in PIK3CA and activation of the PI3K/AKT/mTOR pathway.

Palmoplantar keratoderma (PPK) is a group of -disorders with genetic and phenotypic heterogeneity featuring skin thickening of the palms and soles. More than 60 genes involved in various biological processes are implicated in PPK. PIK3CA is an oncogene encoding p110α, and its somatic variants contribute to a spectrum of congenital overgrowth disorders, including epidermal nevi (EN). To identify the genetic basis and elucidate the pathogenesis of a patient with unilateral focal PPK. Whole-exome sequencing and Sanger sequencing combined with laser capture microdissection (LCM) were performed on genomic DNA extracted from the patient's peripheral blood and skin lesion. Skin biopsies were taken from the lesion of the patient and normal controls for immunofluorescence. Molecular docking was performed using Alphafold2-multimer. A three-year-old girl presented with unilateral focal PPK with an identified missense -variant (c.3140A>G, p.His1047Arg) in PIK3CA from affected tissue. This variant only existed in the lesional epidermis. Elevated PI3K/AKT/mTOR signalling in the affected epidermis and an increased number of Ki67-positive keratinocytes were demonstrated. Molecular docking indicated instability of the p110α-p85α dimer caused by the PIK3CA His1047Arg variant. We describe the first PPK case associated with a variant in PIK3CA, which expands the spectrum of PIK3CA-related disorders. Our study further underscores the importance of the PI3K/AKT/mTOR pathway in the homeostasis of skin keratinization.

Epidermolytic ichthyosis: Clinical spectrum and burden of disease in a large German cohort.

Keratinopathic ichthyoses are a group of hereditary skin disorders caused by pathogenic variants in keratin genes such as KRT1, KRT2 and KRT10, resulting in conditions such as epidermolytic ichthyosis (EI), autosomal-recessive EI, superficial EI and epidermal nevus. Case reports highlight the diversity of clinical manifestations, but only limited information exists regarding the quality of life and burden of disease. The objective of this study was to assess the clinical spectrum, genotype-phenotype correlations and burden of disease in patients with epidermolytic ichthyosis in Germany. We conducted an observational study involving 48 patients diagnosed with EI. Evaluations included the severity of skin involvement using the Investigator's Global Assessment (IGA), the modified Ichthyosis Area Severity Index (mIASI) and complications. The burden of disease was evaluated using the Dermatology Life Quality Index (DLQI) or the Children's Dermatology Life Quality Index (cDLQI). Based on clinical features, mIASI and IGA, EI can be categorized into localized, intermediate and severe forms. Patients with keratin 1 mutations tended to have severe EI, while the three forms were evenly distributed in those with keratin 10 mutations. The study highlights that around half of the patients with EI experienced itch and severe pain. Quality of life was affected, with daily life restrictions of 78% due to care and therapies. Reimbursement for moisturizing ointments by health insurance was insufficient for one-quarter of cases. The results emphasize the need for targeted interventions and comprehensive care strategies to enhance the quality of life for affected individuals.

Megalencephaly: Classification, Genetic Causes, and Related Syndromes

AbstractMegalencephaly is a developmental disorder due to an abnormal neuronal proliferation and migration during intrauterine or postnatal brain development that leads to cerebral overgrowth and neurological dysfunction. This cerebral overgrowth may affect the whole encephalon or only a region; when it involves one hemisphere it is referred to as hemimegalencephaly. Megalencephaly presents with a head circumference measurement of 2 standard deviations above the average measure for age. This group of disorders is clinically characterized by early onset and refractory to therapy epilepsy, neurodevelopmental disorders, behavioral problems, and autism spectrum disorder. Syndromic forms of megalencephaly should be considered when associated with other congenital abnormalities. Megalencephaly in fact could be associated with segmental overgrowth and cutaneous/vascular abnormalities (i.e., Proteus syndrome, CLOVES [congenital lipomatous overgrowth, vascular malformations, epidermal naevi, scoliosis, and/ or skeletal abnormalities] syndrome, Klippel-Trenaunay syndrome, megalencephaly-capillary malformation-polymicrogyria syndrome , megalencephaly-postaxial polydactyly-polymicrogyria-hydrocephalus syndrome, etc.) or generalized overgrowth (i.e., Weaver or Beckwith-Wiedemann syndrome) as well as with nanism in achondroplasia where megalencephaly is associated with disproportionate short stature, primary skeletal dysplasia, characteristic facies (prominent forehead, flat nasal bridge), narrow chest, and normal intelligence. It is possible to identify three main groups of disorders associated with megalencephaly: idiopathic or benign, metabolic, and anatomic. The idiopathic (benign) form indicates an abnormal increased head circumference in absence of neurological impairment, such as in benign familial megalencephaly. In metabolic megalencephaly (such as in organic acid disorders, metabolic leukoencephalopathies, or lysosomal diseases) there is an increase of different constituents that increase the size of the brain, whereas in the anatomical form there are underlying genetic causes. Neuroimaging is crucial for diagnosis, as it can reveal a generalized brain growth or a segmental one and possible specific frameworks associated. In all these conditions it is necessary to identify possible microdeletion-microduplication by chromosomal arrays.

Case of Unilateral Linear Lichen Planus with Bilateral Mucosal Involvement

Abstract A form of lichen planus (LP) which follows the Blaschkos line pattern known as linear LP, presents with lichenoid eruptions and violaceous papules in a linear distribution. It is a rare form of LP affecting &lt;0.2% population with LP. We present a case of a 52-year-old female with hyperpigmented patches and plaques distributed linearly along the Blaschkos line in her right leg. From a clinical perspective, the lesions on the patient’s right leg resembled those of lichenoid epidermal naevus, which is a type of linear verrucous epidermal nevus but the dermoscopic findings and the presence of oral mucosa LP indicate that the patient has the uncommon variant of LP which is called linear LP. It is thus critical for clinicians to distinguish linear LP from other acquired dermatoses following the lines of Blaschko both clinically and dermoscopically.

Dermato-Radiological Evaluation of Congenital Limb Overgrowth Vascular Syndromes

Abstract International Society for the Study of Vascular Anomalies classification defines Congenital Limb Overgrowth Vascular Syndromes (CLOS) as a subset of vascular syndromes with other abnormalities that present with unilateral limb overgrowth. It includes Klippel–Trenaunay Syndrome, Parkes–Weber Syndrome, CLOVES (Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevi, Spinal/Skeletal Anomalies/Scoliosis) Syndrome, Proteus Syndrome, PTEN Hamartomatous Syndrome, and Fibroadipose Vascular Anomaly. Due to their rare and complex nature, a multidisciplinary approach to diagnosis and treatment is required. A thorough clinical and radiological workup can go miles in reflecting on the patient’s outcome. Here we report five cases of CLOS with their detailed dermato-radiological profiles.

Proteus syndrome: clinical and radiological findings through a new case report

BackgroundProteus syndrome (PS) is a complex and uncommon disorder with as its main feature a patchy or mosaic postnatal overgrowth. A high clinical and radiological variability characterizes it.Case presentationWe report the case of a 2-year-old boy presenting with lipomas and diagnosed as PS in front of general criteria (sporadic occurrence, progressive course, and mosaic distribution of lesions) and specific criteria (linear epidermal nevus in the chest and asymmetric and overgrowth in the upper limbs) of Biesecker. The course of the disease was marked by a huge overgrowth of arms despite several surgeries. By the age of 10 years, a painful swelling of the right forearm revealed a venous thrombosis on a venous malformation.ConclusionsThis case report highlights the variability of clinical findings in PS. It also emphasizes the contribution of routine imaging tools for the diagnosis and the follow-up of this rare disease.

Epidural lipomatosis with foci of hemorrhage and acute compression of the spinal cord in a child with CLOVES syndrome: illustrative case.

Congenital lipomatous overgrowth, vascular malformations, epidermal nevi, spinal/skeletal anomalies, and/or scoliosis (CLOVES) syndrome is the most recently described combined vascular anomaly characterized by congenital excessive growth of adipose tissue, vascular malformations, epidermal nevi, and skeletal deformities. This condition exhibits a significant variability in clinical manifestations and a tendency for rapid progression and affects extensive anatomical regions. Information regarding the association of epidural lipomatosis with low-flow venous lymphatic malformations is rare, with few reports in the literature. The authors present a case of a 6-year-old girl who was admitted to the emergency department complaining of rapidly progressing weakness in her lower extremities and partial loss of sensation in the inguinal area. Radiologically, an extradural mass was identified at the T2-6 level, causing acute spinal cord compression. Urgent decompression and partial resection of the mass were performed. Despite satisfactory intraoperative hemo- and lymphostasis, postoperative lymphorrhea/seroma leakage was encountered as a delayed complication and was managed conservatively. CLOVES syndrome is characterized by the combination of various clinical symptoms, not all of which are included in the abbreviation, as well as a progressively deteriorating course, the emergence of new symptoms, and complications throughout the patient's life. This necessitates ongoing monitoring of such patients.

Dermoscopy of Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects Nevus with Unilateral Limb Defects

Here, we report the dermoscopic findings of congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD) nevus with left-sided ichthyosiform erythroderma and left upper-limb aplasia in a 4-month-old baby. The presence of ptychotropism and strict midline demarcation are unique features described in CHILD nevus. Dermoscopy of the CHILD nevus showed linear and dotted vessels with yellowish waxy scales on a pink background. These characteristic dermoscopic findings would also help us to differentiate it from inflammatory linear verrucous epidermal nevus.

Giant Cerebriform Nevus Sebaceous of Jadassohn in an Infant

Nevi are hamartomatous growth of skin or mucosa that usually present at the time of birth or soon after. Nevus sebaceous (NS) is an epidermal nevus comprised predominantly of sebaceous glands. It presents at the time of birth, as yellow-tan-colored plaque, which usually remains constant till puberty and thereafter it increases in size due to the hormonal influence on sebaceous glands. Here, we are reporting a case of giant cerebriform NS of Jadassohn in a 2-month-old male child. Such giant and cerebriform appearance of NS is rarely seen.

SOLAMEN syndrome in a toddler

BackgroundSegmental overgrowth, lipomatosis, arteriovenous malformation, and epidermal nevus (SOLAMEN) syndrome is a segmental overgrowth syndrome that is part of Cowden’s Syndrome, a subset of the PTEN hamartoma tumor syndrome cluster. Due to SOLAMEN disease’s rarity, clinical suspicion should arise if multiple small nonspecific variably low-attenuated nodular lesions in the back, shoulders, and upper arms are present on CT, which are associated with mucocutaneous lesions. We present a rare case of SOLAMEN syndrome with widespread lipomatous growth, greater than reported in literature, with confirmed PTEN genetic testing.Case presentationWe describe a case of a 2-year-old boy with a slowly growing left neck mass since birth. Physical exam revealed macrocephaly and epidermal nevi on left axilla, arm, and fingers, appearing as pink verrucous and has visible veins on chest wall/abdomen. CT and MRI imaging showed a lipomatous hibernoma extending from the leftward neck to the abdominal cavity, encasing vascular structures form the left carotid and subclavian arteries to the diaphragmatic hiatus, in addition to the spleen and kidney. Biopsy of the left shoulder revealed hibernoma, a fatty neoplasm of benign brown fat. Patient had a resection of his left shoulder hibernoma and is currently asymptomatic, undergoing surveillance.ConclusionDue to SOMAMEN syndrome’s rarity, clinical suspicion should arise if a patient presents with multiple small-nonspecific variably low-attenuated nodular lesions on CT and mucocutaneous lesions. Ongoing monitoring should be done as there is an increased risk of cancer.

Clinical characteristics and surgical management of facial infiltrating lipomatosis: a single center experience

BackgroundFacial infiltrating lipomatosis (FIL) is a rare condition characterized by congenital facial enlargement. Beyond its impact on physical appearance, FIL can also impair essential facial functions such as swallowing, chewing, vision, and breathing, imposing a substantial physiological and psychological burden. Currently, fewer than 80 cases of FIL have been reported, and the characteristics and management strategies for FIL remain unclear.MethodsWe reviewed the clinical, surgical, and radiological records of 39 FIL patients who were treated at our center. Of these, genetic testing was performed for 21 patients.ResultsAberrant overgrowth involves subcutaneous fat, bones, muscles, glands, tongue, lips, and teeth. Epidermal nevi could be observed in the dermatomes innervated by the three branches of the trigeminal nerve, with the highest frequency seen in the dermatome of the mandibular branch. Four patients exhibited concurrent hemimegalencephaly (HMEG), with one case presenting HMEG on the opposite side of the FIL. Nineteen patients were confirmed to harbor the PIK3CA mutation. Thirty-three patients underwent surgical procedures, with a post resection recurrence rate of approximately 25%.ConclusionsA variety of maxillofacial structures may be involved in FIL. PIK3CA mutations are important pathogenic factors. Emerging targeted therapies could present an additional treatment avenue in the future. However, surgery currently remains the predominant treatment choice for FIL. The timing and modality of surgery should be individually customized, taking into account each patient's unique circumstances. Notably, there is a significant possibility of postoperative recurrence during childhood and adolescence, necessitating early strategic planning of disease management.

A Clinicopathological Study on Interface Dermatitis

Background: Interface dermatitis (ID), also known as lichenoid tissue reaction, is a form of skin reaction characterized by an inflammatory infiltration that appears to cover the dermo-epidermal junction under inexpensively analysis. A wide range of inflammatory skin disorders demonstrate interface alteration with significant overlap of histological characteristics. Aim of the Study: The purpose of this study was to link interface dermatitis clinicopathologically. Methods: This cross-sectional descriptive type of study was conducted in the department of dermatology and venereology, TMSS Medical College, Bogura, Bangladesh, from January 2021 to December 2022. The study included 200 patients aged 5 to 75. Skin biopsies were obtained from clinically confirmed cases of lichenoid skin lesions and sent for histological investigation. The correlation was then performed with clinical diagnosis. All acquired data was analysed using descriptive statistics in SPSS 11.5. Results: Out of 200 cases evaluated, the most common type of ID was Lichen simplex chronicus (95, 47.5%), with Lichen planus (LP) and its variants coming in second (84, 42%). LP-like keratosis (15, 7.5%), Inflammatory verrucous epidermal nevus (ILVEN) 2 cases, Pityriasis lichenoides et varioliformisacuta (PLE-VA) 2 cases, and Prurigosimplex (PS) 2 cases were the least prevalent. Clinicopathological concordance was seen in 84 (42%) of the lichen planus patients and discordance in 116 (58%) of the cases. Conclusion: In our investigation, the most consistent histological results were basement membrane degenerations such as lymphocytic infiltrates along the dermo-epidermal interface. Interface dermatitis refers to a group of conditions that share clinical and histological characteristics. As a result, comprehensive histological studies are required to identify distinct features of various kinds of interface dermatitis.

Adult epidermal nevus syndrome with hypophosphatemic osteomalacia treated with burosumab: a case study and literature review

Adult epidermal nevus syndrome with hypophosphatemic osteomalacia treated with burosumab: a case study and literature review