False positive diagnosis

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 Authored by: Aimilios Lallas

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False positive dermoscopic 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 is a common error in everyday practice and occurs when a benignis any condition that is harmless in the long run tumor does not display the expected dermoscopic criteriameasure of how well one variable or set of variables predicts an outcome, and, even more, when it exhibits features suggestive of a malignantThis glossary term has not yet been described. 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 melanomaThis glossary term has not yet been described., 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 (BCCAbbreviation for Basal Cell Carcinoma) or squamous cell carcinomaThis glossary term has not yet been described. (SCCThis glossary term has not yet been described.). The most frequent of them are seborrheic keratosesThis glossary term has not yet been described., angiomas, dermatofibromas, adnexal tumors and neviThis glossary term has not yet been described.:

1. Seborrheic keratosisThis glossary term has not yet been described.

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.

1.1. Reticular SK and solar lentigoThis glossary term has not yet been described. (SL). Main false positive diagnosis: melanoma

Comparing to the networkThis glossary term has not yet been described. of melanocyticThis glossary term has not yet been described. 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.

This solar lentigo has areas of network with some heterogeneity in the network. Such a lesion could be confused for an early melanoma.

1.2. 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).

Melanoacanthoma is a heavily pigmented seborrheic keratosis

1.3. Irritated SK. Main false positive diagnosis: SCC, melanoma

Irritated SK lacks the typical SK-related dermoscopic features (comedo-like openings[[Comedo like openings]], milia-like cystsThis glossary term has not yet been described. etc) and is typified by vesselsThis glossary term has not yet been described. 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 wartsThis glossary term has not yet been described. and SK. Some cluesEvidence, in an investigation to discriminate between SCC and irritated SK do exist: irritated SK is usually characterized by a symmetric distribution of structuresThis glossary term has not yet been described. (vessels surrounded by halos), in contrast to the more uneven arrangementThis glossary term has not yet been described. 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.

Irritated seborrheic keratosis with numerous vessels. The presence of keratin and vessels may lead to the incorrect diagnosis of squamous cell carcinoma.

1.4. Clonal SK. Main false positive diagnosis: BCC, melanoma

This peculiar SK variant dermoscopically displays globular structures of brown or blue-gray 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., which might be misinterpreted as irregular globulesGlobules with variability in color, size, shape or spacing and distributed in an asymmetric fashion of a melanoma or blue-gray ovoid nestsclods blue large clustered 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 helpRefers to giving assistance or support to others for mutual benefit to recognize SK.

This is a clonal linear epidermal nevus / seborrheic keratosis
Clonal seborrheic keratosis that could be mistaken for a BCC
This clonal seborrheic keratosis has features overlapping with melanoma and basal cell carcinoma

1.5. Lichen planusThis glossary term has not yet been described.-like keratosis (LPLKThis glossary term has not yet been described.). Main false positive diagnosis: MelanomaThis glossary term has not yet been described.

LPLK is a term used to describe a SK/SL undergoing regressionThis glossary term has not yet been described.. 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.

lichen plans like keratosis like features suggestive of an amelanotic melanoma or basal cell carcinoma
This lichen planes like keratosis has shiny white lines. This lesion has overlapping features with amelanotic melanoma and superficial basal cell carcinoma.

2. 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.

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.

2.1. Targetoid hemosiderotic hemangiomaThis glossary term has not yet been described. (THH). Main false positive diagnosis: Melanoma, Kaposi sarcomaThis glossary term has not yet been described..

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 lacunaeThis glossary term has not yet been described. and a peripheral red-brownish homogeneous area

2.2. 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.. 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.

2.3. Angiokeratomais a benign cutaneous lesion of capillaries, resulting in small marks of red to blue color and characterized by hyperkeratosis. 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 sensitivityThis glossary term has not yet been described. of 93.8% and a specificityThis glossary term has not yet been described. of 99.1% for the diagnosis of angiokeratomais a benign cutaneous lesion of capillaries, resulting in small marks of red to blue color and characterized by hyperkeratosis when compared with several other benign and malignant tumors.

Angiokeratoma can sometimes mimic a melanoma or basal cell carcinoma
Angiokeratoma with features that may be confusing for basal cell carcinoma

3. 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. (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 patchCentral white structureless area and peripheral delicate brownish network. However, several peculiar DF types do exist.

3.1. Atypical dermatofibrmas. Main false positive diagnosis: Melanoma

In addition to the aforementioned “typical” dermoscopic criteria, several other dermoscopic patternsThis glossary term has not yet been described. 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.

3.2. 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.

4. 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.

4.1. 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 globulesThis glossary term has not yet been described.. 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.

4.2. Sebaceous tumors. Main false positive diagnosis: BCC

Sebaceous hyperplasiaThis glossary term has not yet been described. is dermoscopically typified by a whitish umbilicated, polylobular or structureless centre, surrounded by elongated, scarcely branching vessels (crown vesselsRadial serpentine or arborizing vessels at the periphery of the lesion that radiate towards the center but do not cross the midline od the lesion. sebaceous hyperplasia). A similar pattern consisting of central whitish/yellowish structures and crown vessels characterizes sebaceous cysts. The remaining sebaceous tumors are much more difficultneeding much effort or skill to accomplish to recognize. A possible clue is the combinationThis glossary term has not yet been described. of yellowish structures with unfocused arborising vessels.

4.3. Sweat gland tumors. Main false positive diagnosis: BCC, melanoma, SCC

Eccrine poromaThis glossary term has not yet been described. is the most well-studied sweat gland tumor and has been suggested to display a great dermoscopic variability, potentially mimicking all known malignant tumors.

5. NeviThis glossary term has not yet been described.

Overall, nevi and melanoma display significant dermoscopic similarities, since they share similar basic dermoscopic structuresThis glossary term has not yet been described. (pigment networkGrid-like pattern consisting of interconnecting pigmented lines surrounding hypopigmented holes., globules, streakslines radial (always at periphery) streaks Reed nevus melanoma recurrent nevus 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 nevusThis glossary term has not yet been described.) might in fact represent a false negative histopathologic diagnosis. Thus, the histopathologic findings should be always integrated with clinical and dermoscopic morphologyThis glossary term has not yet been described. 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:

5.1. 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”).

5.2. Spitz and Reed nevusThis glossary term has not yet been described.. 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 pseudopodsBulbous and often kinked projections seen at the lesion edge, either directly associated with a network or solid tumor border.. Pigmented Spitz neviThis glossary term has not yet been described. are characterised by the presence of symmetrically distributed globules and white spaces among them (inverse network or reticular depigmentation). Non-pigmentedThis glossary term has not yet been described. 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 streaksThis glossary term has not yet been described., 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 toGives basic instructions and directions to someone on the methods for doing or making something. 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 DermoscopyThe examination of [skin lesions] with a 'dermatoscope'. This traditionally consists of a magnifier (typically x10), a non-polarised light source, a transparent plate and a liquid medium between the instrument and the skin, and allows inspection of skin lesions unobstructed by skin surface reflections. Modern dermatoscopes dispense with the use of liquid medium and instead use polarised light to cancel out skin surface reflections. Society has recently released managementThis glossary term has not yet been described. guidelines (see “ManagementThis glossary term has not yet been described. of Spitz nevi”).

5.3. Combined nevusBenign nevus with 2 different cell population in the same lesion. Most frequently this refers to a junctional nevua in associatoin with a blue 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 nevusis a type of melanocytic nevus that clinically and dermoscopically will appear blue 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.

5.4. 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 skinThis glossary term has not yet been described..

5.5. 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 (pepperingGray dots) regression structuresThis glossary term has not yet been described. 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.