ABSTRACT
Objective: To investigate the clinicopathological characteristics, immunohistochemical profiles, molecular features, and prognosis of subungual melanoma in situ (SMIS). Methods: Thirty cases of SMIS were collected in Fudan University Shanghai Cancer Center, Shanghai, China from 2018 to 2022. The clinicopathological characteristics and follow-up data were retrospectively analyzed. Histopathologic evaluation and immunohistochemical studies were carried out. By using Vysis melanoma fluorescence in situ hybridization (FISH) probe kit, combined with 9p21(CDKN2A) and 8q24(MYC) assays were performed. Results: There were 8 males and 22 females. The patients' ages ranged from 22 to 65 years (median 48 years). All patients presented with longitudinal melanonychia involving a single digit. Thumb was the most commonly affected digit (16/30, 53.3%). 56.7% (17/30) of the cases presented with Hutchinson's sign. Microscopically, melanocytes proliferated along the dermo-epithelial junction. Hyperchromatism and nuclear pleomorphism were two of the most common histological features. The melanocyte count ranged from 30 to 185. Most cases showed small to medium nuclear enlargement (29/30, 96.7%). Pagetoid spread was seen in all cases. Intra-epithelial mitoses were identified in 56.7% (17/30) of the cases. Involvement of nailfold was found in 19 cases, 4 of which were accompanied by cutaneous adnexal extension. The positive rates of SOX10, PNL2, Melan A, HMB45, S-100, and PRAME were 100.0%, 100.0%, 96.0%, 95.0%, 76.9%, and 83.3%, respectively. FISH analysis was positive in 6/9 of the cases. Follow-up data were available in 28 patients, and all of them were alive without disease. Conclusions: SMIS mainly shows small to medium-sized cells. High melanocyte count, hyperchromatism, nuclear pleomorphism, Pagetoid spreading, intra-epithelial mitosis, nailfold involvement, and cutaneous adnexal extension are important diagnostic hallmarks. Immunohistochemistry including SOX10 and PRAME, combined with FISH analysis, is valuable for the diagnosis of SMIS.