False positive diagnosis
False positive dermoscopic diagnosis is a common error in everyday practice and occurs when a benign tumor does not display the expected dermoscopic criteria, and, even more, when it exhibits features suggestive of a malignant tumor. This type of error leads to excisions of benign moles, increasing the number of unnecessary interventions, but is usually not associated with any significant risk. Optimally, the dual goal in daily practice is to identify and excise all malignant tumors, while keeping the number of excisions of benign moles as low as possible. Therefore, it is useful for clinicians to know which benign tumors might mimic melanoma, basal cell carcinoma (BCC) or squamous cell carcinoma (SCC). The most frequent of them are seborrheic keratoses, angiomas, dermatofibromas, adnexal tumors and nevi:
Seborrheic keratosis
The vast majority of SK are easy to recognize dermoscopically, since they display one or more of the dermoscopic criteria that are well-known to typify SK. However, several SK variants do exist, some of them characterised by peculiar dermoscopic features that might mimic a malignant tumor.
Reticular SK and solar lentigo (SL). Main false positive diagnosis: melanoma
Comparing to the network of melanocytic tumors, the network of reticular SK and SL is characterized by thinner lines and larger holes and ends abruptly at the periphery without fading out.
Melanoacanthoma. Main false positive diagnosis: melanoma
Melanoakanthoma is a heavily pigmented variant of SK, which is often “false positive” dermoscopically, mainly because the presence of intense pigmentation does not allow the visualization of SK-related dermoscopic features (5).
Irritated SK. Main false positive diagnosis: SCC, melanoma
Irritated SK lacks the typical SK-related dermoscopic features (comedo-like openings, milia-like cysts etc) and is typified by vessels of various morphologies (hairpin, glomerular, tortuous) which are usually surrounded by whitish halos. The presence of perivascular whitish halos is known to represent a sign of keratinization which might be seen in several keratinizing tumors including squamous cell carcinoma, common warts and SK. Some clues to discriminate between SCC and irritated SK do exist: irritated SK is usually characterized by a symmetric distribution of structures (vessels surrounded by halos), in contrast to the more uneven arrangement of features in SCC. Furthermore, SCC rarely displays multiple white halos surrounding vessels as the only dermoscopic feature. If present, usually white halos in SCC are combined with white circles surrounding hair follicles or structureless whitish areas.
Clonal SK. Main false positive diagnosis: BCC, melanoma
This peculiar SK variant dermoscopically displays globular structures of brown or blue-gray color, which might be misinterpreted as irregular globules of a melanoma or blue-gray ovoid nests of a basal cell carcinoma (4-6). The sharp demarcation of the lesion at the periphery or the co-existence of SK-specific structures (ex. milia-like cysts) might help to recognize SK.
Lichen planus-like keratosis (LPLK). Main false positive diagnosis: Melanoma
LPLK is a term used to describe a SK/SL undergoing regression. LPLK dermoscopically displays the usual features associated to the regression process, namely blue-gray granules and white color. The clinically relevant problem is that precisely the same features typify also regressive nevi and melanomas. In early stages of regression of a LPLK, the typical features of SK/SL might still be present in some parts of the lesion, allowing its recognition. However, the presence of extensive regression usually does not allow a safe recognition of the pre-existing lesion. Therefore, lesions displaying extensive regression should always be histopathologically examined.
Angioma
Similarly to SK, the vast majority of angiomas are easy to recognize, based on the presence of the well-circumscribed vascular lacunas. However, some of them might acquire a peculiar dermoscopic pattern usually as a result of trauma, thrombosis or hyperkeratosis.
Targetoid hemosiderotic hemangioma (THH). Main false positive diagnosis: Melanoma, Kaposi sarcoma.
THH is a peculiar lymphatic malformation usually with a targeted appearance. Dermoscopically, the majority of THH are typified by the presence of central red and/or dark lacunae and a peripheral red-brownish homogeneous area
Thrombosed angioma. Main false positive diagnosis: Melanoma
Occasional thrombosis might occur in any angioma and is often combined with bleeding. Thrombosed blood is black-colored dermoscopically and might be restricted within the lacunas or be more diffuse.
Angiokeratoma. Main false positive diagnosis: Melanoma, BCC
Dark lacunae, red lacunae and whitish veil are the most frequent dermoscopic criteria of angiokeratomas. Dark lacunae represent the most useful feature, having a sensitivity of 93.8% and a specificity of 99.1% for the diagnosis of angiokeratoma when compared with several other benign and malignant tumors.
Dermatofibroma (DF)
As a rule, the clinical diagnosis of DF is mainly based on the palpation of the tumor. Dermoscopically, the most characteristic pattern of DF consists of a central white patch and peripheral delicate brownish network. However, several peculiar DF types do exist.
Atypical dermatofibrmas. Main false positive diagnosis: Melanoma
In addition to the aforementioned “typical” dermoscopic criteria, several other dermoscopic patterns have may be seen in DF: central white network and peripheral network, central homogenous pigmentation and peripheral network, central white patch and peripheral homogeneous pigmentation, white network throughout the lesion etc.
Hemosiderotic and aneurysmal DF. Main false positive diagnosis: Melanoma
The main dermoscopic features of hemosiderotic and aneurysmal DF are a central homogenous bluish to red-brownish area with white linear structures and a peripheral delicate pigment network with vessels of various morphologic types.
Adnexal tumors
Adnexal tumors might be divided in 3 types, according to their origin: follicular, sebaceous and sweat gland tumors. Dermoscopically, several of them have been described to mimic mainly BCC, but also melanoma. Therefore, adnexal tumors represent a frequent cause of false positive diagnosis.
Follicular tumors. Main false positive diagnosis: BCC
In general, the dermoscopic pattern of follicular tumours displays features overlapping with BCC, namely linear branching vessels and blue-grey dots or globules. The common presence of ‘white structures’ has been suggested as a dermoscopic clue, suggestive of the diagnosis of a follicular tumour. Specific dermoscopic criteria have are associated with some tumours, such as the unique ivory-white background colour that typifies desmoplastic trichoepithelioma.
Sebaceous tumors. Main false positive diagnosis: BCC
Sebaceous hyperplasia is dermoscopically typified by a whitish umbilicated, polylobular or structureless centre, surrounded by elongated, scarcely branching vessels (crown vessels). A similar pattern consisting of central whitish/yellowish structures and crown vessels characterizes sebaceous cysts. The remaining sebaceous tumors are much more difficult to recognize. A possible clue is the combination of yellowish structures with unfocused arborising vessels.
Sweat gland tumors. Main false positive diagnosis: BCC, melanoma, SCC
Eccrine poroma is the most well-studied sweat gland tumor and has been suggested to display a great dermoscopic variability, potentially mimicking all known malignant tumors.
Nevi
Overall, nevi and melanoma display significant dermoscopic similarities, since they share similar basic dermoscopic structures (pigment network, globules, streaks et al.). As a rule, in contrast to melanoma, nevi are characterised by an overall symmetry of colours and structures. However, between the 2 edges of perfect symmetry and full asymmetry, there is a continuous morphologic spectrum of lesions that cannot be easily classified. Therefore, numerous nevi are routinely excised in order to rule out melanoma. Two important parameters need to me mentioned: i) The differentiation between nevi with atypic and early melanoma might be particularly difficult even histopathologically. A “false positive dermoscopic diagnosis” (i.e. excising a lesion dermoscopically looking like melanoma but histopathologically diagnosed as a nevus) might in fact represent a false negative histopathologic diagnosis. Thus, the histopathologic findings should be always integrated with clinical and dermoscopic morphology and patient’s characteristics. ii) Excising a lesion because of diagnostic uncertainty does not represent a false positive diagnosis. It is a commonly applied and safe strategy to reduce the risk of missing melanoma. The most frequent nevus subtypes that might display dermoscopic characteristics suggestive of melanoma are the following:
Clark nevus (dysplastic nevus). Main false positive diagnosis: melanoma
The clinical, dermoscopic and histopathologic overlap between some Clark nevi and early melanoma is very well-known. Clark nevi may display one or more of melanoma-specific criteria, such as asymmetry of colours and/or structures, atypical netwok, irregular globules, regression etc. This problem is particularly relevant in patients with the so-called atypical mole syndrome. The most efficient (and safe) strategy to reduce the number of excisions of nevi is the application of the comparative approach, which is based on the notion that the majority of an individuals’ nevi are morphologically similar among them, while melanoma deviates this “signature pattern”. Therefore, the comparative approach suggests that, in individuals with multiple atypical moles, instead of trying to measure the degree of each mole’s atypic, one should search for the morphologically different lesion (“ugly duckling”).
Spitz and Reed nevus. Main false positive diagnosis: melanoma
Three dermoscopic patterns of Spitz and Reed nevi have been thoroughly studied. Reed nevi are typified by the so-called “starburst” pattern, consisting of a dark brown/black/blue centre and symmetrically distributed peripheral streaks or pseudopods. Pigmented Spitz nevi are characterised by the presence of symmetrically distributed globules and white spaces among them (inverse network or reticular depigmentation). Non-pigmented Spitz nevi are typified by the presence of symmetrically distributed vessels (usually dotted) and white spaces among them (inverse network). All the aforementioned patterns are characterised by a symmetric distribution of structures. The same structures (streaks, pseudopods, vessels, inverse network), if not symmetrically distributed, represent melanoma criteria (irregular streaks, irregular pseudopods, atypical vessels etc). Therefore, the morphologic overlap between Spitz/Reed nevi and melanoma is obvious, since any Spitz/Reed nevus deviating the perfect symmetry is, by definition, looking like melanoma. The problem of how to manage a spitzoid-looking lesion gets even more complicated by the fact that spitzoid melanomas perfectly mimicking a symmetric Spitz/Reed nevus do also exist. To address this problem, the International Dermoscopy Society has recently released management guidelines (see “Management of Spitz nevi”).
Combined nevus. Main false positive diagnosis: melanoma
The co-existence of 2 different melanocytes proliferations within the same nevus results in a peculiar, asymmetric dermoscopic pattern, often resulting in a false positive diagnosis of melanoma. The most frequent combination (blue nevus plus compound/dermal nevus) is dermoscopically characterized by peripheral network or globules and a central homogenous blue area. Of note, the blue area is often rather eccentric than central.
Reccurent nevus. Main false positive diagnosis: melanoma
The safest way to classify a recurrent pigmentation within/on a scar is to re-evaluate the histopathologic report of the primary tutor (if available). If not, the differential diagnosis between recurrent nevi and recurrent melanoma is based on the time of recurrence and the precise distribution of the pigmentation. Specifically, nevi typically recur quickly (up to 6 months after excision) and the recurring pigmentation is restricted within the scar of the previous excision. In contrast, melanoma usually recurs several months to years after excision and tends to expand beyond the borders of the scar onto the normal skin.
Sclerosing nevi with pseudomelanomatous features. Main false positive diagnosis: melanoma
This peculiar nevus subtype might clinically and histopathologically mimic regressive melanoma. Dermoscopically, nevi with regression-like fibrosis display both white and blue/gray (peppering) regression structures that usually extend on 10% to 50% of lesion’s surface), without any other melanoma specific criteria. Typically the regression area is located in the centre of the nevus.
