HPV非依赖性、p53野生型疣状棘皮增生性外阴上皮内瘤变7例临床病理学及分子遗传学分析OA
HPV-independent,p53-wild-type,verruciform acanthotic vulvar intraepithelial neoplasia:a clinicopathological and molecular analysis of seven cases
目的 探讨HPV非依赖性、p53野生型疣状棘皮增生性外阴上皮内瘤变[HPV-independent,p53-wild-type,verruciform acanthotic vulvar intraepithelial neoplasia,HPVi(p53wt)vaVIN]的临床病理学特征、分子特征、鉴别诊断、治疗及预后.方法 回顾性分析7例 HPVi(p53wt)vaVIN 的临床特点、病理形态学、免疫表型及分子特征,并复习相关文献.结果 HPVi(p53wt)vaVIN 包括三种组织学亚型,分别是分化性外生型外阴上皮内病变(differentiated exophytic vulvar intraepithelial lesion,DEVIL),外阴棘皮病伴分化改变(vulvar acanthosis with al⁃tered differentiation,VAAD)和疣状慢性单纯性苔藓(verruciform lichen simplex chronicus,vLSC),本组7例均为女性,年龄45～76岁,平均62岁.包括DEVIL 3例,VAAD 1例及vLSC 3例.临床表现为外阴不同程度白斑、激惹、瘙痒、疼痛、溃疡及触血,5例伴赘生物(1例合并鳞状细胞癌);镜下均呈疣状结构,棘层肥厚,中表层细胞高度分化,全层无异型.免疫表型:p53均呈野生型;p16 2例阴性、5例斑驳阳性;Ki67基底层增殖指数升高;CK17在DEVIL/VAAD中全层或基底上均匀中-强阳性,vLSC中浅表层阳性;SOX2均全层强阳性;基底细胞GATA3表达缺失.5例分子检测显示HRAS、TERT、PIK3CA、CDKN2A、FBXW7等基因突变,其中1例伴TP53单等位基因突变.随访1～14个月,均无复发.结论 HPVi(p53wt)vaVIN 作为外阴HPV非依赖性p53野生型鳞状细胞癌的癌前病变,因其病变的罕见性、组织学上鳞状上皮全层无明显异型性,易误诊及漏诊,掌握其临床病理及分子特征有助于准确诊断.
Objective To investigate the clinicopathological features,immunophenotypes and molecular charac⁃teristics of HPV-independent,p53-wild-type,verruciform acanthotic vulvar intraepithelial neoplasia,[HPVi(p53wt)vaVIN]and to discuss their differential diagnoses,treatment and prognosis.Methods The clinical characteristics,pathological morphology,immunophenotypes and molecular characteristics of 7 cases of HPVi(p53wt)vaVIN were ret⁃rospectively analyzed,and relevant literature was reviewed.Results HPVi(p53wt)vaVIN encompasses a variety of histomorphologic subtypes,including differentiated exophytic vulvar intraepithelial lesion(DEVIL),vulvar acantho⁃sis with altered differentiation(VAAD)and verruciform lichen simplex chronicus(vLSC).7 patients(three DEVILs,one VAAD and three vLSCs)were all female ranged 45-76 years old with mean age of 62 years old.Clinical aspects included leukoplakia vulvar,pruritus,irritation,pain,ulcer and so on.Microscopically,the cases all displayed subtle diagnostic features including an absence of significant basal atypia,subtle aberrant maturation(in the form of epithelial pallor,hypergranulosis,or hypogranulosis),lack of viral cytopathic changes,and verruciform acanthosis with either flat or exophytic growth.Immunohistochemically,all cases exhibited wild-type p53 expression and negative or patchy p16 expression.The Ki67 index was high in basal cells.CK17 expression were identified in all cases,with superficial to suprabasal expression in the vLSC subtype and uniform suprabasal expression in the DEVIL and VAAD subtypes.Strong SOX2 expression was demonstrated while the loss of GATA3 expression was shown in the basal squa⁃mous epithelium.Molecular analysis performed in 5 cases identified HRAS,TERT,PIK3CA,CDKN2A,FBXW7 mu⁃tations and 1 TP53 allele mutations in one case.On follow-up(1-14 months),no patient developed.Conclusion HPVi(p53wt)vaVIN is a rare,recently defined HPV-independent,p53-wild-type lesion of the vulva that predisposes to vulvar squamous cell carcinoma(VSCC).Given the rarity of the lesion and subtle histopathologic features,it is a di⁃agnostic challenge.Immunohistochemistry and molecular analysis are useful in the diagnosis of HPVi(p53wt)vaVIN.
陈钡;秦蕾;杨旭西;黄素明;丁晨;李莉;庞玮;张慧娟;周峰
上海交通大学医学院附属国际和平妇幼保健院病理科,上海 200030||上海市胚胎源性疾病重点实验室,上海 200030上海交通大学医学院附属国际和平妇幼保健院病理科,上海 200030||上海市胚胎源性疾病重点实验室,上海 200030上海交通大学医学院附属国际和平妇幼保健院病理科,上海 200030||上海市胚胎源性疾病重点实验室,上海 200030上海交通大学医学院附属国际和平妇幼保健院病理科,上海 200030||上海市胚胎源性疾病重点实验室,上海 200030上海交通大学医学院附属国际和平妇幼保健院病理科,上海 200030||上海市胚胎源性疾病重点实验室,上海 200030上海交通大学医学院附属国际和平妇幼保健院病理科,上海 200030||上海市胚胎源性疾病重点实验室,上海 200030上海交通大学医学院附属国际和平妇幼保健院病理科,上海 200030||上海市胚胎源性疾病重点实验室,上海 200030上海交通大学医学院附属国际和平妇幼保健院病理科,上海 200030||上海市胚胎源性疾病重点实验室,上海 200030上海交通大学医学院附属国际和平妇幼保健院病理科,上海 200030||上海市胚胎源性疾病重点实验室,上海 200030
医药卫生
外阴上皮内瘤变p16p53预后
vulvar intraepithelial neoplasiap16p53prognosis
《临床与实验病理学杂志》 2026 (9)
1165-1171,7
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