Extraordinary Case ReportHyaline Inclusion AcanthomaTran, Tien Anh N. MD*; Parra, Ourania MD†; Linos, Konstantinos MD†,‡ Author Information *Department of Pathology, Advent Health Orlando, FL; †Department of Pathology and Laboratory Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH; and ‡Geisel School of Medicine at Dartmouth, Hanover, NH. Correspondence: Tien Anh N. Tran, MD, Department of Pathology, Advent Health Orlando, 601 East Rollins Street, Orlando, FL 32803 (e-mail: [email protected]). The authors declare no conflicts of interest. The American Journal of Dermatopathology: July 2021 - Volume 43 - Issue 7 - p 525-529 doi: 10.1097/DAD.0000000000001927 Buy Metrics Abstract Eosinophilic hyaline inclusions (EHIs) or globules have been reported in various cutaneous tumors including vascular lesions, myoepithelial neoplasms, and basal cell carcinoma. In basal cell carcinoma, the presence of intracytoplasmic inclusions is reportedly associated with myoepithelial differentiation. In this regard, EHI has not been conclusively documented in a cutaneous lesion of genuine squamous cell lineage without aberrant differentiation. In the current case, a biopsy from the right thigh of a 71-year-old male patient demonstrated a relatively well-demarcated intraepidermal squamous lesion featured an admixture of predominantly enlarged keratinocytes harboring distinct eccentric intracytoplasmic EHI and a smaller population of keratinocytes displaying pale cytoplasm. Cytologic atypia, mitotic activity, and inflammatory cells were not identified. The intracytoplasmic EHI stained red with Masson's trichrome and were negative with periodic-acid Schiff with and without diastase. Immunologically, the lesion was strongly and diffusely positive for various cytokeratins but negative for ubiquitin and myoepithelial markers. Only cytokeratin AE1 revealed a differential staining pattern as the suprabasal lesional cells displayed significantly stronger immunoreactivity in comparison with the adjacent normal keratinocytes. Polymerase chain reaction for low-risk and high-risk human papillomavirus was negative. Molecular studies did not reveal any mutations commonly encountered in seborrheic or lichenoid keratoses. As an analogous lesion has not previously reported in the literature, the term hyaline inclusion acanthoma is proposed for this peculiar lesion. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.