The "Ugly Duckling" Sign: An Early Melanoma Recognition Tool For Clinicians and the Public
Alon Scope, MD
Cutaneous Oncology Fellow
Ashfaq A. Marghoob, MD
Clinical Associate Professor
Memorial Sloan Kettering Cancer Center
New York, NY
The incidence of invasive melanoma (MM) has been rising for several decades;1 currently it is the sixth most common cancer in both males and females.2 The key to preventing deaths due to MM remains detecting the disease early, at a stage when surgical excision of the tumor is still curative. One clinical clue to diagnosis is the "ugly duckling" sign — a useful indicator for MM screening with implications for health care workers and the lay public alike. Given certain limitations of the established ABCDE acronym for early melanoma recognition, we suggest a new, broader way of thinking about the ugly duckling concept and its place in MM detection.
The ABCDEs — What It Can and Can't Do
The ABCD acronym, introduced in 1985 and expanded to ABCDE in 2004, represents an analytical method for the evaluation of melanocytic lesions that clinicians and the general public can utilize to help detect MM early.3 Melanoma often manifests some or all of the ABCDE features, namely asymmetry (A), border irregularity (B), color variability (C), diameter greater than 6 mm (D), and evolution or change (E).4 However, clinicians diagnosing potential skin cancers face the challenge of trying to distinguish MM from many other clinically atypical nevi, which also often display some or all of the ABCDE criteria. In addition, relying solely on the ABCDE approach may result in overlooking MMs that are smaller than 6 mm in diameter or lack the ABCDE criteria.5 The relatively low sensitivity of clinical diagnosis of MM even among dermatologists6 underscores the not inconsequential risk of missing the disease and highlights the need for improved strategies to enhance recognition.
The Advent of the Ugly Duckling Concept
In 1998, Grob, et al7 introduced the ugly duckling concept — the observation that nevi in the same individual tend to resemble one another, and that MM often deviates from this nevus pattern. This clinical realization pointed to the importance of not just evaluating the morphology of the lesion in question, but also comparing it to that of surrounding lesions, looking for an outlier in the background of similar-appearing moles. For example, the outlier lesion can be larger and darker than the surrounding moles (Figure 1A), or conversely, small and red in the background of multiple large dark moles (Figure 1B). Finally, if the patient has few or no other moles (Figure 1C), any changing lesion should be considered a suspicious outlier.
|Three different clinical scenarios are shown where outlier lesions ("ugly ducklings") should prompt suspicion. Squares A, B, and C each represent a body area such as the back. In A, the patient has one dominant mole pattern with slight variation in size. The outlier lesion is clearly darker and larger than all other moles. In B, the patient has two predominant nevus patterns, one with larger nevi and one with small, darker nevi. The outlier lesion is small but lacks pigmentation. In C, the patient shows only one lesion on the back. If this lesion is changing, symptomatic, or deemed atypical, it should be removed.|
The clinician utilizing the ugly duckling sign is engaged in a process called differential recognition. Gachon, et al8 described the three principle mental processes for image recognition: overall pattern recognition, known as gestalt; analytic criteria recognition such as the ABCDEs; and differential recognition — recognizing the differences between objects — i.e., the ugly duckling concept. In their study, Gachon, et al surveyed dermatologists for perception parameters that prompted surgical removal of pigmented lesions. Differential recognition of the ugly duckling sign was more discriminatory between MM and other nevi than the ABCDE criteria.8
The premise underlying the ugly duckling sign is that the patient's "normal" moles resemble each other, like siblings.7 We refer to this premise as "moles breed true." Our team tested this concept on dermoscopic images of nevi. The aim was to investigate whether physicians evaluating dermoscopic images would identify common patterns of nevi within individual patients.9 Images of 205 nevi from 18 patients were evaluated for global dermoscopic pattern. Indeed, 83 percent of patients harbored a dominant global dermoscopic pattern, defined as a pattern occurring in more than 40 percent of their nevi. Most of these patients had 1-2 additional minor patterns, defined as occurring in 20-39 percent of nevi. Thus, in most patients, 80 percent or more of their nevi could be grouped into one, two, or three patterns. Similarly, Hofmann- Wellenhof, et al10 examined 829 nevi on 23 individuals for global dermoscopic pattern. Fifty two percent of the patients displayed a dominant dermoscopic pattern in their nevi.
The Generally Apparent Outlier
However, for the ugly duckling to be a useful screening method, a melanoma would have to be apparent as an outlier, perceived by different observers as distinct from the patient's other moles. To this end, we studied whether the ugly duckling is generally apparent to different observers.11 We showed participants12 clinical overview images of the backs of patients with multiple atypical moles. Five of the images also displayed a MM on the back. The images were evaluated by 34 participants who ranged in expertise from pigmented lesion experts to non-clinical staff members (e.g., research engineers). A generally apparent ugly duckling was defined as a lesion perceived as different by at least two thirds of the participants.
Remarkably, in this virtual setting, all five MMs and only three of 140 other nevi (2.1 percent) were generally apparent as different to the observers. The sensitivity of the ugly duckling sign for MM detection was 0.9 for the whole group of participants, and as high as 0.85 for the non-clinicians. These relatively high sensitivity values for the ugly duckling sign suggest that it should be further assessed in the setting of MM screening by primary health care providers and even for patient self-examination.
For a Broader Interpretation
We propose that broadening the interpretation of the ugly duckling may enhance detection of MM and reduce MM-related mortality. Despite significant public awareness efforts, MM mortality has been increasing in older individuals, particularly elderly males.12 The rise in mortality in elderly men has been attributed to the higher frequency of thicker MM, especially nodular MM.13, 14 Nodular melanoma comprises approximately 20 percent of all MMs, and unlike other subtypes, tends to grow rapidly. Furthermore, it is notorious for lacking the classic ABCDE signs.15 Based on its rapid growth rate and failure to manifest any of the ABCDE analytic criteria, this MM subtype may not be amenable to detection via traditional periodic physician-based screening efforts. Thus, we face the challenge of defining new strategies that both clinicians and the lay public can use to help detect nodular MM.
We suggest thinking of the ugly duckling as the lesion that at a given moment in time looks or feels different than the patient's other moles, or that over time, changes differently than the patient's other moles. Patients may also communicate anxiety about a specific lesion or ill-defined symptoms or sensations related to the lesion; frequently enough, their history on a lesion includes their report that it "feels different." Such patient reports should be taken seriously, and in the absence of clearly reassuring benign features, they should prompt excision or close monitoring.
At times, monitoring lesions using digital photography is a screening strategy for detection of change. Melanoma generally changes at a different rate or with a different pattern than a patient's other moles. This reflects the concept of "E" for evolution that was recently added to the ABCD acronym.4 Patients should be instructed to contact their physician if they notice a rapidly changing ugly duckling; physicians, in turn, should be receptive to see the patient as an acute visit focused on this changing lesion.16, 17 Shorter intervals to biopsy could be important in avoiding a delay in diagnosis of a rapidly growing MM, such as nodular MM, whose growth rate in terms of thickness has been estimated at 0.5 mm per month.15
|Level of Diagnosis||Relevant Signs, Acronyms and Algorithms||Comments|
|Level 1 "Macro" — screening for the outlier lesion||
||Main determinants of sensitivity for melanoma detection|
|Level 2 "Micro" — individual lesion assessment||
||Main determinants of specificity for melanoma detection|
|Level 3 — Biopsy|
How does the ugly duckling sign fit into the overall scheme of early MM detection? The clinical approach to pigmented lesions is presented in the Table. In patients with numerous moles, we screen to identify suspicious lesions by using three variations of the ugly duckling concept: 1) by inquiring about changing or symptomatic lesions, 2) by comparing lesions to baseline images, and 3) by detecting outliers in the background pattern of the patient's moles. Once a suspicious lesion is identified, we focus on it through clinical observation, magnification, and /or dermoscopy, and if its pattern is benign, we move on. If the overall pattern fits the gestalt of a clear-cut MM (e.g., satisfies the ABCDE criteria), we opt for removal. If the pattern cannot be easily categorized into either, we may use analytical criteria (e.g., inspect the lesion in detail to see whether there are any suspicious dermoscopic structures). Depending on what is found, we may then decide to remove the lesion for definitive diagnosis or perform short-term mole monitoring to assess its biological nature.
By broadening the definition of what constitutes an "ugly duckling" and teaching this to clinicians and the lay public, we may have a new, more complete message to convey to achieve early MM detection, namely, "If you spot an ugly duckling (outlier) lesion or a lesion manifesting the ABCDEs, see a dermatologist without delay."
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