Module 19: Spitz and Reed Nevi

• Sophie Spitz (1948): Described a distinct type of melanocytic tumor in childhood displaying epithelioid and spindle cells, originally termed "melanoma of childhood." The lesion now bears her name --- Spitz nevus.
• Richard Reed: Later described a pigmented variant --- the pigmented spindle cell nevus (spindle cell and/or epithelioid cell nevus), now known as Reed nevus.

Although Reed nevus was historically considered a pigmented variant of Spitz nevus, many researchers now regard Spitz and Reed nevi as distinct entities based on differences in age predilection, anatomic site preference, and other features. Nonetheless, based on cellular morphology, they appear to belong to the same spectrum.

The core problem: The biological behavior, natural evolution, and malignant potential of Spitz/Reed nevi have not been fully elucidated. Melanomas can resemble Spitz/Reed nevi clinically, dermoscopically, and even histopathologically. No single test or combination of tests can reliably differentiate Spitz/Reed nevi from melanoma in all cases.

The following terms are used for spitzoid tumors that cannot be confidently classified as benign or malignant:

• Atypical Spitz tumors (ASTs)
• Atypical Spitz nevus
• Spitz nevus with atypia and metastasis
• Metastasizing Spitz tumor
• Melanocytic tumors of unknown malignant potential (MELTUMP)
• Melanocytoma

Dermoscopy of Spitz and Reed nevi reveals a few unique and reproducible findings that enable their clinical recognition --- many of which would not have been diagnosed otherwise. While existing controversies regarding the biologic nature of spitzoid tumors have not been solved, dermoscopy has provided insights that have influenced management.

A systematic review by the International Dermoscopy Society (Lallas et al., 2017) analyzed 896 Spitz nevi from 15 studies and found the following pattern distribution:

Age-related variation (de Mestier et al., 2017): In younger patients (12 years and under), Spitz nevi are more likely to exhibit a globular and nonpigmented homogeneous pattern. Starburst and reticular patterns are more commonly observed on the anterior trunk and acral sites.

4.2.1 Typical Dermoscopic Pattern: Dotted Vessels + White Network

"Classic" nonpigmented Spitz nevi are dermoscopically typified by a pattern of multiple, regularly distributed, dotted vessels. The hallmarks include:

• Dotted vessels: Evenly distributed in a symmetric arrangement. This is the defining vascular pattern.
• Globular/glomerular vessels: In more raised or nodular lesions, vessels tend to be larger and may appear as globular or glomerular vessels.
• Additional vessel types: Comma, hairpin, serpentine, and corkscrew vessels can also be seen in nodular Spitz nevi.
• Negative network (inverse network): Elongated, curvilinear globules that, when aggregated, create a negative (inverse) pigment network. Visible in both pigmented and some nonpigmented variants.
• Shiny white lines (polarized light only): Crisscrossing white lines forming a white network (also termed reticular depigmentation). In nonpigmented Spitz nevi, the shiny white lines of the network appear to surround the vessels.

Key diagnostic combination: The co-occurrence of regularly distributed dotted vessels combined with shiny white lines (white network) in a symmetric arrangement is the exemplar pattern of classic nonpigmented Spitz nevus.

4.2.2 Symmetry as a Defining Feature

The typical dermoscopic pattern of nonpigmented Spitz nevi requires symmetric distribution of both vascular structures and shiny white lines. This symmetry is critical for distinguishing benign from potentially malignant lesions.

4.2.3 Atypical Nonpigmented Spitz Nevi

Nonpigmented Spitz nevi that lack symmetric distribution of structures also exist, including:

• Angiomatous Spitz nevi: Prominent vascular component
• Desmoplastic Spitz nevi: Fibrotic/sclerotic features

Critical warning: A Spitz nevus lacking dermoscopic symmetry cannot be differentiated from melanoma. Any spitzoid-looking lesion that displays an asymmetric distribution of structures should be biopsied and examined histopathologically.

Check Your Understanding

What is the classic dermoscopic pattern of a Spitz nevus?

The classic Spitz nevus shows a starburst pattern with symmetrically distributed streaks (pseudopods and radial lines) at the periphery, often surrounding a central hypopigmented or pink structureless area. The symmetry of the peripheral projections is the hallmark that distinguishes benign Spitz from melanoma.

Key Takeaways

• The starburst pattern (symmetrical peripheral streaks/pseudopods radiating in all directions) is the hallmark of classic Spitz/Reed nevi, indicating active peripheral junctional growth.
• Reed nevus (pigmented spindle cell nevus) typically shows a starburst pattern with dark brown-to-black color, while classic Spitz is often pink-red with subtle features.
• The globular pattern of Spitz nevus (symmetric peripheral globules) is common in children and represents the growth phase of a benign Spitz proliferation.

Clinical Scenario

A 7-year-old girl presents with a 5 mm pink, dome-shaped papule on her left cheek that appeared 4 months ago and has been slowly growing. Dermoscopy reveals multiple regularly distributed dotted vessels in a symmetric arrangement with shiny white lines forming a white network pattern under polarized light.

What is the diagnosis, and how does patient age influence management?

Classic Nonpigmented Spitz Nevus

The symmetric dotted vessels with shiny white lines (white network) is the exemplar pattern of a classic nonpigmented Spitz nevus. In a child under 12, this symmetric pattern strongly favors a benign Spitz nevus. Management per the three-step algorithm: the lesion is symmetric, the patient is under 12, and the lesion is nodular but small -- dermoscopic monitoring at 3-month intervals is appropriate. If the same lesion presented in an adult, excision would be recommended regardless of symmetry due to the increased risk of spitzoid melanoma with age.

4.3.1 Globular Pattern with Negative Network

Pigmented Spitz nevi are dermoscopically typified by the presence of globules:

• Varied globules: Globules that vary in size and color, ranging from different shades of brown to gray and black. This variability is a key distinguishing feature.
• Elongated/curvilinear globules: Can appear elongated and curvilinear, and when aggregated, create the negative network.
• Negative network: Formed by the aggregation of irregular globules, creating a "negative" or "inverse" network pattern.
• Shiny white lines: May also be present. The co-existence of negative network and shiny white lines is very helpful for recognition and is not seen in classic dermal globular nevi.

4.3.2 Differentiation from Classic Dermal Nevi

4.3.3 Starburst Pattern in Pigmented Spitz Nevi

Some researchers suggest that pigmented Spitz nevi are typified by a globular pattern while Reed nevi are typified by a starburst pattern. However, this distinction is not absolute. The starburst pattern in Spitz nevi can manifest with:

• Peripheral tiered globules: Globules layered one on top of another at the periphery
• Peripheral streaks: Streaks arranged around the entire perimeter

Note: Although the starburst pattern composed of peripheral tiered globules is commonly seen in Spitz nevi, it can also be seen in atypical/dysplastic nevi with spitzoid features.

4.4.1 The Starburst Pattern --- Classic Feature

Reed nevus is dermoscopically typified by the starburst pattern, named for its resemblance to an exploding star. Its components are:

• Central area: Dark brown/black/blue pigmentation, often homogeneous
• Peripheral streaks: Multiple pigmented streaks (including both radial streaming and pseudopods) that arise from the center and radially expand toward the periphery of the lesion
• Mandatory symmetry: A starburst pattern always presupposes symmetry in terms of distribution of colors and structures

Histopathologic correlation: The streaks/pseudopods correspond to confluent, elongated nests of melanocytes located at the dermoepidermal junction.

4.4.2 Additional Dermoscopic Patterns in Reed Nevi

Beyond the classic starburst, Reed nevi may display:

4.4.3 Reed Nevus Evolution

Longitudinal follow-up of Reed nevi has demonstrated:

1. Starburst pattern corresponds to the radial growth phase (active growth)
2. Senescence: When a Reed nevus enters senescence, it usually manifests a homogeneous pattern but can also display a reticular pattern
3. Recognition challenge: At the senescent stage, recognition is difficult because several other types of nevi may exhibit similar homogeneous or reticular patterns

Check Your Understanding

What dermoscopic features differentiate a Reed nevus from a Spitz nevus?

Reed nevus (pigmented spindle cell nevus) shows a symmetric starburst pattern with prominent blue-black to dark brown streaks radiating from the periphery, often with a dark central blotch. Unlike Spitz nevus, Reed nevi are deeply pigmented. The key shared feature is symmetry, but Reed nevi are characteristically darkly pigmented while Spitz nevi are often pink or lightly pigmented.

Key Takeaways

• Atypical spitzoid tumors show asymmetric structure, irregular streaks/pseudopods, blue-white veil, or atypical vascular patterns that overlap with melanoma.
• Negative network (serpiginous hypopigmented lines surrounding globules) is seen in both Spitz nevi and melanoma; distribution symmetry is the key differentiating factor.
• Age is a critical modifier: starburst or globular pattern in children strongly favors Spitz nevus, while the same features in adults over 40 raise melanoma concern.

Clinical Scenario

A 25-year-old woman presents with a 4 mm dark brown-black papule on her right thigh that appeared 6 months ago. Dermoscopy reveals a striking starburst pattern with symmetric peripheral streaks radiating in all directions from a homogeneous dark brown-black center.

What is the most likely diagnosis, and how does management differ from pediatric cases?

Reed Nevus (Pigmented Spindle Cell Nevus)

The symmetric starburst pattern with dark brown-black pigmentation is the classic dermoscopic appearance of a Reed nevus. However, in a 25-year-old adult, management differs from a child: the three-step algorithm recommends excision for any spitzoid-looking lesion in patients over 12, even when symmetric, because melanoma can present with a starburst pattern in adults. A starburst pattern in a child under 12 would be monitored; in an adult, excision is strongly recommended to obtain histopathologic confirmation.

Some Spitz/Reed nevi present with a multicomponent pattern, composed of more than one of the three main patterns described above.

Critical management implication: A pigmented lesion displaying a multicomponent pattern should always be considered suspicious for melanoma, and biopsy should be performed on all such lesions.

Check Your Understanding

When should a Spitz/Reed nevus be excised versus monitored?

Excision is recommended for: asymmetric Spitz nevi (atypical spitzoid lesion), any spitzoid lesion in adults (where de novo Spitz nevi are uncommon), nodular growth, ulceration, or size >1 cm. Monitoring may be appropriate for classic symmetric Spitz nevi in children, where the starburst pattern is expected to evolve into a homogeneous or globular pattern over time.

Sequential digital monitoring has revealed a predictable evolutionary sequence for Spitz/Reed nevi:

Stage 1: Early Nevogenesis
 Dense GLOBULAR pattern
 |
 v
Stage 2: Active Growth
 Transformation to STARBURST pattern
 (considered the exemplar, easy-to-identify stage)
 |
 v
Stage 3: Senescence
 HOMOGENEOUS or RETICULAR pattern
 (central blue-white veil may appear)
 |
 v
Stage 4: Terminal Phase
 Retain reticular/homogeneous pattern
 OR
 Undergo spontaneous INVOLUTION
 (partial or complete, over months to years)

Key insight: The starburst pattern, while considered the exemplar dermoscopic pattern of Spitz/Reed nevi, probably simply reflects an easy-to-identify stage in the natural evolution of these nevi. It has been suggested that the globular pattern might represent the initial stage of evolution of a pigmented Spitz nevus.

"Spitzoid" is a term adopted to describe melanomas with similar clinical and dermoscopic characteristics to those associated with Spitz nevi.

4.8.1 Shared Features with Spitz Nevi

Spitzoid melanomas often exhibit features also seen in Spitz nevi:

• Streaks
• Globules
• Dotted vessels
• Negative network
• Shiny white lines

4.8.2 Distinguishing Features of Spitzoid Melanoma

4.8.3 Exceptions and Overlap (Critical)

• Approximately 13% of dermoscopically symmetric spitzoid lesions in patients over 12 years of age are in fact melanomas.
• Some melanomas perfectly mimic symmetric Spitz/Reed nevi, rendering differentiation impossible.
• Some Spitz nevi display an atypical/multicomponent pattern most often associated with melanoma.
• Dermoscopic atypia of Spitz nevi does not necessarily correspond with histologic atypia. A Spitz nevus that looks alarming on dermoscopy may be histologically benign, and vice versa.

Key Takeaways

• Spitz nevi undergo predictable involution: starburst transforms to globular, then homogeneous, and finally reticular or structureless over months to years.
• Short-term digital dermoscopy (3-month follow-up) can be used for equivocal spitzoid lesions in children; symmetric growth supports a benign diagnosis.
• Any spitzoid lesion in an adult over 12 years that shows asymmetry, ulceration, or progressive focal change should be excised and submitted for expert histopathologic review.

4.9.1 Definition

ASTs are melanocytic proliferations with intermediate histopathologic features between Spitz nevi and spitzoid melanoma, and their malignant potential is uncertain.

4.9.2 Three Prevailing Theories

4.9.3 Dermoscopy of ASTs

A multicentric study (Moscarella et al., 2015) of 55 ASTs and 110 Spitz nevi found:

Critical finding: 20% of ASTs mimic classic Spitz nevi by displaying a nonpigmented typical spitzoid pattern (regularly distributed dotted vessels with or without reticular depigmentation). Dermoscopy appears insufficient to discriminate between Spitz nevi and ASTs when both display this typical spitzoid pattern.

Management decisions aim to eliminate the risk of missing a melanoma while minimizing the removal of benign lesions. The three-step algorithm addresses three key factors:

flowchart TD
 A[Spitzoid-Looking<br/>Lesion Identified] --> B{Step 1: Dermoscopic<br/>Symmetry?}
 B -->|Asymmetric /<br/>Disorganized| C[EXCISE to Rule<br/>Out Melanoma]
 B -->|Symmetric /<br/>Organized| D{Step 2: Patient<br/>Age?}
 D -->|Age >= 12 years| E[EXCISE or<br/>Close Monitoring]
 D -->|Age < 12 years| F{Step 3: Clinical<br/>Morphology?}
 F -->|Nodular| G[EXCISE or Close<br/>Monitoring Every 15 Days]
 F -->|Flat / Macular| H[MONITOR Every<br/>3 Months]
 G -->|Asymmetric growth| C
 G -->|Remains symmetric| I[Prolong Intervals:<br/>1 mo, then 2 mo]
 H -->|Stable 6 months| J[Terminate<br/>Monitoring]
 H -->|Asymmetric change| C
 I -->|Stabilized or<br/>involuted| J

Step 1: Assessment of Dermoscopic Symmetry

Is the lesion dermoscopically SYMMETRIC/ORGANIZED?
 | |
 YES NO
 | |
 v v
 Proceed to EXCISE to rule
 Step 2 out melanoma

Is the patient YOUNGER than 12 years?
 | |
 YES NO (12 years or older)
 | |
 v v
 Proceed to EXCISE or
 Step 3 closely MONITOR

Is the lesion NODULAR or FLAT?

NODULAR (symmetric, in child <12): FLAT (symmetric, in child <12):
 | |
 v v
 EXCISE or CLOSE MONITORING MONITOR until stabilization
 - Every 15 days initially - Every 3 months initially
 - Excise if asymmetric growth - Can prolong if remains symmetric
 - If remains symmetric, prolong - Terminate after stabilization
 to 1 month, then 2 months (no change for 6 months)
 - Terminate when stabilized - Alternative: some experts argue
 (6 months no change) or to simply IGNORE flat, pigmented
 involuted symmetric Spitz/Reed in
 prepubertal patients
 - Another viewpoint: excise while
 small to avoid larger scar later

4.12.1 Spitzoid Melanoma vs. Spitz/Reed Nevus

Important caveat: These are trends, not absolute criteria. Exceptions exist in both directions. Dermoscopy and clinical morphology are NOT sufficient to reliably differentiate Spitz/Reed nevi from spitzoid melanoma in all cases.

4.12.2 Broader Differential Diagnosis for Spitzoid Lesions

Key Takeaways

• Complete excision is recommended for atypical spitzoid tumors at any age because histologic distinction from spitzoid melanoma can be extremely difficult.
• In children, symmetric spitzoid lesions can be monitored with serial dermoscopy, but parental counseling about the monitoring protocol is essential.
• BAP1-inactivated melanocytic tumors may present with spitzoid morphology and require immunohistochemistry (BAP1 staining) for definitive classification.