Module 29: Collision Tumors and Exceptions to Rules -- False Positives and False Negatives

A collision tumor consists of either two different neoplasms that are so close to each other that they clinically appear as a single lesion, or the development of one tumor within and intermingled with another. On dermoscopy, the hallmark is a bicomponent or multicomponent pattern -- two or more distinct sets of dermoscopic criteria recognizable within a single lesion. Collision tumors are frequent, particularly on sun-damaged skin, and seborrheic keratosis is almost always one of the two components.

A false positive in dermoscopy refers to a benign lesion that simulates malignancy, leading to unnecessary excision. While this negatively impacts the clinician's benign-to-malignant biopsy ratio, the impact on the individual patient is usually minimal (the lesion is still removed and found to be benign). Examples include irritated SK mimicking amelanotic melanoma, dermatofibromas mimicking melanoma, and hemangiomas mimicking nodular melanoma.

A false negative refers to a malignancy that simulates a benign lesion, potentially leading to delayed diagnosis. This is the more dangerous scenario. While delayed diagnosis of a BCC may not lead to significant negative consequences, a delay in diagnosing melanoma can be catastrophic. Difficult-to-diagnose melanomas include nodular, nevoid, desmoplastic, spitzoid, amelanotic, and lentiginous melanomas on sun-damaged skin.

A nonaccurate diagnosis occurs when a skin cancer is correctly identified as malignant but the specific type is miscalled (e.g., BCC diagnosed as melanoma, or vice versa). This lowers diagnostic accuracy but has no impact on management -- the biopsy is performed regardless, and the cancer is diagnosed histopathologically.

Two cognitive errors are central to misdiagnosis of collision tumors:

• Anchoring bias: The clinician anchors the diagnosis on the most conspicuous features first identified (e.g., comedo openings in an SK) and bases the entire diagnosis on these features.
• Search satisfaction: Once the anchoring diagnosis is made, the clinician stops searching for additional features (e.g., a focus of malignancy within the SK), leaving portions of the lesion unevaluated.

While dermoscopy has significantly improved differentiation between benign and malignant lesions, awareness of its limitations is essential. A combined clinical and dermoscopic approach, supplemented by total body photography and digital dermoscopic monitoring, is necessary to minimize both false positive and false negative diagnoses.

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Dermoscopy has improved the ability to differentiate benign from malignant lesions, but false positive and false negative cases still occur. These scenarios result in two distinct clinical consequences:

1. Unnecessary excisions of benign lesions (false positives)
2. Delayed detection of malignant tumors (false negatives)

Three categories of lesions are particularly prone to misdiagnosis:

• Collision tumors: Lesions with features of two or more entities
• Featureless lesions: Malignancies lacking evident dermoscopic features
• Exception lesions: Lesions displaying structures normally associated with a different diagnosis

Awareness of exceptions to the established rules in dermoscopy is essential to improve diagnostic accuracy. Before discussing specific pitfalls, two important principles must be underscored:

1. Diagnostic accuracy and management decisions may not be coupled. A BCC misdiagnosed as melanoma still gets biopsied -- the management is correct even though the diagnosis is wrong.
2. The consequences of error are asymmetric. False positives (benign mimicking malignant) result in unnecessary biopsies with minimal patient harm. False negatives (malignant mimicking benign) may result in delayed diagnosis of melanoma, with potentially serious consequences.

Definition

Collision tumors include either:

• Two different entities so close to each other that they clinically appear as one lesion
• One tumor developing within and intermingled with another

Prevalence and Demographics

• Collision tumors are frequent in clinical practice
• Most commonly found on sun-damaged skin
• SK is almost always involved as one of the two components
• Collisions between SK and melanocytic lesions are found more commonly in younger patients
• Collisions between SK and BCC are found in persons older than 60 years

Dermoscopic Recognition

The dermoscopic evaluation improves identification of both components. During routine examination, clinicians must keep in mind that collision tumors:

• Can be diagnosed easily if suspected -- the key is maintaining awareness
• Present with two or more distinct sets of dermoscopic criteria within one lesion (the bicomponent pattern)
• Rare cases can be challenging when independent dermoscopic criteria are unrecognizable or the features are intermingled

Cognitive Pitfalls in Collision Tumor Diagnosis

The major cognitive errors that lead to misdiagnosis of collision tumors are:

1. Anchoring bias: Diagnosis is anchored on the most conspicuous features first identified
2. Search satisfaction: The search for features stops once a confident diagnosis is reached

Clinical Example: A lesion with morphologic features consistent with SK. Nonpolarized dermoscopy reveals comedo openings, confirming SK. Search satisfaction occurs when the clinician anchors on the comedo openings and stops searching. With polarized dermoscopy, a focal area reveals shiny white lines -- a feature associated with malignancy. Histopathology proved this to be a BCC of Pinkus arising within a SK.

Check Your Understanding

What is a collision tumor, and how does it appear on dermoscopy?

A collision tumor consists of two or more distinct neoplasms that are contiguous or overlapping but maintain separate histologic identities. On dermoscopy, collision tumors characteristically show two or more distinct dermoscopic patterns within the same lesion, with a relatively sharp demarcation between the different components.

Key Takeaways

• Collision tumors contain two or more distinct neoplasms that have grown together, each maintaining its own dermoscopic features in separate zones of the lesion.
• The most common collision is SK plus melanocytic nevus; recognizing the distinct patterns in different areas prevents misdiagnosis of the combined pattern as melanoma.
• A multicomponent dermoscopic pattern is the hallmark of collision tumors, but the same pattern can indicate melanoma; careful zone-by-zone analysis is essential.

Clinical Scenario

A 73-year-old woman presents with a 14 mm pigmented lesion on her upper back. Dermoscopy reveals two distinct zones: the left half shows comedo-like openings, milia-like cysts, and fissures/ridges (cerebriform pattern), while the right half shows an atypical pigment network with focal blue-white veil and irregular brown-black globules.

What is the diagnosis, and what cognitive error could lead to mismanagement?

Collision Tumor: Seborrheic Keratosis + Melanoma

This lesion demonstrates a bicomponent pattern -- classic SK features in one zone and melanoma-specific features in another. The cognitive error to avoid is anchoring bias: recognizing the SK features first and stopping the examination (search satisfaction error) without evaluating the entire lesion. The melanoma component shows atypical network, blue-white veil, and irregular globules -- all melanoma-specific structures requiring excisional biopsy. Zone-by-zone analysis of the entire lesion is essential when a multicomponent pattern is present.

4.3.1 Nevus + Seborrheic Keratosis

• One of the most common collision combinations in younger patients
• Dermoscopic appearance: One portion of the lesion displays melanocytic features (pigment network, globules), while another portion displays SK features (cerebriform pattern, fissures and ridges, comedo-like openings)
• The upper part shows a heavily pigmented lesion with atypical pigmented network suggesting a melanocytic lesion; the other part shows a cerebriform pattern with fissures and ridges, suggesting SK. Excision confirmed collision between melanocytic nevus and SK.

4.3.2 Melanoma + Seborrheic Keratosis

• Among the most dangerous collision combinations because the SK component may mask the melanoma
• Anchoring bias on SK features (comedo openings, milia-like cysts) may cause the clinician to overlook melanoma-specific features
• Key: Any melanocytic features (atypical network, streaks, blue-whitish veil, irregular globules) within what appears to be an SK should prompt concern

4.3.3 BCC + Seborrheic Keratosis

• Common in patients older than 60 years on sun-damaged skin
• The central part shows an erythematous area with blue-gray ovoid nests and fine in-focus vessels (BCC features), while the periphery shows milia-like cysts, fissures, ridges, and cerebriform pattern (SK features). Excision confirmed collision between BCC and SK.
• The BCC of Pinkus variant may arise within an SK

4.3.4 Melanoma + Nevus

• Melanoma arising within a pre-existing nevus (congenital or acquired)
• The melanoma component may show asymmetric or atypical features arising focally within an otherwise benign-appearing nevus pattern
• Key: Appearance of melanoma-specific structures in a pre-existing nevus -- atypical network, focal negative network, crystalline structures, streaks, irregular blotches, blue-white veil, or regression structures -- should lead to excision

4.3.5 Other Reported Collision Combinations

• BCC + melanocytic nevus
• SCC + SK
• Multiple different benign tumors (e.g., SK + solar lentigo)
• Rare combinations of different malignant tumors

Benign lesions mimicking malignancy will be included in the differential diagnosis of melanoma and other pigmented tumors (melanocytic or nonmelanocytic).

4.4.1 Seborrheic Keratosis Mimicking Malignancy

Standard dermoscopic criteria for SK include milia-like cysts, comedo-like openings (pseudofollicular openings), fissures and ridges (cerebriform pattern), light brown fingerprint-like structures, and hairpin vessels. Although the majority of SK can be diagnosed with confidence, a subset of difficult lesions can resemble skin cancer.

Specific SK Variants Mimicking Malignancy:

1. Melanoacanthoma

• A rare variant of SK
• Histopathology: deeply pigmented benign proliferation of melanocytes and keratinocytes within a SK
• Can produce intense pigmentation mimicking melanoma

1. Inflamed or Irritated SK

• May exhibit irregular and asymmetric vascularization
• Raises differential diagnosis of amelanotic melanoma and SCC
• The inflammatory changes alter the typical SK appearance

1. Lichen Planus-Like Keratosis (LPLK)

• A regressing epidermal neoplasm, most frequently a SK or actinic keratosis
• Granularity (peppering) and regression-like features can mimic regressing melanoma

1. SK with Melanocytic-Like Structures

a. SK with pigment network-like structures:

• This network-like structure is usually thinner with larger holes and abrupt ending compared with the true pigmented network of melanocytic lesions
• Ink spot lentigo (reticular SK): characterized by a prominent black network with a three-dimensional quality; lines can be thick or thin and end abruptly at the edge of the lesion

b. SK with globule-like structures:

• Clonal SK: a rare variant presenting with nests of basaloid cells resembling globular structures seen in melanocytic lesions
• On dermoscopy: light brown to dark brown/blue globules
• Histopathologic correlate: nests of pigmented basaloid cells within an acanthotic epidermis -- these resemble melanocyte nests and project as globules on dermoscopy, potentially leading to incorrect diagnosis of a melanocytic neoplasm

4.4.2 Hemangiomas Mimicking Malignancy

• Cherry angiomas and angiokeratomas: On occasion, vascular lesions can mimic melanoma, particularly when there are deep or thrombosed vessels that produce dark coloration
• Targetoid hemosiderotic hemangiomas: The hemosiderin-related pigmentation can produce brown-black areas resembling melanoma

4.4.3 Dermatofibroma Mimicking Melanoma

Although dermatofibromas have a high positive predictive value when diagnosed with dermoscopy, some DFs may mimic melanoma. Difficult-to-diagnose DFs may present with additional structures such as shiny white lines and atypical vessels, which are also seen in melanoma.

Key Differentiating Features:

Feature	Dermatofibroma	Melanoma
Structure distribution	Shiny white lines and atypical vessels located towards center and over scar-like area	Disorganized pattern with random distribution of structures
Scar-like area	Not associated with other regression structures	Often reveals granularity associated with scar-like areas
Overall pattern	Organized, predictable structure distribution	More chaotic, disorganized pattern

Specific DF Variants Mimicking Melanoma:

1. Atypical dermatofibromas: May reveal atypical network, atypical scar-like area, negative network, and homogeneous pigmentation, making differentiation from melanoma difficult
2. Hemosiderotic and aneurysmal dermatofibromas: Can reveal diffuse or localized homogeneous blue, blue-gray, blue-yellow, or blue-red pigmentation (correlates with siderophages containing hemosiderin and hemosiderin deposition in the dermis)

Additional Clues for Dermatofibroma:

• Palpation: DFs reveal a positive "dimple sign" (central depression when pressed along the margin)
• Peripheral network: Fine, light brown, often associated with ring-like globules located toward the center of the lesion, between the delicate network and the central scar-like area

4.4.4 Adnexal Tumors Mimicking Malignancy

Adnexal tumors can produce dermoscopic features that overlap with melanocytic or other malignant lesions.

4.4.5 Melanocytic Nevi Mimicking Malignancy

1. Blue nevus

• Prototypical pattern: homogeneous blue
• On occasion, this homogeneous blue pigmentation can also be seen in nodular melanoma, dermal melanoma, and cutaneous metastasis of melanoma
• Clues to melanoma or metastasis: history of recent changes and/or a previous invasive melanoma; presence of differing shades of blue, pink, crystalline structures, and atypical vessels

1. Acquired and congenital nevi

• Early superficial spreading melanomas sometimes lack melanoma-specific structures (featureless melanomas)
• Patients with atypical mole syndrome should be followed with digital monitoring to detect early melanomas without increasing unnecessary excisions
• Warning signs in a congenital nevus: appearance of atypical network, focal negative network, crystalline structures, streaks, irregular blotches, blue-white veil, or regression structures

Check Your Understanding

What are the most common combinations seen in collision tumors?

The most common combinations include nevus + seborrheic keratosis, nevus + BCC, seborrheic keratosis + BCC, melanoma + nevus, and melanoma + seborrheic keratosis. The combination of a melanocytic and non-melanocytic component is the most clinically significant because it can mask malignancy.

Clinical Scenario

A 65-year-old man presents with a 10 mm dark brown papule on his trunk. Dermoscopy shows a cerebriform surface with comedo-like openings and fissures resembling an SK, but focal areas of blue-black pigment are present at the base, along with a few irregular brown globules and loss of the typical "stuck-on" sharp demarcation at one border.

What is the concern, and what dermoscopic clues suggest this is not simply an SK?

Verrucous (SK-Like) Melanoma -- A False Negative Trap

The blue-black pigment at the base (blue-black sign), irregular globules, and loss of the sharp border are features inconsistent with a pure SK. Approximately 50% of verrucous melanomas are initially misdiagnosed as SK. The blue-black sign within an apparent SK should always prompt biopsy. The fissures and comedo-like openings can exist in melanoma (crypts and structures are not exclusive to SK). This case illustrates why every portion of a lesion must be evaluated, and why anchoring on SK-like features without completing the examination is dangerous.

False negatives represent the more dangerous category of diagnostic error because malignant lesions are left undiagnosed, potentially leading to delayed treatment. Difficult-to-diagnose melanomas include nodular, nevoid, desmoplastic, spitzoid, amelanotic, and lentiginous melanomas on sun-damaged skin.

4.5.1 Seborrheic Keratosis-Like Melanoma

Melanomas that simulate SK are dermoscopically challenging. However, critical melanoma features can still be identified if the clinician resists anchoring bias:

Features that allow correct diagnosis despite SK-like appearance:

• Blue and black colors (blue-black sign)
• Pigment network
• Pseudopods or streaks
• Blue-white veil

These features, despite the presence of other SK features (comedo openings, milia-like cysts), should lead to correct identification of the melanoma component.

A hyperkeratotic and pigmented lesion on the face of an 80-year-old male, clinically resembling SK. Dermoscopy revealed obliteration of the facial pseudonetwork, central keratin, and comedo-like openings. Despite the keratinizing surface, the presence of the blue-black sign led to ruling out a benign diagnosis. Pathology confirmed invasive cutaneous melanoma (Breslow depth 0.8 mm).

Critical Warning: Some skin cancers, including melanoma, can reveal milia-like cysts and comedo-like openings. These structures should be ignored during the evaluation of lesions that are considered melanocytic, or until the entire lesion has been completely evaluated. Structures that are easily recognized may produce diagnostic errors such as anchoring bias, where the decision-making process is interrupted once the familiar structure is identified, leaving the rest of the lesion without evaluation.

4.5.2 Hemangioma-Like Melanoma

Rarely, melanomas (primary or metastatic) can clinically and dermoscopically resemble vascular lesions such as hemangiomas and angiokeratomas.

Dermoscopic Features of Hemangioma-Like Melanoma:

• Red to purple ill-defined lacunar-like structures
• Usually in combination with atypical vessels
• Milky-red areas

Differentiating True Vascular Lesions from Melanoma:

Feature	Cherry Angioma / Angiokeratoma	Hemangioma-Like Melanoma
Lacunae	Red, dark red, red-blue, or blue-black; well-defined	Red to purple; ill-defined lacunar-like structures
Septae	Well-defined septae separating lacunae	Absent or poorly defined
Vessels within lacunae	Absent or uniform	Atypical vessels within or around lacunae
Milky-red areas	Absent	Present
Shiny white structures	Absent	May be present

Clinical Warning: Clinicians must suspect malignancy in any case of a fast-growing hemangioma-like tumor with atypical vessels within the lacunae, or lacunae-like areas with shiny white and milky-red areas.

A lesion clinically suggestive of capillary hemangioma. Dermoscopy showed ill-defined lacunar-like structures, milky-red areas, and importantly, vessels within the lacunae. The patient had a history of invasive cutaneous melanoma, and this lesion appeared 20 cm from the scar. Biopsy confirmed melanoma metastasis.

4.5.3 Pyogenic Granuloma-Like Melanoma

Despite their characteristic dermoscopic presentation, pyogenic granulomas should always be histopathologically confirmed. Rare amelanotic nodular melanomas and melanoma metastases may have morphology resembling pyogenic granulomas.

4.5.4 Featureless Melanoma

Some cutaneous melanomas may lack any evident dermoscopic features (featureless lesions) to aid in diagnosis. A combined clinical and dermoscopic approach is required for detection:

• Total body photography and digital dermoscopic monitoring have proven to be powerful means for identifying featureless melanomas based on observed changes over time
• Digital monitoring is especially important for patients with the atypical mole syndrome, where early superficial spreading melanomas may not show melanoma-specific structures

4.5.5 Other Difficult-to-Diagnose Melanomas

The following melanoma subtypes are particularly prone to false negative diagnosis:

• Nodular melanoma: May present with a blue-black homogeneous pattern or be amelanotic
• Nevoid melanoma: Closely mimics benign melanocytic nevi
• Desmoplastic melanoma: Often amelanotic, scar-like appearance
• Spitzoid melanoma: Mimics Spitz nevus
• Amelanotic melanoma: Lacks pigmented features; depends on vascular pattern recognition
• Lentiginous melanoma on sun-damaged skin: Facial melanoma with subtle features easily mistaken for benign pigmented changes

Key Takeaways

• Clonal expansion within a single tumor (e.g., melanocytic clones within a SK) can create dermoscopic patterns that mimic collision tumors or melanoma.
• When dermoscopic features from two different lesion types are clearly separated into distinct zones with a sharp border, collision tumor is favored over melanoma.
• Melanoma arising within a nevus (nevus-associated melanoma) is a specific type of collision that shows benign nevus features in one area and melanoma features in another.

Accuracy is established when the dermoscopic diagnosis is shown to be correct. On occasion, skin cancers will be miscalled (e.g., BCC miscalled as melanoma), resulting in lower diagnostic accuracy. However, this miscalling has no impact on the management decision to perform a biopsy, and the skin cancer will be diagnosed.

4.6.1 Basal Cell Carcinoma Mimicking Melanoma (and Vice Versa)

BCC may reveal features that mimic structures seen in melanomas, and vice versa:

Globules:

• In BCC: usually demonstrate a blue-gray color and are not aggregated
• BCCs lack other melanocytic features such as network, aggregated globules, or streaks
• Can simulate globules seen in melanocytic lesions

Leaf-Like Areas vs. Streaks:

• Leaf-like areas (BCC): broader lines that radiate towards the tumor and converge at multiple different focal points, usually at the periphery; each central point is the center of a few lines, resulting in a leaf-like configuration
• Streaks (melanocytic): thinner, centrifugal, and in-focus lines that radiate away from the tumor mass towards normal skin

Shiny White Structures:

• In BCC: appear as blotches and strands, usually more disorganized
• In melanoma: tend to be short lines orthogonally oriented (shiny white lines or crystalline structures)

Homogeneous Blue Pigmentation:

• BCC can present with a large blue ovoid nest occupying almost the entire lesion, simulating a homogeneous blue pattern
• BCC may additionally reveal shiny white blotches and strands, in-focus brown dots, or blue-gray nonaggregated globules

Arborizing Vessels:

• Commonly observed in BCC
• Can also be seen in some melanocytic lesions, including thick melanomas and cutaneous melanoma metastases

4.6.2 Squamous Cell Carcinoma Mimicking Melanoma

Pigmented and nonpigmented SCC can simulate melanoma when specific features are present:

Structureless Lesions:

• Following the two-step algorithm, structureless lesions will be considered melanocytic by default
• These structureless lesions are either monitored using digital dermoscopy (short-term digital monitoring), imaged using confocal microscopy, or biopsied

Brown Dots or Globules in SCC:

• Pigmented SCC can present with focal brown dots or globules that are linearly arranged, often towards the periphery of the lesion

Polymorphous Vessels:

• The clue for any malignant tumor, including melanoma and SCC
• Clinical appearance with keratin in the context of a cancerization field favors SCC
• Any nonspecific tumor with atypical vessels should undergo skin biopsy to rule out malignant skin tumor (angiosarcoma, Merkel cell carcinoma, metastasis, lymphoma)

Check Your Understanding

Why are collision tumors a diagnostic pitfall in dermoscopy, and how should they be managed?

Collision tumors are pitfalls because one component may mask or distract from the other. For example, recognizable seborrheic keratosis features in one portion may cause the clinician to dismiss the entire lesion as benign, missing an adjacent melanoma component. Any lesion with two distinct patterns should be carefully evaluated for malignant features in each component independently. Biopsy should include all components.

The Anchoring Bias Problem

The most important pitfall in collision tumor and exception diagnosis is the tendency to:

1. Identify the most conspicuous feature first
2. Anchor the diagnosis on that feature
3. Stop searching (search satisfaction)
4. Miss additional features that might change the diagnosis

Structures Crossing Diagnostic Boundaries

Dermoscopic structures have strong associations with specific diagnoses. However, occasionally lesions display structures normally associated with a different diagnosis:

Structure	Expected Diagnosis	Can Also Be Seen In
Milia-like cysts	SK	Melanoma, SCC, other malignancies
Comedo-like openings	SK	Melanoma, BCC
Globules	Melanocytic lesions	Clonal SK (basaloid nests), BCC (blue-gray)
Pigment network	Melanocytic lesions	SK (thinner, larger holes, abrupt ending)
Arborizing vessels	BCC	Thick melanoma, melanoma metastasis
Homogeneous blue	Blue nevus	Nodular melanoma, BCC, metastatic melanoma
Lacunae	Hemangioma	Amelanotic melanoma

When Histopathology Explains the Mimicry

Understanding the histopathologic correlates of misleading structures reveals the cause of misdiagnosis:

• Clonal SK: Nests of pigmented basaloid cells within acanthotic epidermis produce globules on dermoscopy, mimicking melanocyte nests
• Hemosiderotic DF: Siderophages containing hemosiderin and hemosiderin deposition in the dermis produce blue-gray pigmentation mimicking melanoma
• SK with network: Basal layer hyperpigmentation in ridged acanthotic epidermis produces a network-like structure

Key Takeaways

• Any collision lesion containing a component that shows features suspicious for malignancy (atypical network, blue-white veil, irregular vessels) should be completely excised.
• Partial biopsy of a collision tumor risks sampling only the benign component and missing an adjacent malignancy; excisional biopsy is preferred.
• Serial dermoscopy is not appropriate for monitoring collision tumors with suspicious components because the malignant component may be obscured by the benign component.

The following scenarios should prompt the clinician to override an algorithmic "benign" classification:

1. Any lesion with a mixed pattern that includes both benign and malignant features -- biopsy to rule out collision tumor
2. Any hemangioma-like lesion that is fast-growing, has atypical vessels within lacunae, or has milky-red areas
3. Any pyogenic granuloma -- should always be histopathologically confirmed
4. Any SK with blue-black sign, pigment network, pseudopods, streaks, or blue-white veil
5. Any homogeneous blue lesion in a patient with history of invasive melanoma (rule out metastasis)
6. Any featureless lesion that is new, changing, or in a patient with atypical mole syndrome
7. Any lesion where search satisfaction may have occurred -- the clinician should deliberately continue the evaluation beyond the first recognized pattern
8. Congenital nevi with new melanoma-specific features -- atypical network, negative network, crystalline structures, streaks, irregular blotches, blue-white veil, or regression structures

Clinical context is indispensable when dermoscopic features are ambiguous:

• Patient age: SK + melanocytic nevus collisions are more common in younger patients; SK + BCC collisions in those older than 60
• Sun-damaged skin: Collision tumors are most frequently found on sun-damaged skin
• Previous melanoma history: A new lesion with homogeneous blue pigmentation or vascular features near a prior melanoma scar should raise suspicion for metastasis
• Lesion evolution: History of recent changes in a blue nevus, or rapid growth of a hemangioma-like lesion, should prompt biopsy
• Anatomic location: Facial location increases risk of lentiginous melanoma on sun-damaged skin being missed
• Digital monitoring: Total body photography and digital dermoscopy are powerful tools for detecting featureless melanomas and early changes in atypical nevi

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Key Takeaways

• The differential for collision tumors includes melanoma (multicomponent pattern), combined nevi (different nevus types), and irritated SK with inflammatory changes.
• A key diagnostic clue for collision tumor is the presence of an abrupt transition between two morphologically distinct zones, each with internally consistent features.
• In clinical practice, most suspected collision tumors are excised because the dermoscopic complexity makes confident benign diagnosis difficult.

Benign Lesion	Mimicked Malignancy	Misleading Features	Differentiating Clues
Melanoacanthoma (SK variant)	Melanoma	Deeply pigmented, proliferation of melanocytes and keratinocytes	SK architecture present; comedo openings, milia-like cysts still visible
Inflamed/Irritated SK	Amelanotic melanoma, SCC	Irregular and asymmetric vascularization	History of irritation; SK features remain identifiable
LPLK (lichen planus-like keratosis)	Regressing melanoma	Granularity, regression-like features	Clinical history of regressing SK or AK; no melanoma-specific structures
SK with pigment network	Melanocytic neoplasm	Network-like structure	Network is thinner, larger holes, abrupt ending vs. true melanocytic network
Ink spot lentigo (reticular SK)	Melanoma	Prominent black network, 3D quality	Lines end abruptly at edge; no melanoma-specific features
Clonal SK	Melanocytic neoplasm	Light brown to dark brown/blue globules	Globules represent basaloid nests, not melanocyte nests; SK architecture present
Cherry angioma / Angiokeratoma	Melanoma	Deep or thrombosed vessels producing dark coloration	Well-defined lacunae, well-defined septae; no milky-red areas
Targetoid hemosiderotic hemangioma	Melanoma	Brown-black hemosiderin pigmentation	Vascular architecture, clinical context
Dermatofibroma	Melanoma	Shiny white lines, atypical vessels (especially atypical and hemosiderotic variants)	Central location of structures, positive dimple sign, fine peripheral network, ring-like globules
Atypical DF	Melanoma	Atypical network, negative network, homogeneous pigmentation	Positive dimple sign, extremity location, firm papule
Hemosiderotic/Aneurysmal DF	Melanoma	Blue, blue-gray, blue-yellow, blue-red homogeneous pigmentation	Peripheral delicate network, dimple sign, hemosiderin-related color
Blue nevus	Nodular melanoma, melanoma metastasis	Homogeneous blue pigmentation	Stable lesion, no history of change; absence of differing shades, pink, crystalline structures, atypical vessels
Acquired/Congenital nevi	Early melanoma	Features may overlap with featureless melanoma	Digital monitoring recommended; melanoma-specific structures absent
Adnexal tumors	Various malignancies	Variable, may overlap with malignant features	Clinical context, histopathologic correlation

Malignancy	Mimicked Benign Lesion	Misleading Features	Clues to Correct Diagnosis
SK-like melanoma	Seborrheic keratosis	Comedo-like openings, milia-like cysts, keratinizing surface	Blue-black sign, pigment network, pseudopods/streaks, blue-white veil (evaluate the ENTIRE lesion)
Hemangioma-like melanoma	Hemangioma / Angiokeratoma	Red-purple lacunar-like structures	Ill-defined lacunae, atypical vessels within lacunae, milky-red areas, shiny white structures
Pyogenic granuloma-like melanoma	Pyogenic granuloma	Nodular, vascular, rapidly growing	Always biopsy pyogenic granulomas; history of melanoma should raise suspicion
Featureless melanoma	Normal skin / Atypical nevus	Lack of any dermoscopic features	Digital monitoring, total body photography, detection of change over time
Nodular melanoma	Blue nevus / Hemangioma	Homogeneous pattern, amelanotic	Rapid growth, atypical vessels, ulceration, differing shades, clinical concern
Nevoid melanoma	Melanocytic nevus	Nevus-like symmetrical pattern	Subtle asymmetry, clinical change, patient age discordance
Desmoplastic melanoma	Scar / Dermatofibroma	Amelanotic, scar-like	Clinical history, location on sun-damaged skin
Spitzoid melanoma	Spitz nevus	Starburst or globular pattern	Patient age, asymmetry, clinical evolution
Amelanotic melanoma	Dermatofibroma / Inflammatory lesion	No pigmented features	Polymorphous vessels, milky-red areas, shiny white structures
Lentiginous melanoma on sun-damaged skin	Solar lentigo / Flat SK	Subtle pigmented changes on face	Asymmetric follicular openings, annular-granular structures, rhomboidal structures

Actual Diagnosis	Miscalled As	Overlapping Features	Impact on Management
BCC	Melanoma	Blue-gray globules, homogeneous blue, shiny white structures	None -- biopsy performed regardless
Melanoma	BCC	Arborizing-like vessels in thick melanoma, shiny white blotches	None -- biopsy performed regardless
BCC	SCC	Overlap in nonspecific lesions	Minimal -- biopsy performed
Pigmented SCC	Melanoma	Brown dots/globules, structureless pigmentation	None -- biopsy performed
Melanoma metastasis	Hemangioma	Vascular-appearing structures	Significant if dismissed as benign -- biopsy required

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