ORIGINAL STUDY Characteristics of Spitzoid Melanoma and Clues for Differential Diagnosis With Spitz Nevus Celia Requena, MD,* Rafael Botella, MD,* Eduardo Nagore, MD,* Onofre Sanmart´ ın, MD,* Beatriz Llombart, MD,* Carlos Serra-Guille ´n, MD,* Carlos Guille ´n, MD,* Luis Requena, MD,* and Victor Traves, MD† Abstract: The different features of spitzoid melanoma are not well characterized in the literature, and the lesion often has to be described in comparison with Spitz nevus. We evaluated the histopathological appearance of spitzoid melanoma by reviewing all spitzoid melanomas treated at our hospital and all referrals from 1998 to 2010. The final study sample comprised 18 cases, 11 from our institution and 7 referrals from other centers. We recorded clinical parameters (eg, age, sex, site, time between onset and excision, recurrence, and death) and a series of histopathological parameters (eg, size, ulceration, symmetry, Clark level, Breslow thickness, cell density, atypia, mitosis). Clinical and histopathological criteria were not available for the 7 referrals. Mean age was 35.2 years (15–56), and 8 patients were women. Mean size of the lesions was 7.27 mm (Clark III/IV and Breslow 2.51 mm), and these were found on the limbs and trunk. Cell density was high in 10 cases and atypia present in 9 (marked in 1). Mitoses were observed in 8 cases (atypical in 4, clusters in 4). Maturation was absent in 9 cases and zonation in 8. Our analysis revealed 5 previously undefined subtypes of spitzoid melanoma (genuine (7 cases), uniform (5 cases), packed (5 cases), polypoid (3 cases) and pigmented (2 cases)]. Four cases showed 2 patterns at the same time. The most useful parameters for the differential diagnosis were cell density, mitosis, zonation, in- filtration pattern, and consumption of the epidermis. Assignation of a spitzoid melanoma to 1 of more of our 5 subtypes can enable a more confident diagnosis to be made. Key Words: diagnosis, histopathology, spitzoid melanoma, spitz nevus (Am J Dermatopathol 2012;34:478–486) INTRODUCTION The histopathological appearance of spitzoid melanoma is not well characterized in the literature, and several different lesions are published under the same denomination. 1–3 In fact, spitzoid melanoma is described as being similar to Spitz nevus but having radically different clinical significance. Thus, spitzoid melanoma seems not to have distinguishing features but is defined in comparison with Spitz nevus. 4–11 We discuss the histological appearance of spitzoid melanoma by reviewing the histopathological features de- scribed in the literature. We evaluate several features involved in the differential diagnosis with Spitz nevus and describe 5 histological patterns of spitzoid melanoma not previously defined elsewhere. MATERIALS AND METHODS We reviewed all spitzoid melanomas treated at our hospital and all referrals from 1998 to 2010. An initial review TABLE 1. Histopathological Differences Between Spitz Nevus and Spitzoid Melanoma Spitz Nevus Spitzoid Melanoma Size ,1 cm .1 cm Ulceration No Yes Symmetry Yes No Depth of infiltration Superficial dermis Deep dermis/ hypodermis Cell density Low High Atypia Mild Marked Mitoses Few or absent Many Superficial Deep/suprabasal Typical Atypical Scarce In clusters Maturation Yes No Kamino bodies Yes No Zonation Yes No Melanin Regular, more superficial Irregular, deeper Clefts Junctional nests- epidermis Subepidermal Dermal infiltration pattern Infiltrative Pushing Lateral epidermal pattern Good delimitation Poor delimitation Solar elastosis Exceptional Frequent Epidermis Hyperplastic Thin Pagetoid extension Focal, central Extensive, lateral Nucleus-to-cytoplasm ratio Preserved Increased Eosinophilic nucleoli Scant, superficial Many, at the bottom Cytoplasm Eosinophilic, homogeneous Vacuolated, irregular From the Departments of *Dermatology and †Pathology, Instituto Valenciano de Oncolog´ ıa, Valencia, Spain. The authors have no funding or conflicts of interest to declare. Reprints: Celia Requena, MD, Department of Dermatology, Instituto Valenciano de Oncolog´ ıa, c/Profesor Beltra ´n Ba ´guena, 5, 46009 Valencia, Spain (e-mail: celiareq@hotmail.com). Copyright Ó 2012 by Lippincott Williams & Wilkins 478 | www.amjdermatopathology.com Am J Dermatopathol  Volume 34, Number 5, July 2012