, we will provide an update on clinical features , pathogenesis , and treatment options . clinically nc is characterized by closely arranged , dilated follicular openings with keratinous plugs resembling classical comedones . it is a rare type of an epidermal nevus usually with predilection for the face and neck area . comedo nevus. nc can occur congenitally or develop later in life , most commonly at the age of approximately 10  years . nc is part of the nevus comedonicus syndrome ( ncs ) , a term coined by engber in 1978 [ 1 , 3 ] . the prevalence of nc has been estimated from 1 in 45,000 to 1 in 100,000 , with no gender or racial preference [ 1 , 3 ] . in 50% of patients , the condition develops shortly after birth and in the majority of patients lesions appear before the age of 10 [ 46 ] . single cases of delayed development of nc and ncs at later age have been reported [ 46 ] . nc is usually asymptomatic and most commonly it affects the face and neck area and , by exception , other anatomical regions , including genital area , palms , and soles . clinically , nc presents with grouped , dilated , plugged follicular ostia in a honeycomb pattern . their appearance resembles black dots but the material can not be easily removed mechanically in contrast to acne comedones [ 1 , 7 ] . nc lesions might present with various patterns of distribution : unilateral , bilateral , linear , interrupted , segmental , or blaschkoid ( figs .  1 , 2 and 3 ) .fig . 1nevus comedonicus : plaque - like lesion with wide open follicles on the neck ( 44-year - old caucasian male)fig . 2stages of treatment of a 29-year - old asian male with linear nevus comedonicus of the leg with multiple follicular openings . 3nevus comedonicus of the neck with pseudoepithelial epidermal hyperplasia in a 39-year - old caucasian nevus comedonicus : plaque - like lesion with wide open follicles on the neck ( 44-year - old caucasian male ) stages of treatment of a 29-year - old asian male with linear nevus comedonicus of the leg with multiple follicular openings . a presentation of linear nevus comedonicus with multiple follicular openings . d with compression garment to avoid postsurgical lymphedema nevus comedonicus of the neck with pseudoepithelial epidermal hyperplasia in a 39-year - old caucasian two types of nc have been identified ; the first is non - pyogenic nc with acne - like characteristics and a second type characterized by formation of cysts , papules , pustules , and abscesses in various stages of development [ 8 , 9 ] . the former type is also known as munro s acne nevus and separated by some authors from nc . differential diagnoses are shown in table  1.table  1histopathological differential diagnoses of nevus comedonicusnevus comedonicustrichofolliculomadilated pore of winerpilar sheath acanthomafolliculocystic and collagen comedo hamartomahair cortexlocalization  head+++  face++++  neck++  trunk(+)+++  limbs+folliclesnumerous open folliclesopen mother folliclesnumerous open folliclessolitary lesionscysts+++hair shafts+ , velluslamellated keratinothersmassive epithelial proliferations without folliclesabundant collagen formation histopathological differential diagnoses of nevus comedonicus the major histopathologic symptoms are large grouped , dilated follicular ostia devoid of hair shafts but filled with keratin layers ( fig . one may observe singular rudimentary glands , which are not , however , obligatory as they may be absent . small cysts , cystic invaginations , and occasionally large cysts may be seen in histopathologic investigation ; the variable cystic structures are lined by keratinizing squamous epithelium [ 1 , 7 ] . hyperkeratosis ( epidermolytic hyperkeratosis ) and acanthosis of the epidermis may be present but not para- or dyskeratosis [ 8 , 1013].fig . 4histopathology of nevus comedonicus . a overview ( hematoxylin and eosin stain [ he ]    2 ) . b details with large follicles containing lamellated keratin but absent hair shafts ( he    4 ) histopathology of nevus comedonicus . a overview ( hematoxylin and eosin stain [ he ]    2 ) . b details with large follicles containing lamellated keratin but absent hair shafts ( he    4 ) an increased number of langerhans cells had been observed by electron microscopy . more abundant tonofilaments in the upper part of the stratum spinosum and numerous keratohyalin granules were also noticed [ 11 , 12 ] . the arrector pili muscles were incompletely differentiated and demonstrated intracellular glycogen particles [ 11 , 12 ] . filaggrin , which is usually located in the granular epidermal layer , occurs in the whole epidermis of closed comedones suggesting its role in their development [ 14 , 15 ] . interaction between fibroblast growth factor ( fgf ) and fgf receptor-2 ( fgfr2 ) is a crucial pathway for mesenchymal  epithelial interplay in pilosebaceous unit development . fgfr2b is exclusively found in epithelial cells including epidermal keratinocytes and sebocytes [ 15 , 16 ] . overstimulation of fgfr2 signaling with increased expression of interleukin-1 may be involved in nc pathogenesis . somatic mutations like ser252trp substation have been identified in individual patients with segmental acne [ 1618 ] . -secretase found in human hair follicle epithelium is another candidate for nc since the absence of this enzyme results in complete conversion of hair follicles to epidermal cysts . ncs ( orpha64754 ) belongs to the group of epidermal nevus syndromes including schimmelpenning syndrome , phacomatosis pigmentokeratotica , angora hair nevus syndrome , and becker nevus syndrome among others where a genetic basis has yet not been identified [ 3 , 4 , 20 ] . ncs is a neurocutaneous disorder which consists of nc with skeletal , ocular , and central nervous system abnormalities . the most common symptoms include cataracts , scoliosis , fused vertebrae , spina bifida , and delayed mental development [ 5 , 6 ] . in addition , seizures , paresis , dysgenesis of corpus callosum , electroencephalographic abnormalities , limb deformities such as absence of the fifth finger , polysyndactyly or clinodactyly , oligodontia , and other skin disorders such as ichthyosis , leukoderma , lichen striatus , linear morphea , sturge - weber syndrome , hemangiomas , and inverse acne have been reported in ncs [ 1 , 3 , 4 , 2022 ] . ncs is associated with epithelial tumors such as trichoepithelioma , pilar sheath tumor or dilated pore of winer , keratoacanthoma , syringocystadenoma papilliferum , hidradenoma papilliferum , and very rarely basal cell carcinoma or squamous cell carcinoma [ 2326 ] . the prevalence of nc has been estimated from 1 in 45,000 to 1 in 100,000 , with no gender or racial preference [ 1 , 3 ] . in 50% of patients , the condition develops shortly after birth and in the majority of patients lesions appear before the age of 10 [ 46 ] . single cases of delayed development of nc and ncs at later age have been reported [ 46 ] . nc is usually asymptomatic and most commonly it affects the face and neck area and , by exception , other anatomical regions , including genital area , palms , and soles . clinically , nc presents with grouped , dilated , plugged follicular ostia in a honeycomb pattern . their appearance resembles black dots but the material can not be easily removed mechanically in contrast to acne comedones [ 1 , 7 ] . nc lesions might present with various patterns of distribution : unilateral , bilateral , linear , interrupted , segmental , or blaschkoid ( figs .  1 , 2 and 3 ) .fig . 1nevus comedonicus : plaque - like lesion with wide open follicles on the neck ( 44-year - old caucasian male)fig . 2stages of treatment of a 29-year - old asian male with linear nevus comedonicus of the leg with multiple follicular openings . a presentation of linear nevus comedonicus with multiple follicular openings . 3nevus comedonicus of the neck with pseudoepithelial epidermal hyperplasia in a 39-year - old caucasian nevus comedonicus : plaque - like lesion with wide open follicles on the neck ( 44-year - old caucasian male ) stages of treatment of a 29-year - old asian male with linear nevus comedonicus of the leg with multiple follicular openings . d with compression garment to avoid postsurgical lymphedema nevus comedonicus of the neck with pseudoepithelial epidermal hyperplasia in a 39-year - old caucasian two types of nc have been identified ; the first is non - pyogenic nc with acne - like characteristics and a second type characterized by formation of cysts , papules , pustules , and abscesses in various stages of development [ 8 , 9 ] . the former type is also known as munro s acne nevus and separated by some authors from nc . differential diagnoses are shown in table  1.table  1histopathological differential diagnoses of nevus comedonicusnevus comedonicustrichofolliculomadilated pore of winerpilar sheath acanthomafolliculocystic and collagen comedo hamartomahair cortexlocalization  head+++  face++++  neck++  trunk(+)+++  limbs+folliclesnumerous open folliclesopen mother folliclesnumerous open folliclessolitary lesionscysts+++hair shafts+ , velluslamellated keratinothersmassive epithelial proliferations without folliclesabundant collagen formation histopathological differential diagnoses of nevus comedonicus the major histopathologic symptoms are large grouped , dilated follicular ostia devoid of hair shafts but filled with keratin layers ( fig .  4 ) . at some locations in the bases of the follicular invaginations one may observe singular rudimentary glands , which are not , however , obligatory as they may be absent . small cysts , cystic invaginations , and occasionally large cysts may be seen in histopathologic investigation ; the variable cystic structures are lined by keratinizing squamous epithelium [ 1 , 7 ] . hyperkeratosis ( epidermolytic hyperkeratosis ) and acanthosis of the epidermis may be present but not para- or dyskeratosis [ 8 , 1013].fig . 4histopathology of nevus comedonicus . a overview ( hematoxylin and eosin stain [ he ]    2 ) . b details with large follicles containing lamellated keratin but absent hair shafts ( he    4 ) histopathology of nevus comedonicus . a overview ( hematoxylin and eosin stain [ he ]    2 ) . b details with large follicles containing lamellated keratin but absent hair shafts ( he    4 ) an increased number of langerhans cells had been observed by electron microscopy . more abundant tonofilaments in the upper part of the stratum spinosum and numerous keratohyalin granules were also noticed [ 11 , 12 ] . the arrector pili muscles were incompletely differentiated and demonstrated intracellular glycogen particles [ 11 , 12 ] . filaggrin , which is usually located in the granular epidermal layer , occurs in the whole epidermis of closed comedones suggesting its role in their development [ 14 , 15 ] . interaction between fibroblast growth factor ( fgf ) and fgf receptor-2 ( fgfr2 ) is a crucial pathway for mesenchymal  epithelial interplay in pilosebaceous unit development . fgfr2b is exclusively found in epithelial cells including epidermal keratinocytes and sebocytes [ 15 , 16 ] . overstimulation of fgfr2 signaling with increased expression of interleukin-1 may be involved in nc pathogenesis . somatic mutations like ser252trp substation have been identified in individual patients with segmental acne [ 1618 ] . -secretase found in human hair follicle epithelium is another candidate for nc since the absence of this enzyme results in complete conversion of hair follicles to epidermal cysts . ncs ( orpha64754 ) belongs to the group of epidermal nevus syndromes including schimmelpenning syndrome , phacomatosis pigmentokeratotica , angora hair nevus syndrome , and becker nevus syndrome among others where a genetic basis has yet not been identified [ 3 , 4 , 20 ] . ncs is a neurocutaneous disorder which consists of nc with skeletal , ocular , and central nervous system abnormalities . the most common symptoms include cataracts , scoliosis , fused vertebrae , spina bifida , and delayed mental development [ 5 , 6 ] . in addition , seizures , paresis , dysgenesis of corpus callosum , electroencephalographic abnormalities , limb deformities such as absence of the fifth finger , polysyndactyly or clinodactyly , oligodontia , and other skin disorders such as ichthyosis , leukoderma , lichen striatus , linear morphea , sturge - weber syndrome , hemangiomas , and inverse acne have been reported in ncs [ 1 , 3 , 4 , 2022 ] . ncs is associated with epithelial tumors such as trichoepithelioma , pilar sheath tumor or dilated pore of winer , keratoacanthoma , syringocystadenoma papilliferum , hidradenoma papilliferum , and very rarely basal cell carcinoma or squamous cell carcinoma [ 2326 ] . being benign , nc does not require aggressive treatment , except for aesthetic reasons or in complicated cases . conservative options include emollients and moisturizer , topical corticosteroids ( for inflammatory lesions ) , keratolytics such as salicylic acid , or 12% ammonium lactate solution . some reports showed better improvement of nc by topical tazarotene as monotherapy or in combination with topical mometasone furoate or calcipotriene [ 2931 ] . oral retinoids , such as isotretinoin , were found to be ineffective in most cases but may be an option in widespread systematized inflammatory variants [ 32 , 33 ] . there have , as yet , been no published studies of other retinoids , such as topical adapalene and systemic or topical bexarotene . of potential interest are fgfr inhibitors with antivascular activity . interleukin-1 inhibitors can be classified into receptor inhibitors , such as anakinra , and monoclonal antibodies against the interleukin itself . currently , there are no data available for nc . another interesting drug target is -secretase ; stimulators of this enzyme such as general control nonderepressible 2 ( gcn2)a subunit of eukaryotic translation factor 2 kinase  might be a future therapeutic option . localized nc can be removed by surgical excision with good aesthetic results in contrast to superficial shaving , comedo extraction , and dermabrasion techniques ( fig . if linear nc is surgically removed on the limbs , complex decongestive therapy including manual lymph drainage and compression garments supports the healing process ( fig . 2d ) . larger lesions may need transplantation for defect closure , or another option is the use of repeat - filling or self - filling osmotic tissue expanders to obtain a resurplus of skin for defect closure [ 38 , 39 ] . laser treatments with 2,940-nm erbium yag , 10,600-nm ultrapulsed co2 , or 1,450-nm diode lasers have shown improvement in single patients [ 4042 ] . erbium yag laser treatment is often followed by delayed relapses . in contrast to ablative lasers , the 1,450  nm diode shrinks sebaceous glands and reduces seborrhea . the combination of 1,450-nm diode laser with 1,550-nm erbium - doped fiber laser has potential for treating nc . with this review we provided an update on clinical features , pathogenesis and treatment option of nc . nc is a rare epidermal nevus . new data are available on signaling pathways in acne - related disorders that may have an impact on nc as well . in contrast to the acne - related comedones , the epithelium is often hyperkeratotic and sometimes acanthotic and comedo extraction is not as easily achieved as with acne comedones . dermatologists should be aware of potential association of nc with skin tumors and extracutaneous findings such as ncs . new developments in laser technology may become an alternative in near future . with a more detailed understanding in molecular pathogenesis , targeted therapy
the intention of this review on nevus comedonicus ( nc ) is to update on clinical features , pathogenesis , and therapy . 
 nc is a rare epidermal nevus type . 
 it is part of the nevus comedonicus syndrome , a neurocutaneous disorder with ocular , skeletal , and central nervous symptoms . 
 recently , acne - related signaling pathways and somatic mutations of tyrosine kinase receptors have been identified and may play a role in nc pathogenesis . 
 on preexistent nc secondary skin tumors can develop , which are often benign . 
 treatment options of nc include topical therapy , laser , and surgery .