CED
Clinical dermatology • Concise report
Clinical and Experimental Dermatology
Atypical naevus spilus: detection by in vivo confocal microscopy M. E. Laing,1,2,3 E. Coates,1,2,3 A. Jopp-McKay,4 R. A. Scolyer3,4,5 and P. Guitera1,2,3,4,5 1
Sydney Melanoma Diagnostic Centre, 3Department of Dermatology, and 4Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, Australia; 2Melanoma Institute Australia, Sydney, Australia; and 5University of Sydney, Camperdown, NSW, Australia doi:10.1111/ced.12354
Summary
Naevus spilus (NS) is a naevoid disorder characterized by hyperpigmented macules or papules scattered over a cafe-au-lait macule. Such cafe-au-lait macules are often present at birth, and the darker pigmented speckles of NS slowly increase in number and size over a period of several years. NS can therefore be difficult to evaluate clinically for the development of melanoma. In vivo confocal microscopy (IVCM) is a novel method that allows examination at cellular resolution of cutaneous lesions in vivo. IVCM has been shown to have twice the specificity of dermoscopy for the diagnosis of melanoma, with comparable sensitivity. It has been shown to be useful in the detection and grading of dysplastic naevi, which are recognized precursors of melanoma in some cases. In this report, we highlight that IVCM can also be used as a tool complementary to dermoscopy to identify areas of dynamic change in clinically and dermoscopically equivocal lesions. IVCM may thereby assist in the early detection of melanocytic atypia and melanoma arising in NS, in turn leading to excision of melanoma at an early stage, which is associated with a favourable outcome. We also outline some of the difficulties encountered in confocal microscopy and histology when differentiating melanoma from dysplastic naevi.
Naevus spilus (NS) is characterized by the presence of hyperpigmented macules or papules scattered over a cafe-au-lait macule. The macule is often present at birth, while the pigmented speckles of NS slowly increase in number and size over a number of years, resulting in difficulty in evaluation for melanoma development. In vivo confocal microscopy (IVCM) allows examination at cellular resolution of cutaneous lesions in vivo. We report a case of NS in which IVCM was used to aid diagnosis, and we also describe some of the difficulties encountered in differentiating melanoma from dysplastic naevi.
Correspondence: Dr Mary E. Laing, Department of Dermatology, Galway University Hospital, Galway, Ireland E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 6 January 2014
616
Clinical and Experimental Dermatology (2014) 39, pp616–619
Report A 54-year-old woman presented with a pigmented lesion on her lateral thigh, which had been present since birth and had recently changed. On physical examination, a cafe-au-lait macule 40 9 50 mm in size was seen, which had superimposed maculopapular speckles, consistent with NS (Fig. 1). There were no dermoscopic features of melanoma or dysplastic naevus. Short-term dermoscopic monitoring of this lesion revealed a subtle change in one area (Fig. 2). IVCM showed well-defined dermal papillae with a normal regular cobblestone pattern in most of the lesion (Fig. 3a; Fig. 3, inset, red box) except for a solitary speckled pigmented macule (Fig. 3a, yellow box at bottom of inset) that corresponded to the changing area identified dermoscopically. This area showed disarray of the normal architecture of the superficial layers, with no clear honeycomb pattern, presence of nonedged papillae (Fig. 3b, arrows) and numerous, scattered, large, irregular, round, pagetoid cells with a dark nucleus and bright cytoplasm (Fig. 4).
ª 2014 British Association of Dermatologists
Atypical NS: detection by in vivo confocal microscopy M. E. Laing et al.
(a)
Figure 1 Clinical photograph of the macule, showing dark-
brown speckles.
(b)
Figure 2 Dermoscopy identified an area (arrow) that changed
during short-term monitoring.
Histopathology of a punch biopsy taken from the atypical area showed large atypical melanocytes with angulated hyperchromatic nuclei. Some of these melanocytes were scattered suprabasally, which was suggestive of a lentiginous dysplastic naevus with focal severe atypia, consistent with the confocal findings (Fig. 5). The lesion was excised with a 5 mm margin and primary closure. Histopathology of the excised tissue revealed a lentiginous proliferation of melanocytes associated with elongated rete ridges and increased basal keratinocyte pigmentation. Focally, the melanocytes had angulated hyperchromatic nuclei, and scattered suprabasal epidermal melanocytes were present (Fig. 5). The histopathological features were originally interpreted as those of a lentiginous dysplastic naevus with focal severe atypia. However on review, when interpreted in the context of the clinical, dermoscopic and
ª 2014 British Association of Dermatologists
Figure 3 (a,b) Confocal field of view (0.5 9 0.5 mm) of (a) one of the speckled pigmented areas, showing well-defined papillae (red arrows) with a normal regular cobblestone-pattern architecture; and (b) the area identified dermoscopically (yellow square) showing disarray of the normal architecture of the superficial layers with no clear honeycomb pattern, nonedged papillae (white arrows) and the appearance of a large pagetoid cell. Original magnification 9 35.
confocal microscopy findings, we considered the histopathological features to be consistent with NS. The focus of the pagetoid melanocytes lacked severe cytological atypia and was located beneath an area of parakeratotic hyperkeratosis, features suggestive of a reaction to superficial ‘irritation’ (rather than in situ melanoma).1 There was no evidence of recurrence at follow-up 12 months later. NS can be difficult to evaluate clinically for the development of melanoma. The need for close follow-up of
Clinical and Experimental Dermatology (2014) 39, pp616–619
617
Atypical NS: detection by in vivo confocal microscopy M. E. Laing et al.
A typical melanocytes migrating in the epidermis
Figure 4 Confocal field of view (0.5 9 0.5 mm) showing atypi-
cal melanocytes migrating upwards in the epidermis and disarray of the normal honeycomb pattern, with round pagetoid cells (white arrows) (original magnification 9 35).
Figure 5 Excision biopsy showing lentiginous melanocytic
proliferation with a focal upward migration of melanocytes (haematoxylin and eosin, original magnification 9 40).
patients with NS is emphasized by reports of several cases of cutaneous melanoma developing within such lesions.2,3 Manganoni et al. 4 reported that 1% of melanomas were associated with NS. IVCM is a recently described method that allows examination at cellular resolution of cutaneous lesions in vivo. It has been shown to have twice the specificity of dermoscopy for the diagnosis of melanoma, with comparable sensitivity, and can therefore dramatically reduce the need for unnecessary excision of benign lesions.5 IVCM has been shown to be useful in the detection and grading of dysplastic naevi, which are recognized precursors of melanoma in some cases.6 In our case, the confocal diagnosis was suspicious for melanoma. There was disarray of the normal
618
Clinical and Experimental Dermatology (2014) 39, pp616–619
architecture of the superficial layers with no clear honeycomb pattern. There were scattered pagetoid cells, and the presence of nonedged papillae. In a recent study by Pellacani et al.,7 evaluating the efficiency of IVCM for the diagnostic accuracy of melanoma and equivocal melanocytic lesions, the presence of epidermal disarray was more frequently observed in melanoma (62.5%), although it was present in onethird of benign naevi. A regular honeycomb pattern was observed in 52% of naevi and 12% of melanomas, while pagetoid infiltration was reported in 78% of melanomas and 19% of benign naevi (OR = 11.1). and nonedged papillae were observed in 90% of melanomas and 41% of naevi (OR 12.3). Difficulties therefore exist in the differentiation of melanoma from atypical naevi using confocal microscopy, as many of the features described above are present in both. On review of our patient’s histology, the features were consistent with NS. Distinguishing between in situ melanoma and ‘pseudomelanoma’ is a well recognized and difficult area in histopathological diagnosis. Although we favour the notion that the pagetoid melanocytes represent a reaction to superficial ‘irritation’, it is indeed possible that other pathologists may interpret the changes as representing a focus of in situ melanoma arising in NS.8 In this report, we highlight that IVCM can be used as a tool complementary to dermoscopy and shortterm monitoring. IVCM enables a detailed analysis at cellular level of regions of dynamic change identified clinically and on sequential digital dermoscopy. IVCM may assist in the early detection of melanocytic atypia and melanoma arising in NS, which in turn may lead to excision of melanoma at an early stage, which is associated with a favourable outcome. We also highlight that both confocal microscopy and histopathology share similar difficulties in the interpretation of melanoma from atypical naevi.
Learning points ● NS is a naevoid disorder characterized by
hyperpigmented macules or papules scattered over a cafe-au-lait macule, which is often present at birth, with the darker pigmented speckles of NS slowly increasing in number and size over several years, leading to difficulties in differentiating NS from melanoma. ● IVCM allows examination at cellular resolution of cutaneous lesions in vivo.
ª 2014 British Association of Dermatologists
Atypical NS: detection by in vivo confocal microscopy M. E. Laing et al.
● IVCM has been shown to have twice the speci-
ficity of dermoscopy for the diagnosis of melanoma, with comparable sensitivity, and can therefore dramatically reduce the need for unnecessary excision of benign lesions. ● IVCM has been shown to be useful in the detection and grading of dysplastic naevi, which are recognized precursors of melanoma in some cases. ● In this report, we highlight that IVCM can also be used as a tool complementary to dermoscopy and short-term monitoring to evaluate at cellular level any areas of dynamic change identified clinically and dermoscopically. ● IVCM may thereby assist in the early detection of melanocytic atypia and melanoma arising in NS, which in turn will lead to excision of melanoma at an early stage, which is associated with a favourable outcome.
2 Haenssle HA, Kaune KM, Buhl T et al. Melanoma arising in segmental nevus spilus: detection by sequential digital dermatoscopy. J Am Acad Dermatol 2009; 61: 337–41. 3 Piana S, Gelli MC, Grenzi L et al. Multifocal melanoma arising on nevus spilus. Int J Dermatol 2006; 45: 1380–1. 4 Manganoni AM, Pavoni L, Farisoglio C et al. Report of 27 cases of naevus spilus in 2134 patients with melanoma: is naevus spilus a risk marker of cutaneous melanoma? J Eur Acad Dermatol Venereol 2012; 26: 129–30. 5 Guitera P, Pellacani G, Longo C et al. In vivo reflectance confocal microscopy enhances secondary evaluation of melanocytic lesions. J Invest Dermatol 2009; 129: 131–8. 6 Pellacani G, Farnetani F, Gonzalez S et al. In vivo confocal microscopy for detection and grading of dysplastic nevi: a pilot study. J Am Acad Dermatol 2012; 66: e109–21. 7 Pellacani G, Guitera P, Longo C et al. The impact of in vivo reflectance confocal microscopy for the diagnostic accuracy of melanoma and equivocal melanocytic lesions. J Invest Dermatol 2007; 127: 2759–65. 8 Braun RP, Gutkowicz-Krusin D, Rabinovitz H et al. Agreement of dermatopathologists in the evaluation of clinically difficult melanocytic lesions: how golden is the ‘gold standard’? Dermatology 2012; 224: 51–8.
References 1 Kornberg R, Ackerman AB. Pseudomelanoma: recurrent melanocytic nevus following partial surgical removal. Arch Dermatol 1975; 111: 1588–90.
ª 2014 British Association of Dermatologists
Clinical and Experimental Dermatology (2014) 39, pp616–619
619
Clinical dermatology • Concise report
Clinical and Experimental Dermatology
Atypical naevus spilus: detection by in vivo confocal microscopy M. E. Laing,1,2,3 E. Coates,1,2,3 A. Jopp-McKay,4 R. A. Scolyer3,4,5 and P. Guitera1,2,3,4,5 1
Sydney Melanoma Diagnostic Centre, 3Department of Dermatology, and 4Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, Australia; 2Melanoma Institute Australia, Sydney, Australia; and 5University of Sydney, Camperdown, NSW, Australia doi:10.1111/ced.12354
Summary
Naevus spilus (NS) is a naevoid disorder characterized by hyperpigmented macules or papules scattered over a cafe-au-lait macule. Such cafe-au-lait macules are often present at birth, and the darker pigmented speckles of NS slowly increase in number and size over a period of several years. NS can therefore be difficult to evaluate clinically for the development of melanoma. In vivo confocal microscopy (IVCM) is a novel method that allows examination at cellular resolution of cutaneous lesions in vivo. IVCM has been shown to have twice the specificity of dermoscopy for the diagnosis of melanoma, with comparable sensitivity. It has been shown to be useful in the detection and grading of dysplastic naevi, which are recognized precursors of melanoma in some cases. In this report, we highlight that IVCM can also be used as a tool complementary to dermoscopy to identify areas of dynamic change in clinically and dermoscopically equivocal lesions. IVCM may thereby assist in the early detection of melanocytic atypia and melanoma arising in NS, in turn leading to excision of melanoma at an early stage, which is associated with a favourable outcome. We also outline some of the difficulties encountered in confocal microscopy and histology when differentiating melanoma from dysplastic naevi.
Naevus spilus (NS) is characterized by the presence of hyperpigmented macules or papules scattered over a cafe-au-lait macule. The macule is often present at birth, while the pigmented speckles of NS slowly increase in number and size over a number of years, resulting in difficulty in evaluation for melanoma development. In vivo confocal microscopy (IVCM) allows examination at cellular resolution of cutaneous lesions in vivo. We report a case of NS in which IVCM was used to aid diagnosis, and we also describe some of the difficulties encountered in differentiating melanoma from dysplastic naevi.
Correspondence: Dr Mary E. Laing, Department of Dermatology, Galway University Hospital, Galway, Ireland E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 6 January 2014
616
Clinical and Experimental Dermatology (2014) 39, pp616–619
Report A 54-year-old woman presented with a pigmented lesion on her lateral thigh, which had been present since birth and had recently changed. On physical examination, a cafe-au-lait macule 40 9 50 mm in size was seen, which had superimposed maculopapular speckles, consistent with NS (Fig. 1). There were no dermoscopic features of melanoma or dysplastic naevus. Short-term dermoscopic monitoring of this lesion revealed a subtle change in one area (Fig. 2). IVCM showed well-defined dermal papillae with a normal regular cobblestone pattern in most of the lesion (Fig. 3a; Fig. 3, inset, red box) except for a solitary speckled pigmented macule (Fig. 3a, yellow box at bottom of inset) that corresponded to the changing area identified dermoscopically. This area showed disarray of the normal architecture of the superficial layers, with no clear honeycomb pattern, presence of nonedged papillae (Fig. 3b, arrows) and numerous, scattered, large, irregular, round, pagetoid cells with a dark nucleus and bright cytoplasm (Fig. 4).
ª 2014 British Association of Dermatologists
Atypical NS: detection by in vivo confocal microscopy M. E. Laing et al.
(a)
Figure 1 Clinical photograph of the macule, showing dark-
brown speckles.
(b)
Figure 2 Dermoscopy identified an area (arrow) that changed
during short-term monitoring.
Histopathology of a punch biopsy taken from the atypical area showed large atypical melanocytes with angulated hyperchromatic nuclei. Some of these melanocytes were scattered suprabasally, which was suggestive of a lentiginous dysplastic naevus with focal severe atypia, consistent with the confocal findings (Fig. 5). The lesion was excised with a 5 mm margin and primary closure. Histopathology of the excised tissue revealed a lentiginous proliferation of melanocytes associated with elongated rete ridges and increased basal keratinocyte pigmentation. Focally, the melanocytes had angulated hyperchromatic nuclei, and scattered suprabasal epidermal melanocytes were present (Fig. 5). The histopathological features were originally interpreted as those of a lentiginous dysplastic naevus with focal severe atypia. However on review, when interpreted in the context of the clinical, dermoscopic and
ª 2014 British Association of Dermatologists
Figure 3 (a,b) Confocal field of view (0.5 9 0.5 mm) of (a) one of the speckled pigmented areas, showing well-defined papillae (red arrows) with a normal regular cobblestone-pattern architecture; and (b) the area identified dermoscopically (yellow square) showing disarray of the normal architecture of the superficial layers with no clear honeycomb pattern, nonedged papillae (white arrows) and the appearance of a large pagetoid cell. Original magnification 9 35.
confocal microscopy findings, we considered the histopathological features to be consistent with NS. The focus of the pagetoid melanocytes lacked severe cytological atypia and was located beneath an area of parakeratotic hyperkeratosis, features suggestive of a reaction to superficial ‘irritation’ (rather than in situ melanoma).1 There was no evidence of recurrence at follow-up 12 months later. NS can be difficult to evaluate clinically for the development of melanoma. The need for close follow-up of
Clinical and Experimental Dermatology (2014) 39, pp616–619
617
Atypical NS: detection by in vivo confocal microscopy M. E. Laing et al.
A typical melanocytes migrating in the epidermis
Figure 4 Confocal field of view (0.5 9 0.5 mm) showing atypi-
cal melanocytes migrating upwards in the epidermis and disarray of the normal honeycomb pattern, with round pagetoid cells (white arrows) (original magnification 9 35).
Figure 5 Excision biopsy showing lentiginous melanocytic
proliferation with a focal upward migration of melanocytes (haematoxylin and eosin, original magnification 9 40).
patients with NS is emphasized by reports of several cases of cutaneous melanoma developing within such lesions.2,3 Manganoni et al. 4 reported that 1% of melanomas were associated with NS. IVCM is a recently described method that allows examination at cellular resolution of cutaneous lesions in vivo. It has been shown to have twice the specificity of dermoscopy for the diagnosis of melanoma, with comparable sensitivity, and can therefore dramatically reduce the need for unnecessary excision of benign lesions.5 IVCM has been shown to be useful in the detection and grading of dysplastic naevi, which are recognized precursors of melanoma in some cases.6 In our case, the confocal diagnosis was suspicious for melanoma. There was disarray of the normal
618
Clinical and Experimental Dermatology (2014) 39, pp616–619
architecture of the superficial layers with no clear honeycomb pattern. There were scattered pagetoid cells, and the presence of nonedged papillae. In a recent study by Pellacani et al.,7 evaluating the efficiency of IVCM for the diagnostic accuracy of melanoma and equivocal melanocytic lesions, the presence of epidermal disarray was more frequently observed in melanoma (62.5%), although it was present in onethird of benign naevi. A regular honeycomb pattern was observed in 52% of naevi and 12% of melanomas, while pagetoid infiltration was reported in 78% of melanomas and 19% of benign naevi (OR = 11.1). and nonedged papillae were observed in 90% of melanomas and 41% of naevi (OR 12.3). Difficulties therefore exist in the differentiation of melanoma from atypical naevi using confocal microscopy, as many of the features described above are present in both. On review of our patient’s histology, the features were consistent with NS. Distinguishing between in situ melanoma and ‘pseudomelanoma’ is a well recognized and difficult area in histopathological diagnosis. Although we favour the notion that the pagetoid melanocytes represent a reaction to superficial ‘irritation’, it is indeed possible that other pathologists may interpret the changes as representing a focus of in situ melanoma arising in NS.8 In this report, we highlight that IVCM can be used as a tool complementary to dermoscopy and shortterm monitoring. IVCM enables a detailed analysis at cellular level of regions of dynamic change identified clinically and on sequential digital dermoscopy. IVCM may assist in the early detection of melanocytic atypia and melanoma arising in NS, which in turn may lead to excision of melanoma at an early stage, which is associated with a favourable outcome. We also highlight that both confocal microscopy and histopathology share similar difficulties in the interpretation of melanoma from atypical naevi.
Learning points ● NS is a naevoid disorder characterized by
hyperpigmented macules or papules scattered over a cafe-au-lait macule, which is often present at birth, with the darker pigmented speckles of NS slowly increasing in number and size over several years, leading to difficulties in differentiating NS from melanoma. ● IVCM allows examination at cellular resolution of cutaneous lesions in vivo.
ª 2014 British Association of Dermatologists
Atypical NS: detection by in vivo confocal microscopy M. E. Laing et al.
● IVCM has been shown to have twice the speci-
ficity of dermoscopy for the diagnosis of melanoma, with comparable sensitivity, and can therefore dramatically reduce the need for unnecessary excision of benign lesions. ● IVCM has been shown to be useful in the detection and grading of dysplastic naevi, which are recognized precursors of melanoma in some cases. ● In this report, we highlight that IVCM can also be used as a tool complementary to dermoscopy and short-term monitoring to evaluate at cellular level any areas of dynamic change identified clinically and dermoscopically. ● IVCM may thereby assist in the early detection of melanocytic atypia and melanoma arising in NS, which in turn will lead to excision of melanoma at an early stage, which is associated with a favourable outcome.
2 Haenssle HA, Kaune KM, Buhl T et al. Melanoma arising in segmental nevus spilus: detection by sequential digital dermatoscopy. J Am Acad Dermatol 2009; 61: 337–41. 3 Piana S, Gelli MC, Grenzi L et al. Multifocal melanoma arising on nevus spilus. Int J Dermatol 2006; 45: 1380–1. 4 Manganoni AM, Pavoni L, Farisoglio C et al. Report of 27 cases of naevus spilus in 2134 patients with melanoma: is naevus spilus a risk marker of cutaneous melanoma? J Eur Acad Dermatol Venereol 2012; 26: 129–30. 5 Guitera P, Pellacani G, Longo C et al. In vivo reflectance confocal microscopy enhances secondary evaluation of melanocytic lesions. J Invest Dermatol 2009; 129: 131–8. 6 Pellacani G, Farnetani F, Gonzalez S et al. In vivo confocal microscopy for detection and grading of dysplastic nevi: a pilot study. J Am Acad Dermatol 2012; 66: e109–21. 7 Pellacani G, Guitera P, Longo C et al. The impact of in vivo reflectance confocal microscopy for the diagnostic accuracy of melanoma and equivocal melanocytic lesions. J Invest Dermatol 2007; 127: 2759–65. 8 Braun RP, Gutkowicz-Krusin D, Rabinovitz H et al. Agreement of dermatopathologists in the evaluation of clinically difficult melanocytic lesions: how golden is the ‘gold standard’? Dermatology 2012; 224: 51–8.
References 1 Kornberg R, Ackerman AB. Pseudomelanoma: recurrent melanocytic nevus following partial surgical removal. Arch Dermatol 1975; 111: 1588–90.
ª 2014 British Association of Dermatologists
Clinical and Experimental Dermatology (2014) 39, pp616–619
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