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450 SHORT COMMUNICATION Disfiguring Nodular Cephalic Xanthoma Disseminatum: An Exceptional Variant of a Forgotten Entity Arturo BONOMETTI 1 , Jessica GLIOZZO 2 *, Chiara MOLTRASIO 2 , Filippo BAGNOLI 3 , Luigia VENEGONI 4 , Emanuela PASSONI 2 , Marco PAULLI 1 and Emilio BERTI 2,4 Unit of Anatomic Pathology, Department of Molecular Medicine, IRCCS San Matteo Foundation, University of Pavia, Pavia, 2 Unit of Dermatology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Pace 9, Milan, 3 Department of Oncology and Hematology, and 4 Department of Pathophysiology and Organ Transplantation, University of Milan, Milan, Italy. E-mail: [email protected] 1 Accepted Jan 7, 2019; E-published Jan 9, 2019 Xanthoma disseminatum (XD) is an extremely rare cu- taneous, normolipidemic, proliferative disorder of the Mononuclear Phagocyte System. It was first described by Von Gräfe and Virchow but recognized as a distinct entity by Montgomery & Osterberg in 1938 (1). Approx- imately 140 cases are reported in the English literature. Clinically, XD is characterized by a symmetrical skin eruption of reddish papules or nodules, with predilec- tion for the head, neck, flexural and intertriginous areas. These lesions, initially isolated, tend to slowly merge into large yellowish plaques, during years. The mean age at presentation is 30 years and male cases outnumber female ones by a ratio of 2:1. XD is generally thought to be a benign disorder with a chronic progressive course (2–4). Caputo et al. (5) recognized 3 clinical variants of XD: 1) a self-healing form; 2) a persistent form and 3) a progressive multi-system (MS) form. The report rate of this entity is becoming even lower now than in past years, perhaps due to its high diagnostic overlap with Erdheim-Chester Disease (ECD) (6, 7). CASE REPORT We hereby describe the case of a previously healthy 47-year-old Caucasian woman presented to our attention in January 2011, with a 2-year long history of cephalic xanthomas. Her lesions consisted of yellow periocular and perioral plaques extending to the zygomatic area as well as small yellow hard-elastic nodules growing next to the inner canthi (Fig. 1). Complete radiological, hematological (blood count, metabolic, renal and liver functions/ profiles) and endocrinological examinations all tested negative and failed to reveal any systemic involvement. During the following 7 years, the lesions displayed a slow but progressive extension with symmetrical involvement of the whole face (Fig. 1). She never developed diabetes insipidus or any other signs of systemic involvement. Previous therapies (hydroxychloroquine and cyclo­ phosphamide) and surgeries (including CO 2 laser therapy) led to constant recurrences and subsequent regrowth of lesions, together with surgery-related keloid scars, resulting in high mechanical, psychological and sociological impairment. Skin biopsy (Fig. 1) showed a polymorphic dense upper- and mid-dermal infiltration consisting of large histiocytes, admixed with few lymphocytes and neutrophils. Histiocytes were mostly characterized by large nuclei often with prominent nucleoli and an abundant pale cytoplasm. Foamy, Touton and Langhans cells were also present, focally in large numbers. There were no signs of epidermotropism. Immu- nohistochemical profile of the histiocytes was positive for CD4, CD11c, CD14, CD68/PGM1, CD163, fXIIIa, vimentin, lysozyme, fascin but tested negative for CD1a, CD34 and CD207/langerin. Ki-67 stained 1–5 % of the cells. BRAF V600E analysis failed to reveal any alteration. Sixteen years after the first manifestation, the patient is alive and in a good clinical condition, although with chronic persistent evolution of the disfiguring lesions. Informed consent was obtained in accordance with local ethical guidelines and with the Helsinki Declaration of 1975. DISCUSSION Histiocytoses have recently been reclassified in 5 dif- ferent groups based on a combination of clinical, ra- diographic, histopathological and molecular findings. XD belongs to the “xanthogranuloma-family” of the C(utaneous)-group, due to its prevalent skin involvement Fig. 1. Clinical and histopatho­ logical features of the patient. The patient came to our attention with yellowish plaques limited to periocular and perioral regions (A, C). During the first 2 years of follow-up the lesions slowly increased in volume and extended to columella (D) and after 5 years they presented as thick tumor/ nodular lesions and confluent plaques extending to the forehead, zygoma, eyelids, outer nostrils and mentolabial sulci (B, E). Skin biopsy revealed a dense and polymorphic histiocytic infiltrate (F) made up of large cells with abundant and often foamy cytoplasm (G) and multinucleated giant cells of the Touton (H) and Langhans type, admixed with small lymphocytes and neutrophils. doi: 10.2340/00015555-3111 Acta Derm Venereol 2019; 99: 450–451 This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica.