Original StudyMitotically Active Nevus and Nevoid Melanoma: A Clinicopathological and Molecular StudyMesbah Ardakani, Nima MD, FRCPA1,2,3; Singh, Shalinder MSc1; Thomas, Carla PhD1; Van Vliet, Chris FRCPA1; Harvey, Nathan Tobias FRCPA1,2; Calonje, Jaime Eduardo MD, DipRCPath4; Wood, Benjamin Andrew FRCPA1,2Author Information 1Department of Anatomical Pathology, PathWest Laboratory Medicine, QEII Medical Centre, Perth, WA, Australia; 2School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA, Australia; 3College of Science, Health, Engineering and Education, Murdoch University, Perth, Western Australia, Australia; and 4St. John's Institute of Dermatology, St Thomas' Hospital, London, United Kingdom. Correspondence: Nima Mesbah Ardakani, MD, FRCPA, Department of Anatomical Pathology, PathWest Laboratory Medicine, QEII Medical Centre, Perth, WA, Australia 6009 (e-mail: [email protected]). The authors declare no conflicts of interest. The American Journal of Dermatopathology: March 2021 - Volume 43 - Issue 3 - p 182-190 doi: 10.1097/DAD.0000000000001721 Buy Metrics Abstract The distinction between nevoid melanoma and a mitotically active nevus can be challenging at the microscopic level. In this study, we performed cytogenetic testing on a cohort of 25 mitotically active melanocytic proliferations resembling common melanocytic nevus from 25 patients. Based on cytogenetic findings, the lesions were classified as “nevoid melanoma” (n = 13) or “mitotically active nevus” (n = 12). Subsequently, we compared the clinicopathological features between these 2 groups. Nevoid melanomas occurred in older patients (P = 0.007); however, there were no significant differences in gender, size, or anatomical distribution between the 2 groups. Histologically, deep/marginal mitoses (P = 0.006), lack of maturation with depth (P = 0.036), and pseudo-maturation (P = 0.006) were significantly more common in nevoid melanomas. Immunohistochemically, complete loss of p16 was an important divisive feature (P = 0.0004), seen in 70% of nevoid melanomas, and highly correlated with loss of CDKN2A gene (chromosome 9p21). Our findings suggest that such reproducible immunomorphological differences can be of value in distinguishing nevoid melanoma from mitotically active nevus. Nevoid melanomas demonstrated a spectrum of chromosomal aberrations similar to those seen in common subtypes of melanoma, which can serve as a powerful adjunct diagnostic tool in morphologically challenging lesions. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.