Opinions Received: December 12, 2012 Accepted after revision: December 18, 2012 Published online: March 12, 2013
Dermatology DOI: 10.1159/000346645
Management Rules to Detect Melanoma Aimilios Lallas a Iris Zalaudek a, d Zoe Apalla e Caterina Longo a Elvira Moscarella a Simonetta Piana b Camilla Reggiani c Giuseppe Argenziano a a
Dermatology and Skin Cancer Unit and b Pathology Unit, Arcispedale Santa Maria Nuova IRCCS, Reggio Emilia, and Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy; d Department of Dermatology, Medical University of Graz, Graz, Austria; e State Clinic of Dermatology, Hospital of Skin and Venereal Diseases, Thessaloniki, Greece c
Key Words Dermoscopy · Dermatoscopy · Melanoma · Nevi · Diagnosis · Management
Abstract Most melanomas are easy to be diagnosed clinically and dermoscopically. The question remains open concerning the correct strategies to detect those melanomas that look morphologically inconspicuous from a clinical and/or dermoscopic point of view. In our estimation, when morphology is not enough to recognize melanoma, one has to use specific management strategies. Herein we summarize the following 7 simple and practical rules that outline the need for a more general approach integrating clinical information with dermoscopic examination: (1) Look basically at all lesions. (2) Undress high-risk patients. (3) Use the 10 seconds rule in single lesions. (4) Compare and monitor multiple moles. (5) Excise doubtful nodular lesions. (6) Combine clinical and dermoscopic criteria. (7) Combine clinical and histopathologic criteria. Copyright © 2013 S. Karger AG, Basel
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Introduction
In daily practice, the most important goal for a clinician is to identify and treat sick patients while saving healthy individuals from unnecessary procedures. Within the field of skin cancer screening, this translates for a clinician as being able to detect all possible melanomas while minimizing the unnecessary excisions of benign lesions. The number needed to excise is a commonly used measure to rate the ability of clinicians in reaching this aim. Reported values achieved by general physicians range from 20 to 40 benign lesions excised to detect one melanoma and from 5 to 15 in the context of dermatologists and more experienced clinicians [1–5]. These number needed to excise rates underline the fact that a certain proportion of benign lesions should be excised even in the hands of experts because they closely resemble melanoma from a clinical and dermoscopic point of view. However, these rates also emphasize that the expertise of a clinician dealing with melanoma screening could be better measured by the number of ignored benign lesions rather than the number of melanomas correctly diagnosed. Giuseppe Argenziano, MD Dermatology and Skin Cancer Unit Arcispedale Santa Maria Nuova Viale Risorgimento 80, IT–42100 Reggio Emilia (Italy) E-Mail g.argenziano @ gmail.com
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Fig. 1. a A clinically banal, small-sized,
symmetric and heavily pigmented lesion on the forearm of a 52-year-old man. b Dermoscopy revealed clear-cut melanoma criteria, i.e. blue-white veil and irregular peripheral streaks. The lesion was excised and histopathologically diagnosed as melanoma in situ. c A 72-year-old man with multiple pigmented lesions on the back. d Dermoscopic view of the melanoma found on his back (arrow in c) after examining a good proportion of the lesions.
As a matter of fact, most melanomas are easy to be diagnosed clinically using the ABCD morphologic criteria and, dermoscopically, using pattern analysis or one of the simplified scoring systems [6–9]. The question remains open concerning the correct strategies to detect those melanomas that look morphologically inconspicuous from a clinical and/or dermoscopic point of view. In our estimation, when morphology is not enough to recognize melanoma, one has to use specific management strategies. In a previous report we described some special dermoscopic clues that may help not to overlook melanoma incognito [10]. Here we summarize 7 simple and practical rules that are not only based on dermoscopic examination but outline the need for a more general approach integrating clinical information with dermoscopic examination.
1. Look Basically at All Lesions
In addition to the well-documented value of dermoscopy in the evaluation of clinically suspicious lesions, the use of this technique helps also uncover clinically occult melanomas [10]. This implies a significant modification in the attitude of clinicians about the use of dermoscopy. If the latter is applied only in clinically worrisome lesions, clinically unsuspicious melanomas, by definition, will be 2
Dermatology DOI: 10.1159/000346645
excluded by the selection. In other words, a clinically benign-looking melanoma will never be uncovered by dermoscopy if not examined with this technique. This is especially relevant for early melanomas like the one presented in figure 1a, whose small size and clinical characteristics do not allow raising any suspicion for malignancy. Dermoscopy of this lesion (fig. 1b) revealed clearcut melanoma features, namely blue-white veil and peripheral irregular streaks, enabling the detection of a melanoma that could be easily clinically overlooked. This example highlights the fact that dermoscopic criteria of melanoma usually become apparent earlier than the clinical ABCD criteria. The rule of examining all lesions is also important in the context of patients with multiple nevi, in which melanoma may be masqueraded among the many benign moles of the patient. Although melanoma in patients like the one presented in figure 1c may be perfectly hidden among the plethora of atypical nevi, the use of dermoscopy for the majority of lesions allowed the recognition of the suspicious one (fig. 1d). Opponents of the method argue that examining dermoscopically all lesions would be time-consuming, but it has been shown that, with experience, dermoscopic examination adds very little extra time (2 min), especially if a polarized-light handheld instrument is used [11].
Lallas /Zalaudek /Apalla /Longo / Moscarella /Piana /Reggiani /Argenziano
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Fig. 2. a A 65-year-old man presenting for
evaluation of a dome-shaped nodular lesion on the right temple. b Dermoscopy confirmed the clinical suspicion of basal cell carcinoma and the tumor was accordingly excised. The patient was dismissed without performing full body examination of the skin and, one and a half year later, he returned for evaluation of a lesion on the pubic area. Clinical (c) and dermoscopic (d) diagnosis of melanoma was straightforward and histopathologic examination revealed a melanoma with a Breslow thickness of 8 mm.
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2. Undress High-Risk Patients
While a certain proportion of melanomas are detected by the patients themselves, the rest remains to be identified by the clinician. Given that the majority of melanomas arise on covered areas, total body skin examination has been recommended as a method to facilitate early detection [12, 13]. In a previous study assessing the risk of missing a skin cancer if total body skin examination was not performed, several patient factors were found to be significantly associated with this risk [14]. Among them, older age was per se associated to an increased risk. Overall, it has been calculated that 400 patients need to be examined to detect one melanoma but only about 200 patients in the group aged 60 years or more. Other associated factors included a previous non-melanoma skin cancer, a fair skin type, and the presence of an equivocal lesion on problem/uncovered areas. In younger individuals, the presence of multiple (>50) melanocytic nevi is considered one of the strongest risk factors for melanoma. Rather than performing a full nevus count, a partial nevus count can be done as a quick and convenient alternative. The latter involves the arms only and is considered high if there are 20 or more nevi present. Thus, total body skin examination should be offered at least to the following higher-risk groups: (i) patients with a personal history of any skin malignancy or a family hisManagement Rules to Detect Melanoma
tory of melanoma (in first-degree relatives), (ii) patients under the age of 50 years who present with more than 20 nevi on the arms, and (iii) patients over the age of 50 years who present with evidence of chronic solar damage. Application of this rule could help avoid undesirable and dangerous delays in melanoma detection, like the one shown in figure 2.
3. Use the 10 Seconds Rule in Single Lesions
With experience, dermoscopic diagnosis of benign and malignant skin tumors requires usually only a few seconds. This is because the vast majority of skin neoplasias exhibit repetitive morphologic characteristics which, if seen enough times previously, are easily recalled and recognized. Of course, as any other imaging technique, dermoscopy requires training, but as soon as the basic knowledge is acquired and with gathering experience, recognition of one of the stereotypical patterns is usually straightforward. While this is true for the majority of cases, a small proportion of moles exhibit a dermoscopic pattern not typical enough to allow a definite diagnosis of a benign or malignant tumor with certainty. This results in a diagnostic dilemma, which is expressed by the prolonged time of dermoscopic examination. These lesions are regarded to be positive to the 10 seconds rule, which Dermatology DOI: 10.1159/000346645
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basically is a rough indication of the time needed to reach a reliable conclusion and thus the threshold of diagnostic uncertainty. A characteristic example is presented in figure 3a, in which a confident diagnosis cannot be established due to the absence of any specific criteria. Clinicians may choose managing such lesions using a short-term digital monitoring approach. This is a reasonable choice, since the occurrence of changes over time represents an additional criterion to diagnose melanomas undetectable at baseline examination. However, in our estimation, in the context of solitary lesions positive to the 10 seconds rule, the threshold for biopsy should be low enough to maximize early excision of possible melanomas. Dermoscopic criteria of melanoma have been established by studies including clear-cut melanomas and, typically, such melanoma-specific criteria are found in advanced tumors that are already suspicious from a clinical point of view [7–9]. Dermoscopy of such melanomas usually allows a confident preoperative diagnosis, since many specific features are present, forming the so-called multicomponent pattern. However, if the goal is to reach a correct diagnosis at an earlier stage, we should expect to find a certain proportion of melanomas that do not fulfil all the classic criteria. This was highlighted in a recent study describing eight novel dermoscopic patterns of in situ melanoma. The authors postulated that the 4
Dermatology DOI: 10.1159/000346645
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Fig. 3. Examples of 10-seconds-positive melanomas which did not yet exhibit fully developed criteria to establish a straightforward diagnosis. When dermoscopy of a single lesion reveals unspecific pattern (a), clear-cut atypical network (b), extensive regression (c) or peripheral streaks (d), the lesion should be excised.
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Fig. 4. The management of patients with multiple nevi requires a
comparative examination of nevi and sequential digital monitoring.
morphologic diversity might reflect a variability in origin or biologic behavior of the tumor [15]. Some of the traditional algorithms have been accordingly modified to a lower threshold for excision of lesions showing only one of the classic criteria that, if prominent, may be judged enough to warrant excision [16]. Atypical netLallas /Zalaudek /Apalla /Longo / Moscarella /Piana /Reggiani /Argenziano
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Fig. 5. Most nevi of the patient shown in figure 4 showed variable degrees of atypical features. Thus, the main point is to find the lesion exhibiting different characteristics (arrow) from the predominant pattern of the patient’s nevi.
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work (fig. 3b) and extensive regression (fig. 3c) are the most common single criteria warranting excision. In addition, since melanomas with a pattern of peripheral streaks mimicking a Spitz nevus have been described (fig. 3d) [17], a solitary lesion characterized by this clue should be excised as well.
4. Compare and Monitor Multiple Moles
While the 10 seconds rule applies for melanoma detection in patients with solitary or few lesions, its use in the context of a patient with the so-called ‘atypical mole syndrome’ would result in unnecessary excision of many benign lesions. This is because it is well known that a significant proportion of these nevi in a given patient will show some degree of dermoscopic irregular features (fig. 4, 5). This subgroup of patients requires a special management procedure, which can be summarized in the ‘compare and monitor’ rule. Comparing refers to the observation that the majority of a given individual’s nevi exhibit a similar dermoscopic pattern, while melanoma reveals different features [18]. In other words, to detect melanoma in this context, a clinician should rather look for the morphologically ‘different’ lesion than for the ‘most atypical’ one (fig. 5). This strategy, in addition to facilitating melanoma detection, results also in decreasManagement Rules to Detect Melanoma
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Fig. 6. Even if the melanoma in situ arrowed in figure 5 escaped detection at the baseline visit (a), it would be easier to recognize after 3 months of follow-up (b) because of the presence of clear-cut
changes on side-by-side image analysis.
ing the rate of unnecessary excision of benign lesions [19, 20]. However, even with application of the comparative approach, some melanomas might still be missed and can only be diagnosed efficiently by monitoring dermoscopic changes over time (fig. 6) [21, 22]. Dermatology DOI: 10.1159/000346645
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Fig. 7. Clinical (a) and dermoscopic (b) ex-
amination of this nodular lesion allows the diagnosis of cherry angioma with great confidence. In contrast, the nodule shown in c and d is more difficult to interpret. Clinically, the differential diagnosis included irritated seborrheic keratosis, traumatized dermal nevus and pyogenic granuloma, but the lesion was excised because dermoscopically the features were not typical enough to allow a final reliable diagnosis. Subsequent histopathologic examination revealed a nodular melanoma with a thickness of 3.2 mm.
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Lesions exhibiting morphologic changes at short-term follow-up (3 months) have an 11% probability to be early melanomas and, accordingly, should be excised [23]. Conversely, long-term follow-up is especially profitable for the detection of slow-growing melanomas, which may change very slowly over a longer period of time [24]. In these melanomas relevant changes usually appear after 12–24 months of follow-up. Thus, in patient with multiple atypical nevi, the first re-examination should be scheduled at 3 months, while prolonged annual monitoring should be performed to avoid missing indolent, slowgrowing melanomas.
5. Excise Doubtful Nodular Lesions
Missing nodular melanoma represents the worst nightmare. Clinically, nodular melanoma usually lacks the classic ABCD criteria and may mimic benign tumors, including dermal nevi, vascular tumors, dermatofibromas or seborrheic keratosis [25]. Dermoscopically, the classic criteria of melanoma may also be missing, since most of them have been described in the context of superficial spreading melanoma, corresponding to melanin in the epidermis or at the dermo-epidermal junction [6–9]. The addition of the blue-black rule, namely the presence of blue and black color within the lesion, has been shown 6
Dermatology DOI: 10.1159/000346645
to enhance discrimination of nodular melanoma from benign nodular tumors [26]. Milky-red areas and polymorphous vascular pattern have been described to characterize nodular melanomas lacking significant pigmentation [27, 28]. Accordingly, nodular tumors positive to the blue-black rule or exhibiting milky-red areas and/or polymorphous vascular pattern should undoubtedly be excised. In our estimation, even with the addition of these rules some nodular melanomas may still be overlooked. Our suggestion is thus very straightforward: when evaluating a nodular tumor, a clinician should rather look for the presence of criteria of benign lesions, and when a safe diagnosis of a benign tumor is not feasible, then the lesion should be excised, while follow-up is strongly discouraged (fig. 7).
6. Combine Clinical and Dermoscopic Criteria
The dermoscope represents a clinical tool and dermoscopic characteristics should be always interpreted within the context of the clinical examination. For example, the lesion shown in figure 8, a recently appearing, solitary and growing lesion on the leg of a 50-year-old woman, is characterized by a relatively innocent dermoscopic pattern. The clinical presentation and the lesion’s history indeed Lallas /Zalaudek /Apalla /Longo / Moscarella /Piana /Reggiani /Argenziano
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Fig. 8. This melanoma in situ is characterized by a relatively innocent dermoscopic pattern (a), but it represents a recently appearing, solitary and growing lesion on the leg of a 50-year-old woman (b). The clinical presentation and the lesion’s history are strong enough to warrant excision.
Fig. 9. This extensively regressed melanocytic lesion (a, b) was initially interpreted as a nevus on histopathologic examination (c, d). After re-evaluation in the light of combined clinical, dermoscopic and histopathologic information, a final diagnosis of melanoma in situ was established.
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contradict the dermoscopic features of a benign-looking lesion, and this contrast should prompt a biopsy. As a rule, benign lesions are characterized by a certain harmony between clinical characteristics and dermoscopic features, with dermoscopic examination revealing, more or less, expected findings. Lesions lacking this kind of correlation should be carefully managed, and when the clinical scenario is strongly suspicious, the lesion should be eventually excised even in the absence of clear-cut melanoma-specific dermoscopic criteria. Management Rules to Detect Melanoma
7. Combine Clinical and Histopathologic Criteria
While histopathologic examination is the gold standard for diagnosing melanocytic lesions, similarly to any other diagnostic method, it is not free of limitations, technique failures, and subjective misinterpretation. Spitzoid tumors represent a characteristic example of the diagnostic limitations of histopathology, underlining that the final diagnosis requires a careful evaluation of combined clinical, dermoscopic and histopathologic information Dermatology DOI: 10.1159/000346645
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[29]. Similarly, lesions exhibiting a high degree of regression features may be difficult to interpret histopathologically (fig. 9) [30]. Another field of discrepancies between clinico-dermoscopic and histopathologic interpretation is nevus-associated melanoma, in which the histopathologic diagnosis of melanoma can be missed if the specimen is evaluated in a non-representative area. Apart from technical issues, one should consider that a clinically and dermoscopically difficult lesion is very likely to be equivocal also histopathologically, especially if the pathologist is not provided with relevant clinical information. As a rule, histopathologic reports should be interpreted in the context of the clinical information, and the diagnosis of lesions lacking a satisfactory clinico-histopathologic correlation should be managed with caution.
Conclusion
Rather than considering dermoscopy as a second-level diagnostic procedure, clinicians should integrate this tool with all relevant information raised by the whole clinical examination. The suggested seven management rules might be helpful in narrowing the gray diagnostic zones and in enhancing the detection of melanomas that do not fulfil the standard morphologic criteria.
Disclosure Statement The authors have no conflicts of interest to declare.
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