CME ArticleClear Cell Proliferations of the Skin: A Histopathologic ReviewZaballos, Pedro MD*; Lara-Valencia, Paola MD†; Van Den Bossche, Karolien MD‡; Sánchez-Martínez, Eva MD§; Roca-Gines, Juncal MD¶; Vila, Borja Gómez MD‖; Requena, Luis MD**Author Information *Associate Staff, Dermatology Department, Hospital Sant Pau i Santa Tecla, Tarragona, Spain; †Associate Staff, Immunology, Genetics & Pathology and Clinical Department of Pathology & Cytology, Uppsala University Hospital, Uppsala, Sweden; ‡Associate Staff, Dermpatopathology Laboratory, Ghent, Belgium; §Resident, Dermatology Department, Hospital Universitario Doctor Peset, Valencia, Spain; ¶Resident, Dermatology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain; ‖Resident, Dermatology Department, Hospital Universitario Central de Asturias, Asturias, Spain; and **Chairman, Dermatology Department, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain. Correspondence: Luis Requena, MD, Department of Dermatology, Fundación Jiménez Díaz, Avda. Reyes Católicos 2, 28040 Madrid, Spain (e-mail: [email protected]). All authors, faculty, and staff in a position to control the content of this CME activity, have disclosed that they have no financial relationships with, or financial interests in, any commercial organizations relevant to this educational activity. The American Journal of Dermatopathology: September 2021 - Volume 43 - Issue 9 - p 607-636 doi: 10.1097/DAD.0000000000001881 Buy CME Test Metrics Abstract Cutaneous clear cell proliferations encompass a heterogenous group of several primary cutaneous neoplasms and metastatic tumors with different histogenesis. Many of these clear cell proliferations may seem strikingly similar under the microscope resulting in challenging diagnosis. In many of these clear cell lesions, the reason for the clear or pale appearance of proliferating cells is unknown, whereas in other ones, this clear cell appearance is due to intracytoplasmic accumulation of glycogen, mucin, or lipid. Artifacts of tissue processing and degenerative phenomenon may also be responsible for the clear cell appearance of proliferating cells. Awareness of the histopathologic findings as well as histochemical and immunohistochemical techniques are crucial to the accurate diagnosis. This review details the histopathologic features of clear cell cutaneous proliferations, classifying them according their type of differentiation and paying special attention to the histopathologic differential diagnosis among them. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.