10.5826/dpc.1204a197
Background:: Early diagnosis can improve melanoma prognosis. Dermoscopy can enhance early melanoma recognition.
Objectives: Examine the dermoscopy features of early melanoma up to a maximum surface diameter of 6mm.
Methods: Consecutive melanoma cases were collected from two medical practices in Sydney, Australia 2019-2021. Dermoscopy features were recorded for melanomas by maximum surface diameter, to the nearest 0.1 mm, to a limit of 6mm.
Results: Total cases numbered 100; with males (n=48) and females (n=52), melanoma in situ (MIS, n=96) and invasive (n=4). The most frequent anatomic sites on both males and females were back (males n=20, females n=16) then knee or leg (males n=8, females n=12). Minimum respective MIS diameters for males/females was 1.2/2.0mm and for invasive cases 2.0/3.4mm. Highest frequency dermoscopy features were: light brown, dark brown, grey and asymmetric melanoma shape. Brown pigment in hair follicles were more frequent on legs compared to other anatomic sites [OR 14.6, 95%CI (1.29-165.17), p 0.03]. Pseudopods were substantially increased in frequency comparing diameters less than 4mm with 4 up to 6mm [OR 8.81, 95%CI (1.05-73.9), p 0.004]. Structureless area cases recorded increased grey [OR 7.08, 95%CI (1.61-31.11) p=0.01]. Melanomas with edge angulation were noted in 20-50% of cases across diameters 1-6mm, less frequent were pigmented circles and polygons.
Conclusion: Watch out! MIS presented with a surface diameter of just 1.2 mm and invasive melanoma 2.5mm. Pseudopods were a strong clue to melanomas with a surface diameter less than 5mm. We found melanomas on leg sites displayed more frequent pigmented hair follicles.
text/xml
2160-9381
2293
en
Andrew  Trang
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
early small melanoma, dermoscopy, confocal microscopy, pigmented hair follicles, pseudopods, polygons.
The hunt for baby melanomas: a prospective study of the dermoscopy features on 100 small melanoma cases with in vivo surface diameters up to a maximum of 6mm.
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2022-10-31
2021-12-31
2022-10-31
2022-12-02
e2022197
Dermatol Pract Concept
Background:: Early diagnosis can improve melanoma prognosis. Dermoscopy can enhance early melanoma recognition.
Objectives: Examine the dermoscopy features of early melanoma up to a maximum surface diameter of 6mm.
Methods: Consecutive melanoma cases were collected from two medical practices in Sydney, Australia 2019-2021. Dermoscopy features were recorded for melanomas by maximum surface diameter, to the nearest 0.1 mm, to a limit of 6mm.
Results: Total cases numbered 100; with males (n=48) and females (n=52), melanoma in situ (MIS, n=96) and invasive (n=4). The most frequent anatomic sites on both males and females were back (males n=20, females n=16) then knee or leg (males n=8, females n=12). Minimum respective MIS diameters for males/females was 1.2/2.0mm and for invasive cases 2.0/3.4mm. Highest frequency dermoscopy features were: light brown, dark brown, grey and asymmetric melanoma shape. Brown pigment in hair follicles were more frequent on legs compared to other anatomic sites [OR 14.6, 95%CI (1.29-165.17), p 0.03]. Pseudopods were substantially increased in frequency comparing diameters less than 4mm with 4 up to 6mm [OR 8.81, 95%CI (1.05-73.9), p 0.004]. Structureless area cases recorded increased grey [OR 7.08, 95%CI (1.61-31.11) p=0.01]. Melanomas with edge angulation were noted in 20-50% of cases across diameters 1-6mm, less frequent were pigmented circles and polygons.
Conclusion: Watch out! MIS presented with a surface diameter of just 1.2 mm and invasive melanoma 2.5mm. Pseudopods were a strong clue to melanomas with a surface diameter less than 5mm. We found melanomas on leg sites displayed more frequent pigmented hair follicles.
Andrew  Trang
2022/10/31
10.5826/dpc.1204a197
e2022197
Faculty of Medicine, The University of New South Wales, Sydney, Australia  
2160-9381
early small melanoma, dermoscopy, confocal microscopy, pigmented hair follicles, pseudopods, polygons.
en
e2022197
Kreusch JF. Vascular patterns in skin tumours. Clin Dermatol. 2002; 20(3): 248-254.
The hunt for baby melanomas: a prospective study of the dermoscopy features on 100 small melanoma cases with in vivo surface diameters up to a maximum of 6mm.
https://dpcj.org/index.php/dpc/article/download/2293/1833
  The Hunt for Baby Melanomas: A Prospective
 Study of the Dermoscopy Features on 100 Small
Melanoma Cases with in Vivo Surface Diameters up
             to a Maximum of 6 mm
       John H Pyne1, Sarah MacDonald1, Susan M Beale1, Esther Myint1, Wei W Huang1,
                            Simon Paul Clark1, Andrew Trang1


1 Faculty of Medicine, The University of New South Wales, Sydney, Australia



Key words: early small melanoma, dermoscopy, confocal microscopy, pigmented hair follicles, pseudopods
Citation: Pyne JH, MacDonald S, Beale SM, et al. The hunt for baby melanomas: a prospective study of the dermoscopy features on
100 small melanoma cases with in vivo surface diameters up to a maximum of 6mm. Dermatol Pract Concept. 2022;12(4):e2022197.
DOI: https://doi.org/10.5826/dpc.1204a197
Accepted: March 27, 2022; Published: October 2022
Copyright: ©2022 Pyne et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-
NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use,
distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing Interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding Author: John Pyne, Associate Professor, Faculty of Medicine, The University of New South Wales, Sydney, 131 Ellesmere Rd
Gymea Bay NSW Australia. Ph +61 414 750 625. Fax +61 2 9525 3193. E-mail: j.pyne@uq.edu.au




  ABSTRACT             Introduction: Early diagnosis can improve melanoma prognosis. Dermoscopy can enhance early
                       ­melanoma recognition.
                       Objectives: Examine the dermoscopy features of early melanoma up to a maximum surface diameter
                       of 6 mm.
                       Methods: Consecutive melanoma cases were collected from two medical practices in Sydney, ­Australia
                       2019-2021. Dermoscopy features were recorded for melanomas by maximum surface diameter, to the
                       nearest 0.1 mm, to a limit of 6 mm.
                       Results: Total cases numbered 100; with males (N = 48) and females (N = 52), melanoma in situ
                       (MIS, N = 96) and invasive (N = 4). The most frequent anatomic sites on both males and females
                       were back (males N = 20, females N = 16) then knee or leg (males N = 8, females N = 12). Minimum
                       ­respective MIS diameters for males/females was 1.2/2.0 mm and for invasive cases 2.0/3.4 mm. High-
                        est frequency dermoscopy features were: light brown, dark brown, gray and asymmetric melanoma
                        shape. Brown pigment in hair follicles were more frequent on legs compared to other anatomic sites
                        (odds ratio [OR] 14.6; 95% CI 1.29-165.17, P 0.03). Pseudopods were substantially increased in
                        frequency comparing diameters less than 4 mm with 4 up to 6 mm (OR 8.81; 95% CI 1.05-73.9,
                        P 0.004). Structureless area cases recorded increased gray (OR 7.08; 95% CI 1.61-31.11, P=0.01).




Original Article | Dermatol Pract Concept. 2022;12(4):e2022197                                                                      1
                     Melanomas with edge angulation were noted in 20%-50% of cases across diameters 1-6 mm, less
                     frequent were pigmented circles and polygons.
                     Conclusions: Watch out! MIS presented with a surface diameter of just 1.2 mm and invasive melano-
                     ma 2.5 mm. Pseudopods were a strong clue to melanomas with a surface diameter less than 5mm. We
                     found melanomas on leg sites displayed more frequent pigmented hair follicles.




Introduction                                                    or greater were excluded. Cases with known previous topical
                                                                or ablative therapies, any previous partial biopsy or adja-
Primary cutaneous melanoma prognosis is optimal when            cent scars were also excluded. Each case was an attempted
early diagnosis leads to prompt effective intervention. How-    full excision with a 2mm dermoscopy identified margin.
ever, small diameter early melanoma cases are often feature     A dermoscopy image for each case was submitted along with
poor and may be difficult to recognize. The use of dermos-      each tissue specimen to the reporting pathologists. Further,
copy has been shown to enhance diagnostic accuracy for          representative Vivascope 1500 confocal images were also
melanoma [1-3]. Some recent publications have addressed         available to the reporting pathologists for difficult to diag-
the dermoscopy features of small early melanoma [4,5].          nose cases.
Additional evidence collated with the dermoscopy features          Excised tissue was examined routinely with hematoxylin
of smaller melanomas may facilitate diagnosing these early      and eosin staining followed with SOX 10 and PRAME stains
cases [6].                                                      if required. Inclusion of each case required an independent
    Recent commentary has questioned the value of diag-         histopathological diagnosis of melanoma from each of two
nosing melanoma with small diameters and suggested sus-         experienced dermato-histopathologists. Cases where only
picious pigmented lesions not be biopsied if less than 6mm      one of two dermato-histopathologists reported melanoma
­diameter [7].                                                  were also excluded.
                                                                   Atypical vessels were defined as dermoscopy identified
                                                                vessels within the melanoma “footprint” displaying a differ-
Objectives                                                      ent morphology or increased number of vessels per unit area
                                                                compared to vessels in the adjacent background skin out to
The main purpose of this study was to quantify the dermos-
                                                                10 mm from the edge of the melanoma, an example is dis-
copy features of melanoma cases with an in vivo maximum
                                                                played in Figure 5B. Asymmetric shape relates to the silhou-
horizontal diameter of up to and including 6 mm. A second
                                                                ette of the melanoma. Atypical network was defined when the
aim was to record how these dermoscopy features varied
                                                                width of lines forming a reticular brown network exceeded
by the surface diameters in 1mm increments for melanomas
                                                                the diameter of the adjacent dermal papillae, see ­Figure 5C.
presenting with a surface diameter of 6 mm or less.
                                                                Polygons were angular lines in polygonal shapes [8], see
                                                                Figure 6B. Structureless areas displayed no distinct features
Methods                                                         within the area concerned and had to occupy at least 20% of
                                                                the melanoma “footprint”, see Figure 5A.
Consecutive melanoma cases were prospectively collected
from routine workflow in 2 medical practices in Sydney,
Australia over 28 months from 2019 until 2021. One prac-
                                                                Results
tice was a referral practice with Vivascope 1500 confocal
­capability. The second practice was a primary care desig-      All cases presented as macules with no overt surface eleva-
nated skin cancer clinic. Ethics Approval was provided by the   tion. Patients had predominately northern European ancestry
­University of Queensland, Brisbane Australia (2016001221).     with fair skin and were typically Australian born. Following
All patients in the study provided informed consent for their   histopathologic diagnostic confirmation, a total of 100 mel-
data to enter the study. There were no exclusions based on      anoma cases were collected. Cases on males numbered 48
patient age or anatomic site.                                   (mean age 56) and on females 52 (mean age also 56), see
    Dermoscopy using either a Heine IC1 or VivaCam der-         Table 1. Study cases by anatomic site and sex are set out
matoscope recorded each case in vivo maximum horizontal         in Table 2. No cases were recorded on the following sites
diameter, measured in 0.1 mm increments, up to and includ-      on either sex: scalp, eyelid, chin, cutaneous or mucosal lip,
ing 6.0 mm. Cases with a maximum surface diameter 6.1mm         hand, fingers or toes. Females had an increased frequency of



2                                                                   Original Article | Dermatol Pract Concept. 2022;12(4):e2022197
                Table 1. Patient characteristics by sex and in vivo melanoma surface diameter.
                                                                               Male (N = 48)                   Female (N = 52)
 Age                                   Range (min, max)                             18-78                            29-90
 (years)                               Mean                                           56                               56
                                       IQR                                          45-66                            42-69
 Diameter of lesion (mm)               < 2.0                                          5                                0
                                       2.0-3.0                                        13                               15
                                       3.1-4.0                                        8                                13
                                       4.1-5.0                                        13                               16
                                       5.1-6.0                                        9                                8

IQR = interquartile range.




                             Table 2. Number of melanoma cases by sex and anatomic site.
               Anatomic Site                                Male (N = 48)                               Female (N = 52)
 Ear                                                               1                                             2
 Forehead                                                          1                                             0
 Nose                                                              1                                             0
 Neck                                                              1                                             1
 Chest                                                             6                                             6
 Back                                                   20 (1 invasive 0.5 mm)                                  16
 Upper arm                                                         2                                  8 (1 invasive 0.4 mm)
 Forearm                                                           3                                             3
 Abdomen                                                2 (1 invasive 0.5 mm)                                    0
 Thigh                                                  2 (1 invasive 0.4 mm)                                    3
 Knee or leg                                                       8                                            12
 Foot                                                              1                                             1

Number of melanoma cases by sex and anatomic site. All cases were melanoma in situ except four invasive cases. These 4 invasive cases are
identified by site and respective Breslow invasion depth.




melanomas on the upper arm compared to males: odds ratio               male case recorded a mitotic count: 1 per mm2 from the case
[OR] 4.16, 95% CI 0.836-20.7, P 0.08. For knee combined                on the back. The only invasive melanoma on a female was
with leg sites females also had more melanomas compared to             on the upper arm with a Breslow of 0.4 mm and 0 mitotic
males: OR 1.49, 95% CI 0.545- 4.05, P 0.44. Males ­recorded            count. There was no microscopic evidence of tumor induced
more melanomas on the back compared to females: OR                     ulceration on all four invasive cases. No cases of acral, nod-
1.61, 95% CI 0.707-3.67, P 0.26. However, none of these                ular or desmoplastic melanoma were recorded in this study.
anatomic site differences reached statistical significance.               When using dermoscopy the colors identified within
    Melanoma in situ was reported in 96 cases. The average             the melanoma with the highest percentage presence in de-
surface diameter for the melanoma in situ cases was 3.9 mm             scending order were: light brown, dark brown and gray,
(N = 96) and for the invasive melanoma cases 3.6 mm                    see ­Figure 1. Figure 1 also displays these dermoscopy fea-
(N = 4). On males the smallest recorded surface diameter for           tures with a typical frequency range from 50% up to 100%
a melanoma in situ case was 1.2 mm (chest) and for invasive            across the recorded range of diameters. In comparison, other
cases 2.5 mm (back). In comparison, on females the small-              dermoscopy identified features with moderate prevalence
est diameter melanoma in situ case was 2.0 mm (thigh) and              (frequency of feature from 15% up to 50%) are set out in
the single invasive case 3.4 mm (upper arm). Three invasive            Figure 2. Lower prevalence features (frequency at or below
melanoma cases were recorded on males: one with a Breslow              25% of cases) are displayed in Figure 4. Although low in
of 0.4 mm (thigh) the other two cases both had a Breslow of            frequency, typically less than 10% of cases, polygons were
0.5 mm (abdomen and back), again see Table 2. Only one                 recorded in cases over 2 mm diameter.



Original Article | Dermatol Pract Concept. 2022;12(4):e2022197                                                                         3
                All colors identified (light and dark brown, gray and                P 0.02. Finally, structureless areas were associated with
pink) within the melanoma rose in frequency as the diame-                            an increased presence of gray within the whole melanoma
ters increased from 1 to 6 mm, again se Figure 1. The excep-                         “footprint” (OR 7.08, 95% CI 1.61-31.11, P 0.01).
tion to this rise in frequency of color was black which had
frequencies 20% to 40% over the full range of diameters,
                                                                                     Conclusions
see Figure 2. Other dermoscopy features also increased in
frequency as diameters increased: asymmetric melanoma                                Nearly all cases in this study were detected by pattern analy-
shape (30 to 65%), atypical network (20 to 57%), grey cir-                           sis involving attention to features dominated by melanin pig-
cles (0 to 25%) and polygons (0 to 12%). Atypical vessels                            ment. Predominant color pink with scant minimum brown
fell from 20 to zero then increased to 12%. Angles at the                            was observed in only one case. There were no cases display-
edge of the melanoma increased then decreased with an                                ing all pink without brown. There may be a selection bias
overall range of frequencies from 20% to 47%.                                        favoring brown pigment cases. Amelanotic melanoma cases:
                A striking finding in this study was how focal pseu-                 those without clinical or dermoscopy evidence of brown pig-
dopods (11% of all cases, N = 11/100) can facilitate very                            ment, may be underrepresented.
small diameter melanoma recognition, see Figure 3. When                                 We integrated and combined all the relevant clinical,
comparing smaller melanomas with a surface diameter                                  dermoscopy and confocal features to facilitate diagnosis as
less than 4.0 mm to larger diameter 4.0 to 6.0 mm inclu-                             previously described to minimize the risk of missing a mel-
sive cases the presence of pseudopods was substantially                              anoma [9]. In equivocal cases all relevant information was
increased (OR 8.81, 95% CI 1.05-73.9, P 0.004). Brown                                readily available to the reporting histopathologists. This may
pigment within hair follicle infundibula were recorded in a                          have increased our diagnostic “pick up” rate compared to
total of eight cases (8%, 8/100). On the leg (3 out of these                         other studies.
8 cases) pigment in follicles were more frequent compared                               We found very similar mean surface diameters for mel-
to other sites (OR 14.6, 95% CI 1.29-165.17, P 0.03). Pink                           anoma in situ (3.9 mm) and invasive melanoma (3.6 mm).
occurred more frequently on non-leg sites (N = 40) out of all                        Previous studies have reported melanoma in situ and i­ nvasive
other sites combined (N = 43), OR 4.72, 95% CI 1.22-18.2,                            melanomas with diameters up to and including 3 mm [10],




                                  100

                                       90

                                       80
    PERCENTAGE OF CASES WITH FEATURE




                                       70

                                       60

                                       50

                                       40

                                       30

                                       20

                                       10

                                        0
                                                n=5                 n = 28          n = 21              n = 29                 n = 17

                                            1              2                  3                4                      5                      6
                                                                      SURFACE DIAMETER OF MELANOMA (mm)

                                                      LIGHT BROWN      DARK BROWN    GREY     PINK      ASSYMETRIC SHAPE

     Figure 1. Dermoscopy features with high prevalence by in vivo melanoma surface diameter.



4                                                                                        Original Article | Dermatol Pract Concept. 2022;12(4):e2022197
                                100

                                            90

                                            80
  PERCENTAGE OF CASES WITH FEATURE




                                            70

                                            60

                                            50

                                            40

                                            30

                                            20

                                            10

                                             0
                                                     n=5            n = 28           n = 21            n = 29        n = 17

                                                 1           2                3                4                 5            6
                                                                      SURFACE DIAMETER OF MELANOMA (mm)

                                                           BLACK     STRUCTURELESS       ANGLE AT EDGE OF MELANOMA

    Figure 2. Dermoscopy features with moderate prevalence by in vivo melanoma surface diameter.




                                     100

                                            90
         PERCENTAGE OF CASES WITH FEATURE




                                            80

                                            70

                                            60

                                            50

                                            40

                                            30

                                            20

                                            10

                                             0
                                                     n=5            n =28            n = 21            n = 29        n = 17

                                                 1           2                3                   4              5            6
                                                                    SURFACE DIAMETER OF MELANOMA (mm)
                                                                 PSEUDOPODS       DOTS        ATYPICAL NETWORK
    Figure 3. Dermoscopy features with progressive variation in prevalence by in vivo melanoma surface diameter.



Original Article | Dermatol Pract Concept. 2022;12(4):e2022197                                                                    5
                                       100

                                       90

                                       80
    PERCENTAGE OF CASES WITH FEATURE




                                       70

                                       60

                                       50

                                       40

                                       30

                                       20

                                       10

                                        0
                                                       n=5                  n =28                n = 21                n = 29                n = 17

                                             1                      2                   3                4                           5                     6
                                                                                  SURFACE DIAMETER OF MELANOMA (mm)

                                                  CIRCLES      PIGMENTED HAIR FOLLICLE OPENING                CLODS       Atypical vessels      Polygons

     Figure 4. Dermoscopy features of melanoma with low prevalence over all surface diameters.




                                                 Figure 5. (ABC) Displaying pseudopods, structureless area, atypical vessels, atypical network and
                                                 angular edge of melanoma.



6                                                                                                         Original Article | Dermatol Pract Concept. 2022;12(4):e2022197
                    Figure 6. (ABC) Displaying pigmented hair follicular opening, polygons and circles.




(N = 23, invasive cases N = 19). These findings sound a warn-         later in development rather than originating or appearing up
ing to both clinicians and pathologists that macules with an          out of infundibula in earlier stage development.
in vivo diameter of 6 mm or even substantially less require               Our finding increased grey associated with structureless
vigilance for melanoma diagnosis and even early metastatic            areas in the melanoma may indicate increased melanin at
potential. Only 5 of our cases had a maximum surface diam-            the level of the papillary dermis following a host immune
eter less than 2 mm. Except for the presence of pseudopods            response. This finding could be substantiated with further
the lack of distinctive features in these very small cases may        investigation. Atypical vessels noted in this study were typi-
account for such a low detection rate.                                cally an increase in dot vessels per unit area within the mel-
    A dermoscopy image of each case was submitted to the              anoma. These dot vessels may represent increased perfusion
reporting Pathologists at the same time as the tissue sub-            in the superficial dermal vessels as previously described [12]
mission. Confocal microscopy images were also available               rather than true tumor induced neovascularization.
to enhance diagnostic certainty for some cases as this has                Clinicians and pathologists need to be vigilant with small
been demonstrated [11]. Future investigation could quantify           suspicious cases displaying melanoma associated features
the contribution of this additional information in small size         presenting with diameters much less than 6 mm. We found
cases compared to just examining the histology slides and             the lowest recognition threshold diameter for melanoma in
the routine notes supplied by the clinician on the pathology          situ was 1.2 mm and for invasive melanomas 2.5 mm.
request documentation.                                                    In descending order, we found the following colors pres-
    One explanation of brown pigment within a hair follicle           ent in melanomas with a maximum surface diameter up to
infundibulum is melanocytes producing melanin at this site.           6 mm: light brown, dark brown, grey, pink then black. Other
We found melanomas in our study with a diameter three mm              dermoscopy features which were clues to these small early
or less did not display brown pigment in hair follicule infun-        melanomas include: asymmetric macule shape, angulation
dibula. Pigment was found in larger melanomas with diam-              on the edge of the melanoma, pseudopods, pigmented fol-
eters over 3 mm, see Figure 3. This finding suggests melanin          licular infundibula, structureless areas, atypical network and
producing melanocytes spread down into the infundibula                pigmented circles.



Original Article | Dermatol Pract Concept. 2022;12(4):e2022197                                                                    7
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