关键词: 痣, 色素, 黑色素瘤, 先天性色素痣, 恶变, 临床表现, 组织病理, HMB45, 5-羟甲基胞嘧啶

Abstract: 【Abstract】 Objective To analyze clinical and histopathological features of malignant transformation of congenital melanocytic nevi （CMN）. Methods From January 2010 to September 2020, 98 patients with clinically and pathologically confirmed malignant transformation of CMN were enrolled from Xijing Hospital, Air Force Medical University, and their clinical and histopathological features as well as immunohistochemical staining and genetic testing results were retrospectively analyzed. Results Among the 98 patients with malignant transformation of CMN, 45（45.9%）were males and 53（54.1%）were females. Their ages ranged from 4 months to 86 years, with a median age of 47 years. The lesions were located on the trunk （34 cases, 34.7%）, limbs （25 cases, 25.5%）, acra （24 cases, 24.5%）, head, face and neck （13 cases, 13.3%）, and mucosa （2 cases, 2.0%）. Among the 98 patients, 95（96.9%） had a history of obvious changes in lesions （sudden enlargement, newly developed papules, ulceration, itching, or pain）, and the interval time from obvious changes in lesions to diagnosis varied from 2 weeks to 5 years; among the 95 cases, the average age at the onset of obvious changes in lesions was 46 years, and the changes of lesions occurred before the age of 18 years in 4 cases （4.1%）, occurred between the age of 18 and 40 years in 35 （35.7%）, and occurred after the age of 40 years in 56 （57.1%）. In addition, 55 （57.9%） patients experienced a sudden enlargement of primary lesions, 52 （54.7%） developed ulcers in the primary lesions, 21 （22.1%） developed red or black papules or nodules on the surface of primary lesions, 4 （4.2%） developed subcutaneous masses, 2 （2.1%） had itching, and 1 （1.1%） only had pain. The remaining 3（3.1%） patients experienced slow enlargement of primary lesions. Among the 98 cases of melanoma originating from CMN, 85 （86.7%） arose from small CMN, 11 （11.2%） from medium CMN, and 2 （2.0%） from large CMN. Histopathological examination showed no residual nevus cells in 86 （87.8%） cases, which only had characteristics of typical melanoma; residual nevus cells were only seen in 12 （12.2%） cases, and melanoma cells in the 12 cases all expressed HMB45, while residual nevus cells did not express HMB45 in 11 of 12 cases. Immunohistochemical staining for 5-hydroxymethylcytosine （5hmC） was conducted in 7 cases, and 6 showed negative staining in tumor cells and positive staining in residual nevus cells. BRAF gene detection was conducted in lesional tissue specimens from 22 patients, and it was negative in 1 case of melanoma originating from large CMN and 10 (47.6%) cases of melanoma from small CMN , and positive in 11 (52.4%) cases of melanoma from small CMN. Conclusion The malignant transformation of CMN mostly occurred on the trunk, and was commonly observed in patients aged over 40 years; most patients had a history of obvious changes（sudden enlargement, newly developed papules, ulceration, etc.） in lesions before diagnosis, and a few patients only felt itching or pain in lesions; immunohistochemical staining of HMB45 and 5hmC could help to distinguish melanoma cells from dermal nevus cells; confirmation of the diagnosis of malignant transformation in CMN should be closely combined with clinical and histopathological results.

Key words: Nevus, pigmented, Melanoma, Congenital melanocytic nevi, Malignant change, Clinical manifestations, Histopathology, HMB45, 5-Hydroxymethyl-cytosin