Recurrent Pigmented Macules After Q-Switched Alexandrite Laser Treatment of Congenital Melanocytic Nevus

Recurrent Pigmented Macules after Q-Switched Alexandrite Laser Treatment of Congenital Melanocytic Nevus

n SEONGHYANG SOHN,PHD, SANGEUN KIM,MD,AND WON HYOUNG KANG,MD,PHD Department of Dermatology and nLaboratory of Cell Biology, Institute for Medical Sciences, Ajou University School of Medicine, Suwon, Korea

BACKGROUND. Q-switch-mode laser treatment of congenital TNF-alpha were determined histochemically in the original nevi nevi does not result in complete histological clearance, and many and RPM. In addition, one RPM was examined by electron patients have partial repigmentation within several months. In microscopy. addition, the number of recurrent pigmented macules (RPMs) RESULTS. Reduced pigmentation in the treated areas was seen in may increase, a major drawback to good cosmetic results. While all cases, but partial repigmentaion was seen as black spots the mechanism of recurrence is not known. within 6 months after the last QSAL treatment. Compared to OBJECTIVE. To help elucidate the mechanism of RPM develop- the original nevi, the RPMs had increased numbers of ment, we evaluated the expression of TNF-alpha and E- melanocytes in the epidermis and reduced nevomelanocytic cadherin on RPM after treatment of congenital nevi with a nests in the dermis. The expression of TNF-alpha and E- Q-switched alexandrite laser (QSAL). cadherin was downregulated in the RPMs compared to the METHODS. Thirteen Korean subjects with congenital nevi original nevi. Electron microscopy confirmed the increase in received QSAL treatment at intervals ranging from 2 to 6 melanocytes in the epidermis of RPMs. months (mean, 4.5 treatments). Two-millimeter punch biopsy CONCLUSION. Our findings suggest that the down-regulation of specimens were obtained at their first visit and from RPMs 3–6 E-cadherin and TNF-alpha may induce the proliferation of months after the last treatment. Expression of E-cadherin and melanocytes, resulting in the formation of RPMs.

SEONGHYANG SOHN, PHD, SANGEUN KIM, MD, AND WON HYOUNG KANG, MD, PHD HAVE INDICATED NO SIGNIFICANT INTEREST WITH COMMERCIAL SUPPORTERS.

CONGENITAL MELANOCYTIC nevi are present in these lasers have been utilized to treat congenital 1% to 2% of newborn infants. Although these nevi are melanocytic nevi.2–7 Following Q-switched-mode laser histologically compound or intradermal, they may treatment, however, congenital melanocytic nevi do differ from acquired nevi by one or more features.1 For not show complete histologic clearance, and many example, nevus cells of congenital melanocytic nevi are patients have partial repigmentation within several present around and within hair follicles, in sweat ducts months after discontinuation of therapy. In addition, and glands, in sebaceous glands, in vessel walls, and in the number of recurrent pigmented macules has been the perineum of nerves, and they extend between found to increase in some patients. collagen bundles in single or double rows, as well as Although treatment of congenital nevi with the Q- into the deepest reticular dermis or the subcutis. In switched ruby laser has been found to result in contrast, nevus cells of acquired nevi do not show any histologic changes, these studies did not evaluate the of these features. recurrence of lesions.3,8 This is especially important In treating congenital melanocytic nevi, the primary because the mechanism of recurrence is not completely difficulty has been to obtain cosmetically good results known. Significantly exaggerated junctional activity without scarring or recurrence. Because treatment of has been demonstrated in recurrent nevi, suggesting benign pigmented lesions with Q-switched mode lasers that the latter arise from melanocytes located at the has been shown to result in a low incidence of scarring, dermoepidermal interface, possibly from sweat ducts, hair follicles, or peripheral epidermis.9 Recurrence of Address correspondence and reprint requests to: Won Hyoung Kang, nevi may be related to the interaction between MD, PhD, Department of Dermatology, Ajou University School of keratinocytes and melanocytes. The adhesion protein Medicine, 5 Wonchon-dong, Paldal-Ku, Suwon, Korea, 442-721, or E-cadherin, which is expressed on normal human 10 e-mail: [email protected]. epidermis, has been shown to have regulatory r 2004 by the American Society for Dermatologic Surgery, Inc. Published by Blackwell Publishing, Inc. ISSN: 1076-0512/04/$15.00/0 Dermatol Surg 2004;30:898–907 Dermatol Surg 30:6:June 2004 SOHN ET AL.: CONGENITAL NEVI TREATMENT WITH AN ALEXANDRITE LASER 899 functions in epidermal morphogenesis and in the Each process (i.e., sectioning, staining, and digital organization of normal skin structure.11 E-cadherin image taking) was performed simultaneously on the is also expressed in human melanocytes and acts as the biopsy specimens obtained from all patients before and prime mediator of melanocyte adhesion to keratino- after treatment. The stained area was measured under cytes in vitro.12 In addition, keratinocytes synthesize constant magnification (Â 200). tumor necrosis factor-a, a paracrine inhibitor of Statistical analysis was performed using Microsoft human melanocyte proliferation and melanogenesis.13 Excel software. Data on the original nevus and To determine the relationship between the expression recurrent pigmented macule were evaluated using of tumor necrosis factor-a and E-cadherin and the Student’s paired t test. Statistical significance was development of recurrent pigmented macule, we defined as a p value less than 0.05. treated 13 Korean patients with congenital melanocytic nevi with the Q-switched alexandrite laser and assayed protein expression immunohistochemically. Results Of the 13 patients examined, 3 were men and 10 were women. Their ages ranged from 3 to 46 years (mean, Materials and Methods 11.3 years; median, 8 years). Ten of the nevi were located on the face, with 1 each on the trunk, leg, and A total of 13 Korean subjects with congenital nevi ear lobe. The interval between the biopsy of recurrent were enrolled in the study. All subjects had Fitzpatrick pigmented macule and the last Q-switched alexandrite skin type III. All nevi were treated by Q-switched laser treatment ranged from 3 to 6 months (mean, 3.9 alexandrite laser (tatoo laser, model TL-1, Candela months; median, 3 months). The congenital melano- Corp., Wayland, MA) at a fluence of 8.0 J/cm2 and a cytic nevi were classified histologically (Table 2) as spot size of 3 mm, using a pulse duration of 100 nsec compound melanocytic nevi and intradermal nevi. and a wavelength of 755 nm. The interval between We observed reduced pigmentation in the treated treatments ranged from 2 to 6 months. The mean areas in all 13 cases, whereas recurrent pigmented number of Q-switched alexandrite laser treatments per macules were observed as multiple brown to black patient was 4.5, with a range of 1 to 10. Clinical spots within 6 months following the last Q-switched photographs were taken before each treatment session, alexandrite laser treatment (Figures 1 and 2). All 2 or 3 weeks after treatment, and 1 years after recurrent pigmented macule did not become fully detection of recurrent pigmented macule In addition, repigmented and did not grow together until 1 years 2-mm punch biopsy specimens were obtained before following their development. treatment and on the follow-up day at which recurrent Histologically, all recurrent pigmented macules pigmented macule was first observed. Tissues were showed reduced nevomelanocytic nests in the upper fixed in 10% formalin, stained with hematoxylin and and reticular dermis and replacement by subtle eosin, and examined by light microscopy. In addition, microscopic scars. Residual nevomelanocytes in the tissue sections were immunohistochemically stained dermis were observed in all recurrent pigmented using primary antibodies (Table 1). Recurrent pigmen- macules. The size and number of dermal nevus cell ted macule from 1 patient was also examined by nests were decreased in all 13 recurrent pigmented electron microscopy. macules, and 4 showed singly dispersed nevomelano- Samples from 12 patients were stained with anti- cytes in the reticular dermis (Figure 3B). body to E-cadherin, whereas samples from all 13 Using NKI-beteb (GP-100), an increased number of patients were stained with antibody to tumor necrosis melanocytes and lentiginous hyperplasia was detected factor-a. For the original nevus and recurrent pigmen- within the epidermis of 11 of 13 recurrent pigmented ted macule the ratio of stained epidermal area to macules. Staining for GP-100 was stronger in the measured epidermal area and staining intensity were epidermis of these 11 recurrent pigmented macules determined by a computed image analysis method.15 than in the epidermis of the original lesions (Figure

Table 1. Primary Antibodies Used and Their Working Dilutions

Stain Target Dilution Incubation Temperature Manufacturer GP-100 (NKI-beteb) Melanocyte 1:20 18 min 451C Monosan Antibody for E-cadherin Cadherin 1:100 Overnight Room Novacastra Antibody for tumor necrosis factor-a Tumor necrosis factor-a 1:100 Overnight Room HyCult 900 SOHN ET AL.: CONGENITAL NEVI TREATMENT WITH AN ALEXANDRITE LASER Dermatol Surg 30:6:June 2004

Table 2. Clinical Data and Histologic Type of 13 Patients undersurface of basal cells. In the suprabasal epider- (Biopsied Before and After Treatment) mis, staining for E-cadherin was localized uniformly around the periphery of the cells (Figure 4) but was Time on absent from the corneal layer. Membranous staining Follow-up n was also present in the outer root sheath cells of the Sex/Age Type of Number of Biopsy hair follicles. Membranous E-cadherin immunoreac- Patient (Years) Site Nevus Treatments (Months) tivity was present in the epidermis of all nevi, as well 1 F/4 Face Intradermal 5 6 as at the borders between epidermal nevus cell nests 2 F/3 Trunk Compound 1 2 and the surrounding keratinocytes. In nine recurrent 3 F/4 Face Intradermal 2 3 pigmented macules with junctional activities, the 4 M/5 Face Intradermal 3 6 staining was not uniformly membranous but more 5 F/5 Face Intradermal 7 3 heterogeneous. Nevertheless, in dermal nevus cell nests 6 M/7 Face Intradermal 3 6 7 F/8 Face Compound 4 3 or residual dermal nevus cells, which are not un- 8 F/10 Leg Intradermal 6 3 common after Q-switched alexandrite laser, there was 9 M/8 Face Intradermal 8 4 no E-cadherin immunoreactivity. 10 F/10 Face Intradermal 5 6 Using computed image analysis, we observed 11 F/17 Face Compound 4 3 statistically signiﬁcant differences in staining intensity 12 F/20 Earlobe Intradermal 10 3 (po0.05) between the original nevi and recurrent 13 F/46 Face Intradermal 1 3 pigmented macule (Table 3, Figure 5). The intensity of nThe interval between the last treatment and the follow-up biopsy of the recurrent E-cadherin expression was down-regulated in 8 of 12 pigmented macule. (67%) and up-regulated in 4 of 12 (33%) nevi, whereas the area of E-cadherin expression per nevus was down-regulated in 5 of 12 (41.7%) and up- 3D). Two of the recurrent pigmented macules, how- regulated in 7 of 12 (58.3%) nevi (Figure 6, Table 5). ever, did not show signiﬁcant differences in GP-100 When we stained with antibodies against tumor immunohistochemical stain when compared to their necrosis factor-a, we observed positive immunoreac- original nevi. tivity throughout the epidermis (Figure 7), but an ab- E-cadherin immunoreactivity was localized along sence of staining from the corneal layer. Although the the lateral and upper surfaces of basal keratinocytes at sebaceous glands, exocrine glands, and hair follicles the site of cell–cell contacts, but it was absent from the were positive for tumor necrosis factor-a, the junctional

Figure 1. Photographic evaluation of Patient 6. (A) Before treatment. (B) Three weeks after three sessions of Q-switched alexandrite laser treatment. (C) recurrent pigmented macule observed 6 months after 3 sessions of Q-switched alexandrite laser treatment.

Figure 2. Photographic evaluation of Patient 5. (A) Before treatment. (B) Three weeks after three sessions of Q-switched alexandrite laser treatment. (C) Recurrent pigmented macule observed 3 months after two sessions of Q-switched alexandrite laser treatment. Dermatol Surg 30:6:June 2004 SOHN ET AL.: CONGENITAL NEVI TREATMENT WITH AN ALEXANDRITE LASER 901

Figure 3. Patient 4. Original nevi (A, C) and recurrent pigmented macule (B, D) stained with hematoxylin and eosin (A, B) and with GP-100 (C, D). Increased epidermal melanocyte and lentigenous hyperplasia were observed 6 months after three sessions of Q-switched alexandrite laser treatments. Note reduced nevus cell nest in the dermis. Magniﬁcation, Â 100. and intradermal nevus cell nests were negative or very 10). We observed an increase in the ratio of basal weakly positive. melanocytes to basal keratinocytes (1:4) relative to the Image analysis revealed statistically signiﬁcant normal range (1:9–1:10). The basal layer of the differences in staining intensity and area stained per epidermis was intact, and epidermal melanocytes were nevus (stained epidermal area to measured epidermal present in the third to fourth layer from the basal layer. area) between the original nevi and recurrent pigmen- We also observed Langerhan’s cells. ted macules (po0.05) (Figure 8, Table 4). We found that the intensity of tumor necrosis factor-a staining was down-regulated in 11 of 13 (84.62%) and up- Discussion regulated in 2 of 13 (15.38%) nevi, whereas the area of tumor necrosis factor-a expression per nevus was In patients with congenital melanocytic nevi treated down-regulated in 8 of 13 (61.54%) and up-regulated with a Q-switched alexandrite laser, we detected in 5 of 13 (38.46%) nevi (Figure 9, Table 5). recurrent pigmented macules as multiple brown to We also examined the ultrastructure of one recur- black spots within 6 months after the last treatment. rent pigmented macule by electron microscopy (Figure These recurrent pigmented macules did not fully 902 SOHN ET AL.: CONGENITAL NEVI TREATMENT WITH AN ALEXANDRITE LASER Dermatol Surg 30:6:June 2004

Figure 4. E-cadherin immunohistochemical staining in (A) original nevus and (B) recurrent pigmented macule 3 months after the last Q-switched alexandrite laser treatment in Patient 5. Note the decrease in epidermal immunoreactivity in the recurrent pigmented macule compared to the original nevus. All magniﬁcations, Â 200.

Table 3. Computed Image Analysis of E-cadherin Immu- with both a Q-switched ruby laser and a Q-switched nohistochemical Staining in Original Nevi and Recurrent Nd:YAG laser could not eradicate all melanocytic Pigmented Macule nevus cell nests.3 A single treatment with a Q-switched laser (ruby, Nd:YAG) often removed only the super- Original Nevi Recurrent Pigmented ficial portion of the congenital melanocytic nevi.8 In (n 5 12) Macules (n 5 12) our study, the GP-100 immunohistochemical stain Staining intensity (mean) 0.80175 0.56454 showed an increased number of melanocytes and Standard deviation 0.35738 0.29375 lentiginous hyperplasia within the epidermis of recur- p value 0.02952 rent pigmented macule whereas electron microscopy Per-area (mean) 0.30925 0.32746 confirmed the lentiginous melanocytic hyperplasia in Standard deviation 0.11668 0.12266 this layer, findings not observed in the epidermis of the p value 0.34017 original nevi. After treatment, the recurrent nevi showed melanocyte proliferation at the dermoepidermal junction, which may have originated from sweat ducts, hair follicles, or the peripheral epidermis.9 repigment and did not grow together until 1 year after Histologically, recurrent melanocytic nevi have been they developed. Nevi have previously been shown to described as pseudomelanomas because of their lighten by an average of 57% after the fourth Q- irregular histologic features, including the confluence switched alexandrite laser treatment session, but of melanocytic nests, the variation in nest size, and within an average of 4.9 months after discontinuation atypical features of the melanocytes.15 Q-switched of therapy, 81% of these patients experienced partial ruby laser irradiation was recently shown to induce repigmentation, and none repigmented fully.3 These alterations in the expression of a4b1 and a5b1 findings are in good agreement with those shown here. integrins in cultured melanoma cells but not in benign The presence of brown to black spots in recurrent melanocytes.16 In another study, Q-switched alexan- pigmented macules may be caused by epidermal drite laser damage to melanoma cell lines led to an melanocytes rather than by dermal nevus cells. We increase in p16 expression, which suggested that DNA found that, compared to their original nevi, recurrent damage could occur following Q-switched alexandrite pigmented macules showed increased numbers of laser.17 Methods to assess potential malignant trans- melanocytes in the epidermis and a reduction in formation in laser-irradiated congenital nevi are nevomelanocytic nests in the upper and reticular currently unavailable, and there have been no reports dermis. We also detected residual nevomelanocytes in of malignant transformation following laser treatment the dermis. It was previously shown that treatment because follow-up time is too short for any definite Dermatol Surg 30:6:June 2004 SOHN ET AL.: CONGENITAL NEVI TREATMENT WITH AN ALEXANDRITE LASER 903

AB 0.5 1.4

1.2 0.4 1

0.3 0.8

0.2 0.6 staining intensity per-area (SA/MA) 0.4 0.1 0.2

0 0 original nevi (n=12) RPM (n=12) original nevi (n=12) RPM (n=12) Figure 5. E cadherin immunohistochemical staining of original nevi and recurrent pigmented macule. (A) Mean area stained per nevus (pigmented area/measured epidermis). (B) Mean staining intensity. npo0.05. RPM, recurrent pigmented macule.

AB Although the mechanism by which residual nevus 200 cells proliferate to form recurrent pigmented macules 400 is not known, it is thought to be linked to the mechanism of general melanocytic proliferation. The ﬁrst step of melanocyte proliferation is thought to be 300 the down-regulation of expression of E-cadherin, which leads to the decoupling of melanocytes from keratinocytes and permits melanocytes to proliferate in 19 200 100 the absence of keratinocyte regulation. As support for this hypothesis, we observed decreased expression

per-area (%) of E-cadherin in recurrent pigmented macules, which

staining intensity (%) may contribute to nevomelanocyte proliferation in 100 recurrent pigmented macule epidermis. Intercellular adhesion of epithelial cells is regulated primarily by E- cadherin.20 This 120-kDa transmembrane glycopro- 0 0 tein, which is localized mainly in the adherence junc- original nevi RPM original nevi RPM tions, mediates cell–cell adhesion through calcium- Figure 6. Computed image analysis of E-cadherin immunohisto- dependent, homotypic interactions of its extracellular chemical staining in each recurrent pigmented macule relative to that domains. The cytoplasmic domain of E-cadherin has in its respective original nevus. (A) Area stained per nevus (ratio of been shown to bind to the alpha, beta, and gamma stained epidermal area to measured epidermal area). Note that catenins,21 a binding essential for the establishment of staining was lower in the recurrent pigmented macules of ﬁve patients tight physical cell–cell adhesion, making the catenins than in their respective original nevi. (B) Staining intensity per nevus. 22,23 Note that staining intensity was lower in the recurrent pigmented regulators of E-cadherin function. macules of nine patients than in their respective original nevi. E-cadherin, which is expressed in normal human epidermis,24 has been shown to regulate epidermal morphogenesis and the organization of normal skin conclusion to be made. So laser treatment for structure.25 In addition, E-cadherin is expressed by congenital melanocytic nevi is still not widely ac- human melanocytes and acts as the prime mediator of cepted. Routine histologic and immunohistochemical the in vitro adhesion of melanocytes to keratino- evaluation of the original and recurrent nevi of 15 cytes.25 In contrast, little or no E-cadherin is expressed patients showed an increased number of melanocytes by human melanoma cell lines,26 which have a within the epidermis of recurrent nevi,18 a ﬁnding decreased ability to adhere to keratinocytes.25 Altered similar to those reported here. It should be remem- expression or function of E-cadherin is associated with bered, however, that these researchers did not differ- an undifferentiated, invasive phenotype of melanoma entiate among treatment modalities, whereas we cells,27,28 and the down-regulation of E-cadherin examined only congenital nevi and only after treat- expression, either on melanocytes or on keratinocytes, ments with a Q-switched alexandrite laser. has been observed to lead to the decoupling of these 904 SOHN ET AL.: CONGENITAL NEVI TREATMENT WITH AN ALEXANDRITE LASER Dermatol Surg 30:6:June 2004

Figure 7. Tumor necrosis factor-a immunohistochemical staining in (A) original nevus and (B) recurrent pigmented macules 6 months after the last Q-switched alexandrite laser treatment in Patient 10. Note the decrease in epidermal immunoreactivity in the recurrent pigmented macule compared to the original nevus. All magniﬁcations, Â 400.

AB 0.8 2.5

2 0.6

1.5 0.4

1 staining intensity per-area (6A/11A) 0.2 0.5

0 0 original nevi (n=13) RPM (n=13) original nevi (n=13) RPM (n=13) Figure 8. Tumor necrosis factor-a immunohistochemical staining of original nevi and recurrent pigmented macule. (A) Mean area stained per nevus (pigmented area/measured epidermis). (B) Mean staining intensity. npo0.05. two cell types. Although the down-regulation of E- Table 4. Computed Image Analysis of Tumor Necrosis cadherin expression results in the loss of gap junctions, Factor-a Immunohistochemical Staining in Original Nevi the biologic consequences of this are not known.19 and Recurrent Pigmented Macule We observed a decrease in tumor necrosis factor-a expression in recurrent pigmented macules compared Original Nevi Recurrent Pigmented to the original nevi. Keratinocytes express and secrete (n 5 13) Macules (n 5 13) both tumor necrosis factor-a and transforming growth Staining intensity (mean) 1.14734 0.51706 factor-b, which act as paracrine inhibitors of human Standard deviation 0.91794 0.24507 melanocyte proliferation and melanogenesis.13 Tumor p value 0.01247 necrosis factor-a expression has been shown to be Per-area (mean) 0.58554 0.49008 greater in vitiligo lesions than in perilesional and non- Standard deviation 0.16031 0.12402 lesional skin.29 In addition, tumor necrosis factor-a p value 0.04944 Dermatol Surg 30:6:June 2004 SOHN ET AL.: CONGENITAL NEVI TREATMENT WITH AN ALEXANDRITE LASER 905

AB growth factor-b down-regulate tyrosinase activity and 200 31 300 melanin formation in B16 melanoma cells, it is likely that a decrease in tumor necrosis factor-a expression might play a role in the development of recurrent pigmented macules. Although the expression of tumor necrosis factor-a 200 and E-cadherin were coordinately down-regulated in most of the recurrent lesions assayed, we did ﬁnd that 100 both were coordinately up-regulated in one nevus. This may indicate that recurrent pigmented macule

per-area (%) development occurs in stages. During the ﬁrst stage, 100

staining intensity (%) the expression of tumor necrosis factor-a and E- cadherin may be down-regulated, enhancing melanocyte proliferation. In a later stage, when melanocytes cease to proliferate, the expression of tumor necrosis 0 0 factor-a and E-cadherin may be again up-regulated, original nevi RPM original nevi RPM leading to a cessation of recurrent pigmented macule Figure 9. Computed image analysis of tumor necrosis factor-a growth. In support of this hypothesis, we found that immunohistochemical staining in each recurrent pigmented macule none of the recurrent pigmented macules grew to the relative to that in its respective original nevus. (A) Area stained per size they had before treatment, a ﬁnding in agreement nevus (ratio of stained epidermal area to measured epidermal area). with previous observations.8 Although our results do Note that staining was lower in the recurrent pigmented macules of eight patients than in their respective original nevi. (B) Staining not indicate the mechanism by which alterations in intensity per nevus. Note that staining intensity was lower in the tumor necrosis factor-a and E-cadherin expression are recurrent pigmented macules of 11 patients than in their respective related to epidermal changes, it is likely that altered original nevi. expression of these molecules causes the observed changes in epidermal pigmentation. Recurrent pigmented macule is characterized by hyperpigmented macules that develop in clinically was observed to down-regulate the expression of clear lesions after treatment. Histologically, recurrent melanocortin-1 receptor mRNA30 and melanocyte- pigmented macules present with lentiginous melano- stimulating hormone receptor-binding activity. Be- cytic hyperplasia in the epidermis as well as decreases cause both tumor necrosis factor-a and transforming in dermal nevus cell nests, but the mechanism

Table 5. Area Stained per Nevus and Staining Intensity for E-cadherin and Tumor Necrosis Factor-a of Recurrent Pigmented Maculesn Compared to Original Nevi by Computed Image Analysis (Values Are Expressed as Percentages of the Original Nevus)

E-cadherin Immunohistochemical Stain Tumor Necrosis Factor-a Immunohistochemical Stain

Patient Per-Area (%) Staining Intensity (%)w Per-Area (%)w Staining Intensity (%)w 1 24.5 133.5 113.2 110.9 2 93.6 41.8 59.3 12.2 3 95.9 106.6 73.9 48.0 4 127.5 94.8 56.5 33.2 5 116.3 47.9 137.5 56.7 6 313.0 72.2 225.3 187.0 7 91.2 108.3 100.2 85.0 8 53.0 56.7 33.5 10.0 9 141.4 58.6 119.3 71.0 10 279.2 31.4 97.3 47.9 11 189.1 89.3 46.3 52.4 12 147.2 93.2 96.6 98.1 13 Not examined Not examined 70.4 36.8 nEach recurrent pigmented macule values is expressed relative to that in its respective original nevus. w Mean value decreased in recurrent lesions (po0.05, compared to the original nevus). 906 SOHN ET AL.: CONGENITAL NEVI TREATMENT WITH AN ALEXANDRITE LASER Dermatol Surg 30:6:June 2004

Figure 10. Electron microscopy of the recurrent pigmented macule epidermis of Patient 3 performed 3 months after the last Q-switched alexandrite laser treatment. Abbreviations: M, melanocyte; K, keratinocyte. Each arrow indicates a melanosome and each arrowhead indicates the nuclear border of a melanocyte.

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Commentary patches that frequently recur after laser surgery or even the development of postinflammatory hyperpigmentation after Given the low prevalence of melanoma in Asia, the use of laser laser treatment. With the advance in the development of for the removal of congenital melanocytic nevi is common immunomodulating agents, findings in this study can have among Asian dermatologists. Sohn and coauthors are to be significant impact to future therapeutic research in reducing the congratulated on this excellent piece of research that examined risk of repigmentation following laser surgery. the molecular event resulting in the formation of recurrent pigmented macules after Q-switched laser treatment for congenital melanocytic nevi. It will be of interest if such HENRY H. L. CHAN,MD(LOND), FRCP findings also apply to benign conditions such as cafe´-au-lait University of Hong Kong