Abstract:

 Objective To summarize the skin histopathological features of graft versus host disease （GVHD） after liver transplantation， and provide valuable reference for the pathological diagnosis and grading of GVHD. Methods Clinical data and skin biopsy pathological features of 10 patients with GVHD after liver transplantation from August 2018 to September 2022 in Transplant Center of Tianjin First Central Hospital were retrospectively analyzed. Enrollment criteria ：complete clinical and pathological data of 10 patients. There was no history of specific medication prior to the appearance of the rash， and no previous history of skin disease. The age， sex， location and time of the first rash were summarized， and the histopathological manifestations of skin biopsy were statistically analyzed. The results included keratinocyte vacuolation， dyskeratosis， basal cell vacuolation， keratinocyte necrosis， basal layer fracture， epidermal total necrosis， epidermal dermal detachment， perivascular lymphocyte infiltration， epidermal atrophy， epithelial foot disappearance， pigment inence， and dermal collagen. HE staining was performed in all skin tissue biopsies and the images were reviewed by 2 pathologists. According to the existing GVHD skin pathological injury criteria， theclassification was performed， and the characteristics and rules of skin pathological changes in each group were statistically analyzed. Results There were 7 males and 3 females in this group，age ranging from 47 to 69 years old， with an average age of （59.5±6.8） years. The time of skin biopsy after transplantation ranged from 9 to 48 days （median time 31 days）. All the 10 patients had skin rash as the first skin symptom， which spread from the abdomen to the limbs， head and neck. The incidence of basal cell vacuolation and lymphocyte infiltration around small vessels was 100%， the incidence of keratinocyte vacuolation and poor keratinization was 60%， and the positive rates of epidermal atrophy and keratinocyte necrosis were about 30%. Basal fissure and pigment incontinence accounted for about 20%. The positive rate of epithelial foot disappearance and dermal collagen was about 10%. No epidermal necrosis and epidermal dermal separation were found in this group， and the positive rate was 0%. The average number of lymphocytes infiltrated around a single vessel in the superficial dermis was 100% in both grade Ⅱ and grade Ⅲ GVHD skin lesions. Therefore， basal cell vacuolation and perivascular lymphocyte infiltration can be used as the important diagnostic basis for GVHD， while keratinocyte vacuolation and keratinized cells can be used as the main diagnostic basis for GVHD. The average number of infiltrated lymphocytes around a single blood vessel in the superficial dermis plays an important role in guiding the classification of GVHD injury. Conclusion The skin pathological features play important roles in the diagnosis and differential diagnosis of GVHD after liver transplantation. The number of infiltrated lymphocytes around a single blood vessel in the superficial dermis is an important histological reference for judging the grade and degree of GVHD injury. 

Key words:

Liver transplantation； Graft versus host disease； Skin； Pathological features ,

摘要：

目的 总结肝移植术后移植物抗宿主病（graft versus host disease，GVHD）的皮肤病理组织学特点，以期为该疾病的病理学诊断及分级提供有价值的参考。方法 对 2018 年 8 月至 2022 年 9 月天津市第一中心医院移植中心 10 例肝移植术后发生 GVHD 患者的临床资料及皮肤活检病理学表现进行回顾性分析。入组标准 ：10 例患者临床资料及病理资料完整 ；皮疹出现前无特殊用药史，且既往无皮肤病史。分别对其年龄、性别、皮疹的首发部位和首发时间进行总结，统计分析皮肤活检组织病理学表现，包括角质形成细胞空泡化、角化不良细胞、基底细胞空泡化、角质细胞坏死、基底层裂隙、表皮全层坏死、表皮真皮分离、小血管周围淋巴细胞浸润、表皮萎缩、上皮脚消失、色素失禁、真皮胶原化的发生情况，所有病例皮肤组织活检均行 HE染色并由 2 名病理医师阅片。根据现有 GVHD 皮肤病理损伤标准进行分级分组，统计分析各组皮肤病理学改变的特点及规律。结果 本组病例中男性 7 例，女性 3 例，平均年龄为（59.5±6.8）岁 ；从移植后皮肤活检时间为 9 ~ 48 d（中位时间 31 d）；10 例患者均以皮疹为皮肤首发症状，发生部位从腹部向四肢及头颈部扩散， 皮肤病理学表现中基底细胞空泡化和小血管周围淋巴细胞浸润发生率均为 100%，角质形成细胞空泡化和角化不良细胞发生率为 60%，表皮萎缩和角质细胞坏死阳性率约为 30% ；基底层裂隙、色素失禁约占 20% ；上皮脚消失、真皮胶原化阳性率约为 10%，本组病例中未见表皮全层坏死和表皮真皮分离现象，阳性率为 0%。其中真皮浅层单个血管周围浸润的淋巴细胞平均数量在GVHD皮肤损伤Ⅱ级和Ⅲ级中的发生率均为 100%。因此，基底细胞空泡化、小血管周围淋巴细胞浸润可作为 GVHD 的重要病理学诊断依据，而角质形成细胞空泡化和角化不良细胞可作为 GVHD 病理学诊断的主要支持依据，且真皮浅层单个血管周围浸润的淋巴细胞平均数量对 GVHD 损伤分级具有重要的临床指导作用。结论 皮肤病理学特征对肝移植术后 GVHD 的诊断和鉴别诊断具有重要作用，真皮浅层单个血管周围浸润的淋巴细胞数量是 GVHD 损伤分级、程度判断的重要组织学参考依据。 

关键词:

肝移植 , 移植物抗宿主病 , 皮肤 , 病理学特征