Dermatology: Practical and Conceptual Quiz | Dermatol Pract Concept 2018;8(1):11 51 DERMATOLOGY PRACTICAL & CONCEPTUAL www.derm101.com The patient A 51-year-old man with a history of recurrent primary cuta- neous marginal zone lymphoma involving his back returned for a follow-up visit at our cutaneous lymphoma clinic. He complained of a several-month history of a new asymptom- atic papule on the mid-thoracic back. He denied fevers, chills, night sweats or fatigue. Clinical examination identified a 3 to 4 mm red to orange-colored papule on the middle back (Figure 1A). Dermoscopic examination of the lesion revealed an erythematous border encircling an orange-yellow area with white linear streaks and few dotted vessels (Figure 1B). A biopsy and histopathological examination performed to exclude recurrence of skin lymphoma demonstrated a nodu- lar dermal infiltrate of histiocytes with vacuolated foamy xanthomatous cytoplasm and Touton-type multinucleated giant cells (Figure 2). The histiocytes stained positively for CD68 and were negative for Sox10. What is your diagnosis? Solitary orange papule on the back of a middle-aged man Shamir Geller1, Melissa Pulitzer2, Patricia L. Myskowski1 1 Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine, New York, NY, USA 2 Department of Pathology, Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine, New York, NY, USA Citation: Geller S, Pulitzer M, Myskowski PL Solitary orange papule on the back of a middle-aged man. Dermatol Pract Concept. 2018;8(1):51-53. DOI: https://doi.org/10.5826/dpc.0801a11 Received: July 13, 2017; Accepted: October 3, 2017; Published: January 31, 2018 Copyright: ©2018 Geller 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: This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748. Competing interests: The authors have no conflicts of interest to disclose. All authors have contributed significantly to this publication. Corresponding author: Shamir Geller, MD, Dermatology Service, Memorial Sloan Kettering Cancer Center, 16 East 60th Street, New York, NY 10022, USA. Email: shamirgeller@gmail.com Figure 1. Clinical image of the red to orange-colored papule on the patient’s upper back marked with a black triangular sticker (A). Polar- ized, non-contact dermoscopy im- ages of the lesion revealing a struc- tureless orange-yellow area with erythematous border. White linear streaks and few dotted vessels are seen in the center of the lesion; 10x original magnification (B). [Copy- right: ©2018 Geller et al.] mailto:shamirgeller@gmail.com 52 Quiz | Dermatol Pract Concept 2018;8(1):11 of cutaneous B-cell lymphoma was highly suspected, but the dermoscopic setting sun pattern was quite different from the typical dermoscopic features of the salmon-colored area and linear-irregular vessels typically seen in such a type of cutane- ous lymphomas [10,11] (Table 1). Reflectance confocal microscopy (RCM) and high-def- inition optical coherence tomography (HD-OCT) features of JXG and adult-onset xanthogranuloma were reported recently. Highly refractive atypical large cells of variable diameter were seen in the dermis, and some of them had pleomorphic nuclei, corresponding to Touton-type giant cells that were seen in histopathologic examination [9,12]. JXG and adult-onset xanthogranuloma can present with characteristic dermoscopic features of an orange-yellow structureless pattern with an erythematous border (setting sun sign) and white streaks. Dermoscopy can be helpful in diagnosing these benign skin conditions in a noninvasive manner. Answer Adult-onset xanthogranuloma (juvenile xanthogranuloma presenting in an adult) Discussion Juvenile xanthogranuloma (JXG) is the most common non- Langerhans cell histiocytosis, which presents either as a single lesion or as multiple asymptomatic pink to red–brown dome-shaped papules or nodules (2 mm to 2 cm in diameter) that become yellow-brown as they mature. JXG most often affects infants and young children; however, it can appear in adults in their 20s and 30s and can even present in the elderly. JXG’s course is usually self-limited in the pediatric population and treatment is not necessary, although, in adults, in whom the term adult-onset xanthogranuloma is favored, it may not regress spontaneously [1]. Histologically, JXG shows a dense histiocytic infiltration involving the dermis but sometimes extending subcutane- ously. Monomorphous histiocytes with eosinophilic cyto- plasm are seen in the early lesions, while in mature JXG the histiocytes acquire a foamy and xanthomatous appearance, Touton giant cells are identified, and lymphocytes, eosino- phils, and plasma cells can be found throughout the infil- trate. Regressing lesions show a proliferation of fibroblasts and fibrosis. The dermoscopic pattern of JXG was first described in 2007 by Palmer et al., who described a characteristic orange-yellow “setting sun” appearance [2]. Other dermo- scopic features that have been reported in JXG cases include clouds of pale yellow globules, subtle pigment network, whitish streaks, and branched linear or dotted vessels [3,4]. Song et al. studied the correlation between dermoscopic appearance and histopathological findings and found that the dermoscopic features correlated with the histologic level of maturation of the JXG lesions. The setting sun appear- ance was found in early evolutionary and in fully developed JXG. In fully developed lesions, the surrounding erythema decreased, and yellow globules became more evident as the histiocytes transformed to more xanthomatous cells, while in late regressive lesions, prominent whitish streaks were identified and were suggested to correspond to fibrosis [5]. It was suggested that dermoscopy might be helpful in differ- entiating JXG from other conditions that appear as solitary yellow-orange lesions [6,7]. The main differential diagnoses of JXG include seba- ceous tumors [8], xanthomatous dermatofibroma, basal cell carcinoma, granulomatous dermatoses, and nonpigmented Spitz nevus [4,9]. Table 1 shows the dermoscopic features of all such conditions. In the present case, the clinical diagnosis Figure 2. Histopathology. Circumscribed nodular dermal infil- trate effacing rete ridges and elevating and attenuating epidermis; hematoxylin-eosin stain, 40x original magnification (A). Foamy his- tiocytes and Touton-type multinucleated giant cells (asterisks) com- prise the majority of the infiltrate. Lymphocytes percolate through the histiocytic tumor; hematoxylin-eosin stain, 100x original magni- fication (B). [Copyright: ©2018 Geller et al.] Quiz | Dermatol Pract Concept 2018;8(1):11 53 8. Moscarella E, Argenziano G, Longo C, et al. Clinical, dermoscopic and reflectance confocal microscopy features of sebaceous neo- plasms in Muir-Torre syndrome. J Eur Acad Dermatol Venereol. 2013;27(6):699-705. 9. Lovato L, Salerni G, Puig S, Carrera C, Palou J, Malvehy J. Adult xanthogranuloma mimicking basal cell carcinoma: dermoscopy, reflectance confocal microscopy and pathological correlation. Dermatology. 2010;220(1):66-70. 10. Geller S, Marghoob AA, Scope A, Braun RP, Myskowski PL. Dermoscopy and the diagnosis of primary cutaneous B-cell lym- phoma. J Eur Acad Dermatol Venereol. 2017. 11. Lallas A, Apalla Z, Lefaki I, et al. Dermoscopy of early stage my- cosis fungoides. J Eur Acad Dermatol Venereol. 2013;27(5):617- 621. 12. Koku Aksu AE, Turgut Erdemir AV, Gurel MS, Bagci IS, Leblebici C. In vivo evaluation of juvenile xanthogranuloma with high- resolution optical coherence tomography and reflectance confocal microscopy and histopathological correlation. Skin Res Technol. 2015;21(4):508-510. 13. Errichetti E, Lallas A, Apalla Z, Di Stefani A, Stinco G. Dermos- copy of granuloma annulare: a clinical and histological correla- tion study. Dermatology. 2017;233(1):74-79. 14. Errichetti E, Stinco G. Dermoscopy in general dermatology: a practical overview. Dermatol Ther (Heidelb). 2016;6(4):471-507. 15. Lallas A, Apalla Z, Ioannides D, et al. Update on dermoscopy of Spitz/Reed naevi and management guidelines by the International Dermoscopy Society. Br J Dermatol. 2017;177(3):645-655. Acknowledgments Dr. Shamir Geller is a recipient of a supplemental grant from the American Physicians and Friends For Medicine in Israel (APF). References 1. Hernandez-Martin A, Baselga E, Drolet BA, Esterly NB. Juvenile xanthogranuloma. J Am Acad Dermatol. 1997;36(3 Pt 1):355- 367; quiz 368-359. 2. Palmer A, Bowling J. Dermoscopic appearance of juvenile xantho- granuloma. Dermatology (Basel, Switzerland). 2007;215(3):256- 259. 3. Rubegni P, Mandato F, Fimiani M. Juvenile xanthogranuloma: dermoscopic pattern. Dermatology. 2009;218(4):380; author reply 381. 4. Cavicchini S, Tourlaki A, Tanzi C, Alessi E. Dermoscopy of solitary yellow lesions in adults. Archiv Dermatol. 2008;144(10):1412. 5. Song M, Kim SH, Jung DS, Ko HC, Kwon KS, Kim MB. Structural correlations between dermoscopic and histopathological features of juvenile xanthogranuloma. J Eur Acad Dermatol Venereol. 2011;25(3):259-263. 6. Pretel M, Irarrazaval I, Lera M, Aguado L, Idoate MA. Dermo- scopic “setting sun” pattern of juvenile xanthogranuloma. J Am Acad Dermatol. 2015;72(1 Suppl):S73-75. 7. Hussain SH, Kozic H, Lee JB. The utility of dermatoscopy in the evaluation of xanthogranulomas. Pediatr Dermatol. 2008;25(4):505-506. TABLE 1. Dermoscopic clues for the differential diagnosis of the studied solitary orange colored papule. Diagnosis Dermoscopic Features Juvenile xanthogranuloma [5] Erythematous border circling an orange-yellow area (“setting sun”), white linear streaks and linear/branched vessels Basal cell carcinoma [9] Arborizing vessels with a pink background, ulcerations, leaf-like structures, blue-gray ovoid nests and white shiny streaks Cutaneous B-cell lymphoma [10] Salmon-colored background/area and serpentine (linear-irregular) vessels Granulomatous dermatoses [13,14] Structureless yellow-orange area with linear or branching vessels Sebaceous tumors [8] • Radially arranged, elongated crown vessels surrounding structureless yellow areas • Yellow comedo-like globules and branching arborizing vessels Nonpigmented Spitz nevus [15] Regularly distributed dotted vessels (coiled, hairpin or linear-irregular in elevated/nodular nevi) with reticular depigmentation (inverse white network) Xanthomatous dermatofibroma [4] Homogeneous yellow area with peripheral delicate pigment network