基于pBCC皮肤镜图像诊断机理及在组织病理三维可视化中的早期响应研究

In recent years, the morbidity of skin cancers in China has been increasing by 6% to 8% year after year and 70% to 90% of those are located in the head and face. Among skin cancers, Pigmented Basal Cell Carcinoma (pBCC) will easily cause relapse, disfigure, even death due to misdiagnosis. Although the rapid development of dermoscopy technology is helpful for the diagnosis of pBCC, the technical popularization has been hindered owing to the lack of theoretical evidence. Our research will realize the verification between the diagnostic indications for pBCC by dermoscopy and 3-D visualization modeling by microscopic appearance; perform operation for pBCC and then finish the follow up; make the serial tissue section for the entire tumor and form the specific and positive images after the expression of molecular pathology and histochemistry; achieve the automatic microscope image scanning, 3-D visualization reconstruction and database modeling; make qualitative, locating, quantitative and control study according to the results; reveal the relationship between the diagnostic indications for pBCC by dermoscopy and the images by histopathology, and resolve the mistakable area that they can not overlap each other; unfold the relations among misdiagnosis, invasiveness, relapse and metastasis for pBCC; state its mechanism for early diagnosis and prognosis evaluation, providing new theoretical evidence for guiding resection range and protecting appearance. Our subject belongs to the multi-interdisciplinary and applicative fundamental research, the theory of which will promote the innovation in the international leading field for dermatology and lay solid foundation for automatic identification by dermoscopy image and early diagnosis for pBCC.

近年国人皮肤癌发病率以6%～8%比例逐年上升，且70%～90%发生在头面部，其中色素型基底细胞癌(pBCC)因易误诊导致复发、毁容、甚至死亡。皮肤镜技术飞速发展对诊断pBCC有帮助，但因缺乏理论依据而阻碍技术推广。本研究拟实现pBCC皮肤镜诊断指征与显微镜图像三维可视化建模验证；对pBCC实施手术切除与术后随访；对完整瘤体进行序列组织连续切片、经分子病理与组化表达后形成特异阳性图像；实现自动显微图像扫描三维可视化重构与数据库建模研究；据此结果进行定性、定位、定量与对照研究；解决pBCC皮肤镜图像诊断指征与组织病理图像之间的联系及两者间不可逾越的理论误区；揭示pBCC误诊、侵袭、复发和转移的关系，阐明其早期诊断预后判断机理，为指导手术范围及保护容貌治疗提供新的理论依据。本项目属多学科交叉技术应用基础研究，其理论将推动皮肤病学科国际前沿创新，为pBCC皮肤镜图像自动识别与早期诊断奠定扎实基础。

近年国人皮肤癌发病率逐年上升，其中基底细胞癌(BCC)是常见皮肤恶性肿瘤，占皮肤癌80%，且常见头面部70%～90%，其中色素型基底细胞癌(pBCC)占BCC亚型中58.1％;因pBCC易与痣细胞痣、恶性黑素瘤、日光角化病、脂溢性角化病、表皮囊肿、血管角皮瘤、皮肤纤维瘤等色素性皮损误诊，其误诊率36.6% ；由于误诊或未能早期发现或盲目诊疗，而造成皮损复发甚至毁容等。近年研究表明，根据pBCC皮肤镜诊断指征，其诊断符合率93-96.06%，无疑提高了诊疗水平。由于pBCC的皮肤镜诊断指征依据二维图像形态和颜色进行诊断，其缺乏与组织病理或微观形态学影像技术间进行比对，或直观验证两种影像技术之间关系，因缺乏理论依据而阻碍该项技术推广与临床应用。 . 近年反射式共聚焦激光扫描显微镜（RCM）技术发展迅速，尤其在BCC诊断中其特异度达97.1% ，可与金标准病理诊断结果媲美。由于RCM技术无创、原位、快速，实时进行X、Y、Z轴三个方向连续扫描和完整存储皮损图像等优点。本研究采用RCM技术获取pBCC图像进行三维可视化重构验证pBCC的皮肤镜诊断指征，在揭示pBCC的皮肤镜图像诊断指征与RCM图像技术之间的密切与对应关系的同时解决两种影像学之间不可逾越的理论误区；阐明pBCC的早期诊断与预后判断机理，为pBCC皮肤镜诊断提供理论依据或进一步提高其诊断符合率奠定扎实基础。据此，还扩大了RCM技术在临床中的应用，尤其为皮肤外科手术切除范围的制订和术后随诊或对其它皮肤疾病诊疗提供参考依据。撰写论文22篇（期刊15篇其中SCI收录3篇、会议7篇）；申请国家发明6项其中有专利权3项，“DERMOSCOPY-Ⅱ皮肤镜图像诊断工作站”荣获2014年国际发明金奖；计算机软件著作权1项；副主编与参编著作4部；博士1名；举办全国性学习班4期；与企业合作“皮肤镜诊断图像处理工作站”取得中华人民共和国医疗器械注册证。基于本研究在国内首家成立“皮肤病影像诊断中心”，截止目前完成检查病例6万余例，取得较好社会效益与经济效益。