Divided Nevus

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Jainam Shah, Sachin Pathuri, Andrew Go Lee, MD, Bruce Becker, MD

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Jainam Shah, Sachin Pathuri, Andrew Go Lee, MD, Bruce Becker, MD

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Divided nevus is a rare congenital melanocytic nevus presenting as two mirror-image pigmented lesions spanning the upper and lower eyelid margins, arising from a single melanocytic proliferation within the fused eyelid tissue that is physically divided when the lids separate at approximately the 24th week of gestation. The diagnosis is clinical, and the lesion is distinguished from other periorbital congenital melanocytic nevi by its pathognomonic bilobed configuration. Management requires a multidisciplinary approach addressing the eyelid lesion, amblyopia surveillance, and, in cases involving large lesions or additional congenital melanocytic nevi elsewhere, assessment for central nervous system involvement.

Overview

Divided Nevus

Divided nevus in a 15-year-old boy extending from the eyebrow to the eyelash-bearing region with cheek involvement.

ICD-10

D22.1

ICD-9

216.1

A divided nevus (also known as a "kissing nevus," "split ocular nevus" and "panda nevus") is a rare congenital dermatological abnormality and type of congenital melanocytic nevus (CMN) that spans both the upper and lower eyelid margins as two mirror-image halves that align when the eye closes. It is a subtype of periorbital CMN, which encompasses any melanocytic nevus present at birth or within the first few months of life in the eyelid and periorbital region. The divided nevus is distinguished from other periorbital CMN by its bilobed, trans-lid configuration, which reflects the specific embryological window during which the lesion forms.

The image on the right shows a divided nevus in a 15-year-old boy extending from the eyebrow to the eyelash-bearing region with cheek involvement. This figure was reproduced from Kosaku et al. under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0) (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Etiology

Embryological Basis

The divided nevus arises as a direct consequence of the embryological fusion and subsequent separation of the eyelids. The upper and lower eyelid folds begin forming from the surface ectoderm during the 6th week of gestation. By the 7th week, distinct upper and lower folds are well defined. At this stage, the upper eyelid begins to assume a dominant role compared with the lower eyelid. By approximately the 8th week of gestation, the eyelids fuse along their margins, forming a continuous epithelial surface. They remain fused until approximately the 24th week of gestation, when they begin to separate via programmed desquamation.

A single melanocytic proliferation is believed to arise within the shared, fused eyelid tissue during this period. When the lids subsequently separate, the nevus is physically divided between the upper and lower lid margins, yielding mirror-image halves. This mechanism accounts for the characteristic kissing appearance: when the eye is closed, the two halves of the nevus precisely re-appose along the line of embryological fusion.

Periorbital Congenital Melanocytic Nevi

Periorbital CMN are a clinically heterogeneous group, classified by size using criteria adapted from those developed for CMN elsewhere on the body. Below are the criteria:

• Small CMN: less than 1.5 cm in greatest diameter
• Medium CMN: 1.5 to 19.9 cm
• Large CMN: 20 cm or greater
• Giant CMN: generally defined as greater than 40 cm, or covering a proportionally large body surface area in an infant

Periorbital CMN encompass lesions of the eyelid skin, eyelid margin, conjunctiva, orbit, and adjacent facial skin. Divided nevi are typically small to medium in size, though larger variants exist. Giant periorbital CMN, though rare, carry a substantially higher risk of associated complications including neurocutaneous melanosis and malignant transformation.

Epidemiology

Divided nevus is uncommon, and no sex or racial association has been established. The vast majority of cases are congenital, noted at birth or during the first weeks of life, though occasional cases may first draw clinical attention during childhood as lesions darken or become more prominent with age. The medial lid margin is the most frequently reported location, though any segment of the upper and lower lid margin may be involved. Bilateral cases (involving both eyes) are exceedingly rare.

Periorbital CMN as a broader group have an estimated birth prevalence of approximately 1% for all sizes combined, with large and giant lesions (greater than 20 cm) being substantially rarer (approximately 1 in 20,000 to 1 in 500,000 live births).

General Pathophysiology

Molecular Basis

CMN arise from neural crest-derived melanocyte precursors (melanoblasts) that migrate to the skin during embryogenesis. In patients with multiple CMN (two or more at birth), the same postzygotic mutation has been identified in different cutaneous lesions, in affected neurological tissue, and in associated malignant tissue, but not in unaffected skin or blood. Kinsler et al. demonstrated that these multiple CMN and associated CNS abnormalities are caused by postzygotic mutations at codon 61 of NRAS in 80% of cases studied. BRAF mutations have been found in individual CMN but have not been shown to be causal in multiple CMN in the same individual.

For typical divided nevi, which are single small-to-medium lesions, the molecular basis of the proliferation is less well characterised; somatic mutations in NRAS or BRAF may be present but cannot be assigned as causal from a single lesion.

Ocular and Periocular Findings

Periorbital CMN, including divided nevi, may involve multiple tissue compartments around the eye. Systematic examination at presentation is necessary because several findings carry independent management implications.

Eyelid

The following findings below are directly attributable to the divided nevus itself.

• Pigmented lid margin lesion with bilobed, mirror-image configuration -- the defining feature of divided nevus
• Hypertrichosis or coarse darkly pigmented lashes within the nevus
• Trichiasis from lash follicle involvement along the lid margin
• Ptosis from infiltration of the levator aponeurosis or anterior lamella by nevus cells
• Lid notching in larger lesions that compromise the structural integrity of the margin
• Punctal or canalicular involvement when the medial lid is affected, leading to epiphora

Conjunctiva and Cornea

• Conjunctival extension is recognised in periorbital CMN near the lid margin; conjunctival nevi typically appear as flat to slightly elevated tan-brown lesions with clear intralesional cysts on slit-lamp examination.

Visual Function

Amblyopia is a critical concern in children, arising through deprivational (visual axis occlusion from a large nevus or ptosis), anisometropic (corneal distortion from lid mass effect), or strabismic mechanisms. Cycloplegic refraction and visual acuity assessment should begin at the initial ophthalmological visit and continue at every follow-up.

Malignant Risk

The malignant transformation risk of divided nevus specifically has not been quantified in large prospective studies. Most divided nevi are small to medium in size, and the available divided nevus surgical series, including Zloto and colleagues (13 patients) and Jia and colleagues (73 patients), report no malignant transformation in any patient.

The broader CMN literature establishes that melanoma risk scales with lesion size and is highest in patients with large or giant CMN accompanied by multiple satellite nevi. For small and medium single CMN, the lifetime risk is considered very low. Divided nevi should be placed within this framework: a small divided nevus carries a low malignant risk, but a large divided nevus or one occurring in a patient with multiple CMN warrants more rigorous surveillance.

Clinical Features That Should Prompt Urgent Evaluation

• Rapid growth of a new nodule or lump within or adjacent to the nevus
• Ulceration, bleeding, or crusting of the surface
• Darkening, color change, or development of a nodular area within a previously stable lesion
• Regional lymphadenopathy

• New neurological symptoms in any patient with multiple CMN or known CNS abnormality

Diagnosis

The diagnosis of divided nevus is clinical. Two mirror-image pigmented lesions at the lid margins, present since birth and precisely aligned on closure, are pathognomonic. No ancillary testing is required to establish the diagnosis, though workup is necessary to characterise associated findings and assess risk.

Differential Diagnosis

Condition	Key Distinguishing Features
CMN of single lid	Affects one lid only; no mirror-image counterpart
Acquired melanocytic nevus	Develops after infancy; single lid involvement
Nevus of Ota	Diffuse periocular, facial, and episcleral pigmentation along trigeminal distribution; no discrete lid margin lesion
Ephelis (freckle)	Flat; UV-dependent; no dermal component
Conjunctival nevus	Bulbar conjunctiva primarily; intralesional cysts on slit lamp; not at the lid margin
Periocular capillary hemangioma	Vascular, compressible, non-pigmented; spontaneous regression common
Plexiform neurofibroma (NF1)	Rubbery, non-pigmented lid thickening; Lisch nodules; cafe-au-lait macules
Primary acquired melanosis	Unilateral flat conjunctival pigmentation; occurs in adults; no lid margin component
Eyelid or conjunctival melanoma	Irregular borders; rapid growth; variegated pigmentation; exceedingly rare in children

Workup

• Slit-lamp biomicroscopy with eyelid eversion (conjunctival extension, posterior lamellar involvement, cornea)
• Intraocular pressure measurement
• Clinical photography and dermoscopy at baseline
• Dilated fundus examination when diffuse periocular pigmentation raises concern for oculodermal melanocytosis; not indicated as routine for an isolated small divided nevus
• MRI brain and whole spine with gadolinium before 6 months of age when the divided nevus is large or giant, when additional CMN are present elsewhere, or when there are clinical features raising concern for CNS involvement; not routinely indicated for an isolated small divided nevus.

• Biopsy with histopathology when atypical features are present or at the time of planned surgical excision

Histopathology

Divided nevi most commonly show an intradermal melanocytic nevus pattern (54.8%), followed by compound (24.7%) and junctional (20.5%) patterns. Typical histological findings include:

• Nests of bland melanocytes at the dermal-epidermal junction and within the dermis
• Extension of nevus cells around adnexal structures (pilosebaceous units, eccrine glands)
• Progressive maturation in the deep dermis, with cells becoming smaller and more spindled
• Infiltration around nerve bundles and blood vessels, characteristic of congenital nevi
• Occasional mitoses, which should not be interpreted as malignancy in the absence of other atypical features

Histological features of malignant transformation include architectural disorganisation, pagetoid spread, marked cytological atypia, prominent nucleoli, frequent mitoses, and necrosis. Genetic analysis (NRAS and BRAF hotspot genotyping and chromosomal copy-number analysis) is recommended alongside histopathology when melanoma is suspected, as copy-number changes distinguish melanoma from benign proliferative nodules.

Management

Multidisciplinary Team

• Ophthalmic plastic and reconstructive surgeon (oculoplastics): primary management of the eyelid lesion, excision, and reconstruction
• Pediatric ophthalmologist: amblyopia screening, refraction, intraocular pressure monitoring
• Pediatric dermatologist: surveillance for change; dermoscopic monitoring; assessment for additional CMN elsewhere on the body
• Pediatric neurologist and neuroradiologist: CNS evaluation when the divided nevus is large or additional CMN are present elsewhere
• Pediatric oncologist: if malignant transformation occurs
• Psychologist or child life specialist: psychosocial support, particularly for cosmetically prominent facial lesions

Observation and Surveillance

Small, asymptomatic divided nevi with no atypical features and no functional impairment may be observed. A practical approach may include:

• Baseline clinical photography and dermoscopy at diagnosis
• Ophthalmological review every 6 to 12 months in the first years of life, assessing visual function, intraocular pressure, and lesion morphology
• Annual review thereafter in stable cases
• MRI brain and whole spine with gadolinium before 6 months of age when the divided nevus is large, when additional CMN are present elsewhere, or when CNS involvement is clinically suspected; not routinely indicated for an isolated small divided nevus as previously mentioned
• Education of patients and families about warning signs for change and neurological symptoms

Surgical Management

Surgical excision is indicated for cosmetically significant or functionally impairing lesions, atypical features, or when families prefer active management. It is the only approach that also provides histopathological confirmation of the diagnosis.

Timing: There is no consensus on optimal timing. Early surgery may reduce psychosocial impact and allows histopathological assessment. Deferred surgery benefits from better anatomical landmarks and avoids general anaesthesia in infancy. Both approaches are used in major centres.

Principles: Both the upper and lower lid components should be excised, either in a single stage or sequentially. Excision must account for anterior lamellar (skin and orbicularis), posterior lamellar (tarsus and conjunctiva), and deeper involvement as needed. When the medial canthal region is involved, canalicular probes placed before incision identify and protect the drainage system.

Reconstruction by defect size:

• Small anterior lamellar defects: direct layered closure
• Full-thickness defects less than one-third of lid length: pentagonal wedge excision and layered direct closure
• Moderate full-thickness defects (one-third to one-half of lid length): lateral canthotomy and cantholysis; Tenzel semicircular advancement flap
• Large full-thickness defects (greater than one-half of lid length): lid-sharing procedures - Hughes tarsoconjunctival flap for lower lid, Cutler-Beard flap for upper lid; staged
• Anterior lamellar replacement: full-thickness skin graft (ipsilateral upper eyelid, retroauricular, or supraclavicular)
• Posterior lamellar replacement: hard palate mucosal graft, buccal mucosa graft, or amniotic membrane as needed
• Medial canthal and canalicular involvement: bicanalicular stenting or conjunctivodacryocystorhinostomy (CDCR) with Jones tube as indicated
• Tissue expansion has been described as an adjunct for larger defects requiring significant skin replacement

Zloto and colleagues reported outcomes in 13 patients across Moorfields Eye Hospital and The Children's Hospital of Philadelphia: mean 1.9 surgeries per patient (range 1 to 5), local flaps used in 3 cases and grafts in 5, and 12 of 13 patients (92%) were satisfied with the final functional and cosmetic result. Complications included trichiasis (15%), lower lid ectropion (15%), and mild ptosis (8%). No recurrence or malignant transformation was observed in any patient. Jia and colleagues reported clinicopathological characteristics and surgical outcomes in 73 patients over a decade, representing the largest published series on this lesion.

Laser Adjuncts

Q-switched laser treatment (Nd:YAG, alexandrite, or ruby) has been used for residual flat pigmentation following surgical excision. It does not provide histopathological assessment and should not substitute for surgery when atypical features are present.

Prognosis

The prognosis for a typical small-to-medium divided nevus is excellent. The available surgical series specific to divided nevus report no malignant transformation, and satisfactory functional and cosmetic outcomes are achievable, though multiple staged procedures may be required for larger lesions. Complications including trichiasis, lid ectropion, and pigmentation recurrence are possible.

Prognosis is less favourable when the lesion is large, when multiple additional CMN are present, when CNS abnormalities are found on MRI in that context, or when malignant transformation occurs. Long-term ophthalmological follow-up is recommended for all patients given the potential for delayed complications including amblyopia and conjunctival melanoma.

Additional Resources

• Conjunctival Melanocytic Tumors
• Nevus of Ota
• Eyelid and Conjunctival Tumors
• Nevus Outreach: https://www.nevus.org/