恶性雀斑／恶性雀斑样黑色素瘤临床病理学分析

Lentigo maligna and lentigo maligna melanoma： a clinicopathologic analysis of twenty-four cases

目的探讨恶性雀斑/恶性雀斑样黑色素瘤（lentigo maligna melanoma，LMM）的临床病理特征、鉴别诊断及预后。方法收集2012至2017年间复旦大学附属肿瘤医院确诊的24例恶性雀斑/LMM，回顾性分析其临床病理特征与随访资料。常规HE和免疫组织化学HRP multimer染色进行组织病理形态学观察。结果24例患者中恶性雀斑7例，LMM 17例；男性10例，女性14例；患者年龄32～88岁（平均67岁），所有病例原发灶均位于头面部。临床上，所有患者均表现为长期存在的浅棕色或棕褐色斑片，部分伴有结节或溃疡，病灶直径0.5～3.0 cm。组织形态学上，所有恶性雀斑及LMM原位病灶均表现为不典型黑色素细胞沿着真皮及表皮交界处显著增生，细胞多形性明显，常累及皮肤附属器，多核巨细胞常见。LMM浸润成分以梭形细胞形态为主（13例）；Breslow厚度平均为1.2 mm（0.1～2.7 mm）。恶性雀斑及LMM病灶普遍存在皮肤日光损伤性改变、真皮内散在淋巴细胞及吞噬黑色素的组织细胞浸润。统计分析显示，LMM病例组中病灶最大径≥0.6 cm、核分裂象≥4个/mm2及表皮内黑色素细胞成巢的病例数显著多于恶性雀斑病例组。免疫组织化学结果显示恶性雀斑及LMM中瘤细胞表达S－100蛋白、HMB45、PNL2、Melan A及SOX－10。所有患者均获得随访，随访时间1～64个月（中位时间23个月），23例行原发灶广泛切除的病例中仅有1例恶性雀斑复发，其余22例均无瘤生存；1例仅行活检术的恶性雀斑病例随访20个月后病灶增大并出现破溃。结论恶性雀斑/LMM是一种多见于老年人头颈部曝光部位的特殊类型恶性黑色素瘤，充分认识其组织病理形态可以与日光损伤性病变及其他类型恶性黑色素瘤相鉴别。恶性雀斑/LMM患者手术治疗后预后较好，但文献报道复发率较高，需长期随访。

ObjectiveTo study the clinicopathologic features, differential diagnosis and prognosis of lentigo maligna （LM） and lentigo maligna melanoma （LMM）.MethodsHistopathologic evaluation and immunohistochemical study by HRP multimer method were carried out in 24 cases of LM and LMM from 2012 to 2017 at Fudan University Shanghai Cancer Center. The clinical information and follow-up data were analyzed.ResultsOf total 24 cases, there were 7 cases of LM and 17 cases of LMM; 10 males and 14 females. The age of patients ranged from 32 to 88 years （mean 67 years）. The male-to-female ratio was 1.0∶1.4. Tumors were all located on head and face. Clinically, all patients presented with mottled light brown or sepia macule located on head and face for a long time, and some of them followed by nodules or ulceration within the lesion. The diameter of lesions ranged from 0.5 to 3.0 cm. Microscopically, LM and in-situ component of LMM were all characterized by a predominantly junctional proliferation of atypical melanocytes with marked pleomorphism, frequently extending down the walls of hair follicles and sweat ducts. Multinucleate cells were frequently present. The invasive components of LMM mainly consisted of atypical melanocytic spindle cells （13 cases, 76.5%）, and the mean Breslow thickness was 1.2 mm （0.1-2.7 mm）. The lesions of LM/LMM were generally associated with severe actinic damage, scattered infiltration of lymphocytes and melanophages. Statistically, the number of cases whose diameter of lesion ≥0.6 cm, mitotic rates ≥4/mm2 and nests of melanocytes within epidermis in group of LMM were significantly more than those in group of LM. Immunohistochemically, atypical melanocytes in LM and LMM were generally positive for S-100, HMB45, PNL2, Melan A and SOX-10. Follow-up was available in all cases, ranging from 1 to 64 months. Only one out of 23 patients with wide surgical excision had local recurrence, and the remaining 22 patients were all alive with no evidence of disease. One LM patient who was merely treated with biopsy was alive with disease progression after 20 months follow-up.ConclusionsLM/LMM is a special subtype of melanoma predominantly located on the sun-exposed skin of elderly people. Recognition of its specific histologic features can help distinguish with sun-damaged diseases and other subtypes of melanoma. The prognosis of LM/LMM patients treated with surgical excision is considered relatively favorable. However, long term follow-up should be recommended in patients with LM/LMM because of high recurrence rates indicated by previous studies.