Module 15: Congenital Melanocytic Nevi

Congenital melanocytic nevi develop as a result of mutations acquired during embryogenesis. They are clinically visible on the skin of 1-2% of newborns. However, at least 6% of the population harbor melanocytic nevi displaying the characteristic morphologic features of CMN.

A lesion is categorized as a CMN if it meets either of the following criteria:

1. Any melanocytic nevus documented to have been present at birth, OR
2. Any congenital nevus-like nevus (CNLN) in which the history is reliable that it was present since early life and the clinical examination or histology is consistent with a CMN.

Tardive CMN are nevi whose mutations are determined in utero but that do not become clinically manifest until months to years after birth. Two hypotheses explain their delayed appearance:

• Small incipient nevus nests may be present in the skin at birth but proliferate later, growing large enough to become clinically apparent.
• The nevus cells may initially lack the ability to form melanin, becoming visible only after melanogenesis is induced.

Some nevi displaying morphologic features of CMN may result from postnatally acquired mutations rather than in utero events. These are termed CNLN, though some within this group may ultimately prove to be tardive CMN.

Category	Diameter	Notes
Small	< 1.5 cm	Most common; generally uniform dermoscopically
Medium	1.5 - 20 cm	Generally uniform dermoscopically
Large	> 20 cm	Often heterogeneous; rugose/nodular surface
Giant	> 40 cm	Encompasses large body segments; highest melanoma risk

CMN are much more variable in size, color, shape, and topography compared with acquired melanocytic nevi:

• Size: From a few millimeters to large segments of the integument
• Surface: Smooth to mamillated (small/medium) or rugose to nodular (larger lesions)
• Color: Light brown to dark brown to blue-black
• Terminal hairs: Often present in CMN, a feature not seen in acquired nevi

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Most small and medium CMN are fairly uniform both clinically and dermoscopically. Large CMN, on the other hand, are often heterogeneous, displaying multiple islands of color and irregular topography.

There are three main dermoscopic structures associated with CMN:

1. Network
2. Globules
3. Diffuse homogeneous pigmentation

These structures combine to produce five recognizable dermoscopic patterns.

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4.1.1 Reticular Pattern (Network)

Description: Network composed of interconnecting dark lines with intervening lighter-colored holes. There tends to be minimal variability in the color and size/thickness of the lines and holes. The network is usually distributed in a symmetric and organized manner.

Two sub-patterns:

• Diffuse reticular pattern: Network distributed throughout the entire lesion.
• Patchy reticular pattern: Network distributed in small foci with intervening hypopigmented structureless areas or follicular openings throughout the lesion.

Quality variations (as catalogued):

Quality	Description
Fine network	Thin, delicate lines forming the network grid
Thick network	Broader, more prominent lines
Homogeneous distribution	Network evenly spread throughout the lesion
Focal (patchy) distribution	Network concentrated in discrete areas
Peripheral distribution	Network present predominantly at the periphery
Hyphae-like fragments	Thick linear network fragments resembling fungal hyphae

Key associations:

• The reticular pattern is seen in superficial CMN and in CMN located on the lower extremities.
• On occasion, the network can appear fragmented, with fragments having a morphology reminiscent of fungal hyphae.

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4.1.2 Globular Pattern

Description: Globules consist of sharply circumscribed, round-to-oval aggregates that are usually brown in color, though they can also appear black or blue. Globules correspond histologically to nests of melanin-containing nevomelanocytes within the dermis.

Sub-patterns:

• Cobblestone pattern: Confluent globules that are large and angulated. This pattern is particularly characteristic of large CMN.
• Globular pattern (diffuse): Multiple globules of similar shape, size, and color distributed throughout the lesion.

Quality variations:

Quality	Description
Small globules	Small round-to-oval aggregates
Large globules	Larger round-to-oval aggregates
Diffuse sparse or dense	Globules spread throughout at varying density
Clustered centrally	Globules concentrated in the center of the lesion
Cobblestone-like	Large, angulated, confluent globules
Target-like (target globules)	Globules present within the holes of the network

Key associations:

• Nevi with a globular pattern are more common in CMN located on the head, neck, and torso.
• A homogeneous brown background color is commonly seen underlying the globular pattern.

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Clinical Scenario

A 3-year-old girl is brought in for evaluation of a 12 cm brown plaque on the upper back present since birth. Dermoscopy reveals large, angulated, closely packed brown globules (cobblestone pattern) with scattered terminal hairs and perifollicular hypopigmentation.

What is the diagnosis, and what dermoscopic features support a congenital origin?

Medium Congenital Melanocytic Nevus (CMN)

The cobblestone globular pattern is characteristic of CMN located on the torso. The terminal hairs (hypertrichosis) and perifollicular hypopigmentation are ancillary features strongly associated with congenital origin rather than acquired nevi. At 12 cm, this is a medium CMN. Melanoma risk is low but present; dermoscopic surveillance is appropriate, focusing on the dermo-epidermal junction and peripheral edge where melanomas in small-to-medium CMN tend to arise.

4.1.3 Mixed Pattern (Reticuloglobular)

Description: CMN can contain both network and globules. The most common reticuloglobular patterns are:

• Central globules with peripheral network: Uniform network at the periphery of the lesion with central globules. This pattern is commonly seen in superficial compound congenital nevi.
• Target network pattern with globules in the holes: A network within whose holes one finds a small globule. This corresponds histologically to the presence of nevomelanocytic nests in the dermal papillae.

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4.1.4 Structureless / Homogeneous Pattern

Description: Diffuse brown pigmentation (with or without network fragments and a few sparse globules) due to the diffuse distribution of melanin in the epidermis and dermis.

• Often, these CMN appear truly structureless (no discernible network or globules).
• Occasionally, a few scattered reticular network fragments and/or globules may be visible focally within the lesion.

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4.1.5 Multicomponent Pattern

Description: The presence of three or more dermoscopic structures in the same lesion creates a multicomponent pattern. The melanocytic structures can include:

• Network
• Streaks
• Negative network
• Globules
• Shiny white lines
• Blotch
• Blue-white veil

Clinical significance: Approximately 7% of CMN manifest a multicomponent pattern. When structures in a multicomponent CMN are distributed asymmetrically, differentiating them from melanoma may prove challenging. Such lesions warrant close monitoring or biopsy.

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The following ancillary features are frequently observed (with approximate frequencies):

4.2.1 Hypertrichosis (79%)

• Increased number of terminal hairs within the lesion
• Characteristic of CMN and a distinguishing feature from acquired nevi
• Often accompanied by perifollicular pigment changes

4.2.2 Blood Vessels of Varying Morphologies (68%)

• Blood vessel morphology can include any or all of the morphologies described for nevi (comma vessels) and melanoma (dotted, linear serpentine, coiled, hairpin)
• Occasionally, blood vessels can be seen within the holes of the network, corresponding to vessels in the dermal papillae
• When a network surrounds these vessels, they create a target structure called "target network with blood vessels"

4.2.3 Milia-Like Cysts (52%)

• White to yellow, rounded, often hazy structures resembling small seeds or millets of various grain grasses
• Correlate histologically with intraepidermal keratin cysts/pseudocysts
• May be scattered throughout the CMN
• Important caveat: While milia-like cysts are a dermoscopic hallmark of seborrheic keratosis, they can also be seen in melanocytic neoplasms including CMN, papillomatous dermal nevi, and rarely, melanomas
• Diagnostic rule: In a lesion deemed to be a nonmelanocytic growth, multiple milia-like cysts favor seborrheic keratosis. In a melanocytic tumor, multiple milia-like cysts favor a diagnosis of CMN -- but milia-like cysts alone are not diagnostic of CMN

4.2.4 Perifollicular Pigment Changes (42%)

• Hypopigmentation or hyperpigmentation occurring around the hair follicles
• Perifollicular hypopigmentation: Lightened haloes surrounding hair follicle openings
• Perifollicular hyperpigmentation: Darkened rings surrounding hair follicle openings
• Both variants are characteristic of CMN

4.2.5 Target Network with Blood Vessels (33%)

• Blood vessels situated within the holes of the network
• Creates a distinctive target-like structure

4.2.6 Target Network with Globules / Target Globules (27%)

• Globules present within the holes of the network
• Corresponds histologically to nevomelanocytic nests in the dermal papillae

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Check Your Understanding

What is the most common dermoscopic pattern of small congenital melanocytic nevi (CMN)?

Small CMN most commonly show a globular pattern with brown globules distributed evenly, or a reticular pattern with a regular pigment network. A cobblestone pattern (closely aggregated large globules) is also common, particularly in papillomatous CMN. These patterns typically show regularity and symmetry.

Body Region	Predominant Pattern
Torso	Globular
Head and neck	Globular
Lower extremities	Reticular

Although any dermoscopic pattern can be present in CMN at any anatomic location, there is a statistically significant tendency for the above distribution.

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Key Takeaways

• Congenital melanocytic nevi (CMN) show globular and cobblestone patterns in early childhood, corresponding to intradermal melanocytic nests.
• Perifollicular hypopigmentation (lighter areas surrounding hair follicles) is a characteristic feature of CMN not seen in acquired nevi.
• The globular pattern in children represents active growth and is considered physiologic; it should not be mistaken for melanoma.

4.4.1 Small CMN (< 1.5 cm)

• Generally uniform dermoscopically
• Any of the major patterns (reticular, globular, mixed, homogeneous) may be seen
• Dermoscopy is ideal for monitoring because melanomas arising in small-to-medium CMN tend to originate at the dermo-epidermal junction (DEJ) and at the peripheral edge, both visible with dermoscopy
• Occasional findings: nonaggregated globules with blue color (rare), cobblestone-like globules, target globules, perifollicular hypopigmentation with peripheral network

4.4.2 Medium CMN (1.5 - 20 cm)

• Generally uniform dermoscopically, though more variable than small CMN
• Commonly display: fine or thick reticular network, patchy reticulation, globules (sparse or dense), reticuloglobular pattern, homogeneous brown background
• Hypertrichosis and perifollicular pigment changes are frequently observed
• Milia-like cysts are a common finding
• Hyphae-like network fragments may be present
• Blood vessels of varying morphologies are common

4.4.3 Large and Giant CMN (> 20 cm and > 40 cm)

• Often heterogeneous, displaying multiple islands of color and irregular topography
• Large globules with homogeneous brown background pigment are characteristic
• Cobblestone pattern is especially associated with large CMN
• Thick, mamillated CMN are often difficult to evaluate using dermoscopy
• These lesions often have ridges, comedo-like openings, and many blood vessels
• The undulating surface creates invaginations resembling crypts and comedo-like openings commonly seen in seborrheic keratosis
• Limitation of dermoscopy: Melanomas developing in large CMN frequently originate below the DEJ (deep dermal), where dermoscopy cannot adequately visualize changes. Palpation, ultrasound, or other imaging modalities may be needed

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Check Your Understanding

What dermoscopic features in a congenital nevus should raise concern for malignant transformation?

Concerning features include the emergence of new asymmetry in pattern or color, new blue-black or gray-blue areas suggesting deep or regressive pigmentation, irregular streaks or pseudopods at the periphery, and atypical vessels. In giant CMN, any new palpable nodule should raise concern regardless of dermoscopic findings.

Clinical Scenario

A 14-year-old boy has a 25 cm brown plaque covering much of his lower back, present since birth. Dermoscopy shows a heterogeneous pattern with cobblestone areas, thick network fragments resembling hyphae, and a new firm 8 mm blue-black nodule within the lesion that appeared 3 months ago.

What is the primary concern, and why is dermoscopy limited in this scenario?

Large CMN with Possible Melanoma Development

The new blue-black nodule within a large CMN is highly concerning for melanoma. In large and giant CMN, melanomas frequently originate below the dermo-epidermal junction (deep dermal), where dermoscopy cannot adequately visualize changes. Any new palpable nodule in a large CMN should prompt urgent excisional biopsy regardless of dermoscopic findings. Complementary imaging (ultrasound, MRI) may help assess depth of the nodule.

Nevus spilus is a CMN variant characterized by a lentiginous background studded with discrete nevi. Two variants exist:

Nevus Spilus Maculosus

• Dark macular speckles over a light brown background
• Speckles are all approximately the same size
• Dermoscopy: reticular or homogeneous appearance of the speckles

Nevus Spilus Papulosis

• Variously sized dark macules and papules distributed over a light brown background
• Dermoscopy: macules and papules can be reticular, homogeneous, or globular; can manifest a combined pattern; on occasion, can even have a spitzoid morphology

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While most CMN remain benign throughout the life of the individual, on rare occasions melanoma can develop in association with a CMN. The risk is proportional to the size of the CMN. The location and age at onset of melanoma differ between size categories:

Melanoma in Small-to-Medium CMN

• Tends to appear after puberty
• More likely to originate at the dermo-epidermal junction (DEJ) and at the peripheral edge of the CMN
• Dermoscopy is ideal for evaluation, since it allows the clinician to observe morphologic changes at the DEJ that may herald melanoma onset

Melanoma in Large CMN

• Tends to develop earlier in life
• Frequently has its origin below the DEJ (deep dermal)
• Palpation becomes an important component of evaluation
• Dermoscopy has a limited role, especially in thick, rugose lesions, since it cannot adequately visualize morphologic changes developing below the papillary dermis

Melanoma in Nevus Spilus

• Although rare, melanoma can develop in any nevus spilus
• Risk is highest in larger speckled lentiginous nevi of the maculosa variant

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Check Your Understanding

How does dermoscopic monitoring of congenital nevi differ in children versus adults?

In children, congenital nevi are expected to undergo physiologic changes including darkening during early childhood and progressive lightening during puberty. These global changes are benign and expected. In adults, congenital nevi should remain relatively stable, and any focal change (new nodule, new color, asymmetric growth) is more concerning and warrants biopsy.

Key Takeaways

• CMN undergo predictable dermoscopic evolution: globular in early childhood, transitioning to reticular or homogeneous patterns through adolescence and into adulthood.
• Large and giant CMN carry a higher melanoma risk and require systematic monitoring; any new nodule or focal change within a CMN warrants biopsy.
• Dermoscopy of CMN in dark skin types shows characteristic perifollicular hypopigmentation and darkly pigmented cobblestone pattern that should not be confused with malignancy.

CMN that deviate from the known dermoscopic patterns or reveal structures not commonly associated with CMN should be viewed with caution. Warning signs that may herald melanoma include:

1. Asymmetric multicomponent pattern: The presence of multiple structures (network, streaks, negative network, globules, blotch, blue-white veil) distributed asymmetrically within the lesion
2. Focal pigment change: New or evolving areas of altered pigmentation within a previously uniform CMN
3. Atypical structures: Irregular dots, atypical network, blue-gray areas -- features commonly associated with melanoma rather than CMN
4. Deviation from known CMN patterns: Any dermoscopic feature or pattern that does not conform to the recognized patterns described for CMN
5. Palpable changes: New nodularity, especially in large CMN (clinical rather than dermoscopic finding)

Illustrative example: A CMN in which melanoma developed showed the classic CMN cobblestone pattern on one side (with hypertrichosis, milia-like cysts, and comma-shaped blood vessels) while the other side revealed irregular dots, atypical network, and blue-gray areas -- features of melanoma. This asymmetric multicomponent pattern prompted excision, which confirmed melanoma arising in a CMN.

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Current management options include:

Observation with Clinical Follow-Up

• Close clinical follow-up with or without baseline photographs
• Most physicians elect to follow CMN, especially those that have a homogeneous clinical appearance and are small to medium in size
• Dermoscopy has improved the ability to clinically monitor CMN, especially smaller ones

Baseline Photography and Dermoscopy

• Baseline photographs and dermoscopy are very helpful in monitoring CMN
• Photographs should include:
• Overview clinical images of the entire lesion
• Dermoscopic images capturing the representative architecture and border
• Supplemental dermoscopic images of any areas of "special interest" within the CMN

Prophylactic Surgical Excision

• Prophylactic excision if feasible, particularly for lesions with concerning features
• More strongly considered for larger CMN or those with evolving dermoscopic patterns

Key Management Principles

• Knowledge of the dermoscopic features and patterns common to CMN aids physicians in following these lesions and recognizing aberrancy suggestive of melanoma
• Dermoscopy is most useful for monitoring small-to-medium, flat CMN where melanoma originates at the DEJ
• For large, thick, rugose CMN, other techniques (palpation, ultrasound, other imaging) may be needed to evaluate the deeper nevus component
• CMN that do not conform to known patterns should be monitored closely or biopsied

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Key Takeaways

• Focal changes (new colors, new structures, asymmetric growth) within a CMN are more concerning than global pattern evolution and warrant biopsy.
• Proliferative nodules in giant CMN can be benign or malignant; any rapidly growing or ulcerating nodule requires urgent histopathologic assessment.
• Serial digital dermoscopy is the standard of care for monitoring medium-to-large CMN, with intervals determined by nevus size and patient age.

Thick, mamillated CMN deserve special mention because they present particular diagnostic challenges:

• Undulating surface creates invaginations resembling crypts and comedo-like openings similar to seborrheic keratosis
• Numerous blood vessels of varying morphologies are present
• This pattern can sometimes mimic a seborrheic keratosis
• Dermoscopy is often inadequate for complete evaluation; supplementary techniques may be required

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Entity	Distinguishing Features from CMN
Acquired melanocytic nevus	Absent terminal hairs; no perifollicular pigment changes; typically smaller and more uniform; no history of presence at birth
Seborrheic keratosis	Comedo-like openings, fissures/ridges, hairpin vessels, sharp demarcation; milia-like cysts favor SK if lesion is nonmelanocytic
Melanoma	Asymmetric distribution of structures, irregular dots/globules, atypical network, regression structures, blue-white veil; irregular streaks; multicomponent asymmetric pattern
Melanoma arising in CMN	Focal area within a CMN showing atypical network, irregular dots, blue-gray areas -- contrasting with the surrounding benign CMN pattern
Nevus spilus	Lentiginous background with discrete speckled nevi (may be considered a CMN variant)
Papillomatous dermal nevus	Can share cobblestone pattern and milia-like cysts, but typically lacks history of presence at birth; usually flesh-colored

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Key Takeaways

• Prophylactic excision of CMN is controversial; the decision is based on melanoma risk (primarily related to nevus size), cosmetic impact, and patient/family preference.
• Satellite nevi (small nevi appearing around a larger CMN) are common and generally benign but should be documented and monitored.
• Neurocutaneous melanosis should be considered in patients with large CMN over the posterior axis or with numerous satellite lesions.