Dermoscopic Evaluation of Longitudinal Melanonychia in Children: A Prospective Study.

BACKGROUND: Longitudinal melanonychia (LM) is a worrisome sign in both children and adults. Nail apparatus melanoma (NAM) can be related to LM, but it is very rare in children. Dermoscopic signs of benign lesions in children can be similar to melanoma; therefore, it is important to review dermoscopy of LM in children to make the best decision in performing biopsy. AIMS: Biopsy taking is very challenging in LM in children. Most lesions are benign in children. The aim of this study was to review dermoscopic signs of LM in children and compare them with adults.
MATERIALS AND METHODS: In this prospective study a total of 108 LM (35 children and 73 adults) were undergone dermoscopy of LM. Dermoscopic features were compared in children and adults; both for benign lesions proven by biopsy or follow up and melanomas diagnosed histopathologically.
RESULTS: Black background, black band color, band color diversity and pseudo-Hutchinson's sign were more frequent in children in comparison with benign adult melanonychia. Some children's dermoscopic features of LM such as broad band width, Band color diversity, Hutchinson's sign, gray band color, asymmetry of pattern, and regression were similar to melanoma, but we did not find any melanoma by biopsy and/or follow up among children. We also detected the newly described "zigzag" pattern in four children.
CONCLUSION: Dermatologists should consider all dermoscopic features of a lesion, dermoscopic sign changes in follow-up, medical, and familial history of the patient in deciding to perform biopsy of LM in children. Copyright:

Introduction

Longitudinal melanonychia (LM) is a pigmented band on the nail plate that extends from nail matrix to the distal edge.[123] There is an undeniable relationship between LM and nail apparatus melanoma,[2] but over the last 50 years, only 16 cases of nail apparatus melanoma (NAM) have been reported in children.[4] Gold standard diagnostic test is histopathology,[1] but biopsy is a painful procedure especially in children and may be associated with permanent nail deformity, so it is performed only on the parental request or in high melanoma suspicion.[24] Dermoscopy is a non-invasive diagnostic method[3] to differentiate benign and suspicious lesions.[5] We evaluated dermoscopic features of LM in children and compared them with benign and malignant adult lesions.

Materials and Methods

In this prospective study, a total number of 108 patients, 73 adults and 35 children (under 18 years old) with LM were included. Patients with non-melanotic pigmentation, systemic, and dermatologic conditions with nail involvement or on medications that may cause nail discoloration were excluded. Dermoscopic examination was performed using FotoFinder® videodermoscopy (medicam 1000) with 20- and 70-fold magnification and in polarizing mode. Patients with suspicious lesion (according to history, clinical, and dermoscopic findings) underwent nail matrix biopsy at first visit. Other patients were followed every three months for at least 2 visits (maximum two years). If any suspicious change occurred during follow up time, biopsy was performed. lesions which were not suspicious at the first visit nor during follow up till the end of study, and which were not biopsied, were considered to be benign lesions. Twelve children were undergone biopsy, six at first and six during the follow-up period, all were done because of parental concern. Dermoscopic features were evaluated by two dermatologists and in case of disagreement a third dermatologist was involved. An expert in dermoscopy reviewed all cases at last. Pattern of pigmentation, background color, band color, asymmetry (pattern, color or both), Hutchinson's sign, pseudo-Hutchinson's sign, micro-Hutchinson's sign, triangular pigmentation, and nail plate changes were analyzed according to the previous literature.[67] Patterns of pigmentation are parallel line, structureless, dot and clot and combinations of these three patterns.

Lesions were categorized into four groups: those which were considered benign in follow-up, and those with the histopathologic diagnosis of melanocytic hyperactivation, nevus, and melanoma.

Statistical analysis was performed with SPSS 24 software and 0.05 was considered as a significant level. For continuous and categorical variables, mean ± standard deviation, and frequency (percentage) was reported. In order to assess the relationship between two categorical variables, Chi-square test, and if needed Fisher exact test was used.

The study protocol was approved by the ethics committee of Tehran university of Medical Sciences (IR.TUMS.MEDICINE.REC.1397.048-Approval Date:2018-05-31).

Results

Total number of 108 (35 children and 73 adults) with LM were included in the study. Histopathologic study was done in 12 children (three melanocytic hyperactivation, and nine nevus) and 43 adults (20 melanocytic hyperactivation, 14 nevus, nine melanoma). Herein we report data in children [Table 1]. Mean follow up time for children was 12 months. Seventeen patients were female. Mean duration of lesions was 21.11 ± 15.65 months. History of acute trauma leading to subungual hemorrhage was positive in seven and single nail involvement was observed in 34 patients. Fingernails, first fingernail, and right side was more frequently involved in both children and adults. Fingernails and thumbnail involvement in children was observed in 82,8% and 48.5%, respectively. Children did not show any important dermoscopic changes during their follow-up period. Brown background was the most common color in all cases (benign and malignant in children and adults). Dermoscopy of benign LM in children and adults were compared; mean width of lesions in children was 24 ± 20.82 versus 19.30 ± 14.38 in adults. Gray background was seen more frequently in adults than children (P = 0.03). In contrast black background, black band color and band color diversity were significantly more frequent in children than adults (P = 0.042, 0.001, and 0.02 respectively). Pseudo- Hutchinson's sign was more frequent in children than adults (P = 0.004). Micro- Hutchinson's sign was not detected in children but was seen in three adult benign lesions. Parallel line pattern was more common in children (P = 0.001), in contrast structureless pattern was more frequent in adults (P = 0.005). Symmetry of pattern and color were more frequent in adults but not significant. Melanoma was only diagnosed in adults. Comparing dermoscopic features of melanoma with benign adults' lesions in children and adults, Hutchinson's sign was detected significantly more in melanoma (P = 0.004). It was only seen in two children and none of benign lesions in adults. Gray band color was detected more in melanoma (P = 0.041), but was also detected in 62% (22) of children and 55% (35) of benign adult lesions. Border fading was detected more in melanoma (P = 0.014), but 48% (17) of children and 39% (25) of benign adults lesions had the sign. Asymmetry of color and pattern was significantly more frequent in melanoma (P = 0.02), but it was detected in 42% (15) of children and 29% (19) of benign lesions of adults as well [Figure 1]. Dermoscopic details of children's LM is presented in Table 2. There was no significant difference in dermoscopic features of children in benign follow-up, melanocytic hyperactivation and nevus groups, except for brown band color which was seen mostly in benign follow-up group (P = 0.04). We compared 7 dermoscopic features in children and melanoma patients, including asymmetry of color and pattern, Hutchinson's sign, gray band color, band color diversity, border fading and width more than one third of the nail plate. Four or more signs were seen in 100% of melanoma patients, in contrast to 42% of the children [Table 3]. The difference was significant (P = 0.002). Zigzag pattern which cannot be seen with the naked eye, was detected in dermoscopy of four children [Figure 2]. To the best of our knowledge, it had been reported in one case series to date.[8] Details are shown in Table 4.

Table 1

Charactristics of lesions in differnet children age ranges

	Age ranges				Total n = 35
	0 - ≤ 5 years	5 - ≤ 10 years	10 - ≤ 15 years	15 - ≤ 18 years
Frequency	13 (37.1%)	12 (34.3%)	7 (20%)	3 (8.6%)
Number of patients underwent biopsy	6	2	3	1	12
Diagnosis
Melanocytic Hyperactivation*	1	1	0	1	3
Nevus*	5	1	3	0	9
Benign in follow-up	7	10	4	2	23
Multiple nail involvement	0	0	1	0	1
Mean age of lesion (month)	13.62	25.75	23.29	30	21.11
Patients’ mean age at onset (year)	2.38	6	11.85	14	6.51
Fingernail involvement (thumbnail)	12 (6)	10 (7)	5 (2)	2 (2)	29 (17)

*Proven by biopsy

Figure 1

(a) Nevus in child shows parallel and dot and clod patterns with brown and black dots, Hutchinson's sign, band color diversity, and asymmetry of color and pattern. Note the brush like structure in dermoscopy of child melanonychia (arrowhead) which is different from haphazard pigmentation known as Hutchinson's sign (arrow in Figure 1c). (b) Nevus in child shows asymmetry, black band color and pseudo-Hutchinson's sign. (c) Melanoma in adult shows structureless pattern, brown background, band color diversity (brown and gray), asymmetry of color Hutchinson's sign, pseudo-Hutchinson's sign nail plate scale and nail dystrophy. (d) Melanoma in adult shows parallel line pattern, brown background, band color diversity (brown and gray), asymmetry of color, pseudo-Hutchinson's sign, nail plate notch, and nail plate scale. (Polarized dermoscopy with 70-fold magnification)

Table 2

Dermoscopic findings of LM in each four groups in children

Dermoscopic features	Benign follow-up n=23	Melanocytic hyperactivation, n=3	Nevus, n=9	P
Pattern				0.69
Parallel line	12	1	7	0.153
	22.6%	4.3%	30.4%
structreless	7	2	1	0.163
	13.2%	8.7%	4.3%
Dot/clod	0	0	0	-
Parallel and structreless	1	0	0	-
	1.9%	0.0%
Parallel and dot/clot	2	0	1	-
	3.8%		4.3%
Structreless and dot/clod	0	0	0	-
	0.0%
All three patterns	1	0	0	-
	1.9%
Dot and clod
Brown	2	0	1	1.00
	3.8%	0.0%	4.3%
Black	2	0	0	1.00
	3.8%
Both	1	0	0	-
	1.9%
Background color
Brown	19	1	9	0.03
	35.8%	4.3%	39.1%
Gray	2	1	0	0.26
	3.8%	4.3%	0.0%
Black	2	1	0	0.26
	3.8%	4.3%
band color diversity	13	1	6	0.56
	24.5%	4.3%	26.1%
Band color				0.59
Brown	7	0	2	0.04
	13.5%	0.0%	8.7%
Gray	2	1	0	0.73
	3.8%	4.3%	0.0%
Black	2	1	0	1
	3.8%	4.3%
Brown/gray	7	1	5	0.43
	13.5%	4.3%	21.7%
Gray/black	1	0	0	-
	1.9%
All three colors	3	0	2	-
	5.8%	0.0%	8.7%
Asymmetry				0.89
None	13	2	5	1
	24.5%	8.7%	21.7%
Color	1	0	1	1
	1.9%	0.0%	4.3%
pattern	0	0	0	1
			0.0%
Both	9	1	3	1
	17.0%	4.3%	13.0%
Hutchinson’s sign	2	0	0	1.00
	3.8%
Pseudo-Hutchinson’s sign	18	1	7	0.26
	34.0%	4.3%	31.8%
Micro-Hutchinson’s sign	0	0	0	-
	0.0%		0.0%
Triangular sign	1	1	0	0.23
	1.9%	4.3%	0.0%
nail plate groove	0	0		-
	0.0%	0.0%
Nail plate dystrophy	0	0	0	-
	0.0%	0.0%	0.0%
Onychoschizia	0	1	1	0.04
	0.0%	4.3%	4.3%
Nail plate notch	2	1	2	0.31
	3.8%	4.3%	8.7%
nail plate ridge	0	0		-
	0.0%	0.0%
nail plate scale	7	1	2	1
	13.2%	4.3%	8.7%

Table 3

Seven dermoscopic features including asymmetry of color and pattern, Hutchinson’s sign, gray band color, band color diversity, border fading and width more than one third of nail plate were evaluated in children and melanoma lesions

Number of dermoscopic features in one lesion, n=7	Melanoma, n=9 (%)	Children, n=35 (%)	P
4 or more	9 (100)	15 (42)	0.002
5 or more	7 (78)	9 (25)	0.007
6 or more	5 (55)	3 (0.08)	0.005
7	1 (11)	1 (0.02)	0.371

Figure 2

(a) Zigzag pattern at the periphery of pigmented band both sides. (b) Zigzag pattern at the periphery of pigmented band one side and as a separate line parallel to the main band. (c) Follow up of patient B. The lesion become lighter and narrower. (Polarized dermoscopy with 70-fold magnification)

Table 4

Demographic and dermoscopic Characteristics of four patients with zigzag pattern

Case ID	P1	P2	P3	P4
Age (year)	14	8	6	12
Duration of lesion	6 months	6 months	3 years	5 years
Duration of follow up (month)	18	6	18	12
Affected nail	Left thumb	Right 2nd finger	Left thumb	Right thumb
Sex	Male	Female	Male	Male
Width (percent)	10	10	20	20
Asymmetry of pattern and color	+	-	+	+
Background color	Gray	Black	Brown	Brown
Band color	Gray/black	Black	Brown/gray/black	Brown/gray/black
Pseudo-Hutchinson’s sign	+	+	+	-
History of trauma	-	-	-	+
Histopathology	-	-	-	Junctional nevus

Discussion

LM in children can be congenital or acquired and is either caused by melanocytic activation or proliferation which is usually benign. Nail matrix melanoma particularly invasive melanoma is extremely rare in children.[1] Melanonychia in children usually has an indolent behavior especially before puberty.[9] In this study we did not find any melanoma in children. The most common dermoscopic findings in children were parallel line pattern, brown background, band color diversity, and pseudo-Hutchinson's sign. Black background, black band color, band color diversity, and pseudo-Hutchinson's sign were more frequent in children in comparison with benign adult melanonychia. LM in childhood can be broader in width and have irregular pattern with dark and multi-color bands, dot and globules, triangular sign, Hutchinson's sign and dystrophy. Contrary to adults these features are not indicative of melanoma.[1346710] Findings in our study confirmed the previous studies that dermoscopic signs in children are different from adults. Comparing dermoscopic features of benign children melanonychia with benign and malignant lesions in adults, they were more frequently like melanoma. Mean width of lesions was wider in children. Gray background was significantly less frequent in children and melanoma than benign adult lesions. Band color diversity was significantly more frequent in children and it was seen in 66% (6) of melanoma cases as well. Hutchinson's sign which is predictive of melanoma in adults was seen in 2 children as well, but no benign adult lesions. It seems that gray band color can be a predictive sign of melanoma (P = 0.041) and asymmetry of pattern and color were significantly more in melanoma; although they all can be detected in benign adult lesions, they are more prevalent in children. Regression is another difference between adults and children[4] as it can be a sign of melanoma in adult but is a common finding in children. Dots along lines can be a sign of regression.[1112] In April 2020, Sahin S. et al. reported zigzag pattern as a new dermoscopic sign in LM of four children and one adult.[8] We detected spiral lines at the borders of the pigmented band in three cases and presenting as a lighter extra line, adjacent to the main band in one case which is a new dermoscopic finding, and according to Sahin S. et al.[8] we named it zigzag pattern. Despite Sahin S. et al. study, we did not detect this finding in any adults. One of these lesions was diagnosed histopathologically as junctional nevus and it was the only case with history of trauma. Sahin S. et al. hypothesized that this sign can occur due to trauma similar to parallel furrow pattern in palmoplantar lesions or may be as a result of fluctuation in production of melanin. During follow-up period the lesion disappeared in one patient and became lighter and narrower in another, so we propose that this sign can be another predictive sign of regression but long-term follow up and more studies are needed. Regression can be due to decreased melanocytic activation[1113] which in case of zigzag pattern could be intermittent. It seems to be a benign sign in dermoscopy.[8]

There is no consensus on follow-up intervals in a patient with benign looking melanonychia. Depending on how much the lesion is suspicious for malignancy, some experts suggest regular 3-6 months follow-up but patients should be aware to inform physician in the case of any change.[111415]

Our study was prospective despite most previous studies but still had some limitations. Sample size was small for melanoma cases and follow up period was short. We could not biopsy all lesions because of patients' refusal. Future studies on dermoscopy of melanonychia especially in children and with clinicopathological correlation is recommended.

Conclusion

Although histopathologic study is needed for the definite diagnosis of LM, but as NAM is extremely rare in children, and biopsy is painful and cause permanent deformity, we suggest using dermoscopy at first and follow-up visits of children and make decision to perform biopsy according to the findings. Of course, in the case of parental worries it is logical to perform biopsy at first. Although dermoscopic signs in children may be similar to those of melanoma in adults to some extent, they are not indicative of malignancy in childhood, as we did not detect any melanoma in this age range group. It should be kept in mind that no single dermoscopic sign can be a good predictor of melanoma and considering a collection of dermoscopic features, changes in follow-up period, personal, and familial history of the patients will help to make the best decision managing LM.

In conclusion although histopathologic study is needed for the definite diagnosis of LM, but as NAM is extremely rare in children, and biopsy is painful and cause permanent deformity, we suggest using dermoscopy at first and follow-up visits of children and make decision to perform biopsy according to the findings. Of course, in the case of parental worries it is logical to perform biopsy at first. Although dermoscopic signs in children may be similar to those of melanoma in adults to some extent, they are not indicative of malignancy in childhood, as we did not detect any melanoma in this age range group. It should be kept in mind that no single dermoscopic sign can be a good predictor of melanoma and considering a collection of dermoscopic features, changes in follow-up period, personal, and familial history of the patients will help to make the best decision managing LM.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.