Original ArticlesAcral Spitz Nevi A Clinicopathologic Study of 50 Cases With Immunohistochemical Analysis of P16 and P21 ExpressionWiedemeyer, Katharina MD*,†; Guadagno, Antonio MD‡; Davey, Jonathan MD§; Brenn, Thomas MD, PhD, FRCPath§,∥Author Information *Laboratory for Dermatohistology and Oral Pathology, Munich †Department of Dermatology, University of Heidelberg, Heidelberg, Germany ‡Unit of Anatomic Pathology, Ospedale dell’Angelo, Venice Mestre, Italy §Department of Pathology, Western General Hospital and The University of Edinburgh, Edinburgh, UK ∥Departments of Pathology & Laboratory Medicine and Dermatology, Cumming School of Medicine, University of Calgary and Alberta Health Services, Calgary, AB, Canada K.W. and A.G. contributed equally. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Thomas Brenn, MD, PhD, FRCPath, Department of Pathology & Laboratory Medicine, Cumming School of Medicine, Univeristy of Calgary, 3535 Research Road NW, Calgary, AB, Canada T2L 2K8 (e-mail: [email protected]). The American Journal of Surgical Pathology: June 2018 - Volume 42 - Issue 6 - p 821-827 doi: 10.1097/PAS.0000000000001051 Buy Metrics Abstract Spitz nevi on acral sites are rare and poorly documented. The combination of Spitzoid cytomorphology and atypical architectural features of the junctional component may lead to an erroneous diagnosis of melanoma. To study the clinicopthologic and immunohistochemical features, 50 Spitz nevi localized on the distal extremities were retrieved from departmental files. Clinical data and follow-up were obtained and the histologic features were analyzed. P16 and P21 immunohistochemical staining of the dermal component was compared with that of 10 acral lentiginous melanomas and 10 acral nevi. Acral Spitz nevi affected young adults (median: 24.5 y; range: 4 to 61 y) with a female predominence and a predilection for the feet. They were pigmented measuring 1 to 15 mm (median: 4 mm). Follow-up, available for 45 patients (median: 48 mo; range: 4 to 228 mo), revealed no local recurrence, metastasis or mortality. Histologically, acral Spitz nevi were composed of large epithelioid and/or spindled melanocytes. They were well circumscribed with occasional asymmetry. The junctional component was broad with a lentiginous and nested growth and shoulder formation. Marked pagetoid spread and transepidermal elimination of junctional nests were common features. Focal active regression of the dermal component was frequently noted but there was no nuclear pleomorphism or dermal mitotic activity. Acral Spitz nevi were characterized by strong and diffuse P16 and P21 expression, which differs from acral nevi and acral lentiginous melanoma. Acral Spitz nevi are a distinctive subgroup of Spitz nevi with benign behavior. Awareness of the subtle histologic differentiating features and the distinctive P16/P21 expression pattern allows separation from melanoma. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.