Extraordinary Case ReportSOX-10 and S100 Negative Desmoplastic Melanoma: Apropos a Diagnostically Challenging CaseKooper-Johnson, Sarah*; Mahalingam, Meera MD, PhD, FRCPath†; Loo, Daniel S. MD‡Author Information *Barnard College, New York, NY; †Dermatopathology Section, Department of Pathology and Laboratory Medicine, VA Boston Healthcare System, Boston, MA; and ‡Dermatology Section, Department of Medicine, VA Boston Healthcare System, Boston, MA. Correspondence: Daniel S. Loo, MD, Dermatology Section, Department of Medicine, VA Boston Healthcare System, 150S. Huntington Avenue, Boston, MA 02130 (e-mail: firstname.lastname@example.org). The authors declare no conflicts of interest. The American Journal of Dermatopathology: September 2020 - Volume 42 - Issue 9 - p 697-699 doi: 10.1097/DAD.0000000000001626 Buy Metrics Abstract An 83-year-old man presented with a tumor of the neck, clinically consistent with an epidermal inclusion cyst. Excisional biopsy revealed a deeply infiltrating spindled cell tumor. Immunohistochemical markers for S100, SOX-10, Melan-A, HMB-45, and NK1/C3 were negative. Based on the presence of an area of lentigo maligna and the histologic pattern of the spindle cell component, a diagnosis of desmoplastic melanoma was made despite the absence of immunophenotypic evidence for melanocytic differentiation. To the best of our knowledge, the complete lack of both S100 and SOX-10 makes this tumor an unprecedented case. To avoid ruling out the diagnosis of desmoplastic melanoma prematurely, physicians should be made aware of this possible immunohistochemical profile. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.