DERMATOLOGY PRACTICAL & CONCEPTUAL www.derm101.com Observation | Dermatol Pract Concept 2012;3(1):9 33 Reflectance confocal microscopy: a useful and non-invasive tool in the in vivo differentiation of benign pigmented skin lesions from malignant melanoma. Report of a case Ramin Mofarrah, M.D.1, Verena Ahlgrimm-Siess, M.D.2, Cesare Massone, M.D.1, Rainer Hofmann-Wellenhof, M.D.1 1 Department of Dermatology, Medical University of Graz, Austria 2 Department of Dermatology, Paracelsus Private Medical University of Salzburg, Austria Key words: reflectance confocal microscopy, seborrheic keratosis, melanoma, histopathology, dermoscopy Citation: Mofarrah R, Ahlgrimm-Siess V, Massone C, Hofmann-Wellenhof R. Reflectance confocal microscopy: a useful and non-invasive tool in the in vivo differentiation of benign pigmented skin lesions from malignant melanoma. Report of a case. Dermatol Pract Conc. 2013;3(1):9. http://dx.doi.org/10.5826/dpc.0301a09. Received: May 7, 2012; Accepted: July 31, 2012; Published: January 31, 2013 Copyright: ©2013 Hofmann-Wellenhof et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: None. Competing interests: The authors have no conflicts of interest to disclose. All authors have contributed significantly to this publication. Corresponding author: Rainer Hofmann-Wellenhof, M.D., Department of Dermatology, Medical University of Graz, Auenbruggerplatz 8, 8036 Graz, Austria. Tel. +43.316.385.2371; Fax. +43.316.385 2466. Email: rainer.hofmann@medunigraz.at. Report of case A 67-year-old man was referred to our department because of a pigmented skin lesion that was clinically suspicious for melanoma. The patient presented with several pigmented skin lesions on the back. He reported that they had been present for a few years and that he had noticed a change in color and slow enlargement in one pigmented skin lesion on his right shoulder. Clinically, there was a light-to-dark brown patch approxi- mately 1.5 cm in diameter. Dermoscopy showed a light-to- dark brown homogenous-reticular pattern with focal gray- brown to gray-white areas (Figure 1A). The clinical and dermoscopic features were most suggestive of a solar lentigo / early seborrheic keratosis (SK) with regression, but a mel- anoma on sun-damaged skin or a collision of a melanoma with an SK were considered in the differential diagnosis. With reflectance confocal microscopy (RCM), a slightly atypical honeycomb pattern was seen at the superficial epidermal lay- ers. At the basal layer, multiple densely packed edged papil- lae of different sizes and shapes were observed (Figure 1B). The diagnosis of seborrheic keratoses (SK) undergoing regression can be challenging clinically and der- moscopically. We report a case of a SK with a history of change and equivocal dermoscopic features, thereby showing confocal features suggestive of solar lentigo/early SK. The present case emphasizes the potential value of reflectance confocal microscopy (RCM) in the differentiation of malignant from benign pigmented skin lesions. ABSTRACT 34 Observation | Dermatol Pract Concept 2012;3(1):9 Figure 1. (A) Dermoscopy showed a light to dark brown homogenous-reticular pattern (insert; area within the dashed square at higher magnification) with focal gray-brown to gray-white areas. (B) On RCM, dense edged papillae (arrows) are observed at the basal layer at low magnification (1.5 x 1.5 mm). (C) At high magnification (0.5 x 0.5 mm), small bright, monomorphous cells are seen outlining dermal papil- lae of different sizes and shapes (arrows). (D) Cord-like structures (arrows) are displayed at the DEJ at low magnification (1.5 x 1.5 mm). (E) Bright, branching tubular structures (“cords,” arrows) are observed at the DEJ at high magnification (0.5 x 0.5 mm). Plump, bright cells are found within the upper dermis (arrowhead). (F) Histology showed epidermal hyperplasia characterized by thin strands of basaloid cells and basal hyperpigmentation without increase of melanocytes. In the superficial dermis, few melanophages and solar elastosis were present. [Copyright: ©2013 Hofmann-Wellenhof et al.] Observation | Dermatol Pract Concept 2012;3(1):9 35 In addition, we observed multiple bright, round to triangu- lar, non-nucleated cells, suggestive of aggregates of melano- phages due to partial regression. Confocal criteria sugges- tive of a melanoma, such as bright, pagetoid nucleated cells, cerebriform cell clusters, or a disarrangement of the DEJ with non-edged papillae were not seen. These findings were in line with the RCM criteria of lichen planus-like keratosis reported by Bassoli et al [11]. In our opinion, the present case demonstrates the poten- tial value of RCM in the diagnosis and differentiation of benign and malignant pigmented skin lesions. RCM may improve the diagnostic accuracy and spare unnecessary exci- sions of benign pigmented skin lesions with equivocal clini- cal and dermoscopic features. References 1. Elgart GW. Seborrheic keratoses, solar lentigines, and lichenoid keratoses. Dermatoscopic features and correlation to histology and clinical signs. Dermatol Clin. 2001;19(2):347-57. 2. Pastar Z, Lipozencić J, Rados J, Stajminger G. Regressing seb- orrheic keratosis—clinically and dermoscopically mimick ing a regressing melanoma. Acta Dermatovenerol Croat. 2007;15(1): 24-6. 3. Braga JC, Scope A, Klaz I, Mecca P, Spencer P, Marghoob AA. Melanoma mimicking seborrheic keratosis: an error of percep- tion precluding correct dermoscopic diagnosis. J Am Acad Der- matol. 2008;58(5):875-80. 4. Argenziano G, Rossiello L, Scalvenzi M, et al. Melanoma sim- ulating seborrheic keratosis: a major dermoscopy pitfall. Arch Dermatol. 2003;139(3):389-91. 5. Rajadhyaksha M, Grossman M, Esterowitz D, Webb RH, An- derson RR. In vivo confocal scanning laser microscopy of hu- man skin melanin provides strong contrast. J Invest Dermatol. 1995;104(6):946–52. 6. Langley RGB, Rajadhyaksha M, Dwyer PJ, et al. Confocal scan- ning laser microscopy of benign and malignant melanocytic le- sions in vivo. J Am Acad Dermatol. 2001;45(3):365-76. 7. Pellacani G, Cesinaro AM, Seidenari S. Reflectance-mode confocal microscopy of pigmented skin lesions—improve- ment in melanoma diagnostic specificity. J Am Acad Dermatol. 2005;53(6):979-85. 8. González S, Gill M, Halpern AC. Reflectance Confocal Micros- copy of Cutaneous Tumors. An Atlas with Clinical, Dermoscopic and Histological Correlations. 2nd ed. London: Informa Health- care, 2011. 9. Langley RG, Burton E, Walsh N, Propperova I, Murray SJ. In vivo confocal scanning laser microscopy of benign lentigines: comparison to conventional histology and in vivo characteristics of lentigo maligna. J Am Acad Dermatol. 2006;55(1):88-97. 10. Hofmann-Wellenhof R, Pellacani G, Malvehy J, Soyer HP (eds). Reflectance Confocal Microscopy for Skin Diseases. Berlin: Springer-Verlag, 2012. 11. Bassoli S, Rabinovitz HS, Pellacani G, et al. Reflectance confocal microscopy criteria of lichen planus-like keratosis. J Eur Acad Dermatol Venereol. 2012;26(5):578-90. The bright cells surrounding the dermal papillae were mono- morphous in size and shape (Figure 1C). In addition, bright branching tubular structures “cords” and bulbous projections were seen at the dermo-epidermal junction (DEJ) (Figure 1D). The superficial dermis displayed aggregated bright, round to triangular, non-nucleated cells, suggestive of melanophages (Figure 1E). The overall RCM impression was of a seborrheic keratosis undergoing regression. The lesion was surgically removed by shave biopsy due to the history of change and the presence of regression struc- tures together with a pigment network in dermoscopy. His- tology showed epidermal hyperplasia characterized by thin strands of basaloid cells, horn cysts and basal hyperpigmen- tation without increase of melanocytes. In the superficial dermis, a few melanophages and solar elastosis were present (Figure 1B). The diagnosis of a reticulated seborrheic kera- tosis was made. Discussion Seborrheic keratoses are benign skin neoplasms that can usu- ally be recognized either clinically or dermoscopically [1]. However, seborrheic keratoses displaying regression struc- tures in dermoscopy can occasionally mimic melanomas. In addition, melanomas arising in association with seborrheic keratoses have been described in the literature [2-4]. RCM is a novel, non-invasive imaging technique that allows for examination of the epidermis and superficial der- mis at a cellular resolution [5]. Confocal criteria for the diag- nosis of benign and malignant melanocytic skin lesions have been extensively described in the literature [6-7]; however, there are only a few reports in the literature dealing with con- focal features of solar lentigines/seborrheic keratoses [8-10]. The main RCM features of solar lentigo/seborrheic keratosis undergoing regression (lichen planus-like keratosis) and their relative frequencies found in the study by Bassoli et al were: (i) typical honeycomb pattern of the spinous layer (78.6%); (ii) elongated cords and/or bulbous projections at the dermal- epidermal junction (75%); and (iii) numerous plump-bright cells and/or bright stellate spots in the superficial dermis (92.9%) [11]. These RCM features correlated with the fol- lowing histopathological findings: (i) spinous-granular lay- ers without significant atypia of keratinocytes; (ii) elongated, bulbous rete ridges; and (iii) dense infiltration of melano- phages and lymphocytes in superficial dermis. With the use of these diagnostic criteria 71.4% of LPLK could be classified correctly, while misclassification of any of the skin cancers as lichen planus-like keratosis was avoided. In our patient, we observed characteristic RCM features of SK, such as densely packed edged papillae, bright branch- ing tubular structures, and bulbous projections at the DEJ.