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Authored by: Ralph P. Braun · Katrin Kerl

Keywords: histopathology · dermatopathology · pathology · histology · dermoscopy · melanoma

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Subchapter(s):
Differences between histologic and dermoscopic criteria
Colors
Dermoscopic structures

DermoscopyDermoscopy is a non invasive diagnostic method. enables the visualization of structures and colors under the surface of the skinThis glossary term has not yet been described., which are not routinely discernible to the naked eye. Dermoscopy allows gross histopathologic examination of the skin by clinicians. Structures and colors observed by dermoscopy have specific histopathologic correlates. To make accurate diagnosisis the identification of the nature and cause of a certain phenomenon. Diagnosis is used in many different disciplines with variations in the use of logic, analytics, and experience to determine "cause and effect". In systems engineering and computer science, it is typically used to determine the causes of symptoms, mitigations, and solutions using dermoscopy, clinicians must have profound knowledge of the dermoscopy criteria and their histopathologic correlation^[1].

Differences between dermoscopic and histopathologic criteria

Histopathologic evaluation is performed on vertical sections of tissue, allowing the assessment of the full depth of the lesion from scanning magnification to a cellular-level magnification.

is performed on paraffin-embedded tissue, allowing for special stains and immunohistochemical techniques that may assist in diagnosis. Dermoscopic evaluation is based on a horizontal view of the entire lesion.

Another advantage of dermoscopy examination is that the clinician can examine the other lesions of the patient and that he or she can integrate the findings in the context of the patient.
and colors are two-dimensional surface projections of tissue structures (e.g., nests and ). The dermoscopist sees the entire skin in the horizontal plane. The inspection of the skin by the dermoscopist is generally limited in depth to the papillary dermis. Another important limitation is that, dermoscopy does not allow the evaluation of the lesion at a cellular level.

In addition the dermatopathologist has access to special stains which provide additional information (MelanA, S100, HMB45 etc.)

An important advantage is dermoscopy allows the follow up of lesions. This provides important information regarding the lesion’s biology and dynamic. With dermoscopy, we can identify “colors” and “structures” that are not perceived by the unaided eye.

Colors

Colors in skin lesions can provide important morphologic information: Melanin is the most important chromophore in pigmented skin lesions. Depending on the anatomic location and concentration of melanin in the skin, the colors perceived on dermoscopy range from black to blue (i.e., Tyndall effect). If melanin is located in the stratum corneum or immediately beneath it, the lesion would appear black on dermoscopy. Melanin at the dermoepidermal junction (DEJ) would be perceived as light brown to dark brown, depending on its density. Melanin in the dermis results in shades of blue to gray. Thus, the colors seen on dermoscopy allow the clinician to predict the anatomic location of the cells that contain melanin (e.g., melanocytes, keratinocytes, and melanophages). Other important determinants of lesion color include hemoglobin in red blood cells (pink to red colors) and collagen fibers in the dermis (white color).

Dermoscopy structures

Pigment Network

The pigment network consists of a grid of intersecting pigmented “linesstreaks” forming a honeycomb pattern. The anatomic basis of the pigment network is melanin in keratinocytes or in melanocytes along the DEJ, representing the way the rete ridgeThis glossary term has not yet been described. pattern of the epidermis appears when viewed in the horizontal plane. The less-pigmented “holes” of the network correspond to tips of the dermal papillae and the overlying suprapapillary plates of the epidermis. A wide diameter of dermal papillae would correspond dermoscopically to wider network “holes,” whereas narrow dermal papillae would result in a denser sieve of the grid. The pigment network in melanocytic lesions is further characterized as typical or atypical:

Typical networkNetwork with minimal variability in the color thickness and spacing of the lines; symmetrically distributed

is regularly meshed and composed of lines that are relatively uniform in width and homogenous in color; the lines often become gradually thinner and fainter in pigmentation at the lesion’s periphery.

On histopathology, the lines of the correspond to pigment in rete ridges. That are relatively uniform in width and equidistant from each other.

The typical network usually corresponds to the junctional component of a nevusThis glossary term has not yet been described.. However, reticulation can also be seen in darkly pigmented normal skin and heavily pigmented rete ridges as encountered in dermatofibromas.

The atypical networkNetwork with increased variability in the color, thickness, and spacing of the lines of the network; asymmetrically distributed; gray color

is irregularly meshed with lines that vary in width and degree of pigmentation and with “holes” that are heterogeneous in area and shape. An atypical network shows foci with broader and darker pigmented lines; the network often ends abruptly at the lesion’s periphery. An atypical network within a lesion may also appear perturbed and broken up, a finding referred to as “branched streaksBroadened or widened network with broken lines and incomplete connections”.

On histolopathology, the irregular lines of an atypical network correspond to variation in the width, length, and spacing of the rete ridges due to variation in the size, spacing, and tendency to confluence of nests of melanocytes. Rete ridges that are elongated and widened by larger junctional nests of melanocytes would appear as darker and wider lines on dermoscopy. The atypical network is often seen in melanomaThis glossary term has not yet been described. and dysplastic neviThis glossary term has not yet been described..

PseudonetworkA structureless pigment area interrupted by non-pigmented adnexal openings

The anatomy of the rete ridge pattern of the faceis a central body region of sense and is also very central in the expression of emotion among humans and among numerous other species. differs from that of nonglabrous skin. Accordingly, the pigment network is usually absent in these locations and is replaced by a pseudonetworkA structureless pigment area interrupted by non-pigmented adnexal openings pattern.

The holes in the reticulation correspond to adnexal structures such as sebacous glands, hair follicles or sweat glands.

Structureless Areas

Areas within a lesion that are devoid of any network or other structures, such as globules or regressionThis glossary term has not yet been described. structures, are called “structureless areas.” Structureless areas are defined as areas with a size that is at least 10% of the lesion’s surface area and are devoid of any discernible structures, such as globulesThis glossary term has not yet been described., network, or regression structures (i.e., scars, pepperingdots gray, granularityThis glossary term has not yet been described., or blue-white veil over flat areas).

Hypopigmented structureless areas

They are hypopigmented compared with the rest of the lesion; however, they manifest the same or slightly more pigment compared with the surrounding normal skin (N.B.: structureless areas that are hyperpigmented are called blotches). Focal structureless areas within a lesion are a common finding in . However, focal tan to light brown structureless areas at the periphery of a melanocytic lesion is commonly associated with melanoma. Peripherally located structureless areas in melanoma tend to have a light brown to fawn color and tend to end abruptly at the edge of a lesion. Histologically, these areas are characterized by flattening of the DEJ (loss of the undulating pattern of rete ridges and dermal papillae) and scattering of atypical melanocytes in suprabasal epidermal layers (i.e., pagetoid cells).

Hyperpigmented structureless areas (Blotches)

A is defined as an area with a size that is at least 10% of the lesion’s surface area and is heavily . In a blotch the melanin pigment is often present throughout the skin, including the stratum corneum, epidermis, and the dermis. The dark pigment in a blotch visually obscures the ability to discern any underlying structures. Blotches can be regular or irregular.

Regular hyperpigmented structureless areablotch If centric hypermelanotic Clark (“dysplastic”) nevus if eccentric melanoma (BlotchDark structureless areas)

Regular blotches are defined as those that display symmetry, regular borders,homogenous dark hue, and are located within the center of the lesion. A pigment network often surrounds a regular blotchOne blotch within center of lesion and surrounded by network. Regular blotches are associated with nevi.

Regular blotches can be seen in “activated” nevi. This structure is due to heavy concentrations of melanin in the stratum corneum. Because the pigment is present in the stratum corneum, it can easily be stripped off using a tape-stripping procedure, thereby revealing underlying structures.

Irregular hyperpigmented structureless area (Blotch)

Irregular blotches are defined as those that are asymmetric, have irregular contours, are located off center, and/or display multiple dark hues (i.e., heterogenous dark hues). Irregular blotches are associated with melanoma.

DotsDots are small, round structures of less than 0.1 mm in diameter that have a red color when corresponding to blood vessels; however, when due to melanin, their color ranges from black, brown, to blue-gray depending on the depth and concentration of the melanin in the skin (Tyndall effect).

Dots are small, round structures of less than 0.1 mm in diameter that have a red color when corresponding to blood vessels; however, when due to melanin, their color ranges from black, brown, to blue-gray depending on the depth and concentration of the melanin in the skin (Tyndall effect). Black dots are often due to melanin pigment accumulation in the stratum corneum, but can also be due to vertical stacking of pigment within the epidermis or due to heavy aggregates of melanin in small clusters of melanocytes or keratinocytes located in the upper layers of the epidermis (just below the stratum corneum). Black dots that are in the stratum corneum are usually found overlying the gridlines of the network and they can easily be tape stripped off the skin. Brown dots are often associated with focal melanin accumulations at the DEJ or spinous layer and they usually correspond histologically to small junctional melanocytic nests. The dotsDots are small, round structures of less than 0.1 mm in diameter that have a red color when corresponding to blood vessels; however, when due to melanin, their color ranges from black, brown, to blue-gray depending on the depth and concentration of the melanin in the skin (Tyndall effect)., resulting from nevus nests located at the tips of rete ridges, tend to be situated overlying the network lines. Less frequently, brown dots correspond to melanocytic nests located in the skin below the stratum corneum or even within the stratum corneum. The nests present within the stratum corneum are probably in the process of being extruded from the skin via transelimination. Brown dots corresponding to small melanocytic nests situated in the papillary dermis appear as dots situated within the holes of the network. These so-called target network with dots/globules or halo dots/globules are a common finding in congenital melanocytic nevi. Although on rare occasions brown dots can be tape stripped off the skin, most brown dots cannot be removed via tapestripping. Black or brown dots may appear after acute ultraviolet exposure; however, these dots tend to disappear over time. It is interesting to note that many non–ultraviolet-induced dots that are successfully tape stripped off the skin reappear with time. Gray-blue dots (also called granules or peppering) are due to fi ne melanin particles within melanophages or as extracellular “dust” in the superficialThis glossary term has not yet been described. dermis; a feature associated with regression.

Regular dotsDots clustered at the center of the lesion, or located on the network lines (also called target network)

Dots clustered at the center of the lesion, or located on the network lines (also called target network)

Irregular dotsAny distribution of dots other than dots as described for regular dots.

Irregular dots tend to be heterogenous in size shape and color and are frequently found at the periphery of a given lesion or scattered throughout the lesion.

GlobulesThis glossary term has not yet been described.

Globules are symmetrical, round to oval, well-demarcated structures with a diameter that is larger than 0.1 mm. They usually correspond to nests of pigmented or melanocytes situated in the lower epidermis, at the DEJ, or in the papillary dermis. On occasion globules may correspond to large clumps of melanin, melanophages, or pigmented milia cysts. Like dots, the color of globules may be brown, black, blue-gray, or red. The significance of these colors is the same as was discussed for dots above. Both dots and globules may occur in nevi as well as in melanoma. In nevi, the globules are uniform in size, shape, and color (mostly brown), and evenly distributed in the lesion, being mostly present at its center surrounded by a network, or circumferentially along the entire perimeter of the nevus, or uniformly distributed throughout the nevus. Dots in nevi are usually brown in color and overlie the pigment network lines. In contrast, in melanomas, globules and dots vary in size, shape, and color, are unevenly distributed in the lesion, and are frequently found focally at the periphery of lesions. Because both dots and globules frequently correlate with nests of melanocytes, they are often described for simplicity and reproducibility as a combined term “’s and globules”.

Streakslines radial (always at periphery) streaks Reed nevus melanoma recurrent nevus

Streaks are linear pigmented projections seen at the periphery of lesions.

Both pseudopods ( with bulbous projections at their tips) and (streaks without bulbous projections at their tips) are considered to be streaks. Streaks in melanoma are usually observed only focally and asymmetrically at the lesion’s periphery and reflect the radial growth phase of the tumor. On the other hand, streaks that are distributed symmetrically around the entire perimeter of the lesion are seen mostly in pigmented spindle cell nevi (Spitz or Reed). Histologically, streaks represent confluent junctional nests of melanocytes. Pseudopods are finger-like projections of dark pigment (brown to black) at the periphery of the lesion. They have small knobs at their tips, and are connected to either a central pigment network or central pigmented blotch. To be considered pseudopods the bulbous knobs must have a maximum diameter that is larger than the network from which it originates. Menzies and colleagues found pseudopods to be one of the most specific features of superficially melanoma. On histopathology, pseudopods correspond to junctional confluent nests of melanocytes at the periphery of the lesion. Confluence of nests is also a criterion in histopathology, typical for dysplastic nevi or malignant melanoma. Depending on which area of the pseudopod is sectioned on , the pathologist will see this structure either as a circular cluster of cells of varying diameters or as an oval-shaped cluster of cells. Only if the section passes exactly through the longitudinal axis of a pseudopod will the pathologist be able to recognize this structure as an elongated tubular cluster of cells.

Needless to say, the statistical probability of this happening is very low unless of course the pathologist uses dermoscopy at the grossing table to orient and oversee the step sectioning process. On occasion, peripheral globulesThis glossary term has not yet been described. and pseudopods can look similar to each other at first glance. However, with peripheral globules one will observe a small clear space separating the globuleThis glossary term has not yet been described. from the main tumor mass.

These peripheral globules are presumed to correspond to junctional melanocytic nests at the tips of rete ridges and they are usually associated with growing/enlarging nevi. In contrast, pseudopods emanatefrom, and are directly connected to, the main tumor mass through a stalk. appears as radial parallel linear extensions at the periphery of the lesion. On histopathology, radial streaming also correlates with confluent junctional nests of pigmented melanocytes.

Negative Pigment Network

The “negativeThis glossary term has not yet been described.” of the pigmented network (also known as reverse or inverse network) consists of relatively lighter areas comprising the apparent grid of the network and relatively darker areas filling the apparent “holes”. The lighter grid lines tend to be serpiginous and the darker areas, when viewed in isolation, resemble elongated tubular or curved globules. Histopathologically, the negative networkSerpiginous interconnecting broadened hypopigmented lines that surround elongated and curvilinear globules. appears to correspond to thin elongated rete ridges accompanied by large melanocytic nests within a widened papillary dermis or to bridging of rete ridges. Although the negative network is highly specific for melanoma (95% specific), it can also be found in some Spitz neviThis glossary term has not yet been described. and rarely in other nevi, such as congenital neviis a type of melanocytic nevus (or mole) found in infants at birth. This type of birthmark occurs in an estimated 1% of infants worldwide; it is located in the area of the head and neck 15% of the time.. In congenital nevi, the negative pigmented network is usually diffuse and symmetrical in its distribution. In contrast, the negative pigmented network seen in melanoma is often focal and asymmetrically distributed.

Shiny white structures

Shiny white streakslines white perpendicular*
Shiny white blotches and strandsWhite structures in the form of circles, oval structures, or large structureless areas that are bright-white longer and less well defined lines oriented parallel or distributed haphazardly, or forming blotches (shiny white clods). Seen only under polarized dermoscopy.
RosettesFour bright white dots or clods arranged together as a square (or a four leaf clover)
Shiny white areas

Christalline structures, are white shiny linear streaks that are seen under polarized dermoscopy, but not under nonpolarized dermoscopy. The white streaks are oriented parallel, and sometimes also orthogonal (perpendicular) to each other. Chrysalis structuresolt term for Chrysalis / Cristalline Structures can be seen in scars, dermatofibromas, basal cell carcinomas, and also in melanomas and Spitz nevi. These structures correlate histopathologically with altered collagen in the dermis (fibrosis). The birefringent properties of collagen bundles causes rapid randomization of polarized lightThis glossary term has not yet been described. and this is, why collagen appears bright white and more conspicuous under polarized dermoscopy.

RegressionThis glossary term has not yet been described. Structures

Regression structures appear dermoscopically as:

white scar-like depigmentationArea of white that is whiter than surrounding normal skin (true scarring). It should not be confused with hypo- or depigmentation due to simple loss of melanin. Shiny white structures and blood vessels are not seen in areas of regression. (lighter than the surrounding skin)
“peppering” (speckled multiple blue-gray granules)

On histopathology fully evolved regression shows fibrosis and melanosis (infiltrate of melanophages), and sparse lymphocytic infiltrates. The normal undulating DEJ pattern formed by rete ridges and dermal papillae is attenuated to completely Flattened. Regression structures consisting of both scar like depigmentation and peppering (granularity) should raise suspicion for melanoma. Regression structures consisting of only peppering can be seen in melanoma, lichen planus like keratosisThis glossary term has not yet been described. and nevi. In lichen planus like keratosis the granularity tends to be coarse and diffusely distributed. In melanocytic lesions the granularity tends to be finer and focally distributed.

White scar-like depigmentation

corresponds to a white discoloration of the lesion, which is lighter than the surrounding normal skin. On histopathology, this dermoscopic structure correlates with fibrosis.

GranularityThis glossary term has not yet been described.

Granularity (also known as “peppering”) is defi ned as accumulation of multiple very small (<0.1 mm), nondescript, blue-grey dots. If a large area shows dense, confluent granularity, it is diffi cult to distinguish from blue-white veil, however, clinically, granularity often is seen in macular portions of the lesion, while blue-white veil in palpable areas. Histopathologically, granularity correlates with melanin in the superficial dermis, either as fine melanin particles in melanophages or extracellular “dust-like” particles. When granularity is encountered in nevi it tends to encompass less than 10% of the lesion’s surface area. In contrast, in melanoma the granularity often encompasses more than 50% of the lesion’s surface area.

Blue-White Veil

Blue-white veil is confluent blue pigmentation with an overlying white “ground-glass” haze. In melanoma, the bluewhite veil does not occupy the entire surface area of the lesion, but rather is present as a focal, ill-defined area. Histopathologically, this dermoscopic structure corresponds to an aggregation of heavily pigmented cells (melanocytes and/or melanophages) or melanin in the dermis (blue color) in combination with compact orthokeratosis . At times, it is difficultneeding much effort or skill to accomplish to distinguish between regression structures (namely melanosis) and blue-white veil by dermoscopy because both structures display blue-white color. However, examining the lesion without dermoscopy can helpRefers to giving assistance or support to others for mutual benefit differentiate between blue-white color due to regression versus due to deep melanocytes. In regression the surface contour will be flat (macular) and in blue-white veil the surface will be raised and palpable. In melanoma the blue-white veil is nonuniform in color and is present focally within the lesion. In contrast, the blue-white veil has a uniform steel-blue color in blue nevi and it occupies the entire surface area of the lesion.

Vascular Structures

In recent years, more attention has been given to the vascular patterns of pigmented and nonpigmented lesions. The increased availability of dermoscopes using polarized light allow for the inspection of a lesion without the need to contact the lesion. This prevents blood vessel compression, which in part helps in making the blood vessel morphologyThis glossary term has not yet been described. more conspicuous. A detailed description of blood vessel morphology can be found in the corresponding.
A detailed description of the vascular structuresThis glossary term has not yet been described. can be found here Vascular structures.

Milia-like Cysts

are round whitish or yellowish structures that are commonly, but not exclusively, seen in . They can also be seen in melanocytic nevi, especially those with a congenital pattern. Sometimes are pigmented and resemble globules. Milia-like cysts correspond to intraepidermal keratin horn pseudocysts.

Comedo-like Openings

Comedo-like openings[[Comedo like openings]] are commonly seen in seborrheic keratosis and rarely in melanocytic nevi with a congenital pattern, such as papillomatous nevi. They appear on dermoscopy as dark roundish structures, and clinically, can be appreciated as surface invaginations. Histopathologically, comedo-like openings[[Comedo like openings]] correspond to the concave, keratin filled, invaginations of the epidermis.

Fissures and Ridges (“Brain-like or Cerebriform Appearance”)

Fissures (invaginations or sulci) are commonly seen in seborrheic keratosis and may also be seen in melanocytic nevi with congenital pattern. In essence, fissures are linear grooves in the epidermis and, like comedo-like openings, correspond to surface invaginations. A pattern that resembles “brain-like appearancelines, curved and thick to describe the pattern and fissures and ridges (former synonyms “gyry and sulci” and “fat fingers”) to describe the structural components of the pattern SK” or cerebriform appearance is created, with the grooves resembling “sulci” and the intervening ridges resembling surface“gyri”. Fissures correspond histopathologically to wedgeshaped, keratin-filled invaginations of the epidermis.

Fingerprint-like Structures

Some flat (also known as ) can show tiny ridges running in parallel and producing a pattern that is reminiscent of fingerprints.

Moth-eaten Border

Some flat seborrheic keratoses have concave borders so that the pigment ends with curved to semi-circular indentations, which has been compared to a moth-eaten garment.

Leaf-like Areas

Leaf-like areasBrown to gray/blue discrete linear or bulbous structures coalescing at a common off center base creating structures that resemble a leaf-like pattern. are seen as brown to gray-blue discrete bulbous blobs that often form a pattern shaped like a leaf. They can sometimes appear as tan, broad, and fuzzy streaks at the periphery of a lesion. In the absence of a pigment networkGrid-like pattern consisting of interconnecting pigmented lines surrounding hypopigmented holes., they are highly suggestive of pigmented basal cell carcinomas. Histopathologically, they represent dermal nodular aggregates of pigmented basal cell carcinomaThis glossary term has not yet been described..

Spoke-wheel-like Structures

Spoke-wheel-like structures are well-circumscribed brown to gray-blue– brown radial projections that radiate out from a dark brown central hub. Sometimes the radial projections are not visible and instead one sees a concentric globule consisting of a round structure with a central darker hub, which is surrounded by a brown halo of pigment. In the absence of a pigment network, spoke-wheels are highly suggestive of basal cell carcinomais the most common skin cancer, and one of the most common cancers in the United States.[1] While BCC has a very low metastatic risk, this tumor can cause significant disfigurement by invading surrounding tissues. Histopathologically, they correspond to the nests of basal cell carcinoma emanating from the undersurface of the epidermis; a common finding is superficial basal cell carcinoma.

Large Blue-Gray Ovoid Nests

Ovoid nests are large, discrete, and well-circumscribed, pigmented ovoidareas, larger than globules. When a network is absent, ovoid nests are highly suggestive of basal cell carcinoma. Ovoid nests correspond on histopathology to dermal aggregates of pigmented basal cell carcinoma.

Multiple Blue-Gray Non-aggregated Dots and Globules

Multiple blue-gray dots and globules are round, discrete, and well circumscribed structures that, in the absence of a pigment network, are highly suggestive of a basal cell carcinoma. These dots and globules usually do not form aggregates as seen in melanocytic lesions. They correlate with dermal aggregates of pigmented basal cell carcinoma and are similar to ovoid nests, but smaller.

LacunaeThis glossary term has not yet been described.

Lacunae are defi ned as multiple, clustered, well-demarcated, red to maroon to blue blobs with a round to oval shape. If the are blueblack in color, then the lesion may be an . The lacunae correspond to cavernous dilated blood vessels.

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↑ An Atlas of Dermoscopy, Second Edition. Marghoob A. et al. CRC Press; 2012.

[1] An Atlas of Dermoscopy, Second Edition. Marghoob A. et al. CRC Press; 2012.

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Annotations
Description	Definition of dermoscopyDermoscopy is a non invasive diagnostic method. criteriameasure of how well one variable or set of variables predicts an outcome such as colorColor (American English) or colour (Commonwealth English) is the characteristic of human visual perception described through color categories, with names such as red, yellow, purple, or blue. and dermoscopy structures and the histopathologyThis glossary term has not yet been described. correlates
Author(s)	Ralph P. Braun · Katrin Kerl
Owner	Ralph Braun → send e-mail
Status	released
Status update	March 1, 2018
Status by	Ralph P. Braun

Histopathologic correlation of dermoscopic structures

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