Congenital melanocytic naevus

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Meet the patient

A term newborn is referred from the postnatal ward with a dark, thickened plaque covering the entire back from shoulders to buttocks, and more than thirty smaller pigmented macules scattered over the scalp, limbs and trunk. The parents have one question, and it is the right one: "does our baby need an MRI?"[2]

The answer turns on three numbers you can read off the skin in under a minute — the projected adult size (this lesion is giant), the axis (posterior — back and scalp), and the satellite count (well over twenty). Those three numbers, not the histology and not the family tree, decide whether this child gets an MRI of brain and spine in the first six months of life.[3]

One birthmark, one mutation, three sizes

A CMN is a melanocytic naevus present at birth — or appearing within the first 4-6 weeks as the "tardive" form. It is built from naevomelanocytes that never finished their migration from the neural crest to the epidermis, arresting instead in the dermis, around adnexae, around nerves and down into the subcutis.[5]

That deep arrest is the whole story of CMN. An acquired naevus keeps its cells in the epidermis and papillary dermis; a congenital one buries them deep — which is why superficial excision never clears a giant lesion, and why melanoma in a giant CMN hides where your eye and your shave blade cannot reach.[5]

Etymology for the viva: naevus is straight Latin for "birthmark". The lesion announces what it is in its name — it was there at birth, and it stays for life.[2]

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The size thresholds that decide everything

CMN are classified by projected adult size — the diameter the lesion will reach in adulthood, estimated from the neonatal measurement by a growth factor (1.7 historically, 2 in current consensus). Size, more than any other feature, sets the melanoma and NCM risk.[2]

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The 2020 international CMN consensus (Ott et al., ERN-Skin) layered three extra axes onto size: satellite count (none, fewer than 20, 20-50, more than 50), morphological features (colour heterogeneity, surface rugosity, subcutaneous or proliferative nodules), and the "CMN syndrome" label when neurological, skeletal or other organ involvement is present. This is the classification fellowship examiners now expect.[3]

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Eponymous giant patterns — name the distribution, name the risk

Giant CMN are described by their cutaneous map, and the map predicts the danger. Posterior-axis lesions carry the highest NCM risk; anterior and limb lesions carry less.[2]

• Bathing-trunk naevus — circumferential lower trunk, buttocks and thighs, the "swimsuit" distribution.
• Cape or shoulder naevus — upper back, shoulders and arms; the highest NCM risk of all patterns (posterior axial).
• Stocking or glove naevus — an entire limb, often with distal sparing.
• Dermal melanocytosis (Mongolian-spot-like) — slate-grey, deep, indistinct; coexists with classic giant CMN in roughly 1-2% of cases.[5]

NRAS Q61 — the genetic signature of the giant lesion

Melanocytes come from the neural crest. A subset of melanoblasts migrates dorsolaterally between ectoderm and somites around weeks 6-8, seeding the epidermis, hair follicles, uveal tract, leptomeninges, mucosae and the striae vascularis. A CMN begins when a single melanoblast in that migrating stream picks up an activating RAS-MAPK mutation; its daughter cells carry the mutation wherever they end up, painting a patchy, sometimes enormous pigmented territory.[6]

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In the remaining 10-20% of CMN the driver is BRAF V600E, or — increasingly recognised since 2024 — a mosaic BRAF fusion. A tiny minority run on HRAS, KRAS or other rare alterations. Knowing the driver now matters clinically, not just academically: it tells you whether a MEK, ERK or BRAF inhibitor is the right targeted lever if the lesion ever needs systemic therapy.[9]

Mosaic, not inherited — reassure the family

The mutation happens after fertilisation, so only a fraction of the body's cells carry it. Mutate early in the melanoblast lineage, before migration, and a huge anatomical territory is seeded with mutant cells — a giant CMN plus clonally related satellites. Mutate late, and the lesion is small.[3]

This is textbook type 1 segmental mosaicism — the older literature called it "paradominant inheritance", a germline-silent mutation that is not transmissible because the germline is unaffected. Either way, the practical consequence is the same and it is the one families most need to hear.[7]

The mantra for the family meeting: mosaic, not inherited — reassure the family. Sibling risk, offspring risk and recurrence in the next pregnancy all sit at the population baseline.[7]

Etymology for the viva: mosaicism borrows from the mosaic artist — the body is a pavement of tiles, some mutant, some wild-type, laid down after a single postzygotic event. The patient is a walking mosaic; the siblings are not.[3]

Oncogene-induced senescence — why most naevus cells stop, and a few do not

Paradoxically, the same NRAS Q61 mutation that builds the CMN also trips oncogene-induced senescence through p16/CDKN2A and p53 — the molecular brake that stops most naevomelanocytes proliferating. The rare cells that escape this brake take the "second hit" and are the ones that become melanoma in a giant CMN.[4]

RASopathies — when CMN is the skin clue to a germline disorder

CMN can be the cutaneous marker of a germline RAS-MAPK disorder — a RASopathy. In these syndromes a germline RAS-pathway mutation plus a somatic second hit in the melanoblast lineage produces the naevus. The index case is a candidate for clinical genetics referral.[3]

• Noonan syndrome (most common; PTPN11, SOS1, RAF1, KRAS, NRAS).
• Cardio-facio-cutaneous (CFC) syndrome (BRAF, MAP2K1, MAP2K2, KRAS).
• Costello syndrome (HRAS).
• Noonan with multiple lentigines (formerly LEOPARD; PTPN11, RAF1) — lentigines, conduction abnormalities, hypertrophic cardiomyopathy.[7]

Why giant CMN turns malignant (and small does not)

Risk tracks size, and giant-CMN melanoma breaks every rule you learned for sporadic melanoma. It arrives before puberty, not in late adult life, and it arises in the deep dermis or CNS, not at the epidermis — which is precisely why it is so hard to spot early and why shave biopsies are dangerous here.[4]

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What everyone forgets: sporadic melanoma is an adult, epidermal, UV-driven disease. Giant-CMN melanoma is a childhood, deep-dermal, mutation-driven disease. Apply the ABCDE rule and you will miss it; the sign that matters is a focal change that is out of step with the rest of the lesion.[4]

Clinical signs of malignant change in any CMN: a new rapidly growing nodule, colour change (darkening, blue-black, depigmentation), ulceration or bleeding, pain, or a satellite that becomes elevated. Any one of these is a biopsy, not a watch.[4]

Neurocutaneous melanocytosis — the 20-satellite rule

NCM is melanocyte proliferation in the leptomeninges (pia and arachnoid) and brain parenchyma. About 5-10% of patients with giant CMN develop symptomatic NCM, and the risk concentrates in one phenotype: posterior-axis giant CMN with 20 or more satellite naevi, virtually all NRAS-driven.[3]

Symptoms follow melanin where it deposits. Seizures, obstructive hydrocephalus (melanin and macrophages clogging the foramina of Magendie and Luschka), developmental delay or regression, cranial nerve palsies, and spinal cord compression from spinal leptomeningeal melanocytosis.[8]

Screen with MRI brain and whole spine in the first 6 months of life — before myelination erases the sensitivity of the scan — for every child with a giant CMN plus posterior-axis location, 20 or more satellites, head or neck involvement with satellites, or any neurological symptom.[3]

Symptomatic NCM is grim. Median survival from symptom onset sits under three years; the commonest causes of death are obstructive hydrocephalus, status epilepticus and primary CNS melanoma. Asymptomatic radiological NCM is managed with neurological surveillance, not intervention.[8]

Proliferative nodule vs melanoma — the bedside rule

A proliferative nodule is a benign nodular burst of naevomelanocytes inside a giant CMN, seen in up to 10% of giant lesions. Clinically it is sudden, fast-growing and often deeply pigmented — exactly the features that terrify the parents and the junior. Histologically it lacks the atypia, mitoses and necrosis of melanoma, but telling them apart can defeat even expert dermatopathologists, and aneuploidy by FISH or CGH plus p16 and p21 stains are the arbiters.[4]

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What else looks like a CMN?

Six congenital or adolescent pigmented lesions compete for the same diagnostic slot. Pick the discriminator first, then commit to a label.[5]

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Other mimics worth a sentence: congenital smooth-muscle hamartoma (hypertrichotic but pale-fawn), congenital pigmented dermatofibroma, congenital juvenile xanthogranuloma (yellow-orange, transient), congenital mastocytoma (Darier's sign positive), and the PHACE or Sturge-Weber spectrum when a facial vascular stain coexists with a CMN.[1]

At the bedside — examination and the limits of ABCDE

A CMN assessment is a skin exam plus a neurological exam plus an eye exam, all on the same visit. Document every lesion, every satellite, and its size, distribution, colour, surface and hair; then assess the fontanelle, head circumference, cranial nerves, tone, gait and seizure history.[2]

1. Total-skin examination — map every CMN and satellite; record largest diameter, colour, surface and hypertrichosis.
2. Neurological examination — conscious level, fontanelle, head circumference, cranial nerves, primitive reflexes in infants, tone, gait, and any seizure history.
3. Ophthalmology assessment — fundoscopy, intraocular pressure and slit-lamp; mandatory in palpebral, head or neck, and any giant CMN.
4. Baseline total-body photography — standardised, age-corrected images at 6, 12 and 24 months, then yearly. This is the single most useful surveillance tool you have.
5. Dermoscopy — useful for smaller CMN and for locking the dermoscopic signature of an individual lesion; giant CMN are too large for standard dermoscopy.
6. Palpation — depth (dermal vs subcutaneous), nodularity, warmth, tenderness.[1]

ABCDE is built for sporadic melanoma and misleads in giant CMN. The baseline colour is heterogeneous, the border is irregular, and the lesion grows constantly — so asymmetry, border and colour are abnormal by default. The only sign that earns its place here is evolution: a focal change in colour, surface, nodularity or ulceration that is out of step with the rest of the lesion.[4]

Investigations

MRI brain and whole spine — the screening window

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What NCM looks like on MRI:[8]

• T1 hyperintense leptomeningeal signal — the paramagnetic effect of melanin.
• T1 hyperintense parenchymal melanocytosis in the temporal lobes, cerebellum, brainstem and thalami.
• Leptomeningeal enhancement after contrast.
• Hydrocephalus — obstructive, from melanin deposition at the foramina of Magendie and Luschka or within the ventricular system.
• Mass lesions — parenchymal or leptomeningeal melanoma.[8]

Biopsy — and the shave you must never do

The classic trap: booking a shave biopsy on a changing nodule in a giant CMN. The shave cannot reach the deep dermis where giant-CMN melanoma arises, and if it does transect a melanoma it destroys your Breslow thickness and stages the disease wrongly. It is the single worst biopsy choice in this topic.[4]

• Excisional biopsy (1-3 mm clinical margin, full-thickness to subcutis, one piece) for a small or medium CMN that has changed.
• Incisional or punch biopsy of a suspicious nodule in a giant CMN — and it must reach the deep dermis to capture the deep naevomelanocytes where melanoma lives.
• Shave biopsy is contraindicated — it misses the deep component and may transect a melanoma, ruining depth measurement.[4]

Histopathology — the five deep features

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Histology does not reliably predict melanoma risk. A banal-looking CMN can give rise to melanoma, and an atypical-looking one can sit quietly for life — which is why surveillance is clinical and photographic, not histological.[5]

Molecular testing

• Targeted NGS panel for NRAS, BRAF, BRAF fusions, KRAS and HRAS — increasingly routine, especially when systemic therapy is on the table.
• FISH or CGH to settle a difficult proliferative-nodule-vs-melanoma call.
• Germline RASopathy panel when a clinical geneticist suspects Noonan, CFC or Costello syndrome.[7]

Reflectance confocal microscopy and high-frequency ultrasound

Used in specialist centres to map the depth and architecture of suspicious areas within a giant CMN. They guide where to biopsy; they never replace it.[1]

Management

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Small and medium CMN — observe, photograph, educate

Most small and medium CMN need an observer, not a surgeon. The melanoma risk sits at population baseline, and the strongest intervention you offer is usually a camera and a conversation.[1]

• Observe with baseline photography; re-photograph at 6 months, 12 months, then yearly.
• Educate parents and the age-appropriate child on ABCDE and the red-flag signs — new nodule, ulceration, bleeding, rapid growth, pain, itch.
• Excision is not mandatory. Consider it for cosmesis, repeated trauma, functional impairment, or any change suspicious for melanoma.
• Lasers (Q-switched ruby, alexandrite) may be used cosmetically; expect repigmentation, scarring and depigmentation.
• Dermatology review every 1-3 years depending on the lesion.[1]

Giant CMN — a multidisciplinary team from birth

A giant CMN is a lifelong multidisciplinary problem, and the team is assembled in the neonatal period, not at the first complication.[2]

• Paediatric dermatology — lead clinician; baseline photography, serial examination, biopsy of any change.
• Paediatric neurology — clinical surveillance; MRI brain and whole spine in the first 6 months if posterior-axis or more than 20 satellites; repeat MRI every 1-2 years if NCM is present.
• Paediatric neurosurgery — for symptomatic NCM with hydrocephalus or mass effect.
• Plastic or paediatric surgery — staged excision, tissue expansion, skin grafts, cultured epithelial autografts.
• Ophthalmology — palpebral and head or neck CMN; baseline assessment, intraocular pressure, fundoscopy.
• Clinical genetics — RASopathy features, sibling and prenatal counselling.
• Psychology or psychiatry — body image, peer interactions, school integration.
• Pain service and wound care — for ulcerated, eroded or pruritic lesions.[3]

Prophylactic excision — controversial, and the confession that goes with it

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Curettage, dermabrasion and laser — cosmetic, not curative

• Curettage or dermabrasion in early infancy (first 4-6 weeks, before naevomelanocytes mature and anchor deep) can lighten the lesion and improve texture. It does not remove deep naevus cells and does not eliminate melanoma risk.
• Ablative laser (CO2, erbium:YAG) flattens the verrucous surface; it does not eliminate risk.
• Pigment-selective laser (Q-switched ruby, alexandrite, Nd:YAG 1064 nm) lightens pigment; repigmentation is common, and depigmentation is a risk in skin of colour.[2]

Bottom line: cosmetic procedures buy quality of life, but none of them removes the deep naevomelanocytes or erases the melanoma risk. The family must hear that before the first laser session.[1]

MEK inhibitors — the emerging targeted lever

The discovery that giant CMN run on NRAS Q61 opened a door that did not exist a decade ago: MEK inhibitor therapy (binimetinib, trametinib, selumetinib). Case reports and early phase 2 work in infants and children with giant CMN, with or without symptomatic NCM, have shown:[6]

• Marked lightening of the cutaneous lesion, visible within 4-12 weeks.
• Stabilisation or improvement of NCM-related seizures and neurological symptoms.
• A tolerable but real toxicity profile — rash, CK elevation, ocular events, and growth-plate effects in young children.[9]

MEK inhibitors are not yet standard of care. They live in specialist centres under trial protocols or compassionate access, reserved for symptomatic NCM, bulky unresectable disease, or where other measures have failed. BRAF-fusion CMN may respond to MEK or ERK inhibition on the same MAPK-pathway rationale.[9]

Management of neurocutaneous melanosis

• Asymptomatic NCM (radiological only) — neurology surveillance, repeat MRI every 1-2 years, antiepileptics if seizures develop.
• Symptomatic NCM — antiepileptics, MEK inhibitor under trial where appropriate, CSF diversion (VP shunt or ETV) for hydrocephalus, and neurosurgical resection of symptomatic mass lesions.
• Prognosis of symptomatic NCM is poor: median survival under 3 years from symptom onset; hydrocephalus, status epilepticus and primary CNS melanoma are the commonest causes of death.[8]

Palpebral CMN — the eye is never optional

A CMN involving the eyelid carries ocular melanocytosis — melanocytes in the uveal tract, conjunctiva and sclera — and with it a real risk of glaucoma and uveal melanoma. Mandatory ophthalmology assessment, serial intraocular pressure and fundoscopy, and staged lid-sparing excision when cosmesis or function warrant it. The eye is never optional in a palpebral CMN.[1]

Complications and classic errors

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Prognosis and disposition

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Follow-up schedule for a giant CMN:[3]

• Dermatology — every 3-6 months for the first 5 years, then 6-12 monthly.
• Neurology — baseline MRI in the first 6 months, repeat at 12-24 months if NCM is present, then every 1-2 years.
• Ophthalmology — baseline, then yearly if palpebral or head and neck CMN.
• Plastic surgery — at diagnosis and as needed for staged excision.
• Psychology — regular review, school support, peer support groups.
• Self and parent surveillance — monthly total-body examination against baseline photographs; any change means same-day dermatology contact.[1]

Disposition. Most small and medium CMN discharge to community dermatology with annual review and self-surveillance. Giant CMN stay in a specialist multidisciplinary service for life — the lesion does not age out of its risk.[2]

Special populations

Pregnancy and prenatal counselling

A CMN in a pregnant woman may darken or become more verrucous under hormonal influence; excision is rarely required during pregnancy. Pre-conception or prenatal counselling for parents of a child with a giant CMN covers four points: reassurance about the postzygotic mosaic nature and the very low recurrence risk; the safety of MRI in the first 6 months (avoid contrast where possible); the emerging in-utero and neonatal MEK-inhibitor experience; and family psychological support.[3]

Paediatric CMN

Melanoma in children is rare, and Spitz naevi and atypical proliferative nodules are the commonest differential inside a giant CMN. The biopsy threshold differs from adults: a single, rapidly growing, ulcerated or bleeding nodule should be excised, but stable heterogeneity and hypertrichosis are not, on their own, indications.[4]

RASopathies

CMN may be the cutaneous marker of an underlying germline RASopathy. An index case with a giant CMN plus any of short stature, broad neck, congenital heart disease (pulmonary stenosis, HCM), developmental delay, characteristic facies, sparse hair or a positive family history goes to clinical genetics for germline testing — PTPN11, SOS1, RAF1, BRAF, MAP2K1 or 2, KRAS, HRAS, NRAS.[7]

Skin of colour (Fitzpatrick V-VI)

CMN in darkly pigmented skin is darker, more verrucous and more hypertrichotic, and early melanomatous change is harder to see against the baseline pigment. Dermoscopy in skin of colour is a specialist skill; clinicopathological correlation is essential. Acral lentiginous and mucosal melanoma are proportionally more common than in lighter skin and must stay in the differential.[1]

Immunosuppression

There is no large evidence base for an increased CMN-melanoma risk in transplant or HIV patients, but general melanoma surveillance is more vigilant in this group, and a giant CMN should continue to be followed in a specialist service.[1]

Evidence base, guidelines and regional differences

The evidence underpinning modern CMN management rests on five pillars:[6]

• NRAS Q61 as the giant-CMN driver — the Kinsler lineage of work, anchored by the 2022 Exp Dermatol spatiotemporal study (PMID 35020224) and the 2020 Br J Dermatol genotype-phenotype study (Polubothu and Kinsler, PMID 31111470). These underpin the modern classification and the rationale for MEK inhibition.
• Mosaic BRAF fusions — Martin et al., J Invest Dermatol 2024 (PMID 37716647), a recurrent and targetable cause.
• Neurocutaneous melanosis — Pellino et al. Epilepsy Behav 2020 (PMID 32272368) systematic review; Ruth Semin Pediatr Neurol 2024 (PMID 39389659) on CMN syndrome.
• Melanoma on CMN — Alos et al. Pathol Res Pract 2024 (PMID 38518732), the deep-dermal, pre-pubertal phenotype.
• The 2020 international CMN consensus (Ott et al., with the ERN-Skin network) — the size-plus-satellite-plus-features classification.[9]

BAD (UK), AAD and ASPS (US) and EDF (EU) guidelines are broadly concordant on the need for multidisciplinary care, MRI screening in high-risk phenotypes, and the controversial status of prophylactic excision. MEK-inhibitor phase 2 trials of binimetinib, trametinib and selumetinib in NRAS-mutant giant CMN are ongoing; endpoints include lesion lightening, NCM stabilisation, quality of life and safety.[6]

Regional differences are mostly logistical. In high-resource settings, MRI screening at 4-6 months is routine; in resource-limited settings the same imaging is available only on clinical indication, and clinical surveillance with baseline photography is the cornerstone.[1]

Exam pearls and high-yield minutiae

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Ward-round test — four stems, thirty seconds each

Stem 1 — the newborn from the top of the topic (answer)

A term newborn has a giant dark plaque covering the entire back and scalp, with more than thirty satellite naevi. The parents ask whether their baby needs an MRI. What is your answer, and on what evidence? Model: Yes — this child meets every criterion for screening. Giant CMN on the posterior axis (back and scalp) with more than 20 satellite naevi is the highest-risk phenotype for neurocutaneous melanocytosis. Arrange MRI brain and whole spine in the first 6 months of life, before myelination erodes the sensitivity of the scan for leptomeningeal melanin. Tell the family the melanoma risk is 5-15% and the NCM risk is 5-10%, and that this lesion is postzygotic mosaic — the next pregnancy carries no added risk.[3]

Stem 2 — the changing nodule and the shave biopsy (answer)

A 4-year-old with a giant back CMN develops a new, firm, blue-black nodule that has grown over six weeks. The surgical SHO books a shave biopsy. What is wrong with the plan, and what is the right biopsy? Model: Shave biopsy is contraindicated. Giant-CMN melanoma arises in the deep dermis, which a shave cannot reach, and if it transects a melanoma it destroys the Breslow thickness and mis-stages the disease. The right biopsy is a full-thickness excisional biopsy to subcutis in a single piece if the nodule is small enough; otherwise an incisional or punch biopsy that reaches the deep dermis to capture the deep naevomelanocytes. Never reassure a parent about a changing nodule in a giant CMN on clinical grounds.[4]

Stem 3 — the family planning another baby (answer)

Parents of a child with a giant NRAS-mutant CMN ask about the chance of the same thing happening in their next pregnancy. What do you say, and why? Model: The recurrence risk is the population baseline — effectively zero added risk. CMN is a postzygotic mosaic event: the NRAS Q61 mutation arose after fertilisation in a single melanoblast, so the germline is unaffected and the mutation is not transmissible. The mantra for the family meeting is mosaic, not inherited — reassure the family. No prenatal genetic testing is indicated on the basis of this child alone.[7]

Stem 4 — the eyelid CMN and the eye you forgot (answer)

A newborn has a medium-sized CMN involving the upper eyelid. The dermatology plan focuses on the skin. What referral is mandatory, and what are you screening for? Model: Ophthalmology, same week. A palpebral CMN carries ocular melanocytosis — melanocytes in the uveal tract, conjunctiva and sclera — and with it a real risk of glaucoma and uveal melanoma. Mandatory baseline and serial assessment includes intraocular pressure, fundoscopy and slit-lamp examination. Staged lid-sparing excision is considered later for cosmesis or function, but the eye is the first call, not an afterthought.[1]

Coverage self-check

If you cannot answer any stem above from this page alone, re-read the matching section — the page is intended to be self-sufficient for fellowship, MRCP and NEET-PG or INICET questions on congenital melanocytic naevus.[1]

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References

1. [1]Camargo CP, Saliba M, Saad EA, et al. Treatments of palpebral congenital melanocytic nevus: a systematic review Acta Cir Bras, 2023.PMID 38055392
2. [2]Viana AC, Gontijo B, Bittencourt FV. Giant congenital melanocytic nevus An Bras Dermatol, 2013.PMID 24474093
3. [3]Ruth J. Congenital melanocytic nevus syndrome: An association between congenital melanocytic nevi and neurological abnormalities Semin Pediatr Neurol, 2024.PMID 39389659
4. [4]Alos L, Carrasco A, Teixidó C, et al. Melanoma on congenital melanocytic nevi Pathol Res Pract, 2024.PMID 38518732
5. [5]Zayour M, Lazova R. Congenital melanocytic nevi Clin Lab Med, 2011.PMID 21549240
6. [6]Aimaier R, Chung M, Zhu H, et al. Spatiotemporal expression of NRAS and occurrence of giant congenital melanocytic nevi Exp Dermatol, 2022.PMID 35020224
7. [7]Polubothu S, Kinsler VA. Does the gene matter? Genotype-phenotype and genotype-outcome associations in congenital melanocytic naevi Br J Dermatol, 2020.PMID 31111470
8. [8]Pellino G, Gencarelli J, Bertelli S, et al. Epilepsy in isolated parenchymal neurocutaneous melanosis: A systematic review Epilepsy Behav, 2020.PMID 32272368
9. [9]Martin SB, Polubothu S, Bruzos AL, et al. Mosaic BRAF Fusions Are a Recurrent Cause of Congenital Melanocytic Nevi Targetable by MAPK Pathway Inhibition J Invest Dermatol, 2024.PMID 37716647