BJD British Journal of Dermatology
C L I N I C A L A N D L A B O R A T O R Y I N V E S TI G A T I O N S
Reticular grey-blue areas of regression as a dermoscopic marker of melanoma in situ S. Seidenari, C. Ferrari, S. Borsari, E. Benati, G. Ponti, S. Bassoli, F. Giusti, S. Schianchi and G. Pellacani Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy
Summary Correspondence Chiara Ferrari. E-mail:
[email protected]
Accepted for publication 9 April 2010
Key words dermoscopy, early diagnosis, melanoma in situ, regression, reticular blue areas
Conflicts of interest None declared. DOI 10.1111/j.1365-2133.2010.09821.x
Background By dermoscopy, regression structures are substantially defined by the presence of white and blue areas in the lesion image. As fibrosis and melanosis are often seen in malignant melanoma (MM), the presence of dermoscopic signs of regression may represent a clue for the diagnosis of malignancy. Objectives To assess the frequency and extent of dermoscopic signs of regression in melanoma in situ (MIS) and to describe its dermoscopic features. Methods Dermoscopic images of 85 MIS, 85 invasive MMs and 85 dermoscopically equivocal lesions with a histological diagnosis of naevus were evaluated by three dermatologists, who assessed the presence of 11 parameters of regression. Results The number of regression parameters per lesion increased according to melanoma thickness. White areas, the grey-blue veil and widespread blue areas were more frequent in invasive MMs than in the other two lesion groups, whereas light brown areas and regression of dermoscopic structures were more frequent in MIS. Peppering was observable in the same percentage of MIS and invasive MMs. Blue areas were more frequently structureless in equivocal lesions and invasive MMs, whereas the reticular pattern prevailed in MIS. Conclusions Frequency, morphology, extent and distribution of regression vary according to melanoma thickness and diameter. Lesions with reticular blue regression and light brown areas should undergo surgical excision for the suspicion of MIS. Moreover, the identification of the reticular pattern of blue regression can be considered a significant discriminator and a reliable predictor of MIS.
Among descriptors employed for detection of malignant melanoma (MM) by dermoscopy, regression equivalents represent important features for MMs diagnosis.1,2 Regression structures are substantially defined by the presence of white areas and blue areas in the dermoscopic lesion image.3 White areas have been described as areas whiter than the surrounding skin (white scar-like areas), whereas blue areas appear as homogeneous or nonhomogeneous areas (blue pepper-like granules or globules), sometimes surmounted by a veil.3–5 Yet, the dermoscopic terminology concerning regression has not been fully standardized so far, and numerous terms have been introduced, which appear scarcely reproducible.4 Histopathologically, great abundance of melanin pigment, within either melanophages or pigmented melanocytes in the dermis, is correlated to a bluish colour and ⁄or larger areas of bluish pigmentation, while if there is only fibroplasia associated with blood vessel formation, the lesion will have a whitish aspect with more or less reddish shades.6 When the classic blue-whitish veil is seen dermoscopically, an acanthotic epidermis with compact orthokeratosis and focal hypergranulosis may
additionally be observed histopathologically above sheets of heavily pigmented melanocytes or melanophages in the dermis.6–9 The presence of white and blue colours in a melanocytic lesion may be simultaneous or these hues may be present separately, suggesting a different therapeutic approach;3 moreover, their distribution and their location in the centre or at the periphery of the lesions may represent an aid to distinguish between different subtypes of melanocytic lesions.3 Regression structures and grey-blue areas are, besides an irregular vascular pattern, the dermoscopic features which best predict histological atypia in naevi.10 Lesions with clear-cut regression structures often carry great histopathological controversy.11 Moreover, regression structures and blue-whitish veil are among the most relevant dermoscopic criteria for differentiation between amelanotic ⁄hypomelanotic MMs and benign melanocytic lesions.1 As fibrosis and melanosis are often seen in MMs, the presence of dermoscopic signs of regression may represent a clue for the diagnosis of malignant lesions. In fact, the absence of regression structures and of a blue-whitish veil is considered a criterion leading to an increased risk of dermo 2010 The Authors
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scopically difficult melanoma.12 The frequency of regression structures varies according to MMs thickness. Stante et al.13 observed that grey-blue areas are more frequently observed in thick MMs, whereas in melanoma in situ (MIS) they are present in only 18% of cases. In contrast, Pizzichetta et al.14 found a similar percentage of regression in MIS and invasive MMs, indicating that regression descriptors are not suitable for the differentiation of invasive and in situ lesions. The aim of this study was to assess the frequency and extent of dermoscopic signs of regression in MIS and to describe its dermoscopic features. The sensitivity and specificity of different regression descriptors were also evaluated employing control populations comprising invasive MMs and equivocal melanocytic lesions.
Materials and methods Dermoscopic images were collected by means of a digital epiluminescence microscope (FotoFinder; TeachScreen software GmbH, Bad Birnbach, Germany), which has already been described elsewhere.15 The study sample comprised 255 melanocytic lesions from a larger series of lesions consecutively recorded by means of the FotoFinder and excised at the Department of Dermatology of the University of Modena in the years 2003–2008. Eighty-five images of MIS represented the entire MIS population of the years 2003–2008, whereas 85 invasive MMs and 85 dermoscopically equivocal lesions (excised with a strong suspicion of a melanoma) with a histological diagnosis of naevus were randomly selected from our files to constitute the control populations. The dermoscopic images were evaluated by three experienced dermatologists, blinded for histopathological diagnosis, who contemporarily assessed the presence or absence of 11 parameters of regression (Table 1). Final judgment on each descriptor derived from a consensus of at least two of three observers. Dermoscopic descriptors Regression was considered present when blue areas and ⁄or peppering and ⁄or blue-whitish veil and ⁄or white areas were
(a)
(b)
Table 1 Eleven variables of regression and their definitions Parameter
Definition
1 Regression
Presence of blue areas and ⁄ or peppering and ⁄ or blue-whitish veil and ⁄ or white areas Bluish and ⁄ or larger areas of grey-blue pigmentation Grey-blue homogeneous pigmentation Coarse blue-grey net, with thick grey-blue lines and large holes Aggregated grey-blue globules Blue, fine pepper-like structures White scar-like areas Compact, structureless, irregular and confluent blue-whitish pigmentation. Similar to a superficial veil, palpable over the lesion Areas of the lesion lighter than the surrounding skin with a pinkish shade Light brown structureless irregular areas Fading of net, globules or pigmentation giving rise to light brown areas or small structureless areas within a structured area
2 Blue areas 2a Structureless 2b Reticular 2c Globular 3 Peppering 4 White areas 5 Blue-whitish veil
6 Pink areas 7 Light brown areas 8 Regression of dermoscopic structures
present. Blue areas were further described as being globular, reticular or structureless (Fig. 1). ‘Globular grey-blue areas’ were represented by aggregated grey-blue globules, whereas the term ‘reticular grey-blue areas’ was employed to define a coarse blue-grey net, with thick grey-blue lines and large holes, corresponding to white or pink regression areas (Fig. 2). Although often present in lesions with a network, reticular grey-blue pigmentation does not correspond to the pigment network, which has smaller meshes and thinner lines. Pink lesion areas, i.e. areas of the lesion lighter than the surrounding skin with a pinkish shade, were also observed. For blue and white areas, both their presence and their extent were assessed. Moreover, we also considered the presence of regression of dermoscopic structures and light brown areas.
(c)
(d)
Fig 1. Dermoscopic patterns of blue regression. (a) Structureless grey-blue areas. This lesion displays a high degree (> 50%) of blue areas with a structureless pattern. In addition, the presence of a veil and of peppering throughout the lesion can be suggestive of melanoma. The histological diagnosis was invasive malignant melanoma (MM) with a Breslow thickness 0Æ85 mm. (b) Globular grey-blue areas. A dermoscopic image of an invasive MMs (0Æ62 mm Breslow thickness) showing large blue areas with a globular pattern in the lower right corner of the lesion. The regression of dermoscopic structures and the veil are also detectable in the lesion. (c) Reticular grey-blue areas. Melanoma in situ with reticular grey-blue pigmentation in > 50% of the lesion and therefore considered as the main pattern. (d) Highlighted reticular grey-blue areas. The same image as in (c) with reticular blue regression emphasized by the blue lines throughout the lesion image. Dermoscopic images; original magnification · 20. 2010 The Authors Journal Compilation 2010 British Association of Dermatologists • British Journal of Dermatology 2010 163, pp302–309
304 Dermoscopic marker of melanoma in situ, S. Seidenari et al.
(a)
(b)
(c)
(d)
Fig 2. Reticular grey-blue areas in melanoma in situ (MIS). (a) Dermoscopic image of an MIS located at the trunk of a 57-year-old man. The presence of pink areas, as well as the fading of the network and regression of dermoscopic structures, suggests the diagnosis of melanoma. (b) MIS located at the right shoulder of a 58-year-old man. This lesion displays a high degree (> 50% of the lesion) of reticular blue regression at the centre and at the periphery of the lesion. (c) Dermoscopic image of an MIS located at the trunk of a 59-year-old man. A high degree (> 50%) of reticular blue regression is clearly seen throughout the lesion and, together with the irregular vascular pattern and pink areas, suggests the diagnosis of melanoma. (d) MIS in the upper limb of a 79-year-old man. Note the widespread reticular aspect of blue areas, the presence of light brown areas and the regression of dermoscopic structures, which may represent the start of the regression phenomenon. Dermoscopic images; original magnification · 20.
Light brown areas were described as light brown structureless irregular areas at the periphery of the lesions by Annessi et al.16 ‘Regression of dermoscopic structures’ was visible when, within a structured area, there was a fading of net, globules or pigmentation giving rise to light brown areas or small structureless areas. Statistics Statistical evaluation was carried out employing the SPSS statistical package (release 12.0.0, 2003; SPSS Inc., Chicago, IL, U.S.A.). The study population was subdivided in three groups, corresponding to equivocal benign lesions, MIS and invasive MMs. Absolute and relative frequencies of the observations were obtained for each regression parameter evaluated. Absolute and relative frequencies of lesions showing only one or a combination of the evaluated dermoscopic features were calculated on the number of lesions presenting regression. Moreover, the relative frequency of regression was calculated by lesion location, patient gender and, in case of MMs, presence of a pre-existing naevus. Significant differences between equivocal benign lesions, MIS and invasive MMs, and smaller and larger lesions belonging to the same diagnostic group, were evaluated by means of the v2 test of independence (Fisher’s exact test was applied if any expected cell value in the 2 · 2 table was < 5). For multivariate analysis, discriminant analysis was performed for identification of the independently significant features for distinguishing between melanomas (invasive MMs + MIS) and naevi, and MIS and invasive MMs. Stepwise forward selection was used to choose the features for the prediction model. Wilk’s lambda was used to determine whether the models adequately described the data. At each step, the predictor with the largest F to Enter value that exceeds the entry criteria (by default, 3Æ84) was added to the model. Variables with F to Enter values smaller than 3Æ84 were left out the model. P < 0Æ05 was considered significant.
Results The study included a total of 255 melanocytic lesions from the trunk and limbs of 255 patients (109 female and 146 male, mean ± SD age 50Æ6 ± 17Æ4 years). Eighty-five lesions were histologically diagnosed as MIS, 85 as invasive MMs (mean ± SD thickness 1Æ5 ± 2Æ4 mm), and 85 as naevi according to conventional histopathological criteria. Table 2 shows the results of the assessment of regression parameters in equivocal lesions, MIS and invasive MMs. In MIS regression structures (i.e. blue areas and ⁄or white areas and ⁄or peppering and ⁄or blue-whitish veil) were present in 77Æ6% of the lesions, whereas in invasive MMs and equivocal lesions regression was observable in 92Æ9% and 90Æ6%, respectively. Blue areas were significantly more represented in equivocal lesions and invasive MMs by comparison with MIS. Peppering was observable in the same percentage of MIS and
Table 2 Frequency (%) of regression descriptors in equivocal lesions, melanoma in situ (MIS) and invasive malignant melanoma (MM) Equivocal lesions MIS Invasive MMs (85 = 100%) (85 = 100%) (85 = 100%) Regressiona present Blue areas Peppering White areas Blue-whitish veil Pink areas Light brown areas Regression of dermoscopic structures
90Æ6 89Æ4 8Æ2 7Æ1 11Æ8 34Æ1 56Æ5 90Æ6
77Æ6b 71Æ8b 36Æ5b 11Æ8 20Æ0 56Æ5b 81Æ2b 91Æ8
92Æ9c 85Æ9c 37Æ6b 29Æ4bc 63Æ5bc 60Æ0b 52Æ9c 71Æ8bc
a
Blue areas and ⁄ or peppering and ⁄ or blue-whitish veil and ⁄ or white areas. bSignificant by comparison with equivocal lesions (P < 0Æ05). cSignificant by comparison with MIS (P < 0Æ05).
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invasive MMs (approximately 37%); in contrast, in equivocal lesions it was found in only 8Æ2% of cases. White areas and blue-whitish veil were noticed in 29Æ4% and 63Æ5% of invasive MMs, respectively: these percentages are significantly greater than those in the other two groups. Pink areas were observed in one-third of equivocal lesions (34Æ1%), in half of the MIS (56Æ5%) and in more than half of invasive MMs (60%). Light brown areas were significantly more present in MIS (81Æ2%) with respect to equivocal lesions and invasive MMs, whereas regression of dermoscopic structures was significantly more frequent in equivocal lesions and MIS than in invasive MMs. On the whole, MIS showed a lower percentage of regression and blue areas and a greater presence of light brown areas with respect to equivocal lesions and invasive MMs; MIS also showed peppering in a higher percentage than equivocal lesions but in a similar percentage to invasive MMs, whereas white areas and blue-whitish veil were less represented than in invasive MMs. Finally, both equivocal lesions and MIS were characterized by regression of dermoscopic structures, which, in contrast, were less frequently observed in invasive MMs. Table 3 shows data regarding pattern and extent of blue areas. Blue areas were more frequently structureless in equivocal lesions and invasive MMs, whereas the reticular pattern prevailed in MIS. In equivocal lesions and MIS blue areas involved 10–50% of the lesion area in approximately 50% of cases, whereas 41Æ1% of invasive MMs showed an involvement of > 50% of the lesion. No significant differences were observed as regards distribution of blue areas in the centre or at the periphery of equivocal lesions, MIS and invasive MMs (data not shown). Blue areas, peppering, blue-whitish veil and white areas were variously combined in the different lesion groups (Table 4). Equivocal lesions were characterized by the presence of blue areas alone in the majority of cases (76Æ6%) (significant with respect to the other groups). In MIS 39Æ4% of the lesions showed only blue areas, 21Æ2% showed blue areas with peppering and 12Æ1% exhibited blue areas associated with blue-whitish veil. In contrast, in invasive MMs blue areas alone were observable in only 15Æ2% of cases; approximately one-third of Table 3 Frequency (%) of pattern and extent of blue areas in equivocal lesions, melanoma in situ (MIS) and invasive malignant melanoma (MM)
Blue areas
Equivocal lesions (76 = 100%)
MIS (61 = 100%)
Invasive MMs (73 = 100%)
Structureless Reticular Globular < 10% 10–50% > 50%
84Æ2 15Æ8 17Æ1 26Æ3 48Æ7 25
63Æ9a 60Æ7a 24Æ6 18 54Æ1 27Æ9
89b 20Æ5b 28Æ8 11a 47Æ9 41Æ1a
invasive lesions showed blue areas associated with the veil, whereas in 17Æ7% of cases blue areas and the blue-whitish veil were observed together with peppering. Peppering was the only expression of regression in four MIS and one invasive MMs. We did not observe isolated white areas in MIS. All four traditional regression parameters were present together in 12Æ7% of invasive MMs, 7Æ6% of MIS and in no equivocal lesions. Table 5 shows the number of regression parameters in the study population. One regression parameter was present in 77Æ9% of equivocal lesions and in a significantly lower percentage in MIS (45Æ5%) and invasive MMs (21Æ5%). The presence of two regression criteria was found in a similar percentage in MIS and invasive MMs, whereas three regression parameters or more were found with a significantly increasing trend from equivocal lesions to invasive MMs (6Æ5%, 18Æ2% and 41Æ8%, respectively). When subdividing our cases according to the diameter of the lesion, we observed a significantly higher percentage of lesions showing regression (blue areas, white areas, peppering and veil) in the groups with a diameter > 1 cm, both MIS (90Æ6% vs. 69Æ8%) and invasive MMs (98Æ1% vs. 84Æ8%), whereas no differences were observed for equivocal lesions. Table 6 shows the frequency, extent, location and pattern of blue areas alone according to lesion diameter (other parameters of regression are not shown). Whereas in equivocal lesions and invasive MMs no differences in the frequency of blue areas in the two lesion groups were observed, blue areas were significantly more frequent in MIS with a diameter > 1 cm than in smaller MIS (84% vs. 64%). In larger invasive MMs blue structures involved a relatively greater area, and showed a more peripheral location with respect to smaller invasive lesions. Moreover, in the former group, 28% of blue areas showed a reticular pattern. As regards the frequency of regression according to clinical parameters, no differences were observed according to different body sites, whereas in males, regression was more frequent if compared with females in all three lesion groups (significant only in MIS). Moreover, regression parameters were detected with a similar frequency in melanoma arising de novo and in melanoma growing on a previous naevus both in in situ and in invasive lesions. Table 7 illustrates the unstandardized coefficients calculated by multivariate analysis, characterizing melanomas vs. naevi and invasive MMs vs. MIS. Naevi are characterized by the presence of blue areas not associated with other regression parameters (blue areas only), whereas independently related features for melanoma are white areas, reticular blue areas, veil and pink areas. Moreover, MIS are distinguished from invasive MMs by the presence of reticular blue areas, regression of dermoscopic structures and light brown areas, whereas regression, white areas and the veil characterize invasive MMs.
Discussion
a
Significant by comparison with equivocal lesions (P < 0Æ05). b Significant by comparison with MIS (P < 0Æ05).
One of the most interesting dermoscopic features commonly seen in MMs is represented by blue-white structures, the
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306 Dermoscopic marker of melanoma in situ, S. Seidenari et al.
Equivocal lesions MIS Invasive MMs (77 = 100%) (66 = 100%) (79 = 100%)
Regression parameters
Only peppering 0 Only blue areas 76Æ6 Only white areas 1Æ3 Only blue-whitish veil 0 Peppering + blue-whitish veil 0 Peppering + blue areas 5Æ2 Peppering + white areas 0 Blue areas + white areas 2Æ6 Blue areas + blue-whitish veil 7Æ8 White areas + blue-whitish veil 0 Blue areas + white areas + blue-whitish veil 2Æ6 Peppering + blue areas + blue-whitish veil 2Æ6 White areas + blue areas + peppering 1Æ3 White areas + blue-whitish veil + peppering 0 All parameters 0
6Æ1 39Æ4a 0 0 0 21Æ2a 1Æ5 1Æ5 12Æ1 0 0 6Æ1 4Æ5 0 7Æ6a
Table 4 Combination of regression parameters among lesions with regression
1Æ3 15Æ2ab 5Æ1 0 0 6Æ3b 1Æ3 1Æ3 27Æ8ab 0 10Æ1 17Æ7ab 1Æ3 0 12Æ7a
a Significant by comparison with equivocal lesions (P < 0Æ05). bSignificant by comparison with MIS (P < 0Æ05). MIS, melanoma in situ; MM, malignant melanoma.
Table 5 Number of regression parameters in lesions with regression Number of regression parameters
Equivocal lesions (77 = 100%)
MIS (66 = 100%)
Invasive MMs (79 = 100%)
1 2 ‡3
77Æ9 15Æ6 6Æ5
45Æ5a 36Æ4a 18Æ2a
21Æ5ab 36Æ7a 41Æ8ab
a Significant compared with equivocal lesions (P < 0Æ05). bSignificant compared with MIS (P < 0Æ05). MIS, melanoma in situ; MM, malignant melanoma.
equivalent of histological regression phenomena.3,17–19 Dermoscopic signs of regression are considered important for the diagnosis of melanoma.20,21 Blue-white structures comprise white areas, scar-like or associated with a reddish shade, blue areas2,4–6,14,22–30 or a combination of both. Histologically, white areas correspond to fibrosis, whereas blue areas correspond to melanophages in the dermis.3,7–9,31 Despite different histopathological substrates,6 blue areas and the bluewhitish veil are dermoscopically difficult to distinguish.3,4 They represent ambiguous terms because of the unfeasibility of a precise classification, and display a poor interobserver reproducibility.4,32,33 Therefore, they are generally considered together and described by the unifying definition of blue structures, which include any type of blue coloration. Features of partial regression are found in a variable percentage of primary MMs cases34,35 and in half of equivocal lesions.3 The presence of regression might be a confounding feature both for histopathological differentiation between melanoma and naevus and for the assessment of the level of invasion in melanoma.11 In MMs, features of regression vary according to MMs progression. Regression is a dynamic
phenomenon, a continuum of dermal changes which include neoangiogenesis, dense infiltrate with lymphocytes and melanophages (especially in the early stages) and, in the late phases, diffuse fibrosis with tumour obliteration and ⁄or dense infiltrate of melanophages, and corresponds to a reorganization of the lesion during the process of growth. Stante et al.13 found a significant association between the presence of an irregular pigment network and MMs thinner than 0Æ75 mm, whereas MMs thicker than 0Æ75 mm were associated with radial streaming, atypical vascular pattern and grey-blue areas. The latter were present in only 18% of MIS, but in 100% of MMs thicker than 1Æ5 mm. In contrast, Pizzichetta et al.14 found the same frequency of grey-blue areas in invasive MMs and in MIS, namely 79% and 76%, respectively. We found that invasive MMs show aspects of regression in 93% of cases, whereas in MIS regression was observed in 78%. The high percentage of equivocal lesions showing regression in our study indicates that melanocytic lesions with features of regression are more frequently selected for removal and considered as equivocal lesions even in the absence of other suspicious dermoscopic features. In fact, our equivocal lesions showed, in most cases, blue areas with a structureless pattern as the only sign of regression, whereas peppering, white areas and the veil were rarely observed. Moreover, only one quarter of the lesions showed an involvement by regression in more than 50% of their area, and the amount of regression did not increase when the lesion showed a larger diameter. In the study by Zalaudek et al.3 the majority of naevi exhibited blue areas with a central distribution and involving < 50% of the lesion surface; in contrast, 80% of equivocal lesions revealed a combination of white and blue areas with an irregular distribution and involving > 50% of the lesion area. The presence of extensive regression should represent an indication for biopsy even in the absence of dermoscopic criteria for MMs.21 2010 The Authors
Journal Compilation 2010 British Association of Dermatologists • British Journal of Dermatology 2010 163, pp302–309
Dermoscopic marker of melanoma in situ, S. Seidenari et al. 307 Table 6 Frequency (%), extent, location and pattern of blue areas according to lesion diameter Equivocal lesions
Blue areas (number of lesions £ 1 cm and > 1 cm) Extent < 10% 10–50% > 50% Localization Central Peripheral Both Pattern Structureless Reticular Globular
MIS
Invasive MMs
£ 1 cm (n = 70)
> 1 cm (n = 15)
£ 1 cm (n = 53)
> 1 cm (n = 32)
£ 1 cm (n = 33)
> 1 cm (n = 52)
62 = 100%
14 = 100%
34 = 100%
27 = 100%
26 = 100%
47 = 100%
25Æ8 51Æ6 22Æ6
28Æ6 35Æ7 35Æ7
26Æ5 47Æ1 26Æ5
7Æ4 63Æ0 29Æ6
15Æ4 61Æ5 23Æ1
8Æ5 40Æ4 51Æ1a
30Æ6 17Æ7 51Æ6
28Æ6 7Æ1 64Æ3
35Æ3 17Æ6 47Æ1
37Æ1 14Æ8 48Æ1
53Æ8 7Æ7 38Æ5
23Æ4 14Æ9a 61Æ7
85Æ5 14Æ5 12Æ9
78Æ6 21Æ4 35Æ7a
61Æ8 58Æ8 23Æ5
66Æ7 63Æ0 25Æ9
80Æ8 7Æ7 34Æ6
93Æ6 27Æ7a 25Æ5
a
Significant by comparison with lesions of the same population with diameter £ 1 cm (P < 0Æ05). MIS, melanoma in situ; MM, malignant melanoma.
Table 7 Unstandardized coefficients calculated by multivariate analysis, characterizing melanomas vs. naevi and melanoma in situ (MIS) vs. invasive malignant melanoma (MM)
Melanomas vs. naevi
MIS vs. invasive MMs
Parameter
Unstandardized coefficienta
White areas Reticular blue areas Veil Pink areas Blue areas only
3Æ02 2Æ60 0Æ93 0Æ62 )0Æ89
Parameter Regression White areas Veil Light brown areas Regression of dermoscopic structures Reticular blue areas
Unstandardized coefficientb )0Æ93 )0Æ90 )0Æ85 0Æ55 0Æ66 1Æ26
a
Positive values are correlated to melanoma. bPositive values are correlated to MIS.
Based on our data, regression is not only more frequent and extensive in invasive MMs with respect to in situ lesions, but it also has a different morphological expression. Whereas in invasive lesions it is frequently detectable as grey-blue structureless areas often associated with a bluish veil and white structures, in MIS it is often visible as a coarse blue-grey net, with thick grey-blue lines and large holes, corresponding to pink regression areas (reticular blue areas). In the latter lesion group, the fading of the net or of other dermoscopic structures in circumscribed zones of the lesion gives rise to areas of structureless light brown pigmentation. As regards lesion size, in invasive MMs the regression process evolves in parallel with horizontal proliferation. According to our data, the surface involved by regression increases according to lesion diameter, and blue areas are greater in extent and peripherally located in larger lesions. The differences in the frequency and distribution of various dermoscopic descriptors of regression in the different growth phases of
MMs are based on histopathological changes depending on tumour depth. Grey-blue areas, as an expression of the presence in the mid-reticular dermis of pigmented melanocytes or melanophages, are observed in thick MMs, probably because of neoplastic melanocytic infiltration in the mid-reticular dermis.13 In contrast, in in situ lesions grey-blue areas are presumably due to a deep melanophagic infiltration.13 Light brown areas may represent the start of the regression phenomenon, followed by a disarrangement later expressed by reticular blue structures. In lesion zones of MIS corresponding to light brown areas, the disappearance of the rete ridges and the scarcity of intraepidermal melanin may explain the lack of an evident pigment network and the light brown diffuse pigmentation.16 In conclusion, our study shows that frequency, morphology, extent and distribution of regression vary according to MMs thickness and diameter, and that the dermoscopic correspondence of regression phenomena varies in benign and
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308 Dermoscopic marker of melanoma in situ, S. Seidenari et al.
malignant lesions. Most thick melanomas show a combination of different dermoscopic descriptors of regression. On the other hand, lesions with blue areas with a structureless pattern as the only sign of regression have high probabilities to be benign lesions and do not need removal. Finally, lesions with reticular blue regression and light brown areas should undergo surgical excision for the suspicion of an MIS. Dermoscopic markers of thin MMs are extremely useful for early diagnosis and patient recovery. Most at-risk patients periodically attending our outpatient department for early diagnosis of melanoma are subjects with numerous equivocal and in situ malignant lesions. Thus, the most interesting point of our study was the identification of the reticular pattern of blue regression as a statistically significant discriminator and a reliable predictor of MIS.
What’s already known about this topic? • Dermoscopic parameters of regression represent important diagnostic criteria for melanoma.
What does this study add? • Our study shows that frequency, morphology, extent and distribution of regression vary according to melanoma thickness and diameter. • Lesions with reticular blue regression areas and light brown areas should be excised with the suspicion of an early melanoma, as the reticular pattern of blue regression represents a significant predictor and a reliable marker of melanoma in situ.
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