The Ringlike Pattern in Vulvar Melanosis a New Dermoscopic Clue for Diagnosis

OBSERVATION The Ringlike Pattern in Vulvar Melanosis A New Dermoscopic Clue for Diagnosis

Angela Ferrari, MD; Pierluigi Buccini, MD; Renato Covello, MD; Paola De Simone, MD; Vitaliano Silipo, MD; Giustino Mariani, MD; Laura Eibenschutz, MD; Luciano Mariani, MD; Caterina Catricalà, MD

Background: Vulvar melanosis is a benign pigmented like and reticularlike patterns in 4 (5%). A significant as- lesion that may clinically mimic melanoma. Whereas the sociation was found between the distribution of multi- dermoscopic features of other pigmented skin lesions have focal lesions showing a ringlike vs a nonringlike pattern been extensively described, little is known about vulvar (82% vs 52%; P=.008), whereas a weak association was melanosis. found between anatomical site and the different patterns (P=.55). The ringlike pattern was frequently com- Observations: A retrospective dermoscopic study was bined with multifocality and simultaneous occurrence at conducted on 87 lesions with histopathologically proved the labia majora and the labia minora. melanosis. We describe and define, for the first time to our knowledge, a ringlike pattern, found in 28 of 87 mela- Conclusion: Dermoscopy can be useful for the clinical notic lesions (32%), characterized by multiple round to detection of vulvar melanosis, and the ringlike pattern oval structures, white to tan, with dark brown, well- may represent a new dermoscopic clue for the diagnosis defined regular borders. The structureless and globular- of this lesion. like patterns were observed in 18 of 87 lesions (21%), the parallel pattern in 15 (17%), and the cobblestone- Arch Dermatol. 2008;144(8):1030-1034

ULVAR MELANOSIS (VM) spectively.14 The aims of this study are to de- (also called genital mela- scribe the dermoscopic patterns of VM in a nosis/lentiginosis and vul- database of pigmented lesions and to inves- var melanotic macule) is a tigate the age of the patients, the clinical ap- benign pigmented lesion pearance as a single or multifocal macule, thatV usually takes the shape of multiple flat and the distribution of the lesions in specific asymmetrical macules, with a tan-brown sites of the vulvar region for each pattern. to blue-black color, irregular borders, and variable size. In most cases, it develops on METHODS the labia minora, but it can also occur on the labia majora, perineum, introitus, va- 1-3 We performed a multidisciplinary, retrospec- gina, and cervix. tive, dermoscopic study of histopathologically Although VM is a benign lesion, its cor- proved pigmented vulvar lesions collected at the relation with mucosal melanoma is still un- Melanoma Unit of Santa Maria and San Galli- der debate. It often poses a diagnostic chal- cano Dermatological Institute between Janu- lenge because it shows many clinical ary 1, 2004, and December 31, 2006, and se- features consistent with those of mela- lected after a gynecologic visit to Regina Elena noma.3-5 In such cases, biopsy and histo- National Cancer Institute. The computerized pathologic examination are necessary to digital imaging system consisted of a videoder- moscope with a fiberoptic probe connected to define a correct diagnosis. a video terminal with 2 magnification lenses The improved accuracy of dermoscopy (ϫ20 and ϫ50) and a 17-in Pentium IV per- Author Affiliations: in diagnosing pigmented skin lesions has sonal computer (Videocap 200; DS-Medi- Department of Dermatologic been widely demonstrated.6-9 Despite this, group, Milan, Italy). The dedicated software al- Oncology, Santa Maria and the role of dermoscopy in the diagnosis of lows the storage of clinical and dermoscopic San Gallicano Dermatologic mucosal pigmented lesions has been inves- digital images of the lesions and access to the Institute (Drs Ferrari, Buccini, tigated in few studies. The structureless and patient’s database for entering personal infor- De Simone, Silipo, G. Mariani, parallel patterns have been described as the mation and data concerning the patient’s own Eibenschutz, and Catricalà), history of melanoma and nonmelanoma skin mostfrequentdermoscopicfindingsofmela- and Departments of Pathology 10-15 cancers and that of his or her family. This tech- (Dr Covello) and Gynecologic nosis with a vulvar location. Other der- nique allows evaluation of the lesion’s border Oncology (Dr L. Mariani), moscopic patterns, such as cobblestonelike and its minimum and maximum diameters; in Regina Elena National Cancer and reticularlike, have occasionally been re- this way, it is possible to calculate its area and Institute, Rome, Italy. ported at this same site and on the lip, re- its circumference. All the lesions were ob-

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©2008 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/02/2021 served by 3 independent dermatologists (A.F., P.B., and C.C.), experts in dermoscopy, for the evaluation of the lesion’s dermo- Table 1. Characteristics of 71 Patients scopic aspect; a specific pattern was considered present when 2 With Melanotic Lesions of the 3 observers agreed. The age of the patient, the clinical appearance as a single or multifocal lesion, and localization at a Characteristic Valuea specific vulvar site were investigated for each pattern. A 4- to 6-mm Age, median (range), y 41 (22-78) punch biopsy was performed for lesions larger than 1 cm in di- Clinical appearance ameter, whereas in the case of multiple lesions, the most sus- Single macule 28 (39) pect among them was treated by means of full surgical removal. Multifocal macule 43 (61) Descriptive statistics were used to summarize the information Vulvar site yielded by the study. The association between variables was tested Labia majora 18 (25) using the Pearson ␹2 test or the Fisher exact test. Multiple corre- Labia minora 44 (62) spondence analysis, a descriptive/exploratory technique designed Labia majora and labia minora 9 (13) to analyze simple 2-way and multiway tables, was used to iden- Pigmentation tify clinical and dermoscopic profiles. The results provide infor- Homogeneous 43 (61) mation similar to that yielded by factor analysis techniques, which Nonhomogeneous 28 (39) allow exploration of the structure of the categorical variables included in the table. The most common table of this type is the 2-way a Data are given as number (percentage) of patients unless otherwise frequency cross-tabulation table. This representation aims to si- indicated. multaneously visualize the similarities and differences of profiles, identifying the dimensions whose data show greater variability. The position of the points in the multiple correspondence analy- in 15 of 87 lesions (17%) (Figure 3A). This pattern was sis graph is informative. Categories that plot close to each other found alone in 9 of 15 lesions (60%) and combined with are statistically related and have patterns of relative frequencies. other patterns in 6 (40%). The cobblestonelike pattern, fea- This association is statistically reliable (using the Lebart statistic) turing aggregated tan to dark brown polygonal structures, when the points are located far from the origin of the graph, which was observed only as a single pattern in 4 of 87 lesions (5%) represents a mean, uninformative profile. A statistical software pro- (Figure 3B). The reticularlike pattern, found in 4 of 87 le- gram (SPSS version 11.0; SPSS Inc, Chicago, Illinois) was used.16 sions (5%), appeared similar to the pigment network dis- played by melanocytic lesions, from which it differed in the RESULTS oval or round shape (not polygonal) of the meshes. This pattern was characterized by a regular distribution of the Of 115 white patients with pigmented vulvar lesions, 71 grids and meshes and by the abrupt ending of the lines all (median age, 41 years; age range, 22-78 years) showed along the border of the lesion (Figure 3C). It was found 87 histopathologically proved melanotic spots. The vul- combined with other patterns in 2 of 4 lesions (50%). var sites involved were the labia minora in 44 of 71 pa- A multifocal aspect was observed in 23 of 28 mela- tients (62%), the labia majora in 18 (25%), and the labia notic spots (82%) featuring a ringlike pattern, in 7 of 18 minora and the labia majora simultaneously in 9 (13%). (39%) with a structureless pattern, in 10 of 18 (56%) At clinical examination, melanosis appeared as a multi- showing a globularlike pattern, in 7 of 15 (47%) with a focal lesion in 43 of 71 patients (61%) and as a single parallel pattern, in 4 of 4 (100%) with a cobblestonelike macule in 28 (39%), with homogeneous pigmentation pattern, and in 3 of 4 (75%) with a reticularlike pattern. in 43 (61%) and irregular pigmentation variable from A significant association between the distribution of mul- brown to black in 28 (39%) (Table 1). tifocal lesions featuring ringlike and nonringlike pat- At dermoscopic analysis, 6 different patterns were ob- terns was found (82% vs 52%; P=.008). No significant served, alone in 60 of 87 lesions (69%) and combined in association with a specific site (labia minora vs labia ma- 27 of 87 lesions (31%). In 28 of 87 lesions (32%), we ob- jora) at the vulvar region (P=.55) or with the patient’s served a ringlike pattern characterized by multiple round age (P=.50) was observed (Table 2). to oval structures, white to light brown, with hyperpig- The interrelationship of each examined dermoscopic mented well-defined regular borders arranged in a grape- pattern, the patient’s age, the clinical appearance of the like manner in some areas (Figure 1). It was found as a lesion, and a specific vulvar site was evaluated by using single pattern in 21 of 28 lesions (75%) and combined with multiple correspondence analysis (Figure 4). This analy- other patterns in 7 (25%). A structureless pattern charac- sis allows a visual illustration of the associations among terized by diffuse homogeneous or variegated brown to gray- the evaluated variables. Values of absolute and relative blue pigmentation—in the absence of typical dermo- contributions produced by statistical analysis (the Leb- scopic criteria for melanocytic lesions, such as dots and art statistic) showed, along the first axis, a contrast be- globules, pigment network, and streaks—was observed in tween 2 groups. One group (C) was characterized by a 18 of 87 lesions (21%) (Figure 2A). A globularlike pat- stronger association between the ringlike, cobblestone- tern showing aggregated round to oval structures, tan to like, and reticularlike patterns and the multifocal aspect dark brown, similar to globules of melanocytic lesions, was and by a weaker association of the previously men- also found in 18 of 87 melanotic spots (21%) (Figure 2B). tioned patterns with a specific vulvar site; the other group The structureless and globularlike patterns were observed (B), which is complementary to C, included parallel, struc- alone in 10 of 18 melanotic spots (56%) and combined with tureless, and globularlike patterns as dermoscopic fea- other patterns in 8 (44%). tures that shared a clinical appearance as a single lesion. A parallel pattern, which appeared as linear or curved In this group, the dermoscopic patterns were not asso- streaks running parallel to the skin surface, was observed ciated with the anatomical site. No association was ob-

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Figure 1. Two examples of vulvar melanosis dermoscopically featuring a ringlike pattern characterized by multiple round to oval structures, white to light brown, with hyperpigmented well-defined regular borders, arranged in a grapelike manner in some areas (A and B). In A, the inset is a clinical image showing a multifocal melanosis characterized by irregular multiple black spots localized at the internal side of the labia minora pudendi of a 43-year-old woman. In B, the inset is a clinical image displaying a multifocal melanosis characterized by a large black macule with an irregular border localized at the internal side of the left labium minus pudendi, and smaller spots at the clitoris and at the fourchette of a 66-year-old patient.

A B

Figure 2. Vulvar melanosis dermoscopically featuring a structureless pattern characterized by diffuse, variegated brown to gray-blue pigmentation in the absence of dots and globules, pigment network, and streaks (A) and a globularlike pattern featuring aggregated round to oval brown structures (B). In A, the inset shows a symmetric single lesion that was clinically observed at the clitoris of a 44-year-old woman. In B, the inset shows multifocal melanosis clinically characterized by irregular dark brown to black macules that can be seen at the internal side of the labia minora pudendi of a 49-year-old patient.

served between the different patterns and the age of the COMMENT patients (A and D). On histopathologic examination, all the lesions ob- Recently, dermoscopy has proved to be a useful tool for served showed variable distribution of the melanin pig- improving accuracy in diagnosing VM by disclosing some ment along the epidermal basal layer and several mela- features not visible to the naked eye.14,15,17 Mannone et nophages in the dermis from normal to slightly increased, al14 previously reported the structureless pattern as the with no increase in the number of melanocytes. The his- dermoscopic hallmark of VM, especially in the case of topathologic findings of the ringlike and parallel patterns clinically equivocal lesions with a large diameter. were similar: both were characterized by moderate to Instead, the most frequent pattern that we described, marked hyperpigmentation of elongated and clubbed rete and defined for the first time to our knowledge, was the ridges along the basal epidermal layer. The ringlike pat- ringlike pattern. It was characterized by multiple round tern differed in there being “skip” areas of pigmentation to oval structures, white to tan, with dark brown well- present at the top of the dermal papillae; the parallel pat- defined regular borders, arranged in a grapelike manner tern differed in there being more pronounced melanin pig- in some areas. This pattern lacked any pigmented struc- ment at the tip of the rete ridges, in the absence of the pre- ture typical of melanocytic lesions, such as pigment net- viously mentioned skip areas (Figure 5). work, dots or globules, streaks, and a blue-whitish veil.

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©2008 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/02/2021 A Table 2. Lesion Characteristics and Patient Age in the Ringlike and Nonringlike Patterns

No. (%) of Lesions or Patients

Ringlike Nonringlike P Variable Pattern Pattern Value Clinical appearance Single lesion 5 (18) 28 (47) .008 Multifocal lesion 23 (82) 31 (53) Vulvar site Labia majora pudendi 5 (18) 14 (24) Labia minora pudendi 18 (64) 39 (66) .55 Labia majora pudendi and 5 (18) 6 (10) labia minora pudendi Patient age, ya Յ41 12 (55) 22 (46) B .50 Ͼ41 10 (45) 26 (54)

a Data are missing for 1 patient.

1.5 A B

1.0

Labia minora pudendi Parallel 0.5 Single lesion Aged >41 y Globularlike

Structureless 0.0 Reticularlike Second Axis C Multifocal lesion Ringlike –0.5 Aged <41 y Cobblestonelike –1.0 Labia majora pudendi

Labia majora pudendi and labia minora pudendi C D –1.5 –1.0 –0.5 0.0 0.5 1.0 1.5 First Axis

Figure 4. Multiple correspondence analysis showing the associations among dermoscopic pattern, patient age, clinical appearance of the lesion, and specific vulvar site. A and D indicate the groups in which no association was observed between the different patterns and the age of the patients; B, which is complementary to C, the group with parallel, structureless, and globularlike patterns as dermoscopic features that shared a clinical appearance as a single Figure 3. Dermoscopy of melanotic lesions showing a parallel pattern with lesion (in this group, the dermoscopic patterns were not associated with the curved streaks that run parallel to the skin surface (A), a cobblestonelike anatomical site); and C, the group characterized by a stronger association pattern featuring aggregated brown polygonal structures (B), and a between the ringlike, cobblestonelike, and reticularlike patterns and the reticularlike pattern featuring oval meshes and abrupt ending of the lines at multifocal aspect, and by a weaker association of the previously mentioned the borders (C). In A, the inset is a clinical image showing multiple black patterns with a specific vulvar site. The numbers on the axes represent a score spots at the external side of the left labium minus pudendi of a 41-year-old indicating the contribution of each factor (or variable) to overall variability. woman. In B, the inset shows diffuse gray to black pigmentation that can be clinically seen at the labia minora pudendi of a 27-year-old woman. In C, the them could rule out the diagnosis of melanocytic lesion. inset is a clinical image showing an asymmetric single dark brown to black macule at the left labium minus pudendi of a 30-year-old patient. In addition, the blue-gray pigmentation, featuring the first pattern, increased the suspicion index because, in dermoscopy, the blue hue is known to be related to malig- The structureless and globularlike patterns were ob- nancy.15,18,19 The parallel pattern, observed in VM and in served in the same percentage of lesions. The first pat- labial melanosis by Argenziano et al15 and in clinically tern, as reported by other researchers, was character- typical, small melanotic macules of the lip and of the pe- ized by a diffuse dark brown to blue-gray pigmentation, nis by Mannone et al,14 may be considered typical of mela- whereas the second pattern featured aggregated struc- nosis, although it is commonly found in melanocytic le- tures, round to oval and tan to dark brown. Neither of sions at specific anatomical sites (ie, the palms and soles).

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©2008 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/02/2021 for the first time to our knowledge, may represent a new A dermoscopic clue for the diagnosis of VM. However, we suggest not considering the ringlike pattern to be predictive until a more in-depth study, with a strong histopathologic correlation with dermoscopic features, is performed. In addition, we underline the importance of a multidisciplinary approach to VM by dermatologists and gynecologists, and wealsosuggestthatapunchbiopsybeperformedinalldoubt- ful lesions to rule out the diagnosis of melanoma. Accepted for Publication: December 28, 2007. Correspondence: Angela Ferrari, MD, Department of Der- matologic Oncology, Santa Maria and San Gallicano Dermatologic Institute, IFO of Rome, Via Elio Chianesi B 53, 00144 Rome, Italy ([email protected]). Author Contributions: Dr Ferrari had full access to all of the data in the study and takes responsibility for the integ- rity of the data and the accuracy of the data analysis. Study concept and design: Ferrari and Catricalà. Acquisition of data: Buccini, Covello, De Simone, Silipo, G. Mariani, Eiben- schutz, and L. Mariani. Drafting of the manuscript: Ferrari, Covello, De Simone, Silipo, G. Mariani, Eibenschutz, and L. Mariani. Critical revision of the manuscript for important intellectual content: Buccini and Catricalà. Administrative, technical, or material support: Covello, G. Mariani, and Figure 5. Histopathologic findings of the ringlike and parallel patterns L. Mariani. Study supervision: Catricalà. (hematoxylin-eosin, original magnification ϫ20): the ringlike pattern shows hyperpigmented elongated and clubbed rete ridges with “skip” areas of Financial Disclosure: None reported. pigmentation at the top of the dermal papillae (A) and the parallel pattern Additional Contributions: Isabella Sperduti, PhD, Bio- shows accentuation of melanin pigment at the tip of the rete ridges in the statistic Unit, Regina Elena National Cancer Institute, absence of skip areas (B). provided statistical analysis.

The cobblestonelike and reticularlike patterns were sel- REFERENCES dom observed; they featured brown polygonal structures 1. Barnhill RL, Albert LS, Shama SK, Goldenhersh MA, Rhodes AR, Sober AJ. larger than globules and pigment network, respectively, Genital lentiginosis. J Am Acad Dermatol. 1990;22(3):453-460. which are common findings in melanocytic lesions. Com- 2. Rudolph RI. Vulvar melanosis. J Am Acad Dermatol. 1990;23(5, pt 2):982-984. pared with melanocytic lesions, the shape of the meshes 3. Rock B. Pigmented lesions of the vulva. Dermatol Clin. 1992;10(2):361-370. 4. Jih DM, Elder DE, Elenitsas R. A histopathologic evaluation of vulvar melanosis. of the pigment network in the reticularlike pattern was either Arch Dermatol. 1999;135(7):857-858. round or oval (not polygonal), and, unlike the atypical pig- 5. Lenane P, Keane CO, Connell BO, Loughlin SO, Powell FC. Genital melanotic macules. ment network of melanoma, in VM, the grids and the J Am Acad Dermatol. 2000;42(4):640-644. 6. Pehamberger H, Binder M, Steiner A, Wolff K. In vivo epiluminescence microscopy. meshes were more regularly distributed. However, in all J Invest Dermatol. 1993;100(3):356S-362S. these lesions, a punch biopsy is strongly recommended to 7. Steiner A, Pehamberger H, Wolff K. In vivo epiluminescence microscopy of pigmented skin lesions, 2: diagnosis of small pigmented skin lesions and early de- confirm the diagnosis. In contrast to the present results, tection of malignant melanoma. J Am Acad Dermatol. 1987;17(4):584-591. 14 Mannone et al found a reticularlike pattern combined with 8. Soyer HP, Argenziano G, Chimenti S, Ruocco V. Dermoscopy of pigmented skin melanosis of the areola and, rarely, of the lip. lesions. Eur J Dermatol. 2001;11(3):270-277. 9. Argenziano G, Soyer HP, Chimenti S, et al. Dermoscopy of pigmented skin lesions. By statistical analysis, the clinical appearance of the J Am Acad Dermatol. 2003;48(5):679-693. lesions as single or multifocal macules was the most dis- 10. de Giorgi V, Massi D, Salvini C, Mannone F, Carli P. Pigmented seborrheic kera- criminant factor in the different dermoscopic patterns, toses of the vulva clinically mimicking a malignant melanoma: a clinical, dermoscopic-pathologic case study. Clin Exp Dermatol. 2005;30(1):17-19. which were not strongly related to a specific vulvar site 11. de Giorgi V, Massi D, Salvini C, Mannone F, Cattaneo A, Carli P. Thin melanoma and had no association with the patient’s age. Melanotic of the vulva: a clinical, dermoscopic-pathologic case study. Arch Dermatol. 2005; 141(8):1046-1047. lesions featuring the ringlike, cobblestonelike, and re- 12. De Giorgi V, Massi D, Carli P. Dermoscopy in the management of pigmented le- ticularlike patterns most frequently appeared as multi- sions of the oral mucosa. Oral Oncol. 2003;39(5):534-535. focal macules located at the labia majora and labia mi- 13. Betti R, Menni S, Crosti C. Melanoma of the glans penis. Eur J Dermatol. 2005; 15(2):113-115. nora; lesions featuring the globularlike, structureless, and 14. Mannone F, de Giorgi V, Cattaneo A, Massi D, De Magnis A, Carli P. Dermo- parallel patterns most commonly developed as single le- scopic features of mucosal melanosis. Dermatol Surg. 2004;30(8):1118-1123. sions and were not associated with a specific vulvar site. 15. Argenziano G, Soyer HP, de Giorgi V, et al. Interactive Atlas on Dermoscopy. Mi- lan, Italy: EDRA Medical Publishing and New Media; 2001. Inconclusion,dermoscopycanbeausefulaidfortheclini- 16. Lebart L, Marineau A, Werwick K. Multivariate Descriptive Statistical Analysis. cal detection of VM, especially when it appears as a single New York, NY: John Wiley & Sons; 1984. 17. Carli P, de Giorgi V, Cattaneo A, Giannotti B. Mucosal melanosis clinically mim- macule, and can represent a tool to strengthen the suspicion icking malignant melanoma. Eur J Dermatol. 1996;6:434-436. of melanosis when it occurs in the shape of multifocal mac- 18. Argenziano G, Fabbrocini G, Carli P, De Giorgi V, Delfino M. Epiluminescence ules,whichisthemostfrequentclinicalpresentationofmela- microscopy: criteria of cutaneous melanoma progression. J Am Acad Dermatol. 1997;37(1):68-74. nosis. The ringlike pattern, the one most frequently observed 19. Massi D, de Giorgi V, Carli P, Cantucci M. Diagnostic significance of the blue hue in in multifocal macules in this series, which we defined dermoscopy of melanocytic lesions. Am J Dermatopathol. 2001;23(5):463-469.

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