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Large congenital melanocytic nevus(CMNS)

MedGen UID:
330752
Concept ID:
C1842036
Finding; Neoplastic Process
Synonyms: Bathing trunk nevus; CMNS; Congenital giant melanocytic nevus; Congenital giant pigmented nevus; Congenital melanocytic nevus - large; Giant congenital nevus; Giant hairy nevus; Giant pigmented hairy nevus; MELANOCYTIC NEVUS SYNDROME, CONGENITAL, SOMATIC; PIGMENTED MOLES
SNOMED CT: Giant pigmented nevus (10291008); Intermediate and giant congenital nevus (10291008); LCMN - large congenital melanocytic nevus (1260467009); GCMN - giant congenital melanocytic nevus (1260467009); Giant congenital melanocytic nevus (1260467009); Large congenital pigmented melanocytic nevus of skin (1260467009)
Modes of inheritance:
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Genes (locations): HRAS (11p15.5); NRAS (1p13.2)
 
HPO: HP:0005600
Monarch Initiative: MONDO:0044792
OMIM®: 137550
Orphanet: ORPHA626

Definition

Congenital melanocytic nevus syndrome is characterized by pigmentary skin defects apparent at birth. Most individuals have 1 or more large or giant lesions greater than 20 cm and up to over 60 cm in diameter, which may cover up to 80% of total body area. These lesions may or may not be hairy. Smaller 'satellite' pigmented lesions numbering in the hundreds may also be present all over the body. Congenital melanocytic nevi (CMN) can be associated with malignant melanoma (see CMM1, 155600), but the risk appears to be low, ranging from 1 to 2% for all individuals, but rising to 10 to 15% in those with very large nevi (greater than 40 cm). A small subset of patients with CMNS have abnormalities of the central nervous system, known as 'neurocutaneous melanosis' or 'neuromelanosis' (249400), which may be symptomatic. Patients with CMNS also tend to have a characteristic facial appearance, including wide or prominent forehead, periorbital fullness, small short nose with narrow nasal bridge, round face, full cheeks, prominent premaxilla, and everted lower lip (summary by Kinsler et al., 2008; Kinsler et al., 2012). Spitz nevi are benign melanocytic melanomas composed of epithelioid or spindle cell melanocytes. They usually present as solitary skin tumors but can occur in multiple patterns, having agminated, dermatomal, and disseminated forms (summary by Sarin et al., 2013). Nevus spilus, also known as speckled lentiginous nevus, is a congenital hyperpigmented patch that progressively evolves, with affected individuals developing dark macules and papules during childhood and adolescence. Over time, nevus spilus may give rise to common lentigines, melanocytic nevi, Spitz nevi, and melanomas (summary by Sarin et al., 2014). [from OMIM]

Additional description

From MedlinePlus Genetics
Giant congenital melanocytic nevus is a skin condition characterized by an abnormally dark, noncancerous skin patch (nevus) that is composed of pigment-producing cells called melanocytes. It is present from birth (congenital) or is noticeable soon after birth. The nevus may be small in infants, but it will usually grow at the same rate the body grows and will eventually be at least 40 cm (15.75 inches) across. The nevus can appear anywhere on the body, but it is more often found on the trunk or limbs. The color ranges from tan to black and can become darker or lighter over time. The surface of a nevus can be flat, rough, raised, thickened, or bumpy; the surface can vary in different regions of the nevus, and it can change over time. The skin of the nevus is often dry and prone to irritation and itching (dermatitis). Excessive hair growth (hypertrichosis) can occur within the nevus. There is often less fat tissue under the skin of the nevus; the skin may appear thinner there than over other areas of the body.

People with giant congenital melanocytic nevus may have more than one nevus (plural: nevi). The other nevi are often smaller than the giant nevus. Affected individuals may have one or two additional nevi or multiple small nevi that are scattered over the skin; these are known as satellite or disseminated nevi.

Affected individuals may feel anxiety or emotional stress due to the impact the nevus may have on their appearance and their health. Children with giant congenital melanocytic nevus can develop emotional or behavior problems.

Some people with giant congenital melanocytic nevus develop a condition called neurocutaneous melanosis, which is the presence of pigment-producing skin cells (melanocytes) in the tissue that covers the brain and spinal cord. These melanocytes may be spread out or grouped together in clusters. Their growth can cause increased pressure in the brain, leading to headache, vomiting, irritability, seizures, and movement problems. Tumors in the brain may also develop.

Individuals with giant congenital melanocytic nevus have an increased risk of developing an aggressive form of skin cancer called melanoma, which arises from melanocytes. Estimates vary, but it is generally thought that people with giant congenital melanocytic nevus have a 5 to 10 percent lifetime risk of developing melanoma. Melanoma commonly begins in the nevus, but it can develop when melanocytes that invade other tissues, such as those in the brain and spinal cord, become cancerous. When melanoma occurs in people with giant congenital melanocytic nevus, the survival rate is low.

Other types of tumors can also develop in individuals with giant congenital melanocytic nevus, including soft tissue tumors (sarcomas), fatty tumors (lipomas), and tumors of the nerve cells (schwannomas).  https://medlineplus.gov/genetics/condition/giant-congenital-melanocytic-nevus

Clinical features

From HPO
Malignant melanoma of skin
MedGen UID:
57486
Concept ID:
C0151779
Neoplastic Process
Most melanomas affect only the outermost layer of skin (the epidermis). If a melanoma becomes thicker and involves multiple layers of skin, it can spread to other parts of the body (metastasize).\n\nMelanoma may develop from an existing mole or other normal skin growth that becomes cancerous (malignant); however, many melanomas are new growths. Melanomas often have ragged edges and an irregular shape. They can range from a few millimeters to several centimeters across. They can also be a variety of colors: brown, black, red, pink, blue, or white.\n\nA large number of moles or other pigmented skin growths on the body, generally more than 25, is associated with an increased risk of developing melanoma. Melanoma is also a common feature of genetic syndromes affecting the skin such as xeroderma pigmentosum. Additionally, individuals who have previously had melanoma are nearly nine times more likely than the general population to develop melanoma again. It is estimated that about 90 percent of individuals with melanoma survive at least 5 years after being diagnosed.\n\nMelanoma is a type of skin cancer that begins in pigment-producing cells called melanocytes. This cancer typically occurs in areas that are only occasionally sun-exposed; tumors are most commonly found on the back in men and on the legs in women. Melanoma usually occurs on the skin (cutaneous melanoma), but in about 5 percent of cases it develops in melanocytes in other tissues, including the eyes (uveal melanoma) or mucous membranes that line the body's cavities, such as the moist lining of the mouth (mucosal melanoma). Melanoma can develop at any age, but it most frequently occurs in people in their fifties to seventies and is becoming more common in teenagers and young adults.
Prominence of the premaxilla
MedGen UID:
412683
Concept ID:
C2749369
Finding
Prominent positioning of the premaxilla in relation to the rest of the maxilla, the facial skeleton, or mandible. Not necessarily caused by an increase in size (hypertrophy of) the premaxilla.
Round face
MedGen UID:
116087
Concept ID:
C0239479
Finding
The facial appearance is more circular than usual as viewed from the front.
Open mouth
MedGen UID:
116104
Concept ID:
C0240379
Finding
A facial appearance characterized by a permanently or nearly permanently opened mouth.
Broad nasal tip
MedGen UID:
98424
Concept ID:
C0426429
Finding
Increase in width of the nasal tip.
Prominent forehead
MedGen UID:
373291
Concept ID:
C1837260
Finding
Forward prominence of the entire forehead, due to protrusion of the frontal bone.
Narrow nasal ridge
MedGen UID:
373404
Concept ID:
C1837761
Finding
Decreased width of the nasal ridge.
Deep philtrum
MedGen UID:
374311
Concept ID:
C1839797
Finding
Accentuated, prominent philtral ridges giving rise to an exaggerated groove in the midline between the nasal base and upper vermillion border.
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Broad forehead
MedGen UID:
338610
Concept ID:
C1849089
Finding
Width of the forehead or distance between the frontotemporales is more than two standard deviations above the mean (objective); or apparently increased distance between the two sides of the forehead.
Everted lower lip vermilion
MedGen UID:
344003
Concept ID:
C1853246
Finding
An abnormal configuration of the lower lip such that it is turned outward i.e., everted, with the Inner aspect of the lower lip vermilion (normally opposing the teeth) being visible in a frontal view.
Short nose
MedGen UID:
343052
Concept ID:
C1854114
Finding
Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip.
Long philtrum
MedGen UID:
351278
Concept ID:
C1865014
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border.
Full cheeks
MedGen UID:
355661
Concept ID:
C1866231
Finding
Increased prominence or roundness of soft tissues between zygomata and mandible.
Periorbital fullness
MedGen UID:
1710990
Concept ID:
C4760994
Finding
Increase in periorbital soft tissue.
Nevus spilus
MedGen UID:
87538
Concept ID:
C0346099
Neoplastic Process
A tan, regularly bordered patch with darker macules within the lesion.
Large congenital melanocytic nevus
MedGen UID:
330752
Concept ID:
C1842036
Neoplastic Process
Congenital melanocytic nevus syndrome is characterized by pigmentary skin defects apparent at birth. Most individuals have 1 or more large or giant lesions greater than 20 cm and up to over 60 cm in diameter, which may cover up to 80% of total body area. These lesions may or may not be hairy. Smaller 'satellite' pigmented lesions numbering in the hundreds may also be present all over the body. Congenital melanocytic nevi (CMN) can be associated with malignant melanoma (see CMM1, 155600), but the risk appears to be low, ranging from 1 to 2% for all individuals, but rising to 10 to 15% in those with very large nevi (greater than 40 cm). A small subset of patients with CMNS have abnormalities of the central nervous system, known as 'neurocutaneous melanosis' or 'neuromelanosis' (249400), which may be symptomatic. Patients with CMNS also tend to have a characteristic facial appearance, including wide or prominent forehead, periorbital fullness, small short nose with narrow nasal bridge, round face, full cheeks, prominent premaxilla, and everted lower lip (summary by Kinsler et al., 2008; Kinsler et al., 2012). Spitz nevi are benign melanocytic melanomas composed of epithelioid or spindle cell melanocytes. They usually present as solitary skin tumors but can occur in multiple patterns, having agminated, dermatomal, and disseminated forms (summary by Sarin et al., 2013). Nevus spilus, also known as speckled lentiginous nevus, is a congenital hyperpigmented patch that progressively evolves, with affected individuals developing dark macules and papules during childhood and adolescence. Over time, nevus spilus may give rise to common lentigines, melanocytic nevi, Spitz nevi, and melanomas (summary by Sarin et al., 2014).
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Large congenital melanocytic nevus in Orphanet.

Conditions with this feature

Large congenital melanocytic nevus
MedGen UID:
330752
Concept ID:
C1842036
Neoplastic Process
Congenital melanocytic nevus syndrome is characterized by pigmentary skin defects apparent at birth. Most individuals have 1 or more large or giant lesions greater than 20 cm and up to over 60 cm in diameter, which may cover up to 80% of total body area. These lesions may or may not be hairy. Smaller 'satellite' pigmented lesions numbering in the hundreds may also be present all over the body. Congenital melanocytic nevi (CMN) can be associated with malignant melanoma (see CMM1, 155600), but the risk appears to be low, ranging from 1 to 2% for all individuals, but rising to 10 to 15% in those with very large nevi (greater than 40 cm). A small subset of patients with CMNS have abnormalities of the central nervous system, known as 'neurocutaneous melanosis' or 'neuromelanosis' (249400), which may be symptomatic. Patients with CMNS also tend to have a characteristic facial appearance, including wide or prominent forehead, periorbital fullness, small short nose with narrow nasal bridge, round face, full cheeks, prominent premaxilla, and everted lower lip (summary by Kinsler et al., 2008; Kinsler et al., 2012). Spitz nevi are benign melanocytic melanomas composed of epithelioid or spindle cell melanocytes. They usually present as solitary skin tumors but can occur in multiple patterns, having agminated, dermatomal, and disseminated forms (summary by Sarin et al., 2013). Nevus spilus, also known as speckled lentiginous nevus, is a congenital hyperpigmented patch that progressively evolves, with affected individuals developing dark macules and papules during childhood and adolescence. Over time, nevus spilus may give rise to common lentigines, melanocytic nevi, Spitz nevi, and melanomas (summary by Sarin et al., 2014).

Professional guidelines

PubMed

Jahnke MN, O'Haver J, Gupta D, Hawryluk EB, Finelt N, Kruse L, Jen M, Horii KA, Frieden IJ, Price H, Coughlin CC
Pediatrics 2021 Dec 1;148(6) doi: 10.1542/peds.2021-051536. PMID: 34845496
Vourc'h-Jourdain M, Martin L, Barbarot S; aRED
J Am Acad Dermatol 2013 Mar;68(3):493-8.e1-14. Epub 2012 Nov 19 doi: 10.1016/j.jaad.2012.09.039. PMID: 23182059
Marghoob AA
Dermatol Clin 2002 Oct;20(4):607-16, viii. doi: 10.1016/s0733-8635(02)00030-x. PMID: 12380048

Recent clinical studies

Etiology

Polat Ekinci A, Kiliç S, Baykal C
Pediatr Dermatol 2016 May;33(3):307-10. Epub 2016 Mar 2 doi: 10.1111/pde.12823. PMID: 26935480
Baykal C, Solakoğlu S, Polat Ekinci A, Yazganoğlu KD
Pediatr Dermatol 2015 Jul-Aug;32(4):514-7. Epub 2015 May 4 doi: 10.1111/pde.12610. PMID: 25940669
Shah KN
Semin Cutan Med Surg 2010 Sep;29(3):159-64. doi: 10.1016/j.sder.2010.06.007. PMID: 21051009
Bittencourt FV, Marghoob AA, Kopf AW, Koenig KL, Bart RS
Pediatrics 2000 Oct;106(4):736-41. doi: 10.1542/peds.106.4.736. PMID: 11015516
DeDavid M, Orlow SJ, Provost N, Marghoob AA, Rao BK, Wasti Q, Huang CL, Kopf AW, Bart RS
J Am Acad Dermatol 1996 Oct;35(4):529-38. doi: 10.1016/s0190-9622(96)90674-x. PMID: 8859278

Diagnosis

Alsaidan MS, Aljarbou OZ
Int J Surg Pathol 2024 Feb;32(1):196-200. Epub 2023 May 4 doi: 10.1177/10668969231171130. PMID: 37143310
Schaffer JV, Chang MW, Kovich OI, Kamino H, Orlow SJ
J Am Acad Dermatol 2007 May;56(5):862-8. Epub 2007 Feb 5 doi: 10.1016/j.jaad.2006.11.022. PMID: 17280739
Nakatsura T, Nishimura Y
BioDrugs 2005;19(2):71-7. doi: 10.2165/00063030-200519020-00001. PMID: 15807627
Morioka M, Hamada J, Ohmori Y, Kageshita T, Ushio Y
Neurosurgery 2004 Oct;55(4):983-4. doi: 10.1227/01.neu.0000137280.84648.ce. PMID: 15934183
DeDavid M, Orlow SJ, Provost N, Marghoob AA, Rao BK, Wasti Q, Huang CL, Kopf AW, Bart RS
J Am Acad Dermatol 1996 Oct;35(4):529-38. doi: 10.1016/s0190-9622(96)90674-x. PMID: 8859278

Therapy

Ambros T, Furian R, Riccardi F
Pediatr Dermatol 2011 Nov-Dec;28(6):729-731. Epub 2011 Sep 25 doi: 10.1111/j.1525-1470.2011.01398.x. PMID: 21950562

Prognosis

Viana ACL, Goulart EMA, Gontijo B, Bittencourt FV
An Bras Dermatol 2017 Mar-Apr;92(2):200-205. doi: 10.1590/abd1806-4841.20175176. PMID: 28538879Free PMC Article
Polat Ekinci A, Kiliç S, Baykal C
Pediatr Dermatol 2016 May;33(3):307-10. Epub 2016 Mar 2 doi: 10.1111/pde.12823. PMID: 26935480
Spiller SE, Hawkins DS, Finn LS, Sze RW, Sybert V
Pediatr Blood Cancer 2005 Jul;45(1):60-3. doi: 10.1002/pbc.20200. PMID: 15800910
Bittencourt FV, Marghoob AA, Kopf AW, Koenig KL, Bart RS
Pediatrics 2000 Oct;106(4):736-41. doi: 10.1542/peds.106.4.736. PMID: 11015516
DeDavid M, Orlow SJ, Provost N, Marghoob AA, Rao BK, Wasti Q, Huang CL, Kopf AW, Bart RS
J Am Acad Dermatol 1996 Oct;35(4):529-38. doi: 10.1016/s0190-9622(96)90674-x. PMID: 8859278

Clinical prediction guides

Viana ACL, Goulart EMA, Gontijo B, Bittencourt FV
An Bras Dermatol 2017 Mar-Apr;92(2):200-205. doi: 10.1590/abd1806-4841.20175176. PMID: 28538879Free PMC Article
Polat Ekinci A, Kiliç S, Baykal C
Pediatr Dermatol 2016 May;33(3):307-10. Epub 2016 Mar 2 doi: 10.1111/pde.12823. PMID: 26935480
Baykal C, Solakoğlu S, Polat Ekinci A, Yazganoğlu KD
Pediatr Dermatol 2015 Jul-Aug;32(4):514-7. Epub 2015 May 4 doi: 10.1111/pde.12610. PMID: 25940669
Lee CJ, Park JH, Lee SI
J Craniofac Surg 2006 Nov;17(6):1216-8. doi: 10.1097/01.scs.0000221514.34620.c0. PMID: 17119434
Nakatsura T, Kageshita T, Ito S, Wakamatsu K, Monji M, Ikuta Y, Senju S, Ono T, Nishimura Y
Clin Cancer Res 2004 Oct 1;10(19):6612-21. doi: 10.1158/1078-0432.CCR-04-0348. PMID: 15475451

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