Minireview Submitted: 9.2.2014 Accepted: 8.4.2014 Conflict of interest None.
Jelena Stojkovic-Filipovic1, Harald Kittler2 (1) Clinic of Dermatovenereology, Clinical Center of Serbia, Department of Dermatovenereology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia (2) Department of Dermatology, Medical University of Vienna, Austria
DOI: 10.1111/ddg.12368
Dermatoscopy of amelanotic and hypomelanotic melanoma
Summary Amelanotic melanoma is a subtype of cutaneous melanoma without pigment. The clinical diagnosis is challenging because it may mimic benign or malignant melanocytic and non-melanocytic neoplasms and inflammatory skin diseases. In synchrony with the improvement of the diagnosis of pigmented lesions, dermatoscopy may assist the clinician in the diagnosis of non-pigmented skin neoplasms in general and of amelanotic melanoma in particular. We have searched the literature to extract the most relevant dermatoscopic clues to diagnose amelanotic and hypomelanotic melanomas by dermatoscopy. In addition we present eight consecutive cases and discuss their clinical and dermatoscopic characteristics in the light of published data.
Introduction Amelanotic/hypomelanotic melanoma (AHM) represents a subtype of cutaneous melanoma with little or no pigment on clinical examination [1–3]. Completely amelanotic melanomas are rare [2, 3]. Hypomelanotic melanomas with slight pigmentation are more frequent [2, 3]. Approximately 2–8 % of all melanomas are AHM [1–5], but the real incidence is difficult to estimate because they are often misdiagnosed. The final diagnosis is usually delayed [5]. Similar to the pigmented variant of melanoma, the anatomic site of AHM differs by gender [5]. In males they are mainly found on the trunk and in females on the limbs [5]. Das et al. also described cases of amelanotic melanoma in the vagina and on the breasts as unusual sites in females [6]. AHM has been classified into three groups according to the presence and the amount of melanin – amelanotic, partially pigmented and lightly colored melanoma [1]. Amelanotic melanoma is characterized by complete lack of melanin even under dermatoscopy. In partially pigmented melanoma, pigmentation is found in less than 25 % of the lesion. Light colored lesions have a faint brown pigmentation that covers more than 25 % of the lesion but
without dark brown, blue or black pigmentation [1, 7]. In accordance with the classification of pigmented melanoma, it has been suggested that there are two types of AHM, nodular and superficial spreading melanoma. Like in pigmented melanomas the nodular variant is said to grow faster than the superficial spreading variant [8]. To explain the lack of pigment it has been hypothesized that AHM is a poorly differentiated subtype of conventional melanoma [5]. It is also known that the pigmentation of melanomas depend on skin phototype and on the genetic background [9]. Any subtype of cutaneous melanoma may be amelanotic, but it is more common in subungual (25 %) and desmoplastic melanoma [2, 4]. Most studies do not consider regressive melanoma a subtype of AHM [1, 10]. AHM tends to occur in sun-exposed skin, especially in older individuals with chronic UV-damage [3, 4]. Clinically, it may appear in various forms like, for example, as erythematous macule or patch [3, 4], or as skin-colored nodule with or without ulceration [3, 4]. Due to different clinical presentation AHM can be easily misdiagnosed. The spectrum of clinical differential diagnosis is wide. AHM can simulate inflammatory diseases or benign and malignant neoplasms [2]. Like in pigmented
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1206
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melanoma, the prognosis of amelanotic melanoma depends mainly on tumor thickness. Amelanotic type has a poorer prognosis [5], most probably due to delay of treatment [2]. For unclear reasons the prognosis of the patients with amelanotic metastases is worse than for pigmented metastasis [2].
Dermatoscopy of amelanotic/ hypomelanotic melanoma Dermatoscopy (dermoscopy) is a non-invasive technique that can assist the clinician in the diagnosis of suspicious skin lesion in general, particularly pigmented skin tumors [11–18]. It improves diagnostic accuracy for pigmented lesions compared to examination with the naked eye [12, 17, 19–21]. Dermatoscopy can also be helpful in the diagnosis of non-pigmented skin neoplasms [12, 14–16, 22–25]. Although there are many diagnostic algorithms to analyze pigmented lesions, the dermatoscopic criteria for amelanotic proliferations are not so well established. Due to the lack of pigment, other criteria, such as vessel morphology, are needed to come to the correct diagnosis. Vascular patterns have already been analyzed and confirmed as a useful clue in non-pigmented melanocytic neoplasms [1, 3, 7, 23, 24, 26–32]. It has been suggested that, in analogy to pattern analysis for pigmented skin lesions [11], vascular morphology should be analyzed in a structured way based on simple terminology to avoid misleading and confusing metaphoric terms [23].
Dermatoscopic evaluation of vascular structures in AHM Different types of vessels have been reported in AHM. Due to the fact that different terminologies have been used, it is difficult to integrate the reports. As a general rule, vessel morphology in AHM differs between flat and raised lesions. In flat lesions vessels as dots predominate whereas in raised lesions linear vessels becomes more prominent [3, 7, 24, 29, 33]. According to Menzies at al. linear irregular vessels are the predominant vessel type in AHM [7]. In a series published by Jaimes at al. serpentine vessels were found in 85 % of cases of AHM [27] and in amelanotic cutaneous melanoma metastases [34]. Coiled vessels (“glomerular vessels”) or highly tortuous vessels were also noted [34–36]. Looped vessels (“hairpin vessels”) have been noted in several publications on AHM [3, 7, 24, 26, 35, 37, 38]. Menzies et al. considered it as one of the most predictive vascular features of AHM [7]. Hairpin vessels have been observed in amelanotic melanoma metastases as well [34]. Vessels as dots
468
are specific for flat melanocytic lesions, but can be found in raised lesions as well. Usually they are found in combination with other types of vessels [7, 15, 18, 24, 26, 30, 32, 35, 37–40]. The reported frequency varies from 40 % (Pizzicheta et al.) [3] to 100 % (Bono et al.) [29]. Cavicchini et al. suggested that dotted vessels should be considered as the most useful dermatoscopic features for the diagnosis of amelanotic melanomas [36]. Dotted vessels (red dots) have been found mainly in flat AHM [3, 7, 24, 29, 33]. Pizzicheta et al. found combination of dots and irregular linear vessels as useful criteria in distinguishing AHM from other lesions [3], and Menzies at al. confirmed it as one of the most predictive vascular features for AHM [7]. Zalaudek et al. reported dotted vessels in combination with linear serpentine vessels [24]. Milky red areas/globules have been observed in several reports of AHM [3, 7, 18, 24, 27, 39, 41]. Pizzicheta et al. have noted milky red areas in 60 % cases of AHM [3], and Jaimes et al. in 80 % cases of amelanotic melanoma that are not nodular subtype [27]. Menzies et al. confirm milky red-pink areas as a characteristic vascular feature of amelanotic melanoma [7]. Cavicchini et al. found that milky red globules/areas and linear irregular vessels as the most useful dermatoscopic features for the diagnosis of truly amelanotic melanomas [36]. With regard to arrangement of vessels Menzies et al. found predominant central vessels as one of the most positive predictor for AHM [7]. Linear curved vessels (“comma vessels”), typical for dermal nevi (“Unna nevi”), have been reported by Menzies et al. as a negative predictive factor for melanoma [7]. According to a recent suggestion by Rosendahl et al. it is important to differentiate between flat and raised amelanotic melanoma [42]. Flat amelanotic melanomas are typified by polymorphic vessels that include a pattern of vessels as dots. Nodular amelanotic melanoma should be suspected in any non-pigmented nodule that lacks a specific distribution of vascular structures and when a specific benign diagnosis cannot be made with confidence. They also pointed out the importance of other clues such as ulceration and white structures [42].
Other clues Menzies et al. reported on scar-like depigmentation as positive predictor for the diagnosis of AHM [7]. Bories et al . noted scar-like depigmentation in all lesions (100 %) of fully regressed melanomas [10]. In the series reported by Puig et al. 40 % of amelanotic melanomas were ulcerated [9]. Pizzicheta et al. reported ulceration in 20 % of amelanotic melanomas [3], and it was one of the characteristics of amelanotic melanoma in case study of deGiorgi et al. [26]. Ulcerations were noted with greater frequency in thick compared to thin AHM [3, 7]. In similar percentage (23 %) ulcerations were
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1206
Minireview
Figure 1 Clinical presentation of all cases. Flat cases (a–c), an amelanotic case with flat and elevated parts (d), elevated (nodular) cases (e–h). Invasion thickness (a: 1.8 mm, b: 0.7 mm, c: 1.1 mm, d: 2.2 mm, e; 3.0 mm, f: 1.1 mm, g: 1.5 mm, h: 1.5 mm)
found in cases of AH melanoma metastases [34]. In the algorithm suggested by Rosendahl et al. ulceration and white structures are regarded as significant dermatoscopic clues to a malignant diagnosis in general [42] and that white lines are a clue to amelanotic melanoma in particular. With regard to the specific problem of differentiating amelanotic melanoma from Spitz nevus the study by Zalaudek et al. deserves further attention [43]. They reported that reticular white lines (white network) are more common in Spitz nevi than in amelanotic or hypomelanotic melanoma. However, they also stated that this clue is not 100 % specific and does not exclude melanoma and recommend excision of all tumors that show this pattern [43].
Review of eight cases with clinical and dermatoscopic evaluation This series included eight patients, five males and three females. The mean age was 65 years (range 38–86 years). The anatomic sites were: lower limb (3 patients), upper limb (2 patients), back (1 patient), trunk-chest (1 patient), head/ neck (1 patient). Three lesions were flat, four were substantially elevated (nodular) and one was flat and had an elevated part (Figure 1). All lesions were pink clinically. Ulcerations/ erosions were noted in two of eight lesions (25 %). Dermatoscopic features as captured with a polarized dermatoscope
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1206
469
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Table 1 Dermatoscopic vascular features of eight amelanotic lesions (melanomas). Vessel morphology
1
2
3
4
5
6
7
8
Dots
+
+
+
+
–
+
–
+
Clods
+
–
–
–
+
–
–
–
Linear straight
–
–
–
+
+
–
–
–
Linear looped
–
–
–
–
–
–
–
+
Linear curved
+
+
+
+
+
+
+
+
Linear serpentine
+
+
+
+
+
+
+
+
Linear helical
–
–
–
–
–
–
–
–
Linear coiled
+
+
+
+
+
+
+
+
Figure 2 Dermatoscopic images of six of the eight cases. Dermatoscopy of flat lesions of amelanotic melanoma with polymorphous vessels (vessels as dots plus linear vessels) (a–c) and elevated nodular lesions with polymorphous linear vessels and prominent white lines (d–f).
are given in Table 1 and dermatoscopic images of six cases are presented in Figure 2. Three cases (37.5 %) were amelanotic melanomas and five cases (62.5 %) were hypomelanotic melanoma with slight pigmentation on the periphery of the
470
lesions. Three lesions had brown eccentric structureless zones, two had brown eccentric reticular pattern, and one had black eccentric clods. White lines and a polymorphic arrangement of vessels were noted in all lesions.
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1206
Minireview
Summary Dermatoscopy is useful tool to improve the detection of AHM. Our small case series confirmed that polymorphous vascular pattern with no specific arrangement of vessels is a dermatoscopic characteristic of AHM. In flat AHM in particular the combination of dotted vessels and linear vessels may be a strong clue to melanoma. Among non-vascular features we consider white lines as the most important clue for AHM. Ulceration/erosion may indicate thicker tumors. Correspondence to Harald Kittler, MD Department of Dermatology, Division of General Dermatology Medical University of Vienna Währinger Gürtel 18—20 1090 Vienna, Austria E-mail: [email protected]
12
13 14 15
16
17
18
19 20
References 1
Moloney FJ, Menzies SW. Key points in the dermoscopic iagnosis of hypomelanotic melanoma and nodular melanoma. d J Dermatol 2011; 38: 10–5. 2 Koch SE, Lange JR. Amelanotic melanoma: the great masquerader. J Am Acad Dermatol 2000; 42: 731–4. 3 Pizzichetta MA, Talamini R, Stanganelli I et al. Amelanotic/ hypomelanotic melanoma: clinical and dermoscopic features. Br J Dermatol 2004; 150: 1117–24. 4 Adler MJ, White CR Jr. Amelanotic malignant melanoma. Semin Cutan Med Surg 1997; 16: 122–30. 5 Cheung WL, Patel RR, Leonard A et al. Amelanotic melanoma: a detailed morphologic analysis with clinicopathologic correlation of 75 cases. J Cutan Pathol 2012; 39: 33–9. 6 Das P, Kumar N, Ahuja A, et al. Primary malignant melanoma at unusual sites: an institutional expertise with review of literature. Melanoma Res 2010; 20: 233–9. 7 Menzies SW, Kreusch J, Byth K et al. Dermoscopic evaluation of amelanotic and hypomelanotic melanoma. Arch Dermatol 2008; 144: 1120–7. 8 Gualandri L, Betti R, Crosti C. Clinical features of 36 cases of amelanotic melanomas and considerations about the relationship between histologic subtypes and diagnostic delay. J Eur Acad Dermatol Venereol 2009; 23: 283–7. 9 Puig S, Argenziano G, Zalaudek I et al. Melanomas that failed dermoscopic detection: a combined clinicodermoscopic approach for not missing melanoma. Dermatol Surg 2007; 33: 1262–73. 10 Bories N, Dalle S, Debarbieux S et al. Dermoscopy of fully regressive cutaneous melanoma. Br J Dermatol 2008; 158: 1224–9. 11 Kittler H. Dermatoscopy: introduction of a new algorithmic method based on pattern analysis for diagnosis of pigmented
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skin lesions. Dermatopathology: Practical & Conceptual 2007; 13: 3. Rosendahl C, Tschandl P, Cameron A, Kittler H. Diagnostic accuracy of dermatoscopy for melanocytic and nonmelanocytic pigmented lesions. J Am Acad Dermatol 2011; 64: 1068–73. Braun RP, Rabinovitz HS, Oliviero M et al. Dermoscopy of pigmented lesions. J Am Acad Dermatol 2005; 52: 109–21. Zalaudek I, Argenziano G, Di Stefani A et al. Dermoscopy in general dermatology. Dermatology 2006; 212: 7–18. Argenziano G, Zalaudek I, Ferrara G et al. Dermoscopy features of melanoma incognito: indications for biopsy. J Am Acad Dermatol 2007; 56: 508–13. Bowling J, Argenziano G, Azenha A et al. Dermoscopy key points: recommendations from the international dermoscopy society. Dermatology 2007; 214: 3–5. Argenziano G, Ferrara G, Francione S et al. Dermoscopy the ultimate tool for melanoma diagnosis. Semin Cutan Med Surg 2009; 28: 142–8. Sbano P, Nami N, Grimaldi L, Rubegni P. True amelanotic melanoma: the great masquerader. J Plast Reconstr Aesthet Surg 2010; 63: 307–8. Kittler H, Pehamberger H, Wolff K, Binder M. Diagnostic accuracy of dermoscopy. Lancet Oncol 2002; 3: 159–65. 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: 679–93. Vestergaard ME, Macaskill P, Holt PE, Menzies SW. Dermoscopy compared with naked eye examination for the diagnosis of primary melanoma: a meta-analysis of studies performed in a clinical setting. Br J Dermatol 2008; 159: 669–76. Zalaudek I. Dermoscopy subpatterns of nonpigmented skin tumors. Arch Dermatol 2005; 141: 532. Kittler H, Riedl E, Rosendahl C, Cameron A. Dermatoscopy of unpigmented lesions of the skin: a new classification of vessel morphology based on pattern analysis. Dermatol Pract Concept 2008; 14(4): 4. Zalaudek I, Kreusch J, Giacomel J et al. How to diagnose nonpigmented skin tumors: a review of vascular structures seen with dermoscopy: part I. Melanocytic skin tumors. J Am Acad Dermatol 2010; 63: 361–74. Zalaudek I, Kreusch J, Giacomel J et al. How to diagnose nonpigmented skin tumors: a review of vascular structures seen with dermoscopy: part II. Nonmelanocytic skin tumors. J Am Acad Dermatol 2010; 63: 377–86. de Giorgi V, Sestini S, Massi D et al. Dermoscopy for “true” amelanotic melanoma: a clinical dermoscopic-pathologic case study. J Am Acad Dermatol 2006; 54: 341–4. Jaimes N, Braun RP, Thomas L, Marghoob AA. Clinical and dermoscopic characteristics of amelanotic melanomas that are not of the nodular subtype. J Eur Acad Dermatol Venereol 2012; 26: 591–6. Zalaudek I, Argenziano G, Kerl H et al. Amelanotic/hypomelanotic melanoma – is dermatoscopy useful for diagnosis? J Dtsch Dermatol Ges 2003; 1: 369–73. Bono A, Maurichi A, Moglia D et al. Clinical and dermatoscopic diagnosis of early amelanotic melanoma. Melanoma Res 2001; 11: 491–4.
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30 Stoecker WV, Stolz W. Dermoscopy and the diagnostic challenge of amelanotic and hypomelanotic melanoma. Arch Dermatol 2008; 144: 1207–10. 31 Argenziano G, Fabbrocini G, Carli P et al. Epiluminescence microscopy for the diagnosis of doubtful melanocytic skin lesions: comparison of the ABCD rule of dermatoscopy and a new 7-point checklist based on pattern analysis. Arch Dermatol 1998; 134: 1563–70. 32 Kreusch JF. Vascular patterns in skin tumors. Clin Dermatol 2002; 20: 248–54. 33 Argenziano G, Zalaudek I, Corona R et al. Vascular structures in skin tumors: a dermoscopy study. Arch Dermatol 2004; 140: 1485–9. 34 Jaimes N, Halpern JA, Puig S et al. Dermoscopy: an aid to the detection of amelanotic cutaneous melanoma metastases. Dermatol Surg 2012; 38: 1437–44. 35 Gencoglan G, Inanir I, Miskioglu M, Temiz P. Acral amelanotic verrucous melanoma: dermoscopic findings. Dermatol Surg 2011; 37: 107–10. 36 Cavicchini S, Tourlaki A, Bottini S. Dermoscopic vascular patterns in nodular ‘‘pure’’ amelanotic melanoma. Arch Dermatol 2007; 143: 556.
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Piccolo D, Lozzi GP, Altamura D et al. Dermoscopic evolution of vascular pattern in two cases of amelanotic melanoma. Acta Derm Venereol 2010; 90: 83–5. Blum A, Metzler G, Bauer J. Polymorphous vascular patterns in dermoscopy as a sign of malignant skin tumors. A case of an amelanotic melanoma and a porocarcinoma. Dermatology 2005; 210: 58–9. Zell D, Kim N, Olivero M et al. Early diagnosis of multiple primary amelanotic/hypomelanotic melanoma using dermoscopy. Dermatol Surg 2008; 34: 1254–7. Johr RH. Pink lesions. Clin Dermatol 2002; 20: 289–96. Pizzichetta MA, Canzonieri V, Massarut S et al. Pitfalls in the dermoscopic diagnosis of amelanotic melanoma. J Am Acad Dermatol 2010; 62: 893–4. Rosendahl C, Cameron A, Tschandl P et al. Prediction without Pigment: a decision algorithm for non-pigmented skin malignancy. Dermatol Pract Concept 2014; 4: 9. Zalaudek I, Kittler H, Hofmann-Wellenhof R et al. “White” network in Spitz nevi and early melanomas lacking significant pigmentation. J Am Acad Dermatol 2013; 69: 56–60.
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1206
Jelena Stojkovic-Filipovic1, Harald Kittler2 (1) Clinic of Dermatovenereology, Clinical Center of Serbia, Department of Dermatovenereology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia (2) Department of Dermatology, Medical University of Vienna, Austria
DOI: 10.1111/ddg.12368
Dermatoscopy of amelanotic and hypomelanotic melanoma
Summary Amelanotic melanoma is a subtype of cutaneous melanoma without pigment. The clinical diagnosis is challenging because it may mimic benign or malignant melanocytic and non-melanocytic neoplasms and inflammatory skin diseases. In synchrony with the improvement of the diagnosis of pigmented lesions, dermatoscopy may assist the clinician in the diagnosis of non-pigmented skin neoplasms in general and of amelanotic melanoma in particular. We have searched the literature to extract the most relevant dermatoscopic clues to diagnose amelanotic and hypomelanotic melanomas by dermatoscopy. In addition we present eight consecutive cases and discuss their clinical and dermatoscopic characteristics in the light of published data.
Introduction Amelanotic/hypomelanotic melanoma (AHM) represents a subtype of cutaneous melanoma with little or no pigment on clinical examination [1–3]. Completely amelanotic melanomas are rare [2, 3]. Hypomelanotic melanomas with slight pigmentation are more frequent [2, 3]. Approximately 2–8 % of all melanomas are AHM [1–5], but the real incidence is difficult to estimate because they are often misdiagnosed. The final diagnosis is usually delayed [5]. Similar to the pigmented variant of melanoma, the anatomic site of AHM differs by gender [5]. In males they are mainly found on the trunk and in females on the limbs [5]. Das et al. also described cases of amelanotic melanoma in the vagina and on the breasts as unusual sites in females [6]. AHM has been classified into three groups according to the presence and the amount of melanin – amelanotic, partially pigmented and lightly colored melanoma [1]. Amelanotic melanoma is characterized by complete lack of melanin even under dermatoscopy. In partially pigmented melanoma, pigmentation is found in less than 25 % of the lesion. Light colored lesions have a faint brown pigmentation that covers more than 25 % of the lesion but
without dark brown, blue or black pigmentation [1, 7]. In accordance with the classification of pigmented melanoma, it has been suggested that there are two types of AHM, nodular and superficial spreading melanoma. Like in pigmented melanomas the nodular variant is said to grow faster than the superficial spreading variant [8]. To explain the lack of pigment it has been hypothesized that AHM is a poorly differentiated subtype of conventional melanoma [5]. It is also known that the pigmentation of melanomas depend on skin phototype and on the genetic background [9]. Any subtype of cutaneous melanoma may be amelanotic, but it is more common in subungual (25 %) and desmoplastic melanoma [2, 4]. Most studies do not consider regressive melanoma a subtype of AHM [1, 10]. AHM tends to occur in sun-exposed skin, especially in older individuals with chronic UV-damage [3, 4]. Clinically, it may appear in various forms like, for example, as erythematous macule or patch [3, 4], or as skin-colored nodule with or without ulceration [3, 4]. Due to different clinical presentation AHM can be easily misdiagnosed. The spectrum of clinical differential diagnosis is wide. AHM can simulate inflammatory diseases or benign and malignant neoplasms [2]. Like in pigmented
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1206
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melanoma, the prognosis of amelanotic melanoma depends mainly on tumor thickness. Amelanotic type has a poorer prognosis [5], most probably due to delay of treatment [2]. For unclear reasons the prognosis of the patients with amelanotic metastases is worse than for pigmented metastasis [2].
Dermatoscopy of amelanotic/ hypomelanotic melanoma Dermatoscopy (dermoscopy) is a non-invasive technique that can assist the clinician in the diagnosis of suspicious skin lesion in general, particularly pigmented skin tumors [11–18]. It improves diagnostic accuracy for pigmented lesions compared to examination with the naked eye [12, 17, 19–21]. Dermatoscopy can also be helpful in the diagnosis of non-pigmented skin neoplasms [12, 14–16, 22–25]. Although there are many diagnostic algorithms to analyze pigmented lesions, the dermatoscopic criteria for amelanotic proliferations are not so well established. Due to the lack of pigment, other criteria, such as vessel morphology, are needed to come to the correct diagnosis. Vascular patterns have already been analyzed and confirmed as a useful clue in non-pigmented melanocytic neoplasms [1, 3, 7, 23, 24, 26–32]. It has been suggested that, in analogy to pattern analysis for pigmented skin lesions [11], vascular morphology should be analyzed in a structured way based on simple terminology to avoid misleading and confusing metaphoric terms [23].
Dermatoscopic evaluation of vascular structures in AHM Different types of vessels have been reported in AHM. Due to the fact that different terminologies have been used, it is difficult to integrate the reports. As a general rule, vessel morphology in AHM differs between flat and raised lesions. In flat lesions vessels as dots predominate whereas in raised lesions linear vessels becomes more prominent [3, 7, 24, 29, 33]. According to Menzies at al. linear irregular vessels are the predominant vessel type in AHM [7]. In a series published by Jaimes at al. serpentine vessels were found in 85 % of cases of AHM [27] and in amelanotic cutaneous melanoma metastases [34]. Coiled vessels (“glomerular vessels”) or highly tortuous vessels were also noted [34–36]. Looped vessels (“hairpin vessels”) have been noted in several publications on AHM [3, 7, 24, 26, 35, 37, 38]. Menzies et al. considered it as one of the most predictive vascular features of AHM [7]. Hairpin vessels have been observed in amelanotic melanoma metastases as well [34]. Vessels as dots
468
are specific for flat melanocytic lesions, but can be found in raised lesions as well. Usually they are found in combination with other types of vessels [7, 15, 18, 24, 26, 30, 32, 35, 37–40]. The reported frequency varies from 40 % (Pizzicheta et al.) [3] to 100 % (Bono et al.) [29]. Cavicchini et al. suggested that dotted vessels should be considered as the most useful dermatoscopic features for the diagnosis of amelanotic melanomas [36]. Dotted vessels (red dots) have been found mainly in flat AHM [3, 7, 24, 29, 33]. Pizzicheta et al. found combination of dots and irregular linear vessels as useful criteria in distinguishing AHM from other lesions [3], and Menzies at al. confirmed it as one of the most predictive vascular features for AHM [7]. Zalaudek et al. reported dotted vessels in combination with linear serpentine vessels [24]. Milky red areas/globules have been observed in several reports of AHM [3, 7, 18, 24, 27, 39, 41]. Pizzicheta et al. have noted milky red areas in 60 % cases of AHM [3], and Jaimes et al. in 80 % cases of amelanotic melanoma that are not nodular subtype [27]. Menzies et al. confirm milky red-pink areas as a characteristic vascular feature of amelanotic melanoma [7]. Cavicchini et al. found that milky red globules/areas and linear irregular vessels as the most useful dermatoscopic features for the diagnosis of truly amelanotic melanomas [36]. With regard to arrangement of vessels Menzies et al. found predominant central vessels as one of the most positive predictor for AHM [7]. Linear curved vessels (“comma vessels”), typical for dermal nevi (“Unna nevi”), have been reported by Menzies et al. as a negative predictive factor for melanoma [7]. According to a recent suggestion by Rosendahl et al. it is important to differentiate between flat and raised amelanotic melanoma [42]. Flat amelanotic melanomas are typified by polymorphic vessels that include a pattern of vessels as dots. Nodular amelanotic melanoma should be suspected in any non-pigmented nodule that lacks a specific distribution of vascular structures and when a specific benign diagnosis cannot be made with confidence. They also pointed out the importance of other clues such as ulceration and white structures [42].
Other clues Menzies et al. reported on scar-like depigmentation as positive predictor for the diagnosis of AHM [7]. Bories et al . noted scar-like depigmentation in all lesions (100 %) of fully regressed melanomas [10]. In the series reported by Puig et al. 40 % of amelanotic melanomas were ulcerated [9]. Pizzicheta et al. reported ulceration in 20 % of amelanotic melanomas [3], and it was one of the characteristics of amelanotic melanoma in case study of deGiorgi et al. [26]. Ulcerations were noted with greater frequency in thick compared to thin AHM [3, 7]. In similar percentage (23 %) ulcerations were
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1206
Minireview
Figure 1 Clinical presentation of all cases. Flat cases (a–c), an amelanotic case with flat and elevated parts (d), elevated (nodular) cases (e–h). Invasion thickness (a: 1.8 mm, b: 0.7 mm, c: 1.1 mm, d: 2.2 mm, e; 3.0 mm, f: 1.1 mm, g: 1.5 mm, h: 1.5 mm)
found in cases of AH melanoma metastases [34]. In the algorithm suggested by Rosendahl et al. ulceration and white structures are regarded as significant dermatoscopic clues to a malignant diagnosis in general [42] and that white lines are a clue to amelanotic melanoma in particular. With regard to the specific problem of differentiating amelanotic melanoma from Spitz nevus the study by Zalaudek et al. deserves further attention [43]. They reported that reticular white lines (white network) are more common in Spitz nevi than in amelanotic or hypomelanotic melanoma. However, they also stated that this clue is not 100 % specific and does not exclude melanoma and recommend excision of all tumors that show this pattern [43].
Review of eight cases with clinical and dermatoscopic evaluation This series included eight patients, five males and three females. The mean age was 65 years (range 38–86 years). The anatomic sites were: lower limb (3 patients), upper limb (2 patients), back (1 patient), trunk-chest (1 patient), head/ neck (1 patient). Three lesions were flat, four were substantially elevated (nodular) and one was flat and had an elevated part (Figure 1). All lesions were pink clinically. Ulcerations/ erosions were noted in two of eight lesions (25 %). Dermatoscopic features as captured with a polarized dermatoscope
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1206
469
Minireview
Table 1 Dermatoscopic vascular features of eight amelanotic lesions (melanomas). Vessel morphology
1
2
3
4
5
6
7
8
Dots
+
+
+
+
–
+
–
+
Clods
+
–
–
–
+
–
–
–
Linear straight
–
–
–
+
+
–
–
–
Linear looped
–
–
–
–
–
–
–
+
Linear curved
+
+
+
+
+
+
+
+
Linear serpentine
+
+
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Linear helical
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Figure 2 Dermatoscopic images of six of the eight cases. Dermatoscopy of flat lesions of amelanotic melanoma with polymorphous vessels (vessels as dots plus linear vessels) (a–c) and elevated nodular lesions with polymorphous linear vessels and prominent white lines (d–f).
are given in Table 1 and dermatoscopic images of six cases are presented in Figure 2. Three cases (37.5 %) were amelanotic melanomas and five cases (62.5 %) were hypomelanotic melanoma with slight pigmentation on the periphery of the
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lesions. Three lesions had brown eccentric structureless zones, two had brown eccentric reticular pattern, and one had black eccentric clods. White lines and a polymorphic arrangement of vessels were noted in all lesions.
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1206
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Summary Dermatoscopy is useful tool to improve the detection of AHM. Our small case series confirmed that polymorphous vascular pattern with no specific arrangement of vessels is a dermatoscopic characteristic of AHM. In flat AHM in particular the combination of dotted vessels and linear vessels may be a strong clue to melanoma. Among non-vascular features we consider white lines as the most important clue for AHM. Ulceration/erosion may indicate thicker tumors. Correspondence to Harald Kittler, MD Department of Dermatology, Division of General Dermatology Medical University of Vienna Währinger Gürtel 18—20 1090 Vienna, Austria E-mail: [email protected]
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