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Differential 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 |
Mimickers
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| Negative Network
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MelanomaThis glossary term has not yet been described.
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Ridges of Seborrheic keratosesThis glossary term has not yet been described.
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| Spitz/Reeds
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Globular Structures of dermatofibromas
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| Severe Dysplastic neviThis glossary term has not yet been described.
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| CMN
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| Streakslines radial (always at periphery) streaks Reed nevus melanoma recurrent nevus
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Melanoma
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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. of BCCThis glossary term has not yet been described.
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| Spitz/Reeds nevusThis glossary term has not yet been described.
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Ridges (fat-fingers) of seborrheic keratosesThis glossary term has not yet been described.
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| Pigmented periphery of Bowenalso known as squamous cell carcinoma in situ[1] is a neoplastic skin disease. It can be considered as an early stage or intraepidermal form of squamous cell carcinoma. It was named after John T. Bowen's disease
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| Pigmented periphery of cutaneous mets
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| Network
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NeviThis glossary term has not yet been described.
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Fingerprintinglines brown curved parallel thin of solar lentiginesThis glossary term has not yet been described.
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| Melanoma
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Cerebriform pattern of seborrheic keratoses
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| Solar lentigoThis glossary term has not yet been described.
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| Ink spot lentigo
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| DermatofibromaDermatofibromas are hard solitary slow-growing papules (rounded bumps) that may appear in a variety of colours, usually brownish to tan; they are often elevated or pedunculated. A dermatofibroma is associated with the dimple sign; by applying lateral pressure, there is a central depression of the dermatofibroma.
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| Accessory nipple
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| MastocytosisThis glossary term has not yet been described.
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| GlobulesThis glossary term has not yet been described.
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NevusThis glossary term has not yet been described.
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Lacuna
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| Melanoma
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Ovoid nests
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| Clonal Seborrheic keratosisThis glossary term has not yet been described.
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Blue-gray ovoid nestsclods blue large clustered
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| Cutaneous metastasis
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Pigmented cysts
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Comedo-like openings[[Comedo like openings]]
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| Pepperingdots gray/granularityThis glossary term has not yet been described.
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Melanoma
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Blue-gray dots of BCC
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| Lichen planusThis glossary term has not yet been described.-like keratosis
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Linear brown dots of pigmented Bowen’s disease
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| Pigmented actinic keratosisActinic keratosis (also called solar keratosis and senile keratosis; abbreviated as AK) is a pre-cancerous patch of thick, scaly, or crusty skin. These growths are more common in fair-skinned people and those who are frequently in the sun. They usually form when skin gets damaged by ultraviolet (UV) radiation from the sun or indoor tanning beds. AKs are considered potentially pre-cancerous; left untreated, they may turn into a type of cancer called squamous cell carcinoma. Untreated lesions have up to a 20% risk of progression to squamous cell carcinoma, so treatment by a dermatologist is recommended.
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| Nevi (focal and limited)
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| VesselsThis glossary term has not yet been described.
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Various melanocyticThis glossary term has not yet been described. and non-melanocytic lesions
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Small ulcerations as in superficialThis glossary term has not yet been described. BCC
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| Linear brown/red dots of pigmented Bowen’s disease
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| Red globules of BCC
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| Background vesselsThis glossary term has not yet been described. in normal skin and sun-damaged skinThis glossary term has not yet been described.
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| BlotchDark structureless areas
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Melanoma
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Subcorneal hemorrhage
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| Clark's neviThis glossary term has not yet been described.
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Thrombosed angiomaAngiomas are benign tumors derived from cells of the vascular or lymphatic vessel walls (endothelium) or derived from cells of the tissues surrounding these vessels.[1][2] Angiomas are a frequent occurrence as patients age, but they might be an indicator of systemic problems such as liver disease. They are not commonly associated with malignancy.
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| Blue nevusis a type of melanocytic nevus that clinically and dermoscopically will appear blue
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Black lamella
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| Reed's nevi
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Exogeneous pigmentation
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Heavily pigmented seborrheic keratoses
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Heavily pigmented BCC
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Venous angiomas
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| Shiny-white streakslines radial (always at periphery) streaks Reed nevus melanoma recurrent nevus
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Melanoma
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Negative networkSerpiginous interconnecting broadened hypopigmented lines that surround elongated and curvilinear globules.
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| Spitz nevusThis glossary term has not yet been described.
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White lines of scalp nevi
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| BCC
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Wickham striae
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| Dermatofibroma
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Rail lines (pyogenic granulomaThis glossary term has not yet been described.)
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| Scar
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| Circles-white
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Actinic keratoses
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Milia-like cystsThis glossary term has not yet been described.
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| SCCThis glossary term has not yet been described.
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Lobules of sebaceous hyperplasiaThis glossary term has not yet been described.
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White clods of BCC
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Lacunes of lymphangiomas
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White globules of balloon cell nevi
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Folliculitis
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Molluscum
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| Circles-brown
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Dermatofibroma
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Curved lines of solar lentigines and seborrheic keraotoses
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| Bowen's disease
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Comedo-like openings
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| Facial melanomaThis glossary term has not yet been described.
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| Facial nevi
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| Facial solar lentigines
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| Angulated lines(polygons, zig-zag pattern) Gray-brown lines that are connected at an angle or coalescing to form polygons
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Melanoma of sun-damaged skin
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Spoke-wheel areas
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| Pigmented actinic keratosis
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Fingerprinting
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| Lichen planus-like keratosis
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Prominent network of 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. and Clark's nevi
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Prominent lines of ink spot lentigo
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Lattice like pattern of acralAcral melanoma is a type of skin cancer that occurs on fingers, palms, soles, and nail beds. nevi
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The two-step dermoscopyDermoscopy is a non invasive diagnostic method. algorithm aims to differentiate between melanocytic and non-melanocytic lesions and to determine if a melanocytic lesion is benignis any condition that is harmless in the long run or malignantThis glossary term has not yet been described.. While algorithms serve as guidelines that apply to the majority of cases, one should remember that every rule has exceptions. The recognition of the exceptions is essential for the maintenance of high diagnostic precision.
Misclassification of non-melanocytic lesions
Occasionally non-melanocytic lesions display a network, globulesThis glossary term has not yet been described., streaks, or homogenous pigmentation potentially leading to the incorrect 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 of a melanocytic lesion.
Pigment networkGrid-like pattern consisting of interconnecting pigmented lines surrounding hypopigmented holes.
The reticular network reflects a pigmented basal layer, with its grid representing the pigmented rete ridges and the holes representing the lesser pigmented suprapapillary plates. Whenever there is a corrugated and pigmented basal layer, whether its’ pigment lies within keratinocytes or within melanocytes, a corresponding reticular network appears on dermoscopy. Apart from melanocytic lesions, this structure could be seen in a solar lentigoThis glossary term has not yet been described., seborrheic keratosisThis glossary term has not yet been described., dermatofibromaDermatofibromas are hard solitary slow-growing papules (rounded bumps) that may appear in a variety of colours, usually brownish to tan; they are often elevated or pedunculated. A dermatofibroma is associated with the dimple sign; by applying lateral pressure, there is a central depression of the dermatofibroma. and accessory nipple.
Solar lentigo
Solar lentiginesThis glossary term has not yet been described. not uncommonly display a reticular network. Differentiation from a melanocytic lesion is usually based on the network being regular, faint and delicate, demarcated with a sharp border or a moth-eaten borderThis glossary term has not yet been described., accompanied by the occasional presence of a clinical jelly sign fingerprintinglines brown curved parallel thin, milia-like cystsThis glossary term has not yet been described. and comedo-like openings[[Comedo like openings]]. A distinct type of lentigo is the ink-spot lentigo showing a unique dark brown thickened network that ends abruptly, commonly appearing following sun burns.
Seborrheic keratosis
Pigmented seborrheic keratoses occasionally demonstrate network-like structuresThis glossary term has not yet been described., typically in which the grid is thickened and the holes are wider than those formed by melanocytic lesions. The grid corresponds to ridgeThis glossary term has not yet been described. and the holes to the sulci or fissures. The grid can thicken to create a cerebriform appearance, formerly known as the “fat finger”. As with solar lentigines, the network- like structures of seborrheic keratosis end abruptly. When there is a blue white veilBlue-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 and linear irregularlinear vessels with multiple bends vessels, the observer might mistake the lesion for a melanoma. Gray granularity observed in inflamed or regressed lesions might further add to the diagnostic difficulty.
Dermatofibroma
Dermatofibromas classically reveal on dermoscopy a delicate, tan-colored peripheral network, surrounding a central scar-like area. The delicate networklight brown, thin network lines corresponds to the “dirty feet” histologic appearance of the pigmented basal layer. At the inner edge of the network, circles are commonly seen, representing the widened rete ridges at the edges of the scar. The scar like area can display vessels, and under polarized lightThis glossary term has not yet been described. can show white lines overlying a pink background. As this pattern, along with a clinical dimple sign represent the prototype of dermatofibromas’ appearance, the two step algorithms specifically emphasizes it as an exception. Thus, when the above pattern is observed, a dermatofibroma can be diagnosed with certainty during the first step.
Supernumerary nipples
The areolar basal pigmentation of the nipple results in a dermoscopic delicate network, occasionally leads to the misdiagnosis as nevi or dermatofibromas. Diagnostic cluesEvidence, in an investigation for supernumerary nipples are their clinical appearance as soft papules present along the milk-line, typically with a stable history.
Dots and globules
Although dots and globules are commonly observed in melanocytic lesions, they can appear in a variety of non-melanocytic lesions, including dermatofibromas, seborrheic keratoses, pigmented Bowen’s disease, basal cell carcinomas and cutaneous metastasis.
Dermatofibroma
As noted above, the inner edge of the network of dermatofibromas tends to show ring-like globular structure. This feature’s presence is probably related to the elongated rete ridges overlying the central scar-like area. A combination of clinical and dermoscopic clues including the dimple sign and central scar-like area featuring crystalline structures and occasional vessels are an aid to diagnosis.
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
The dermoscopy of pigmented basal cell carcinomas reflects the histologic pigmented tumor islands. Basal cell carcinomas can display and blue-gray non-aggregated globules and small and focused brown dots typically arranged in a “buckshot scatter” pattern. White shiny streaks, arborizing vesselsanalytic term is branched vessels; Bright red sharply in focus large or thick diameter vessels dividing into smaller vessels; BCC and a pink-white shiny background are suggestive of BCC although could appear on melanomas. That said, the misdiagnosis of a BCC as a melanoma would generally result in a similar, yet conceivably more rigorous managementThis glossary term has not yet been described. strategy.
Seborrheic keratosis
Globules are not a common finding in seborrheic keratoses. However occasionally they are present, reflecting the epidermal pigmented horn cyst or comedo-like openings. The presence of a sharp border, ridges and sulci and milia-like-cysts are an aid to the correct diagnosis. A more challenging dermoscopic variant is the clonal seborrheic keratosis in which variable-sized pigmented globular structures are aggregated throughout the lesions, occasionally leading the observer to expand the differential diagnosis to include a melanoma or a BCC.
Pigmented Bowen’s disease
Pigmented Bowen’s disease can display brown focal 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)., often arranged in peripheral linear tracks {Cameron, 2010 #2342}. The presence of scale and dotted or glomerular vesselsThis glossary term has not yet been described. are an aid to the correct diagnosis.
Cutaneous metastasis
Tumors metastasizing to the skin can acquire melanin from epidermal melanocytes or become colonized with melanocytes leading to pigmented structures as irregular dotsAny distribution of dots other than dots as described for regular dots. and globuleThis glossary term has not yet been described., not uncommonly having the appearance of an atypical melanocytic lesion.
Pigmented streaks
Pigmented streaks are linear projections present at the periphery of the lesion. In melanocytic lesions they correspond to confluent junctional melanocytic proliferation but can be seen in variety of non-melanocytic lesions.
Seborrheic keratoses
Seborrheic keratoses display pigmented bulbous rete ridge on histologyThis glossary term has not yet been described.. In the same manner as this histologic feature could reflect a thickened network when present in the center of the lesion, its’ present at the periphery could result in corresponding dermoscopic streak-like structures. In seborrheic keratoses the streaks tend to be thick and occasionally branched. This structure leads to the description of the starburst-like seborrheic keratosis. Clinically distinguishing the stuck-on lesions, those with a negative wobble signThis glossary term has not yet been described., and those that are featuring dermoscopic clues as milia like-cysts and comedo-like openingRound to oval keratin filled clefts facilitate the correct diagnosis.
Basal cell carcinoma
BCC’s at times show thick streak- like structures arraigned radially, connecting to a common base. This is usually a variant of the leaf like structure of spoke-wheel structure.
Pigmented Bowen’s disease
Irregular peripheral streaks corresponding to pigmented dendritic melanocytes are occasionally seen in pigmented Bowen’s disease, a rather rare variant of Bowen’s disease. Scale, ulceration and dotted or glomerular vessels are a clue to correct diagnosis.
Cutaneous metastasis
If epidermal melanocytes or melanin colonize skin metastasis at the periphery of the lesions, streaks could form in the same manner they are formed in melanocytic lesions.
Homogenous blue pigmentation
Due to Raleigh scattering, the shorter wavelengths (blue) are scattered, while the longer wavelengths (red) are mostly absorbed. Owed to this phenomenon, melanin and hemoglobin located deep in the dermis appear blue. Although the classic example of homogenous blue pigmentation is the blue nevusis a type of melanocytic nevus that clinically and dermoscopically will appear blue, this feature can appear in malignant melanocytic lesions (primary and metastatic melanoma) and in non-melanocytic lesions including Basal cell carcinomas, tattoos, cysts and vascular lesions.
Tattoos
Foreign material such as asphalt (traumatic tattoo) lead (pencil lead tattoo) or carbon ink (radiation tattoo) can create a homogenous blue lesion occasionally confused with a blue nevus. History is the main key to the correct diagnosis.
Basal cell carcinoma
Pigmented nodular BCC’s rarely appear as homogenous blue lesions. This feature, when present, probably results form a coalition of large ovoid nests.
Epidermal Cysts
Epidermal cysts occasionally have faint blue homogenous appearance. This results from the deeply located keratinous material covered by epithelial lining. Clinically the lesions generally feature as dermal bluish or yellowish nodules. The overlying epidermis occasionally features a punctum.
Vascular lesions
When angiomas and angiokeratomas are located deep in the dermis, occasionally the distinction between the vascular structuresThis glossary term has not yet been described. (lacunas) are not clear. Due to Rayleigh scattering these lesions can appear as homogenous blue or red blue lesions.
Dermatofibromas
Special variants of dermatofibromas such as hemosiderotic and aneurysmatic can display homogenous blue pigmentation due to hemosiderin deposition and large deep vascular channels. The dimple sign and a delicate peripheral network are an aid to the correct diagnosis.
Misclassification of melanocytic lesions
When melanocytic lesions do not display clear-cut melanocytic features, or on the contrary show features associated with non melanocytic lesionsThis glossary term has not yet been described., the diagnostic process could result in their misclassification as non-melanocytic.
Melanomas mimicking Basal cell carcinomas
When a melanoma expresses a pink background, crystalline structures and/or arborizing vessels, it could be misdiagnosed as a 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. Of the features noted above only arborizing vessels are considered specific for basal cell carcinomas, having a PPD of 94%. However, this feature has been described infrequently in melanomas, challenging the dermoscopic distinction of the two entities and having the final diagnosis made by the pathologist.
Melanomas mimicking benign non-melanocytic lesions
Melanomas occasionally display features seborrheic keratoses such as milia-like cysts and comedo-like openings. One should remember not to rule out a melanocytic lesion by noticing non-melanocytic structures. Adhering to the algorithms’ first step by deciding whether a lesion is melanocytic based on the presence or absence of a network, globules, streaks or a homogenous blue pattern, would helpRefers to giving assistance or support to others for mutual benefit avoiding this misclassification.
Melanomas mimicking dermatofibromas
The gestalt pattern of melanomas and dermatofibromas can be similar, thus to achieve high diagnostic accuracy it is imperative to notice specific structure which support the global pattern. As stated above, contrary to dermatofibromas, melanomas generally do not show vessels and crystalline structures within the scar-like areas and lack a dimple sign. However, whenever an atypical dermatofibroma is suspected a reasonable management strategy would be to biopsy the lesion.
melanomas mimicking lichen planusThis glossary term has not yet been described.-like keratosis
Both melanomas and LPLKThis glossary term has not yet been described.’S can feature pigmentation and extensive regressionThis glossary term has not yet been described. structure making their distinction occasionally challenging. A clue to lplkThis glossary term has not yet been described.This glossary term has not yet been described.’s diagnosis is a seborrheic keratosis or solar lentigo at the periphery of the lesion and rather coarse blue gray granules in contrast to the fine granularity associated with melanoma. In addition, both lesions can at times exhibit a pink structureless pattern with remnants of a pigment networkGrid-like pattern consisting of interconnecting pigmented lines surrounding hypopigmented holes., and the definite diagnosis is rendered though histologic examination.
Melanomas mimicking pyogenic granulomas
Both amelanotic melanomas and pyogenic granulomas can present as red evolving nodules, occasionally ulcerated or eroded. Pyogenic granulomas can exhibit vascular structures, further adding to the confusion .Considering the dismal consequences of missing a nodular melanomaThis glossary term has not yet been described., it is strongly suggested that all pyogenic granulomas would be removed and sent to histologic examination.
Discussion
As the human decision making is an intricate process, its’ reduction into a stepwise linear process can result in oversimplification leading to the incorrect diagnosis. Confusing a melanoma with a malignant non-melanocytic lesion (ie BCC or pigmented Bowen’s disease) would frequently result in similar management. However, confusing a malignant lesion with a benign lesion could have dismal consequences. It is essential to integrate history and clinical features with the algorithmic process and diagnostic clues in order to reduce diagnostic errors.
Table 1- Features and mimickers
