Anatomic mapping and clinicopathologic analysis of benign acral melanocytic neoplasms: A comparison between adults and children

DERMATOPATHOLOGY

Anatomic mapping and clinicopathologic analysis of benign acral melanocytic neoplasms: A comparison between adults and children Na Hee Kim, MD,a Yoo Duk Choi, MD, PhD,b Hyun Ju Seon, MD, PhD,c Jee-Bum Lee, MD, PhD,a and Sook Jung Yun, MD, PhDa Gwangju, Korea Background: The clinicopathologic features of benign acral melanocytic neoplasms (BAMNs) remain poorly understood. Objective: To define the clinicopathologic features of BAMNs. Methods: We analyzed clinical data and mapped BAMNs anatomically. We also reviewed the histopathologic features of BAMNs and compared these between adults and children. Results: We included 396 cases of BAMN: 335 adults and 61 children (376 acquired and 20 congenital lesions). Anatomic mapping revealed that the nonweight-bearing portion of the foot was the most common site in adults (120/335, 35.8%) and the forefoot the most common site in children (17/61, 27.9%) for BAMNs. The long axes of the BAMNs paralleled the dermatoglyphic lines on the palms and soles, as did most tissue sections. The lesion diameters were \5.7 mm in all acquired lesions. Histopathologically, we diagnosed 69 lentigo simplex, 201 junctional, 114 compound, 8 intradermal, and 4 blue nevi. Corneal pigmentation, nests located between rete ridges, dendrite prominence, and cytologic atypia were all significantly more common in children than adults. Limitations: The retrospective study design and acquiring patients from a single institution of a single country limited the research results. Conclusion: BAMNs develop most commonly on nonweight-bearing regions of the soles in adults and on the forefoot in children. The long axis of the lesion follows the dermatoglyphics, and cytologic atypia is more common in children. ( J Am Acad Dermatol http://dx.doi.org/10.1016/j.jaad.2017.02.041.) Key words: adults; anatomic mapping; benign acral melanocytic neoplasms; children; clinical features; cytological atypia; histopathological analysis.

M

elanocytic nevi of special sites refer to nevi on the skin of particular body regions, such as the genitals, acral or flexural sites, and the head and neck.1-5 Nevi at such sites overlap in

From the Departments of Dermatology,a and Pathology,b Chonnam National University Medical School, Gwangju; and Department of Radiology, Chosun University School of Medicine, Gwangju.c Funding sources: Supported by Chonnam National University Hwasun Hospital Institute for Biomedical Science (grant HCRI 15 016-22). Conflicts of interest: None declared. Accepted for publication February 16, 2017.

Abbreviation used: BAMNs:

benign acral melanocytic neoplasms

Reprint requests: Sook Jung Yun, MD, PhD, Department of Dermatology, Chonnam National University Medical School, 160 Baekseo-Ro, Dong-Gu, Gwangju 61469, South Korea. E-mail: [email protected]. Published online July 1, 2017. 0190-9622/$36.00 Ó 2017 by the American Academy of Dermatology, Inc. http://dx.doi.org/10.1016/j.jaad.2017.02.041

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Anatomic mapping of BAMNs terms of architectural and cytologic features with The acral sites were subdivided into various those of dysplastic nevi or melanomas.1 Melanocytic regions, as described previously.10 We divided the nevi on acral volar sites are especially challenging to diagnose. Acral melanocytic nevi have been referred sole into 3 regions (forefoot, midfoot, and heel) and to as melanocytic acral nevi having intraepidermal each region into various areas based on the extent of ascending cells6 and acral lentiginous nevi of physical stress to which the area was subjected. The forefoot is the metatarsal area of the sole and is a plantar skin7 because of their similarities to melaweight-bearing area. The nomas. Benign acral melanomidfoot includes the medial cytic neoplasms (BAMNs) CAPSULE SUMMARY arch (nonweight-bearing) describe all benign melanoand the cuboid bone cytic proliferations, including Benign acral melanocytic neoplasms (weight-bearing). The heel lentigo simplex and melanohave received minimal attention in is the most weight-bearing cytic nevi. The differential clinicopathologic studies. portion of the sole. We histopathologic diagnosis of Benign acral melanocytic neoplasms marked BAMNs on the acral junctional nevi and more commonly develop on the palms, soles, and the volar acral lentiginous melanoma nonweight-bearing regions of the sole in surfaces of the fingers and is sometimes difficult; the adults and the forefoot in children; the toes. We reviewed all clinical final diagnosis is often long axis of the lesion parallels the photographs to determine if based on clinicopathologic dermatoglyphics. the long axes of the BAMNs correlations.8 Dermoscopy ran parallel to the dermatohas become essential for Prominent dendrites and cytologic glyphic lines of the palms differentiating BAMNs from atypia are more common in children. and soles. acral melanomas9; however, histopathologic analysis of Histopathologic analysis BAMNs remains the diagnostic gold standard. In A total of 396 formalin-fixed paraffin-embedded our present study, we defined the clinical and histospecimens were examined. We determined whether pathologic features of BAMNs in Korean patients, each specimen had been cut in a direction perpenand we compared the anatomic locations of BAMNs dicular or parallel to that of the creases in the skin to those of acral melanomas.10 We reviewed the (the dermatoglyphics). We explored both architecmorphologic shapes of the nevi and correlated these tural and cellular morphologic features, following data with the histopathologic features of BAMNs on the suggestions of Viros et al.11 We histopathologiboth adults and children. cally diagnosed lentigo simplex, junctional nevi, compound nevi, intradermal nevi, and blue nevi. METHODS Congenital nevi included both compound and intraPatients dermal nevi with congenital features. However, our We evaluated 396 patients with BAMNs who were diagnoses did not distinguish congenital features treated at Chonnam National University Hospital and histopathologically. Chonnam National University Hwasun Hospital from 2004 through 2015. We included the patients for Analysis of architectural pattern: Shoulders, whom we had both clinical photographs and histobridges, and pagetoid scatter pathology slides available documenting their BAMN First, we analyzed the epidermal architecture lesions. Almost all patients with BAMNs treated (normal, thinned, or thickened) by BAMN type. We during the study period were included in the next explored shoulder and bridge formation. A analysis; most patients consented to skin biopsy. shoulder was defined as an epidermal nest of We performed anatomic mapping. We reviewed melanocytes extending laterally from the central medical records, clinical photographs, and clinical dermal component. A bridge was defined as a fusion data. We divided BAMNs into acquired and congenof elongated rete ridges. The extent of upward ital (present since birth) lesions by taking patient (pagetoid) scatter was graded from 1 to 3 based on histories and conducting histopathologic analyses. the following scale: a score of 1 was assigned if the Lesion size can help differentiate benign from mamajority (75%-100%) of melanocytes were located at lignant lesions, so we measured the length and width the dermoepidermal junction with only a few scatof all lesions. We considered those \15 years of age tered in the epidermis; a score of 2 was assigned if to be children. The study protocol was approved by the proportion of intraepidermal melanocytes the institutional review board of Chonnam National located at the dermoepidermal junction were almost University Hwasun Hospital. d

d

d

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Table I. Demographic data on 335 adults with benign acral melanocytic neoplasms

Table II. Demographic data of 61 children with benign acral melanocytic neoplasms

Variables

Variables

Sex Male Female Age distribution at diagnosis, years 16-30 31-40 41-50 51-60 61-70 71-80 811 Disease duration Congenital lesion Acquired lesion Site of lesion Palm Sole Forefoot Midfoot Heel Finger volar Toe volar Size of lesion Congenital lesion Length Width Acquired lesion Length Width Tissue section direction Parallel to dermatoglyphics Perpendicular to dermatoglyphics Histopathological subtype Lentigo simplex Junctional nevus Compound nevus Intradermal nevus Blue nevus

n (%) 75 (22.4) 260 (77.6) n (%) 82 (24.5) 69 (20.6) 91 (27.2) 68 (20.3) 21 (6.3) 4 (1.2) 0 (0) Mean 6 SD, months 367.5 6 121.2 85.4 6 119.4 n (%) (right/left) 22 (6.5) (8/14) 258 (77.0) (143/115) 52 (20.2) (29/23) 120 (46.5) (71/49) 86 (33.3) (43/43) 16 (4.8) (8/8) 39 (16.5) (14/25) Mean 6 SD, mm 19.5 6 5.3 9.3 6 1.5 5.7 6 2.9 4.6 6 2.1 n (%) 301 (89.9) 34 (10.1) n (%) 63 (18.8) 162 (48.6) 99 (29.6) 7 (2.1) 4 (1.2)

SD, Standard deviation.

equivalent with the proportion in the higher epidermal layers; and a score of 3 was assigned if most ([50%) intraepidermal melanocytes were located in the upper epidermal layers. Histopathologic analysis of melanocytic nests Nesting was graded as follows: a 0 was given if intraepidermal melanocytes were all singular and not forming nests; a 1 was given if there were predominantly single melanocytes with only a few in nests; a 2 was given if the numbers of single melanocytes and nests were almost equal; and a 3 was given if there were predominantly

Sex n (%) Male 29 (47.5) Female 32 (52.5) Age distribution at diagnosis, years n (%) 0-5 15 (24.6) 6-10 27 (44.3) 11-15 19 (31.1) Disease duration Mean 6 SD, months Congenital lesion 88.7 6 56.4 Acquired lesion 34.7 6 38.6 Site of lesion n (%) (right/left) Palm 5 (8.2) (4/1) Sole 41 (67.2) (20/21) Forefoot 17 (41.5) (9/8) Midfoot 15 (36.6) (7/8) Heel 9 (21.9) (4/5) Finger volar 5 (8.2) (1/4) Toe volar 10 (16.4) (5/5) Size of lesion Mean 6 SD, mm Congenital lesion Length 11.1 6 5.2 Width 6.3 6 3.6 Acquired lesion Length 5.1 6 2.8 Width 3.6 6 1.8 Tissue section direction n (%) Parallel to dermatoglyphics 54 (88.5) Perpendicular to dermatoglyphics 7 (11.5) Histopathological subtype n (%) Lentigo simplex 6 (9.8) Junctional nevus 39 (63.9) Compound nevus 15 (24.6) Intradermal nevus 1 (1.6) SD, Standard deviation.

intraepidermal nests with only a few single melanocytes. We graded nest confluence and discohesion (poor cell-to-cell contact) as follows: 0 for no nests, 1 for 1 nest, 2 for 2-5 nests, and 3 for [5 nests. We determined whether the nests were situated at the tips, sides, or between epidermal rete ridges. Eccrine duct involvement was determined by checking whether the nests were located at an epidermal acrosyringium or a dermal eccrine duct.

Histopathologic analysis of the cytologic features of BAMNs The most distinctive epidermal melanocyte cell type was evaluated as round epithelioid, nevoid, oval, elongated, spindle, or Spitzoid. The presence of giant cells was also noted. We assessed the nature of single cell proliferation along the dermoepidermal junction as continuous, focally continuous, or

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Fig 1. Anatomic mapping of benign acral melanocytic neoplasms (BAMNs) on the volar feet. A, In 335 adults, 120 BAMNs were on nonweight-bearing portions of the foot, and 73 were on weight-bearing portions. B, In 61 children, the forefoot was the most common site for BAMNs when lesions on the right and left sides were mapped in combination.

noncontinuous. Prominent dendrites were also recorded. Cytologic atypia (mild, moderate, or severe), melanocyte mitosis, and dermal inflammation were recorded.

proliferation of melanocytes, prominent dendrites, severe cytologic atypia, and dermal mitoses. All lesions fulfilling these criteria for acral melanoma were excluded from study.

Exclusion criteria for BAMNs BAMNs were diagnosed by correlating clinical and histopathologic criteria. A diagnosis of acral melanoma might be made by considering a combination of several factors, including a larger acquired lesion, extensive pagetoid scatter, continuous

Statistical analysis All statistical analyses were performed using SPSS version 20.0 software (SPSS Inc, Chicago, IL). The Chi-squared test or Fisher’s exact test was used to compare differences in the histopathologic characteristics between adults and children. A P value \.05

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Fig 2. The long axes of benign acral melanocytic neoplasms in both adults and children run parallel to the dermatoglyphics of the forefoot (A), midfoot (B-D), and heel (E and F).

Fig 3. A and B, The furrows and ridges are readily apparent in specimens cut perpendicular to the dermatoglyphics. C and D, Furrows and ridges features are not seen in specimens cut parallel to the dermatoglyphics. (B and D, Hematoxylin-eosin stain; original magnifications: 340.)

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Table III. Histopathologic comparison of the features of acral lentigo simplex in adults and children

Features

Corneal pigmentation Absent Furrow dominant Ridge dominant Universal Architectural disorder Shoulder Bridge Pagetoid scatter Absent A few in epidermis Equal Mostly in epidermis Single cell proliferation Absent Continuous Focal continuous Noncontinuous Dendrites of melanocytes Prominent Not prominent Cytological atypia Absent Mild Moderate Severe Mitoses Present (epidermal melanocytes) Absent Dermal inflammation Absent Mild Moderate Severe

Adults (n = 63), N (%)

Children (n = 6), N (%)

Table IV. Histopathological comparison of the features of acral junctional nevi in adults and children P value

1.000 47 0 4 12

(74.6) (0) (6.3) (19.0)

0 (0) 27 (42.9)

5 0 0 1

(83.3) (0) (0) (16.7)

0 (0) 2 (33.3) .442

50 11 2 0

(79.4) (17.5) (3.2) (0)

4 2 0 0

(66.7) (33.3) (0) (0) 1.000

0 0 15 48

(0) (0) (23.8) (76.2)

0 0 1 5

(0) (0) (16.7) (83.3) .311

3 (4.8) 60 (95.2)

1 (16.7) 5 (83.3)

54 6 3 0

5 1 0 0

.624 (85.7) (9.5) (4.8) (0)

0 (0)

(83.3) (16.7) (0) (0)

0 (0)

63 (100.0)

6 (0)

62 1 0 0

6 0 0 0

1.000 (98.4) (1.6) (0) (0)

(100.0) (0) (0) (0)

was considered to indicate statistical significance. All statistical tests were 2 sided.

RESULTS Demographic data We enrolled 396 BAMN patients: 335 adults and 61 children. We analyzed adults (Table I) and children (Table II) separately. The adult cohort contained 75 male and 260 female patients (Table I). Only 25 patients were[60 years of age (7.5%), and no patient was [80 years of age. Specimens were cut parallel to

Features

Corneal pigmentation Absent Furrow dominant Ridge dominant Universal Architectural disorder Shoulder Bridge Pagetoid scatter Absent A few Many Nest degree Absent Mostly single cells Equal Mostly nest Confluence of nests Absent 1 nest 2-5 nests [5 nests Discohesion of nests Absent 1 nest 2-5 nests [5 nests Nests location Tips of rete ridge Side of rete ridge Between of rete ridge Around eccrine ducts Single cell proliferation Absent Continuous Focal continuous Noncontinuous Dendrites of melanocytes Prominent Not prominent Cytological atypia Absent Mild Moderate Severe Mitoses Present (epidermal melanocytes) Absent

Adults (n = 162), N (%)

Children (n = 39), N (%)

56 34 1 71

5 13 1 20

P value

.017 (34.6) (21.0) (0.6) (43.8)

(83.3) (33.3) (2.6) (51.3)

0 (0) 93 (57.4%)

0 (0) 18 (46.2)

71 (43.8) 86 (53.1) 5 (3.1)

15 (41.7) 20 (55.6) 1 (2.8)

0 93 40 29

(0) (57.4) (24.7) (17.9)

0 28 5 6

(0) (71.8) (12.8) (15.4)

127 24 7 4

(78.4) (14.8) (4.3) (2.5)

34 4 1 0

(87.2) (10.3) (2.6) (0)

98 23 31 10

(60.5) (14.2) (19.1) (6.2)

23 5 9 2

(59.0) (12.8) (23.1) (5.1)

156 45 46 75

(96.3) (27.8) (28.4) (46.3)

36 17 20 16

(92.3) (43.6) (51.3) (41.0)

2 10 57 93

(1.2) (6.2) (35.2) (57.4)

0 2 19 18

(0) (5.1) (48.7) (46.2)

.215 .834

.207

.768

.949

9 (5.6) 153 (94.4)

7 (17.9) 32 (82.1)

.380 .055 .006 .553 .462

.018 .002

90 55 16 1

(55.6) (34.0) (9.9) (0.6)

10 20 9 0

(25.6) (51.3) (23.1) (0) .051

2 (1.2)

3 (7.7)

160 (98.8)

36 (92.3) Continued

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Table IV. Cont’d

Features

Dermal inflammation Absent Mild Moderate Severe

Adults (n = 162), N (%)

Children (n = 39), N (%)

P value

.763 111 37 13 1

(68.5) (22.8) (8.0) (0.6)

27 6 3 0

(75.0) (16.7) (8.3) (0)

the dermatoglyphics in 301 patients (89.9%) and perpendicular in 34 (10.1%). The histopathologic diagnoses were lentigo in 63 cases, junctional nevi in 162, compound nevi in 99, intradermal nevi in 7, and blue nevi in 4. The cohort of children consisted of 29 boys and 32 girls (Table II). Specimens had been cut parallel to the dermatoglyphics in 54 patients (88.5%) and perpendicular in 7 (11.5%). The histopathologic diagnoses were lentigo simplex in 6 cases, junctional nevi in 39, compound nevi in 15, and intradermal nevus in 1. Lesion size differed for acquired and congenital lesions. The mean lesion dimensions in adults were 5.7 mm 3 4.6 mm in 327 patients with acquired lesions and 19.5 mm 3 9.3 mm in 8 patients with congenital nevi; the dimensions in children were 5.1 mm 3 4.6 mm in 49 patients with acquired lesions and 11.1 mm 3 6.3 mm in 12 patients with congenital nevi.

Anatomic mapping and clinical features of BAMNs We marked the sites of BAMNs. Among the 335 adults, 38 lesions were on the volar hands and 297 on the volar feet. A total of 120 BAMNs were located on nonweight-bearing portions of the foot, and 73 were on weight-bearing portions (Fig 1, A). Among the 61 children, 10 lesions were on the volar hands and 51 on the feet (Fig 1, B). In children, we mapped lesions onto a single sole (thus combining data from the right and left soles) because of the small number of patients. Interestingly, the long axes of the BAMNs in both adults and children ran parallel to the dermatoglyphics when the lesions were not circular (Fig 2). To study histopathologic features, we cut most specimens (;90%) parallel to the dermatoglyphics and examined microscopically. In specimens cut perpendicular to the dermatoglyphics, furrows and ridges were easily seen (Fig 3, A and B), but specimens cut parallel did not reveal the presence of furrows or ridges clearly (Fig 3, C and D).

Histopathologic features of acral lentigo simplex of adults and children Bridges were commonly noted in acral lentigo simplex samples from both adults and children (Table III). Mild pagetoid scatter and prominent dendrites were somewhat more common in children, but statistical significance was not attained. Continuous cell proliferation with severe cytologic atypia was evident, but no melanocytic mitoses were observed. Histopathologic features of the acral junctional nevi of adults and children Corneal pigmentation, nests between epidermal rete ridges, prominent dendrites, and cytologic atypia were more frequent in children (Table IV). Architectural bridges were commonly present in acral junctional nevi (Fig 4, A). Proliferation of single melanocytes along the basal layer was more common than nest formation in children (Fig 4, B). Mild pagetoid scatter was frequently observed. Discoherent nests were evident (Fig 4, C ); these were mostly located at the tips of rete ridges. Nests around eccrine ducts were observed in about 46% of adults and 41% of children (Fig 4, D). Prominent dendrites were more frequent in children (Fig 5, A-C ). Mild-to-moderate cytologic atypia was significantly more frequent in children (Fig 5, D). Only a few epidermal melanocytic mitoses were noted; no dermal mitoses were observed. Histopathologic features of acral compound nevi in adults and children Architectural shoulders and bridges were commonly seen in both adults and children (Table V). Mild-to-moderate pagetoid scatter was also frequent, and proliferation of single melanocytes along the basal layer (rather than nest formation) was common (Fig 6, A). Prominent dendrites were more frequent in children (Fig 6, B). Large discohesive nests with moderate cytologic atypia were commonly observed in the congenital melanocytic nevi of children (Fig 6, C and D). Mitoses in intraepidermal melanocytes were observed in 2 adults. Only prominent dendrites differed significantly between the acral compound nevi of adults and children.

DISCUSSION We analyzed the anatomic locations and clinical morphologies of BAMNs. Female patients predominated (78%) in the present study, although acral melanoma affects men and women in equal proportions.10 This could potentially be explained by women being more apprehensive of skin lesions and

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Fig 4. Histopathologic features of benign acral melanocytic neoplasms. A, Bridges between rete ridges of acral compound nevus. B, Single-cell proliferation along the basal layer. C, Discohesive nests in the epidermis of compound nevus. D, Nests along the eccrine duct of the dermis. (A-D, Hematoxylin-eosin stain; original magnifications: 3100).

Fig 5. Histopathologic features of benign acral melanocytic neoplasms. A, Continuous singlecell proliferation of spindle cells along the basal layer. B and C, Prominent dendrites visible. D, Cytologic atypia (large cells with prominent nucleoli) are apparent in compound nevus. (A and D, Hematoxylin-eosin stain; original magnifications: 3200; B and C, Melan A stain; original magnifications: 3200.)

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Table V. Histopathological comparison of the features of acral compound nevi in adults and children

Features

Corneal pigmentation Absent Furrow dominant Ridge dominant Universal Architectural disorder Shoulder Bridge Pagetoid scatter Absent A few in epidermis Equal Mostly in epidermis Nest Degree Absent Mostly single cells Equal Mostly nests Confluence of nests Absent 1 nest 2-5 nests [5 nests Discohesion of nests Absent 1 nest 2-5 nests [5 nests Nests location Tips of rete ridge Side of rete ridge Between of rete ridge Around eccrine ducts Single cell proliferation Absent Continuous Focal continuous Noncontinuous Dendrites of nevus cells Prominent Not prominent Cytological atypia Absent Mild Moderate Severe Mitoses Present (epidermal melanocytes) Absent Dermal inflammation Absent

Adults (n = 99), N (%)

Table V. Cont’d

Children (n = 15), N (%) P value

.814 35 20 0 44

(35.4) (20.2) (0) (44.4)

6 2 0 7

(40.0) (13.3) (0) (46.7)

49 (49.5) 7 (46.7) 62 (62.6) 9 (60.0) 42 54 3 0

(42.4) 3 (54.5) 11 (3.0) 1 (0) 0

(20.0) (73.3) (6.7) (0)

1 75 14 9

(1.0) 1 (75.8) 10 (14.1) 3 (9.1) 1

(6.7) (66.7) (20.0) (6.7)

74 14 8 3

(74.7) 10 (14.1) 1 (8.1) 4 (3.0) 0

(66.7) (6.7) (26.7) (0)

64 6 24 5

(64.6) (6.1) (24.2) (5.1)

7 2 5 1

(46.7) (13.3) (33.3) (6.7)

97 31 25 59

(98.0) 14 (31.3) 3 (25.3) 3 (59.6) 7

(93.3) (20.0) (20.0) (46.7)

1 1 53 44

(1.0) (1.0) (53.5) (44.4)

(0) (0) (60.0) (40.0)

.838 .845 .162

.329

.173

.328

0 0 9 6

.348 .372 .660 .345 .838

.017 7 (7.1) 4 (26.7) 92 (92.9) 11 (73.3) .143 52 35 12 0

(52.5) (35.4) (12.1) (0)

6 5 3 1

(40.0) (33.3) (20.0) (6.7) 1.000

2 (2.0)

0 (0)

97 (98.0) 15 (100.0) .231 85 (85.9) 11 (73.3) Continued

Features

Mild Moderate Severe

Adults (n = 99), N (%)

Children (n = 15), N (%) P value

11 (11.1) 3 (20.0) 1 (1.0) 1 (6.7) 2 (2.0) 0 (0)

thus more likely to visit a clinic. Mapping showed that, in adults, most BAMNs lay inside the arch of the midfoot, whereas acral melanomas developed on the weight-bearing regions of the sole.10 Similar differences in anatomic location were also noted by Pack et al,12 suggesting that chronic pressure or trauma might trigger acral melanomas but not BAMNs.10 In addition, the data suggest that most BAMNs are not risk factors for, or precursors of, acral melanomas, as also suggested by Rouhara et al.13 However, in children, BAMNs were common on the weight-bearing forefoot and heel, where acral melanomas also develop. Lesion size can help differentiate benign from malignant melanomas, and the sizes of acquired and congenital nevi differ. We found that the mean diameter of acquired lesions was \5.7 mm in both adults and children, and congenital lesions were larger. The long axes of BAMNs ran parallel to the dermatoglyphics in both adults and children, which is also true of acral melanomas.10 Therefore, both BAMNs and acral melanomas spread along the dermatoglyphics, suggesting that pressure and long-term physical stress influence the progression of both types of lesions.10 The principal dermoscopic features of BAMNs are a parallel furrow pattern, a lattice-like presentation, and fibrillar features; acral melanomas exhibit a parallel ridge pattern.14,15 The dermoscopic patterns of BAMNs correlate well with the histopathologic features.16-19 However, the characteristic features are most apparent when tissue sections are cut perpendicular to the direction of the skin markings.18-20 Most histopathologic tissue sections excised from BAMNs run parallel to the dermatoglyphics, and the histologic findings do not correlate with the dermoscopic features. Therefore, the histopathologic features of BAMNs are difficult to distinguish from those of dysplastic nevi or acral melanomas in situ. We found that certain architectural features of dysplastic nevi, including shoulders and bridges, were very common in BAMNs.1 Most BAMNs were cases of lentigo simplex and junctional nevi; shoulders were evident in approximately half of all compound nevi, and bridges were seen in over half

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Fig 6. Histopathologic features of benign acral melanocytic neoplasms of children. A, Continuous single-cell proliferation of spindle cells along the basal layer and many pagetoid scatters in acral junctional nevus. B, Prominent dendrites are visible. C, Discohesive nests and moderate cytologic atypia (epithelioid cells with prominent nucleoli) D, Transepidermal nest elimination in congenital junctional nevus. (A and C, Hematoxylin-eosin stain; original magnifications: 3100; B and D, Melan A stain; original magnifications: B, 3200, D, 3100.)

of all BAMNs. Lamellar fibroplasia around rete ridges (another feature of dysplastic nevi) was not evaluated in the present study because such fibroplasia is easily visible in both BAMNs and normal acral skin. Therefore, the diagnostic features of dysplastic nevi are replicated in BAMNs, suggesting that dysplastic nevi of acral skin should not be diagnosed on the basis of the architectural pattern. Boyd and Rapini21 also considered that neither bridges nor lamellar fibroplasia were of any diagnostic or prognostic utility when an acral melanocytic neoplasm was suspected. The degree and extent of pagetoid scatter can be used to differentiate BAMNs from melanomas. Mild pagetoid scatter was apparent in approximately half of all BAMNs of adults and in about 73% of all BAMNs of children. Boyd and Rapini21 reported mild pagetoid scatter in approximately 82% of all BAMNs. Thus, mild pagetoid scatter is not a sign of malignancy and is particularly common in children.22,23 BAMNs were dominated by single cells or contained almost equal numbers of single cells and nests. The nests were often confluent and discohesive, and were usually located on the tips of ridges. The nevi of certain sites (especially the genitals and breasts) are dominated by confluent discohesive

nests.1,2,24 However, BAMNs tend to exhibit a single cell-dominant pattern. Extensive proliferation is a characteristic feature of acral lentiginous melanomas. Therefore, the continuous or focally continuous cell proliferation characteristic of BAMNs is shared by acral melanomas.8 Mild-to-moderate cytologic atypia was significantly more frequent in children than adults, and 74.4% of the junctional nevi of children were cytologically atypical. Prominent dendrites were also common in children, and mitosis was apparent in 3 junctional nevi. Therefore, childhood BAMNs tend to have more atypical cytologic features, in agreement with an earlier report.23 The differential diagnosis of BAMNs from acral melanomas should be based on a combination of clinical and histopathologic characteristics. Clinically, patient age and lesion size can aid diagnoses. Acral melanomas usually develop in adults at the mean age of 55.3 years10 and have larger lesion sizes than BAMNs. Histopathologically, extensive pagetoid scatter, continuous melanocyte proliferation, prominent dendrites, severe cytologic atypia, and dermal mitoses are important features of acral melanomas. Therefore, clinicopathologic correlations must be made for effective diagnosis of acral melanocytic neoplasms.

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In conclusion, our work suggests that BAMNs tend to occur on nonweight-bearing areas of the sole in adults, and in the forefoot in children, with the long axes running parallel to the dermatoglyphics. The histopathologic features of BAMNs might be atypical, especially in children.

14. 15.

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