Verrucous epidermal nevus as a manifestation of a type 2 mosaic PTEN mutation in Cowden syndrome

Linear Cowden nevus, also known as linear PTEN nevus, is a type of epidermal nevus, first described in 2007, which is seen in patients with PTEN hamartoma tumor syndrome. It is considered to be a type 2 form of segmental mosaicism, and we suggest that it has certain clinical features that distinguish it from epidermal nevi seen in similar conditions, such as Proteus syndrome. We present a case of linear Cowden nevus in a 4-year-old boy and review the literature.     

Keratinocytic epidermal nevi associated with localized fibro-osseous lesions without hypophosphatemia

Keratinocytic epidermal nevi (KEN) are characterized clinically by permanent hyperkeratosis in the distribution of Blaschko's lines and histologically by hyperplasia of epidermal keratinocytes. KEN with underlying RAS mutations have been associated with hypophosphatemic rickets and dysplastic bone lesions described as congenital cutaneous skeletal hypophosphatemia syndrome. Here, we describe two patients with keratinocytic epidermal nevi, in one associated with a papular nevus spilus, who presented with distinct localized congenital fibro-osseous lesions in the lower leg, diagnosed on both radiology and histology as osteofibrous dysplasia, in the absence of hypophosphatemia or rickets, or significantly raised FGF23 levels but with distinct mosaic HRAS mutations. This expands the spectrum of cutaneous/skeletal mosaic RASopathies and alerts clinicians to the importance of evaluating for bony disease even in the absence of bone profile abnormalities.     

The role of E-cadherin in nevogenesis: an experimental study using epidermal reconstructs

BACKGROUND: In the development of congenital nevi, how nevus cells migrate in the dermis remains unclear. As shown in an earlier study designed to investigate Unna's Abtropfung hypothesis, dermal invasion does not occur when nevus cells are seeded on epidermal reconstructs. In melanoma, the decrease of E-cadherin expression is associated with the dermal invasion of melanoma cells. OBJECTIVE: To study the expression of E-cadherin in dermal-cultured nevus cells from congenital nevi and its relevance to explain the absence of dermal invasion noted in epidermis reconstructed with cultured nevus cells. METHODS: Comparison of the immunohistochemical expression pattern of E-cadherin in congenital nevi in vivo and after culture in monolayers and in a three-dimensional system. RESULTS: E-cadherin was not expressed in vivo by dermal nevus cells, either isolated or in nests. However, in monolayer cultures, dermal nevus cells expressed E-cadherin. When these cells were used in reconstructed epidermis, nevus cells did not invade the dermis and they expressed E-cadherin when isolated and just weakly or not when grouped in junctional nests. CONCLUSIONS: The absence of dermal invasion of nevus cells could be due to the expression of E-cadherin in these cells in reconstructed epidermis. Our experiments suggest, a restoration of the control of keratinocytes, that nevus cells escape in the dermal compartment.     

Familial papular epidermal nevus with “skyline” basal cell layer and multiple pilomatricomas: A new association?

Papular epidermal nevus with “skyline” basal cell layer is a newly described keratinocytic nevus. Recently, papular epidermal nevus with “skyline” basal cell layer has been reported in association with extracutaneous involvement, and the term papular epidermal nevus with “skyline” basal cell layer syndrome is used to indicate a neurocutaneous syndrome characterized by the presence of papular epidermal nevus with “skyline” basal cell layer and different neurologic symptoms that seem to improve during infancy and adolescence. Multiple pilomatricomas have been reported in association with various syndromes. We report herein papular epidermal nevus with “skyline” basal cell layer associated with multiple pilomatricomas in two members of a family with the aim of drawing attention to this peculiar epidermal nevus to improve our knowledge of the syndrome.     

Nevoid follicular mucinosis: a new type of hair follicle nevus

Follicular mucinosis represents a term for a histopathologic reaction pattern in follicular epithelium. It is a characteristic of alopecia mucinosa. However, it may also occur in a variety of unrelated conditions. Epidermal nevi are considered to be hamartomatous disorders and they can show a predominant component of non‐organoid (keratinocytes) and/or organoid nevi. All the cases of epidermal nevi described with mucin deposits until now are reported as mucinous nevus or mucinous eccrine nevus; in the first type of disorder, diffuse mucin deposition is only seen in the papillary dermis, and in the second type, the mucin is found around the proliferation of eccrine structures. We believe this is the first reported case of epidermal nevus along Blaschko's lines exhibiting typical microscopic findings of mucinosis exclusively distributed inside the follicular epithelia.     

Epidermal nevus syndromes

The term "epidermal nevus syndrome" (ENS) has been used to describe the association of epidermal hamartomas and extra-cutaneous abnormalities. Epidermal nevi follow the lines of Blaschko. The majority of the extra-cutaneous manifestations involve the brain, eye, and skeletal systems. Several subsets with characteristic features have been delineated including the nevus sebaceous syndrome, Proteus syndrome, CHILD syndrome, Becker nevus syndrome, nevus comedonicus syndrome, and phakomatosis pigmentokeratotica. Epidermal nevi have been associated with benign and malignant neoplasms. Advances in molecular biology have revealed that the manifestations of ENS are due to genomic mosaicism. It is likely that the varied clinical manifestations of ENS are due in great part to the functional effects of specific genetic defects. Optimal management of the patient with ENS involves an interdisciplinary approach. Amelioration of the cutaneous features of ENS has been difficult but there have been advances, especially in the use of lasers.     

Epidermal nevus syndromes

The term "epidermal nevus syndrome" (ENS) has been used to describe the association of epidermal hamartomas and extra-cutaneous abnormalities. Epidermal nevi follow the lines of Blaschko. The majority of the extra-cutaneous manifestations involve the brain, eye, and skeletal systems. Several subsets with characteristic features have been delineated including the nevus sebaceous syndrome, Proteus syndrome, CHILD syndrome, Becker nevus syndrome, nevus comedonicus syndrome, and phakomatosis pigmentokeratotica. Epidermal nevi have been associated with benign and malignant neoplasms. Advances in molecular biology have revealed that the manifestations of ENS are due to genomic mosaicism. It is likely that the varied clinical manifestations of ENS are due in great part to the functional effects of specific genetic defects. Optimal management of the patient with ENS involves an interdisciplinary approach. Amelioration of the cutaneous features of ENS has been difficult but there have been advances, especially in the use of lasers.     

Nd:YAG Q-switched laser for the treatment of a hemicorporal epidermal nevus: A safe and effective option

Epidermal nevi are benign proliferations of the epidermis for which different treatments have been used with disappointing results due to their recurrences and anesthetic scars. Topical therapies have generally been ineffective and surgical treatment provides more definitive results, but with high risk of scarring. In recent years, multiple laser modalities have been described for the treatment of these lesions. In the literature, there are no reported cases of treatment of these lesions with Neodymium-doped Yttrium aluminum garnet (Nd:YAG) laser. We present the case of a 3-year-old patient with a hemicorporal epidermal nevus treated with Nd:YAG laser at an early stage with good results.     

Inflammatory linear verrucous epidermal nevus associated with erosive monoarthritis

Inflammatory linear verrucous epidermal nevus and linear psoriasis are different entities with clinical and histopathologic similarities. Isolated reports of inflammatory linear verrucous epidermal nevus with concomitant psoriasis or a positive family history of psoriasis have been described, and the possibility that inflammatory linear verrucous epidermal nevus may be a mosaic form of cutaneous psoriasis has been postulated. We report a 17‐year‐old boy with a congenital, linear, erythematous, keratotic plaque on the dorsum of the fifth finger of the left hand with ipsilateral nail dystrophy. Histopathologic examination showed epidermal hyperplasia with alternating orthokeratosis and parakeratosis. During follow‐up, he developed erosive monoarthritis of the distal interphalangeal joint. This case seems to confirm the association between inflammatory linear verrucous epidermal nevus and arthritis and supports a possible relationship between inflammatory linear verrucous epidermal nevus and psoriasis.     

Laser therapy for cutaneous hyperpigmentation and pigmented lesions

ABSTRACT: Selective treatment of pigmented lesions can be accomplished as a result of the recent technologic advancements made in cutaneous laser surgery. Melanin-specific, high-energy, pulsed lasers are being used successfully to remove most benign epidermal and dermal pigmented lesions, including lentigines, café-au-lait macules, melanocytic and blue nevi, drug-induced and infraorbital hyperpigmentation, Becker's nevus, and nevus spilus. These acquired and congenital cutaneous pigmented lesions can be lightened and even permanently eradicated after a series of outpatient laser treatments, with minimal risk of permanent sequelae, such as scarring, skin atrophy, or pigmentary irregularities. Because of the enhanced cosmetic effect of these lasers and their relative ease of use, they are becoming the mainstay of treatment for a variety of pigmented lesions and pigmentary disorders.     

Epidermal nevi with aberrant epidermal structure in keratinocytes and melanocytes

Epidermal nevi are congenital cutaneous hamartomas caused by embryonic somatic mutations. Ultrastructural features of adult epidermal nevi have rarely been investigated. Herein, we report a case involving a Japanese adult who had epidermal nevi with right congenital blindness and a right accessory nipple. The histopathologic and ultrastructural studies showed divergent abnormal epidermal structures in both melanocytes and keratinocytes. Our case indicates the need to further investigate histopathologic, ultrastructural, and genetic associations in adult epidermal nevi.     

Phacomatosis pigmentokeratotica: a further case without extracutaneous anomalies and review of the condition

Epidermal nevus syndrome is the term for the association of an epidermal nevus and extracutaneous anomalies, including neurologic, ophthalmic, and skeletal defects. Epidermal nevus syndromes include different disorders that share the feature of mosaicism. Phacomatosis pigmentokeratotica (PPK) is a distinctive new epidermal nevus syndrome first described in 1996 characterized by the presence of multiple organoid nevi with sebaceous differentiation, a speckled lentiginous nevus, and skeletal and neurologic abnormalities. Only a handful of cases of PPK without extracutaneous manifestations have been reported. We report here an individual with PPK with only cutaneous signs and confirm this distinctive syndrome has two subtypes according to the presence or absence of extracutaneous involvement.     

成人表皮痣综合征1例

 报告1例成人表皮痣综合征。患者男,28岁,因皮疹、智力低下、多动28年,间断抽搐27年就诊。皮肤科检查：额部、眼周、颈部可见弥漫性密集的淡褐至褐黑色乳头瘤样角化性丘疹,触之坚硬,似高起鱼鳞病、先天性良性黑棘皮病样。躯干、双上肢、四肢皮损角质增厚,较额部、眼周、颈部薄,可见弧形带状或旋涡状排列,不规则斑片状或斑点状色素脱失斑,与增生性皮损及正常皮肤相互交错。颈部皮损组织病理检查示纤维上皮性息肉改变,胸部皮损组织病理检查示表皮痣样改变。脑电图：脑电图异常伴高中波幅尖波及4~7 Hz的θ节律短阵出现。诊断为表皮痣综合征。     

Linear Cowden nevus: a new distinct epidermal nevus

Within the group of epidermal nevi, a so far nameless disorder is described under the term "linear Cowden nevus". This non-organoid epidermal nevus is caused by loss of heterozygosity, occurring at an early developmental stage in an embryo with a germline PTEN mutation, giving rise to Cowden disease. Hence, linear Cowden nevus can be categorized as a characteristic feature of type 2 segmental Cowden disease. Until now, several authors had mistaken this epidermal nevus as a manifestation of Proteus syndrome. The concept of linear Cowden nevus implies that Proteus syndrome is by no means caused by PTEN mutations. As a clinical difference, linear Cowden nevus is markedly papillomatous and thick, whereas linear Proteus nevus tends to be rather flat. Moreover, the spectrum of possibly associated cutaneous or extracutaneous anomalies differs in the two types of nevi. In conclusion, linear Cowden nevus, that may also be called "linear PTEN nevus", represents a distinct clinicogenetic entity.     

Mucinous nevus

A 15-year-old boy first noticed multiple firm papules on his right upper chest two years before presenting to our clinic. These papules were densely distributed and showed epidermal nevus-like linear arrangement at some sites. The number, size, and distribution of these papules remained unchanged for one year of our observation. The papules flattened leaving scars and did not recur within a year after one shaving abrasion using a scalpel. Histopathologically, epidermis of the papule displayed acanthosis with elongated rete ridges. Accumulation of mucin was apparent in the papillary and subpapillary dermis. In mucinous nevus, the origin of cells with nevoid proliferation is obscure. In contrast with common collagenous connective tissue nevus, it is hard to define the localized persistent mucin accumulation as a nevoid manifestation. The present case of mucinous nevus might be caused by significantly stimulated glycosaminoglycan synthesis in a kind of epidermal nevus without extreme hyperkeratosis.     

The Epidermal Nevus Syndrome: Case Report and Review

A 33-year-old woman had multiple basal cell epitheliomas complicating a large, unilateral nevus sebaceus. Other unilateral epidermal nevi and a contralateral pigmentary nevoid disorder were noted on cutaneous examination. There were signs of skeletal, neurologic, and vascular involvement. This patient illustrates the unpredictable features of the epidermal nevus syndrome and the importance of close follow-up to manage attendant complications.     

Dysplastic nevus syndrome with development of multiple melanomas. A surgical concept for prophylaxis

A 58‐year‐old man presented in 2001 with dysplastic nevus syndrome with at least 300 nevi and about 100 clinically highly atypical nevi. Three melanomas had been excised by a private dermatologist within the past year. We then removed two additional melanomas. Between 2002 and 2003, 117 nevi which were atypical on dermatoscopy were removed; most by horizontal (shave) excision. Adequate clinical and dermatoscopic control was not feasible due to the large number of atypical nevi. In order to reduce the number of nevus cells, we treated test sites with both dermabrasion and split‐thickness excision. The latter proved to be more efficient and was used to completely excise the skin of the back, as well as parts of the arms and chest in two sessions under general anesthesia. Wound healing was uneventful. Following these procedures, adequate clinical and dermatoscopic monitoring of the remaining nevi was possible and only a few had to be removed. No more melanomas appeared in the treated areas.     

Successful Treatment of Dark-colored Epidermal Nevus with Ruby Laser

The pulsed ruby laser has a selective thermolytic effect. Recently, it has been available for the treatment of superficial pigmented disorders. We studied 5 cases of epidermal nevus treated with the pulsed ruby laser. In comparison with the usual methods including electrocautery, cryotherapy and skin abrasion, ruby laser therapy is an excellent tool due to technological ease and rapid improvement. Depigmentation after treatment in 2 cases was the only side effect of this therapy. Bose cases had a dark pigmentation of the skin. Despite of the risk of discoloration, the ruby laser is one of the most effective tools for therapy of pigmented epidermal nevus.     

Dysplastic nevus (atypical nevus)

Atypical nevum (dysplastic) is considered an important factor associated with increased risk of developing cutaneous melanoma. It is believed that atypical nevi are precursor lesions of cutaneous melanoma. They may be present in patients with multiple melanocytic nevi (atypical nevus syndrome) or isolated and in small numbers in a non-familial context. The disease usually begins at puberty and predominates in young people. It has a predilection for sun-exposed areas, especially the trunk. The major challenge in relation to atypical nevi lies in the controversy of defining its nomenclature, clinical diagnosis, dermoscopic criteria, histopathological diagnosis and molecular aspects. This review aims at bringing knowledge, facilitating comprehension and clarifying doubts about atypical nevus.     

Epidermal nevus syndromes: clinical findings in 35 patients

Of the patients with epidermal nevi, 10-18% may have disorders of the eye, nervous, and musculoskeletal systems. A predisposition to malignant neoplasms in ectodermal and mesodermal structures may also be found. There are six different epidermal nevus syndromes described so far: Proteus, congenital hemidysplasia with ichthyosiform nevus and limb defect syndrome, phakomatosis pigmentokeratotica, sebaceous nevus, Becker nevus, and nevus comedonicus. Thirty-five patients with epidermal nevus syndrome seen at the National Institute of Pediatrics in Mexico City during a 31-year period are described. This syndrome represented 7.9% of 443 patients with epidermal nevi; its relative frequency was 1 case per 11,928 pediatric patients and 1 case per 1080 dermatologic patients. Nine epidermal nevus syndrome patients (26%) had Proteus syndrome. Sebaceous nevus syndrome was found in six patients (17%), while the nevus comedonicus syndrome was found in three (8%). Two patients were diagnosed with phakomatosis pigmentokeratotica and one patient with congenital hemidysplasia with ichthyosiform nevus and limb defect syndrome. This is the first report of phakomatosis pigmentokeratotica and congenital hemidysplasia with ichthyosiform nevus and limb defect syndrome in Mexican patients. One patient had an inflammatory linear verrucous epidermal nevus with systemic involvement. Thirteen patients (37%) had keratinocytic nevi with systemic involvement. We propose the keratinocytic nevus syndrome to be defined as the association of a keratinocytic nevus with neuronal migration and/or musculoskeletal disorders in addition to a higher risk for mesodermal neoplasms.