J Cutan Pathol 2013: 40: 788 – 795 doi: 10.1111/cup.12192 John Wiley & Sons. Printed in Singapore  2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Journal of Cutaneous Pathology Rosette-like structures in the spectrum of spitzoid tumors Background: Spitz nevi demonstrate a diverse spectrum of morphologies. Recently, there have been two reported examples of Spitz nevi with rosette-like structures similar to Homer-Wright rosettes. Rosettes have also been described in melanomas and in a proliferative nodule arising in a congenital nevus. Methods: A retrospective review of 104 cases of Spitz nevi and variants (n = 51), pigmented spindle cell nevi (n = 26), combined melanocytic nevi with features of Spitz (n = 8), atypical Spitz tumor (AST, n = 9), and spitzoid melanoma (n = 10). Results: Rosette-like structures were present in 3 of the 104 cases (2.9%), including a compound Spitz nevus, a desmoplastic Spitz nevus, and an AST. All three cases demonstrated several foci of small nests of epithelioid cells with peripherally palisaded nuclei arranged around a central area of fibrillar eosinophilic cytoplasm. Immunohistochemical staining of the three spitzoid lesions demonstrated that the rosette-like structures express S100 protein, Melan-A, and neuron specific enolase (NSE) and lacked expression of neurofilament, glial fibrillary acidic protein and synaptophysin. Conclusions: While uncommon, rosette-like structures can occur as a focal feature in Spitz nevi and AST. Rosette-like structures may represent a normal morphologic finding in Spitz nevi, and awareness of them may prevent misdiagnosis as a neural tumor or melanoma. Keywords: melanoma, rosette, Spitz nevi Arps DP, Harms PW, Chan MP, Fullen DR. Rosette-like structures in the spectrum of spitzoid tumors. J Cutan Pathol 2013; 40: 788 – 795.  2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd David P. Arps 1 , Paul W. Harms 1,2 , May P. Chan 1,2 and Douglas R. Fullen 1,2 1 Department of Pathology, University of Michigan, Ann Arbor, MI, USA and 2 Department of Dermatology, University of Michigan, Ann Arbor, MI, USA Douglas R. Fullen, MD, Department of Pathology, University of Michigan Health System, Medical Science I, 1301 Catherine St., M-3261, Ann Arbor, MI 48109, USA Tel: +1 734 764 4460 Fax: +1 734 764 4690 e-mail: dfullen@med.umich.edu Accepted for publication May 19, 2013 Spitz nevi typically present as pink or flesh-colored papules or nodules most commonly in children and young adults. Histopathologically, such nevi are composed of spindled or epithelioid cells, or both. Many variants, including pagetoid, angiomatoid, desmoplastic, myxoid and tubular Spitz nevi, have been described. 1 Although generally considered a distinct entity, pigmented spindle cell nevus of Reed often has some histopathologic features overlapping with Spitz nevi and may be considered a related lesion occupying the spindled end of the spectrum. Recognition of these variants helps to avoid diagnostic confusion that may lead to overdiagnosis of melanoma. The term ‘rosette’ is used to describe a ring of cells arranged around a central lumen or cytoplasmic space, and is often regarded as evidence of neu- ronal differentiation. 2 Homer-Wright rosettes are characterized by radially arranged cells with central fibrillary cell processes. There is no true lumen formation, unlike Flexner-Wintersteiner rosettes. Homer-Wright rosettes, while nonspecific, are typically associated with neural tumors such as neu- roblastoma and peripheral neuroectodermal tumor. 788