Clinics in Dermatology (2014) 32, 94–100
Diagnosis and management of facial pigmented macules Aimilios Lallas, MD a , Giuseppe Argenziano, MD a , Elvira Moscarella, MD a , Caterina Longo, MD a , Vito Simonetti, MD a , Iris Zalaudek, MD a,b,⁎ a
Skin Cancer Unit, Arcispedale Santa Maria Nuova, Istituto di Ricovero e Cura a Carattere Scientifico, Viale Risorgimento 80, 42100 Reggio Emilia, Italy b Department of Dermatology, Medical University of Graz, Auenbruggerplatz 8, 8036 Graz, Austria
Abstract The differential diagnosis of pigmented macules on the mottled chronic sun-damaged skin of the face is challenging and includes lentigo maligna (LM), pigmented actinic (solar) keratosis, solar lentigo, and lichen-planus-like keratosis. Although dermatoscopy improves the diagnostic accuracy of the unaided eye, the accurate diagnosis and management of pigmented facial macules remains one of the most challenging scenarios in daily practice. This is related to the fact that pigmented actinic (solar) keratosis, lichen-planus-like keratosis, and LM may reveal overlapping criteria, making their differential diagnosis clinically difficult. For this reason, practical rules have been introduced, which should help to minimize the risk for inappropriate diagnosis and management of LM. © 2014 Published by Elsevier Inc.
Introduction
Clinical features of facial pigmented macules
The differential diagnosis of pigmented macules on the mottled chronic sun-damaged skin of the face is challenging and includes lentigo maligna (LM), pigmented actinic (solar) keratosis (PAK), solar lentigo (SL), and lichenplanus-like keratosis (LPLK).1,2 Given that the natural course and prognosis vary significantly among these different entities, accurate diagnosis is mandatory to ensure appropriate management. Dermatoscopy improves the diagnostic accuracy compared with the unaided eye and accordingly, dermatoscopy became an integral part of the clinical examination of skin tumors3; however, the accurate diagnosis and management of pigmented macules on the face remains one of the most challenging scenarios in daily practice, even if coupled with dermatoscopy.4
LM, SL, seborrheic keratosis (SK), LPLK, and PAK are common facial lesions that typically develop after the fourth decade of life. 1,2,5,6 They share the clinical appearance of a flat, pigmented macule of different size and color. Accordingly, neither age nor clinical criteria appear useful for differentiating between these entities; however, there are some clinical differences between LM and the other nonmelanocytic skin lesions that should be considered in the differential diagnosis. First, LM and PAK reveal significant sex-related differences. Whereas PAK occurs at higher frequency in men, LM has a certain predilection for women7,8; thus, sex should be always considered in the differential diagnosis of pigmented macules on the face. Second, whereas PAK typically reveals a scaly and rough surface, LM appears smooth on palpation.1,2 Accordingly, palpation of a given facial lesion represents an important part of the clinical examination. Finally, LM develops more commonly as solitary or different-looking lesion compared with SL and PAK, which
⁎ Corresponding author. Tel.: +43 676 33 282 69; fax: +39 069 762 5822. E-mail address: [email protected] (I. Zalaudek). 0738-081X/$ – see front matter © 2014 Published by Elsevier Inc. http://dx.doi.org/10.1016/j.clindermatol.2013.05.030
Pigmented facial macules typically present as multiple spots with a similar appearance.1,2,9 Accordingly, a solitary lesion appears to be more suggestive of LM, whereas multiple similar lesions favor somewhat the diagnosis of SL or PAK.
Dermatoscopic patterns of facial pigmented macules The dermatoscopic aspects of facial melanocytic lesions differ from the ones described for other locations (Figure 1). A pigment network representing the dermatoscopic hallmark of melanocytic tumors on the torso and extremities is only rarely detected in facial melanocytic skin tumors.9 This is reasonable, because pigment network results from epidermal melanin (either in melanocytes or keratinocytes) along elongated rete ridges, whereby the tips of the rete ridges appear as network holes and the lateral borders as network lines.10 Instead, the dermoepidermal junction of chronically sundamaged facial skin appears flattened and may even lack rete ridges. Pigmented keratinocytes or melanocytes along this flattened dermoepidermal junction appear as structureless diffuse brown pigmentation on dermatoscopy; however, this otherwise structureless diffuse brown pigmentation on the face is interrupted by numerous, variable broad and hypopigmented “holes,” which correspond to hair follicles and sweat gland openings. Because the combination of diffuse brown pigmentation and nonpigmented adnexal openings is reminiscent of a kind of network, the pattern of
95 facial melanocytic and nonmelanocytic pigmented macules is also called a “pseudonetwork” pattern.9,11 It is important to emphasize that the pseudonetwork pattern occurs likewise in melanocytic and nonmelanocytic lesions.11,12 Accordingly, the diagnosis of a given pigmented facial macule relies on the detection of additional specific criteria. The specific dermatoscopic criteria of melanocytic and nonmelanocytic skin lesions are summarized in Table 1.
A dermatoscopic model in the progression of LM A 2000 study proposed based on dermatoscopic criteria a four-step model in the progression of LM.13 According to this model, asymmetric pigmented follicular openings (also called gray circles), gray dots within the follicular opening or so-called circles within circles, represent the very initial criteria in the development of LM. These structures subsequently develop into a so-called annular-granular pattern, which consists of aggregated fine gray dots, gray globules, and streaks around the follicle. With further progression, these streaks become longer and intersect with neighboring streaks, forming finally rhomboidal structures (ie, angulated lines between hair follicles). Finally, beginning invasion is characterized by the development of obliterated hair follicles (filled with black or blue-gray blotches) and structureless blue areas, white scarlike areas, and milky-red areas (Figure 2).
Fig. 1 Dermatoscopic-histopathologic correlates of pigment network (left upper and lower images) and facial pseudonetwork (right upper and lower image). True pigment network correlates with pigmentation along elongated rete ridges, whereas pseudonetwork results from a structureless brown pigmentation, which is intermingled by nonpigmented follicular openings. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this contribution.)
96 Table 1
A. Lallas et al. Dermatoscopic criteria of flat facial lesions
Lentigo maligna
Pigmented actinic keratosis
Solar lentigo/early seborrheic keratosis
Lichen-planus-like keratosis
Pseudonetwork
Pseudonetwork
Pseudonetwork
Asymmetric pigmented follicular openings Slate gray dots
Slate-gray dots
Light brown fingerprint areas Yellow opaque areas
Brownish gray granules localized or diffuse Bluish gray granules localized or diffuse Whitish gray granules localized or diffuse Any other criterion of SK or SL
Slate gray globules Rhomboidal structures Annular-granular pattern Gray brown streaks Dark/blue homogenous areas White scarlike areas Milky red areas Increased density of the vascular network Red rhomboidal structures Targetlike patterns Darkening at dermatoscopic examination Circle within a circle Zigzag pattern
Annular-granular pattern Rhomboidal structures Black globules Slate-gray globules Black dots Asymmetric pigmented follicular openings Circle within a circle Slate-gray areas Gray-brown streaks
Horny pseudocysts Milialike cysts Cerebriform structures Moth-eaten border Sharp demarcation Jelly sign Hairpin vessels Asymmetric pigmented follicular openings
Broken pseudonetwork Keratin plugs
It appears remarkable that according to this model, the earliest signs of LM development are related to predominant follicular involvement and not to the interfollicular epidermis. This observation has led some to question whether LM arises from cancer stem cells of the hair bulge rather than from transformed epidermal melanocytes.14
Dermatoscopic differential diagnosis of facial pigmented macules Reasonably, if a lesion exhibits fully developed clinical and/or specific dermatoscopic criteria, a straightforward diagnosis is feasible in most cases.
Fig. 2 Dermatoscopic patterns of lentigo maligna. Panel A, Gray dots within the hair follicle (arrows); panel B asymmetric pigmented hair follicles and gray circles within a circle (arrows); panel C rhomboidal structures appearing as gray lines (arrows) forming a rhomboid; and panel D annular-granular structures (arrows) and obliterated hair follicles appearing as gray-blue structureless blotches (circle). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this contribution.)
Pigmented facial macules LM, PAK, and LPLK may show at times overlapping features (Table 1); for these equivocal cases, the clinically relevant question is whether dermatoscopy aids the correct management. With regard to this question, it must be admitted that appropriately designed diagnostic accuracy studies are lacking, although preliminary data suggest a profitable role of dermatoscopy in differentiating LM from other nonmelanocytic macules.
Criteria of LM versus SL and SK Comparison of criteria between LM, SK, and SL allowed the identification of a set of four criteria that allowed prediction of diagnosis of LM with a sensitivity of 89% and a specificity of 96%.13 These criteria are asymmetric pigmented follicular openings, dark rhomboidal structures, slate-gray globules, and slate-gray dots. Although each single criterion may be seen also in SK or SL, the presence of all four features is strongly suggestive of LM. In contrast, light brown fingerprint areas, yellow opaque areas, milia cysts, moth-eaten border, and sharp demarcation (jelly sign) have been significantly associated with the diagnosis of SK or SL.13,15–17 More recently, elongated brown circles (fat fingers) have been added as criteria of early SK18 (Figure 3).
97
Criteria of LM versus LPLK LPLK is a term referring to an SL or SK undergoing regression.6 The discrimination between LPLK and LM is problematic and can be basically made only if areas of the preexisting benign lesion (SK or SL) are still preserved.19 Instead, fully or nearly fully regressed LPLK is characterized by diffuse brownish gray granules, which may coalescence to form globules, streaks, or even structures similar to rhomboids.19 Because LM may exhibit the same features, a biopsy of a lesion dermatoscopically characterized by signs of evident regression (ie, localized or diffuse gray granules) should always be performed (Figure 4).
Criteria of PAK versus LM A recent comparative study confirmed previous observations suggesting that LM and PAK exhibit strikingly similar patterns on dermatoscopy.20 Effectively, any of the established criteria of LM can be also seen in PAK, although black blotches within the follicular opening as seen in the late stage of melanoma progression occur at higher frequency in LM than PAK.20 Conversely, keratin plugs and a broken-up, superficial brown pseudonetwork is more suggestive of PAK.4,21 In doubtful cases, histopathology is required to differentiate between LM and PAK; however, the
Fig. 3 Dermatoscopic patterns of solar lentigo (SL) and early seborrheic keratosis (SK). Panel A, Fingerprintlike structures appearing as wavy parallel brown lines. Panel B, Sharp demarcation with convex and concave ends (moth-eaten borders). Panel C, SK developing from SL: Although the central fully developed SK reveals classic criteria of SK such as multiple milia cysts and comedo openings, the peripheral flat part of SL reveals fingerprintlike structures. Panel D, Light brown elongated circles reminiscent of “fat” fingers (arrows). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this contribution.)
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Fig. 4 Side-by-side comparison between lentigo maligna (LM) (panel A) and lichen-planus-like keratosis (panel B) showing overlapping features of gray dots. Side-by-side comparison between LM (panel C) and pigmented actinic (solar) keratosis (panel D) showing rhomboidal structures. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this contribution.)
discrimination between the two entities may be even histopathologically difficult, when it is not clear whether the pigmented atypical cells in the basal layer are keratinocytes or melanocytes1,2 (Figure 4).
practical rules may help to minimize the risk for inappropriate diagnosis and management.
Importance of gray color Practical rules and clues for the diagnosis and management of facial pigmented macules Although dermatoscopy provides valuable additional morphologic information, the differential diagnosis of flat pigmented macules on the face remains a challenge. Three
The single most important criterion in the differential diagnosis of LM from SL and SK is related to the presence versus absence of gray color, respectively (Figure 5). This can be explained by the different histopathologic correlates of colors in dermatoscopy. Melanin located in the stratum corneum, at the dermoepidermal junction, upper dermis, and
Fig. 5 Gray color is the single best criterion in the differential diagnosis of solar lentigo and seborrheic keratosis from lentigo maligna. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this contribution.)
Pigmented facial macules deep dermis gives rise to black, brown, gray, and blue, respectively.22,23 That SL and SK contain melanin exclusively at the epidermal level (ie, pigmented keratinocytes) explains why these lesions display only brown color on dermatoscopy.24 Instead, free or intracellular melanin in the upper dermis or intrafollicular melanin give rise to gray structures such as gray dots, globules, lines, or circles as typically seen in LM.13 Dermal melanin and its correlated gray dermatoscopic color are also seen in PAK and LPLK.19,20 Gray color is therefore insufficient to differentiate among LM, LPLK, and PAK.
Importance of correlating clinical, dermatoscopic, and histopathologic findings Dermatoscopic and histopathologic findings should always be combined with clinical information and interpreted within the clinical context of the patient. For instance, a different management approach should be applied in patients with a solitary lesion compared with patients with multiple lesions. More specifically, the presence of multiple lesions favors the diagnoses of PAK, SK, or SL, whereas development of multiple LMs is exceedingly rare.1,2,5 The comparative approach (ie, examination of all lesions) can be of further help in the management of patients with multiple facial spots because it allows the identification of similar patterns among all lesions (ie, signature pattern of PAK or SL). On the contrary, the threshold for biopsy should be lowered if examining a solitary lesion that cannot be confidently diagnosed as PAK, SK, or SL. Histopathology is regarded as gold standard in the diagnosis of clinically equivocal melanocytic and nonmelanocytic skin tumors, but it must be emphasized that it is not
99 free of limitations. The diagnosis of facial lesions in particular may be challenging because LM can escape the histopathologic diagnosis, if the biopsy has been performed in a nonrepresentative area.25 Dermatoscopy can improve the selection of representative areas to undergo biopsy; in detail, biopsy should be performed in areas showing the most suggestive features of LM (Figure 6).13 Early LM may display unremarkable features on histopathology.26 This carries a certain risk for underdiagnosis of melanoma as a junctional nevus. Clinicians should always pay particular attention if confronted with a given histopathologic diagnosis of a “junctional nevus” on the face of an elderly patient and critically review such diagnosis in the context of the patient (considering the history, age, sex, location, and clinical or dermatoscopic features of the lesion).
Never perform ablative treatment of equivocal lesions Although LM, PAK, SL, SK, and LPLK share several similar clinical, dermatoscopic, and histopathologic characteristics, they require a quite different management approach. Surgical excision is undoubtedly the treatment of choice for LM.27 Instead, nonablative modalities such as cryotherapy or laser therapy are reasonable options in the treatment of PAK or cosmetically disturbing SK, SL, and LPLK.28 Although radiotherapy, cryotherapy, and laser therapy represent alternative treatment options for LM in selected cases when surgical approach is not feasible, these options are problematic for two reasons: First, these options have been associated with a high risk for recurrence.29 Second, there are cases reporting a rapid progression of slow-growing LM to invasive, biologically aggressive nodular melanoma after cryotherapy. This suggests a possible influence of minimally invasive surgical procedures on the biological behavior of melanoma. Consequently, nonsurgical treatment modalities should be persevered for unequivocal cases that can be diagnosed as surely benign. Any doubtful lesion should undergo biopsy or at least regularly followed up using sequential digital dermatoscopic monitoring; destructive modalities should be avoided in the management of equivocal facial lesions.30–32
References
Fig. 6 Dermatoscopy helps the selection of the most representative area to undergo biopsy. In the case shown, the biopsy was made from the area showing gray asymmetric pigmented hair follicles (circle) and reveals melanoma in situ. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this contribution.)
1. Cohen LM. Lentigo maligna and lentigo maligna melanoma. J Am Acad Dermatol. 1995;33:923-936. 2. Uhlenhake EE, Sangueza OP, Lee AD, et al. Spreading pigmented actinic keratosis: A review. J Am Acad Dermatol. 2010;63:499-506. 3. Argenziano G, Soyer HP, Chimenti S, et al. Dermoscopy of pigmented skin lesions: Results of a consensus meeting via the internet. J Am Acad Dermatol. 2003;48:679-693. 4. Zalaudek I, Ferrara G, Leinweber B, et al. Pitfalls in the clinical and dermatoscopic diagnosis of pigmented actinic keratosis. J Am Acad Dermatol. 2005;53:1071-1074.
100 5. Mehregan AH. Lentigo senilis and its evolution. J Invest Dermatol. 1975;65:429-433. 6. Jang KA, Kim SH, Choi JH, et al. Lichenoid keratosis: A clinicopathologic study of 17 patients. J Am Acad Dermatol. 2000;43:511-516. 7. Memon AA, Tomenson JA, Bothwell J, et al. Prevalence of solar damage and actinic keratosis in a Merseyside population. Br J Dermatol. 2000;142:1154-1159. 8. Cohen LM, McCall MW, Hodge SJ, et al. Successful treatment of lentigo maligna and lentigo maligna melanoma with Mohs micrographic surgery aided by rush permanent sections. Cancer. 1994;73: 2964-2970. 9. Stolz W, Schiffner R, Burgdorf WH. Dermatoscopy for facial pigmented skin lesions. Clin Dermatol. 2002;20:276-278. 10. Braun RP, Rabinovitz HS, Oliviero M, et al. Dermoscopy of pigmented skin lesions. J Am Acad Dermatol. 2005;52:109-121. 11. Argenziano G, Soyer HP, De Giorgi V, et al. Dermoscopy: An Interactive Atlas. Milan, Italy: EDRA. 2000. 12. Johr RH, Stolz W. Lentigo maligna and lentigo maligna melanoma. J Am Acad Dermatol. 1997;37:512. 13. Schiffner R, Schiffner-Rohe J, Vogt T, et al. Improvement of early recognition of lentigo maligna using dermatoscopy. J Am Acad Dermatol. 2000;42:25-32. 14. Zalaudek I, Marghoob AA, Scope A, et al. Three roots of melanoma. Arch Dermatol. 2008;144:1375-1379. 15. Stante M, De Giorgi V, Stanganelli I, et al. Dermoscopy for early detection of facial lentigo maligna. Br J Dermatol. 2005; 152:361-364. 16. Sahin MT, Ozturkcan S, Ermertcan AT, et al. A comparison of dermatoscopic features among lentigo senilis/initial seborrheic keratosis, seborrheic keratosis, lentigo maligna and lentigo maligna melanoma on the face. J Dermatol. 2004;31:884-889. 17. Tanaka M, Sawada M, Kobayashi K. Key points in dermatoscopic differentiation between lentigo maligna and solar lentigo. J Dermatol. 2011;38:53-58. 18. Kopf AW, Rabinovitz H, Marghoob A, et al. “Fat fingers”: A clue in the dermatoscopic diagnosis of seborrheic keratoses. J Am Acad Dermatol. 2006;55:1089-1091. 19. Zaballos P, Marti E, Cuellar F, et al. Dermoscopy of lichenoid regressing seborrheic keratosis. Arch Dermatol. 2006;142:410.
A. Lallas et al. 20. Akay BN, Kocyigit P, Heper AO, et al. Dermatoscopy of flat pigmented facial lesions: Diagnostic challenge between pigmented actinic keratosis and lentigo maligna. Br J Dermatol. 2010;163:1212-1217. 21. Peris K, Micantonio T, Piccolo D, et al. Dermatoscopic features of actinic keratosis. J Dtsch Dermatol Ges. 2007;5:970-976. 22. Weismann K, Lorentzen HF. Dermatoscopic color perspective. Arch Dermatol. 2006;142:1250. 23. Rosendahl C, Cameron A, Tschandl P, et al. The cause of dermatoscopic grey circles in non-invasive melanomas: An hypothesis supported by histopathological correlation. Poster presented at: 2nd Congress of the International Dermoscopy Society; November 12–14, 2009; Barcelona, Spain. Available from: http://www.greycircles. blogspot.com. Accessed September 28, 2010. 24. Braun RP, Rabinowitz H, Oliviero M, et al. Dermatoscopy of pigmented lesions. Ann Dermatol Venereol. 2002;129:187-202. 25. Larsen TE, Grude TH. A retrospective histological study of 669 cases of primary cutaneous malignant melanoma in clinical stage I. Acta Pathol Microbiol Scand. 1979;87:255-260. 26. Larsen TE, Little JH, Grell SR, et al. International pathologists congruence survey on quantitation of malignant melanoma. Pathology. 1980;12:245-253. 27. Bichakjian CK, Halpern AC, Johnson TM, et al. Guidelines of care for the management of primary cutaneous melanoma. J Am Acad Dermatol. 2011;65:1032-1047. 28. Stockfleth E, Ferrandiz C, Grob JJ. Development of a treatment algorithm for actinic keratoses: A European Consensus. Eur J Dermatol. 2008;18:651-659. 29. Zalaudek I, Horn M, Richtig E, et al. Local recurrence in melanoma in situ: Influence of sex, age, site of involvement and therapeutic modalities. Br J Dermatol. 2001;148:703-708. 30. Dummer R. About moles, melanomas, and lasers: The dermatologist's schizophrenic attitude toward pigmented lesions. Arch Dermatol. 2003;139:1405-1406. 31. Gottschaller C, Hohenleutner U, Landthaler M. Metastasis of a malignant melanoma 2 years after carbon dioxide laser treatment of a pigmented lesion: Case report and review of the literature. Acta Derm Venereol. 2006;86:44-47. 32. Rocamora V, Puig L, Romani J, et al. Amelanotic lentigo maligna melanoma: Report of a case and review of the literature. Cutis. 1999;64: 53-56.
Diagnosis and management of facial pigmented macules Aimilios Lallas, MD a , Giuseppe Argenziano, MD a , Elvira Moscarella, MD a , Caterina Longo, MD a , Vito Simonetti, MD a , Iris Zalaudek, MD a,b,⁎ a
Skin Cancer Unit, Arcispedale Santa Maria Nuova, Istituto di Ricovero e Cura a Carattere Scientifico, Viale Risorgimento 80, 42100 Reggio Emilia, Italy b Department of Dermatology, Medical University of Graz, Auenbruggerplatz 8, 8036 Graz, Austria
Abstract The differential diagnosis of pigmented macules on the mottled chronic sun-damaged skin of the face is challenging and includes lentigo maligna (LM), pigmented actinic (solar) keratosis, solar lentigo, and lichen-planus-like keratosis. Although dermatoscopy improves the diagnostic accuracy of the unaided eye, the accurate diagnosis and management of pigmented facial macules remains one of the most challenging scenarios in daily practice. This is related to the fact that pigmented actinic (solar) keratosis, lichen-planus-like keratosis, and LM may reveal overlapping criteria, making their differential diagnosis clinically difficult. For this reason, practical rules have been introduced, which should help to minimize the risk for inappropriate diagnosis and management of LM. © 2014 Published by Elsevier Inc.
Introduction
Clinical features of facial pigmented macules
The differential diagnosis of pigmented macules on the mottled chronic sun-damaged skin of the face is challenging and includes lentigo maligna (LM), pigmented actinic (solar) keratosis (PAK), solar lentigo (SL), and lichenplanus-like keratosis (LPLK).1,2 Given that the natural course and prognosis vary significantly among these different entities, accurate diagnosis is mandatory to ensure appropriate management. Dermatoscopy improves the diagnostic accuracy compared with the unaided eye and accordingly, dermatoscopy became an integral part of the clinical examination of skin tumors3; however, the accurate diagnosis and management of pigmented macules on the face remains one of the most challenging scenarios in daily practice, even if coupled with dermatoscopy.4
LM, SL, seborrheic keratosis (SK), LPLK, and PAK are common facial lesions that typically develop after the fourth decade of life. 1,2,5,6 They share the clinical appearance of a flat, pigmented macule of different size and color. Accordingly, neither age nor clinical criteria appear useful for differentiating between these entities; however, there are some clinical differences between LM and the other nonmelanocytic skin lesions that should be considered in the differential diagnosis. First, LM and PAK reveal significant sex-related differences. Whereas PAK occurs at higher frequency in men, LM has a certain predilection for women7,8; thus, sex should be always considered in the differential diagnosis of pigmented macules on the face. Second, whereas PAK typically reveals a scaly and rough surface, LM appears smooth on palpation.1,2 Accordingly, palpation of a given facial lesion represents an important part of the clinical examination. Finally, LM develops more commonly as solitary or different-looking lesion compared with SL and PAK, which
⁎ Corresponding author. Tel.: +43 676 33 282 69; fax: +39 069 762 5822. E-mail address: [email protected] (I. Zalaudek). 0738-081X/$ – see front matter © 2014 Published by Elsevier Inc. http://dx.doi.org/10.1016/j.clindermatol.2013.05.030
Pigmented facial macules typically present as multiple spots with a similar appearance.1,2,9 Accordingly, a solitary lesion appears to be more suggestive of LM, whereas multiple similar lesions favor somewhat the diagnosis of SL or PAK.
Dermatoscopic patterns of facial pigmented macules The dermatoscopic aspects of facial melanocytic lesions differ from the ones described for other locations (Figure 1). A pigment network representing the dermatoscopic hallmark of melanocytic tumors on the torso and extremities is only rarely detected in facial melanocytic skin tumors.9 This is reasonable, because pigment network results from epidermal melanin (either in melanocytes or keratinocytes) along elongated rete ridges, whereby the tips of the rete ridges appear as network holes and the lateral borders as network lines.10 Instead, the dermoepidermal junction of chronically sundamaged facial skin appears flattened and may even lack rete ridges. Pigmented keratinocytes or melanocytes along this flattened dermoepidermal junction appear as structureless diffuse brown pigmentation on dermatoscopy; however, this otherwise structureless diffuse brown pigmentation on the face is interrupted by numerous, variable broad and hypopigmented “holes,” which correspond to hair follicles and sweat gland openings. Because the combination of diffuse brown pigmentation and nonpigmented adnexal openings is reminiscent of a kind of network, the pattern of
95 facial melanocytic and nonmelanocytic pigmented macules is also called a “pseudonetwork” pattern.9,11 It is important to emphasize that the pseudonetwork pattern occurs likewise in melanocytic and nonmelanocytic lesions.11,12 Accordingly, the diagnosis of a given pigmented facial macule relies on the detection of additional specific criteria. The specific dermatoscopic criteria of melanocytic and nonmelanocytic skin lesions are summarized in Table 1.
A dermatoscopic model in the progression of LM A 2000 study proposed based on dermatoscopic criteria a four-step model in the progression of LM.13 According to this model, asymmetric pigmented follicular openings (also called gray circles), gray dots within the follicular opening or so-called circles within circles, represent the very initial criteria in the development of LM. These structures subsequently develop into a so-called annular-granular pattern, which consists of aggregated fine gray dots, gray globules, and streaks around the follicle. With further progression, these streaks become longer and intersect with neighboring streaks, forming finally rhomboidal structures (ie, angulated lines between hair follicles). Finally, beginning invasion is characterized by the development of obliterated hair follicles (filled with black or blue-gray blotches) and structureless blue areas, white scarlike areas, and milky-red areas (Figure 2).
Fig. 1 Dermatoscopic-histopathologic correlates of pigment network (left upper and lower images) and facial pseudonetwork (right upper and lower image). True pigment network correlates with pigmentation along elongated rete ridges, whereas pseudonetwork results from a structureless brown pigmentation, which is intermingled by nonpigmented follicular openings. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this contribution.)
96 Table 1
A. Lallas et al. Dermatoscopic criteria of flat facial lesions
Lentigo maligna
Pigmented actinic keratosis
Solar lentigo/early seborrheic keratosis
Lichen-planus-like keratosis
Pseudonetwork
Pseudonetwork
Pseudonetwork
Asymmetric pigmented follicular openings Slate gray dots
Slate-gray dots
Light brown fingerprint areas Yellow opaque areas
Brownish gray granules localized or diffuse Bluish gray granules localized or diffuse Whitish gray granules localized or diffuse Any other criterion of SK or SL
Slate gray globules Rhomboidal structures Annular-granular pattern Gray brown streaks Dark/blue homogenous areas White scarlike areas Milky red areas Increased density of the vascular network Red rhomboidal structures Targetlike patterns Darkening at dermatoscopic examination Circle within a circle Zigzag pattern
Annular-granular pattern Rhomboidal structures Black globules Slate-gray globules Black dots Asymmetric pigmented follicular openings Circle within a circle Slate-gray areas Gray-brown streaks
Horny pseudocysts Milialike cysts Cerebriform structures Moth-eaten border Sharp demarcation Jelly sign Hairpin vessels Asymmetric pigmented follicular openings
Broken pseudonetwork Keratin plugs
It appears remarkable that according to this model, the earliest signs of LM development are related to predominant follicular involvement and not to the interfollicular epidermis. This observation has led some to question whether LM arises from cancer stem cells of the hair bulge rather than from transformed epidermal melanocytes.14
Dermatoscopic differential diagnosis of facial pigmented macules Reasonably, if a lesion exhibits fully developed clinical and/or specific dermatoscopic criteria, a straightforward diagnosis is feasible in most cases.
Fig. 2 Dermatoscopic patterns of lentigo maligna. Panel A, Gray dots within the hair follicle (arrows); panel B asymmetric pigmented hair follicles and gray circles within a circle (arrows); panel C rhomboidal structures appearing as gray lines (arrows) forming a rhomboid; and panel D annular-granular structures (arrows) and obliterated hair follicles appearing as gray-blue structureless blotches (circle). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this contribution.)
Pigmented facial macules LM, PAK, and LPLK may show at times overlapping features (Table 1); for these equivocal cases, the clinically relevant question is whether dermatoscopy aids the correct management. With regard to this question, it must be admitted that appropriately designed diagnostic accuracy studies are lacking, although preliminary data suggest a profitable role of dermatoscopy in differentiating LM from other nonmelanocytic macules.
Criteria of LM versus SL and SK Comparison of criteria between LM, SK, and SL allowed the identification of a set of four criteria that allowed prediction of diagnosis of LM with a sensitivity of 89% and a specificity of 96%.13 These criteria are asymmetric pigmented follicular openings, dark rhomboidal structures, slate-gray globules, and slate-gray dots. Although each single criterion may be seen also in SK or SL, the presence of all four features is strongly suggestive of LM. In contrast, light brown fingerprint areas, yellow opaque areas, milia cysts, moth-eaten border, and sharp demarcation (jelly sign) have been significantly associated with the diagnosis of SK or SL.13,15–17 More recently, elongated brown circles (fat fingers) have been added as criteria of early SK18 (Figure 3).
97
Criteria of LM versus LPLK LPLK is a term referring to an SL or SK undergoing regression.6 The discrimination between LPLK and LM is problematic and can be basically made only if areas of the preexisting benign lesion (SK or SL) are still preserved.19 Instead, fully or nearly fully regressed LPLK is characterized by diffuse brownish gray granules, which may coalescence to form globules, streaks, or even structures similar to rhomboids.19 Because LM may exhibit the same features, a biopsy of a lesion dermatoscopically characterized by signs of evident regression (ie, localized or diffuse gray granules) should always be performed (Figure 4).
Criteria of PAK versus LM A recent comparative study confirmed previous observations suggesting that LM and PAK exhibit strikingly similar patterns on dermatoscopy.20 Effectively, any of the established criteria of LM can be also seen in PAK, although black blotches within the follicular opening as seen in the late stage of melanoma progression occur at higher frequency in LM than PAK.20 Conversely, keratin plugs and a broken-up, superficial brown pseudonetwork is more suggestive of PAK.4,21 In doubtful cases, histopathology is required to differentiate between LM and PAK; however, the
Fig. 3 Dermatoscopic patterns of solar lentigo (SL) and early seborrheic keratosis (SK). Panel A, Fingerprintlike structures appearing as wavy parallel brown lines. Panel B, Sharp demarcation with convex and concave ends (moth-eaten borders). Panel C, SK developing from SL: Although the central fully developed SK reveals classic criteria of SK such as multiple milia cysts and comedo openings, the peripheral flat part of SL reveals fingerprintlike structures. Panel D, Light brown elongated circles reminiscent of “fat” fingers (arrows). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this contribution.)
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Fig. 4 Side-by-side comparison between lentigo maligna (LM) (panel A) and lichen-planus-like keratosis (panel B) showing overlapping features of gray dots. Side-by-side comparison between LM (panel C) and pigmented actinic (solar) keratosis (panel D) showing rhomboidal structures. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this contribution.)
discrimination between the two entities may be even histopathologically difficult, when it is not clear whether the pigmented atypical cells in the basal layer are keratinocytes or melanocytes1,2 (Figure 4).
practical rules may help to minimize the risk for inappropriate diagnosis and management.
Importance of gray color Practical rules and clues for the diagnosis and management of facial pigmented macules Although dermatoscopy provides valuable additional morphologic information, the differential diagnosis of flat pigmented macules on the face remains a challenge. Three
The single most important criterion in the differential diagnosis of LM from SL and SK is related to the presence versus absence of gray color, respectively (Figure 5). This can be explained by the different histopathologic correlates of colors in dermatoscopy. Melanin located in the stratum corneum, at the dermoepidermal junction, upper dermis, and
Fig. 5 Gray color is the single best criterion in the differential diagnosis of solar lentigo and seborrheic keratosis from lentigo maligna. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this contribution.)
Pigmented facial macules deep dermis gives rise to black, brown, gray, and blue, respectively.22,23 That SL and SK contain melanin exclusively at the epidermal level (ie, pigmented keratinocytes) explains why these lesions display only brown color on dermatoscopy.24 Instead, free or intracellular melanin in the upper dermis or intrafollicular melanin give rise to gray structures such as gray dots, globules, lines, or circles as typically seen in LM.13 Dermal melanin and its correlated gray dermatoscopic color are also seen in PAK and LPLK.19,20 Gray color is therefore insufficient to differentiate among LM, LPLK, and PAK.
Importance of correlating clinical, dermatoscopic, and histopathologic findings Dermatoscopic and histopathologic findings should always be combined with clinical information and interpreted within the clinical context of the patient. For instance, a different management approach should be applied in patients with a solitary lesion compared with patients with multiple lesions. More specifically, the presence of multiple lesions favors the diagnoses of PAK, SK, or SL, whereas development of multiple LMs is exceedingly rare.1,2,5 The comparative approach (ie, examination of all lesions) can be of further help in the management of patients with multiple facial spots because it allows the identification of similar patterns among all lesions (ie, signature pattern of PAK or SL). On the contrary, the threshold for biopsy should be lowered if examining a solitary lesion that cannot be confidently diagnosed as PAK, SK, or SL. Histopathology is regarded as gold standard in the diagnosis of clinically equivocal melanocytic and nonmelanocytic skin tumors, but it must be emphasized that it is not
99 free of limitations. The diagnosis of facial lesions in particular may be challenging because LM can escape the histopathologic diagnosis, if the biopsy has been performed in a nonrepresentative area.25 Dermatoscopy can improve the selection of representative areas to undergo biopsy; in detail, biopsy should be performed in areas showing the most suggestive features of LM (Figure 6).13 Early LM may display unremarkable features on histopathology.26 This carries a certain risk for underdiagnosis of melanoma as a junctional nevus. Clinicians should always pay particular attention if confronted with a given histopathologic diagnosis of a “junctional nevus” on the face of an elderly patient and critically review such diagnosis in the context of the patient (considering the history, age, sex, location, and clinical or dermatoscopic features of the lesion).
Never perform ablative treatment of equivocal lesions Although LM, PAK, SL, SK, and LPLK share several similar clinical, dermatoscopic, and histopathologic characteristics, they require a quite different management approach. Surgical excision is undoubtedly the treatment of choice for LM.27 Instead, nonablative modalities such as cryotherapy or laser therapy are reasonable options in the treatment of PAK or cosmetically disturbing SK, SL, and LPLK.28 Although radiotherapy, cryotherapy, and laser therapy represent alternative treatment options for LM in selected cases when surgical approach is not feasible, these options are problematic for two reasons: First, these options have been associated with a high risk for recurrence.29 Second, there are cases reporting a rapid progression of slow-growing LM to invasive, biologically aggressive nodular melanoma after cryotherapy. This suggests a possible influence of minimally invasive surgical procedures on the biological behavior of melanoma. Consequently, nonsurgical treatment modalities should be persevered for unequivocal cases that can be diagnosed as surely benign. Any doubtful lesion should undergo biopsy or at least regularly followed up using sequential digital dermatoscopic monitoring; destructive modalities should be avoided in the management of equivocal facial lesions.30–32
References
Fig. 6 Dermatoscopy helps the selection of the most representative area to undergo biopsy. In the case shown, the biopsy was made from the area showing gray asymmetric pigmented hair follicles (circle) and reveals melanoma in situ. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this contribution.)
1. Cohen LM. Lentigo maligna and lentigo maligna melanoma. J Am Acad Dermatol. 1995;33:923-936. 2. Uhlenhake EE, Sangueza OP, Lee AD, et al. Spreading pigmented actinic keratosis: A review. J Am Acad Dermatol. 2010;63:499-506. 3. Argenziano G, Soyer HP, Chimenti S, et al. Dermoscopy of pigmented skin lesions: Results of a consensus meeting via the internet. J Am Acad Dermatol. 2003;48:679-693. 4. Zalaudek I, Ferrara G, Leinweber B, et al. Pitfalls in the clinical and dermatoscopic diagnosis of pigmented actinic keratosis. J Am Acad Dermatol. 2005;53:1071-1074.
100 5. Mehregan AH. Lentigo senilis and its evolution. J Invest Dermatol. 1975;65:429-433. 6. Jang KA, Kim SH, Choi JH, et al. Lichenoid keratosis: A clinicopathologic study of 17 patients. J Am Acad Dermatol. 2000;43:511-516. 7. Memon AA, Tomenson JA, Bothwell J, et al. Prevalence of solar damage and actinic keratosis in a Merseyside population. Br J Dermatol. 2000;142:1154-1159. 8. Cohen LM, McCall MW, Hodge SJ, et al. Successful treatment of lentigo maligna and lentigo maligna melanoma with Mohs micrographic surgery aided by rush permanent sections. Cancer. 1994;73: 2964-2970. 9. Stolz W, Schiffner R, Burgdorf WH. Dermatoscopy for facial pigmented skin lesions. Clin Dermatol. 2002;20:276-278. 10. Braun RP, Rabinovitz HS, Oliviero M, et al. Dermoscopy of pigmented skin lesions. J Am Acad Dermatol. 2005;52:109-121. 11. Argenziano G, Soyer HP, De Giorgi V, et al. Dermoscopy: An Interactive Atlas. Milan, Italy: EDRA. 2000. 12. Johr RH, Stolz W. Lentigo maligna and lentigo maligna melanoma. J Am Acad Dermatol. 1997;37:512. 13. Schiffner R, Schiffner-Rohe J, Vogt T, et al. Improvement of early recognition of lentigo maligna using dermatoscopy. J Am Acad Dermatol. 2000;42:25-32. 14. Zalaudek I, Marghoob AA, Scope A, et al. Three roots of melanoma. Arch Dermatol. 2008;144:1375-1379. 15. Stante M, De Giorgi V, Stanganelli I, et al. Dermoscopy for early detection of facial lentigo maligna. Br J Dermatol. 2005; 152:361-364. 16. Sahin MT, Ozturkcan S, Ermertcan AT, et al. A comparison of dermatoscopic features among lentigo senilis/initial seborrheic keratosis, seborrheic keratosis, lentigo maligna and lentigo maligna melanoma on the face. J Dermatol. 2004;31:884-889. 17. Tanaka M, Sawada M, Kobayashi K. Key points in dermatoscopic differentiation between lentigo maligna and solar lentigo. J Dermatol. 2011;38:53-58. 18. Kopf AW, Rabinovitz H, Marghoob A, et al. “Fat fingers”: A clue in the dermatoscopic diagnosis of seborrheic keratoses. J Am Acad Dermatol. 2006;55:1089-1091. 19. Zaballos P, Marti E, Cuellar F, et al. Dermoscopy of lichenoid regressing seborrheic keratosis. Arch Dermatol. 2006;142:410.
A. Lallas et al. 20. Akay BN, Kocyigit P, Heper AO, et al. Dermatoscopy of flat pigmented facial lesions: Diagnostic challenge between pigmented actinic keratosis and lentigo maligna. Br J Dermatol. 2010;163:1212-1217. 21. Peris K, Micantonio T, Piccolo D, et al. Dermatoscopic features of actinic keratosis. J Dtsch Dermatol Ges. 2007;5:970-976. 22. Weismann K, Lorentzen HF. Dermatoscopic color perspective. Arch Dermatol. 2006;142:1250. 23. Rosendahl C, Cameron A, Tschandl P, et al. The cause of dermatoscopic grey circles in non-invasive melanomas: An hypothesis supported by histopathological correlation. Poster presented at: 2nd Congress of the International Dermoscopy Society; November 12–14, 2009; Barcelona, Spain. Available from: http://www.greycircles. blogspot.com. Accessed September 28, 2010. 24. Braun RP, Rabinowitz H, Oliviero M, et al. Dermatoscopy of pigmented lesions. Ann Dermatol Venereol. 2002;129:187-202. 25. Larsen TE, Grude TH. A retrospective histological study of 669 cases of primary cutaneous malignant melanoma in clinical stage I. Acta Pathol Microbiol Scand. 1979;87:255-260. 26. Larsen TE, Little JH, Grell SR, et al. International pathologists congruence survey on quantitation of malignant melanoma. Pathology. 1980;12:245-253. 27. Bichakjian CK, Halpern AC, Johnson TM, et al. Guidelines of care for the management of primary cutaneous melanoma. J Am Acad Dermatol. 2011;65:1032-1047. 28. Stockfleth E, Ferrandiz C, Grob JJ. Development of a treatment algorithm for actinic keratoses: A European Consensus. Eur J Dermatol. 2008;18:651-659. 29. Zalaudek I, Horn M, Richtig E, et al. Local recurrence in melanoma in situ: Influence of sex, age, site of involvement and therapeutic modalities. Br J Dermatol. 2001;148:703-708. 30. Dummer R. About moles, melanomas, and lasers: The dermatologist's schizophrenic attitude toward pigmented lesions. Arch Dermatol. 2003;139:1405-1406. 31. Gottschaller C, Hohenleutner U, Landthaler M. Metastasis of a malignant melanoma 2 years after carbon dioxide laser treatment of a pigmented lesion: Case report and review of the literature. Acta Derm Venereol. 2006;86:44-47. 32. Rocamora V, Puig L, Romani J, et al. Amelanotic lentigo maligna melanoma: Report of a case and review of the literature. Cutis. 1999;64: 53-56.
