EBV相关淋巴组织增生性疾病的分类进展（3）

REACTIVE PROLIFERATIONS WITH VARIED MALIGNANT POTENTIAL	不同恶性潜能的反应性增生
（2）种痘样水疱病  Hydroa Vacciniforme
定义和临床特征：
Hydroa vacciniforme (HV) is a rare idiopathic photodermatosis that is considered as a subcategory of chronic active EBV (CAEBV).	种痘样水疱病（HV）是一种罕见的特发性光照性皮肤病，被认为是CAEBV的一个亚类。
It usually occurs during childhood and is characterized by vesicles and crust formation after sunlight exposure and typically heals by vacciniform scarring.	它通常发生在儿童时期，其特征是在阳光照射后形成水疱和结痂，通常通过种痘样疤痕愈合。
The classic form of the disease has a low risk of progression and usually resolves spontaneously in adolescence; however, many patients show disease progression and develop severe and extensive skin lesions with facial edema and ulceration that are not limited to sunexposed areas along with systemic manifestations including fever, hepatosplenomegaly, and lymphadenopathy.	该病的经典型是进展风险很低，通常在青春期会自然消退；然而，许多患者表现为疾病进展，并出现严重和广泛的皮损，伴有颜面浮肿和溃疡，这些皮损不仅限于暴露在阳光下的区域，还有全身表现，包括发烧，肝脾肿大，淋巴结肿大。
Many patients eventually develop a clonal T-cell population but, given the lack of reliable clinical or molecular criteria that can predict clinical outcomes, it is not designated as a lymphoma but as HV-like lymphoproliferative disorder in the 2016 WHO classification to encompass the broad clinical spectrum of the disease.	许多患者最终发展出克隆性T细胞群，但由于缺乏可预测临床结果的可靠临床或分子标准，在2016年世卫组织的分类中，它不是淋巴瘤，而是HV样淋巴增生性疾病，以涵盖该疾病的广泛临床谱。
形态学特点：
A dermal lymphoid infiltrate with angiocentric and angiodestructive features is usually seen and is composed in most cases of CD8-positive cytotoxic T cells, but cases with CD4-positive or NK-cell phenotype have been reported.	常见皮肤淋巴浸润具有血管中心性和血管破坏性特征，大多数病例由CD8阳性细胞毒T细胞组成，但也有CD4阳性或NK细胞表型的病例报道。
发病机制（Pathogenesis）：
The cause of the disorder is largely unknown. Although the EBV status was not studied in the initial Western studies on the classic HV cases, studies on Asian populations showed that HV is an EBV-associated disorder.	这种疾病的原因在很大程度上是未知的。尽管开始西方国家对典型的HV病例没有进行EBV状态研究，但对亚洲人群的研究表明，HV是一种EBV相关疾病。
Genetic predisposition may play a major role given the geographic and ethnic distribution of the disorder, similar to that seen in other EBV associated T/NKcell lymphoproliferative disorders.	考虑到疾病的地区和种族分布，遗传倾向可能起主要作用，类似于其他EBV相关T/NKcell淋巴增生性疾病。
临床病程与预后：
The clinical course is variable, with many patients experiencing recurrent skin lesions for 10 to 15 years before systemic progression. T-cell clonality, the density of the infiltrate, and the number of EBV-positive cells do not predict clinical outcome or disease progression.	临床病程不一，许多患者在全身进展前10到15年内反复出现皮肤病变。T细胞克隆性、浸润密度和EBV阳性细胞数不能预测临床结局或疾病进展。
EBV潜伏模式：
Latency II.	II型潜伏模式
EBV原位杂交染色模式（EBER）：
The number of EBV-positive cells by in situ hybridization varies from one case to another, but many EBV-positive T cells are usually seen.	原位杂交EBV阳性细胞的数目因病例而异，但通常可见许多EBV阳性T细胞。

（3）严重蚊虫叮咬过敏 Severe Mosquito Bite Allergy
定义和临床特征：
This allergy is a rare, exaggerated reaction to mosquito bites in children that presents as intense local skin lesions, including erythema, bullae, ulcers, skin necrosis, and deep scarring. Patients have circulating EBV-positive NK cells in the peripheral blood and are at an increased risk of developing hemophagocytic syndrome and progression to an overt NK/T-cell lymphoma or aggressive NK-cell leukemia over the longstanding course of the disease.	这是一种罕见、夸张的对蚊子叮咬的过敏反应，表现为强烈的局部皮损，包括红斑、大疱、溃疡、皮肤坏死和深疤痕。患者外周血中有循环的EBV阳性NK细胞，并且在疾病的长期过程中，有更高的风险发展为噬血细胞综合征，并发展为显性NK/T细胞淋巴瘤或侵袭性NK细胞白血病。
Patients usually have high serum immunoglobulin (Ig) E titers and high EBV DNA load in the peripheral blood in addition to the NK-cell lymphocytosis.	除NK细胞淋巴细胞增多外，患者外周血IgE滴度高，EBV-DNA载量高。
形态学特点：
A dermal infiltrate that extends into the subcutaneous tissue with features of angiodestruction is usually seen. Most of the infiltrating cells have an NK-cell phenotype.	通常可见真皮浸润，延伸到皮下组织具有血管破坏的特征。大多数浸润细胞具有NK细胞表型。
发病机制（Pathogenesis）：
The pathogenesis of the disease is unknown, although it is thought that the severe mosquito bite allergy may play a role in the reactivation of EBV in NK cells inducing the expression of LMP1, which stimulates NK-cell proliferation and the eventual development of aggressive NK-cell leukemia in some patients.	该病的发病机制尚不清楚，尽管有人认为，严重的蚊虫叮咬过敏可能在NK细胞中EBV重新激活，诱导LMP1的表达，从而刺激NK细胞增生，并最终在一些患者中发展为侵袭性NK细胞白血病。
临床病程与预后：
Most patients have a prolonged clinical course with increased risk of hemophagocytic lymphohistiocytosis (HLH) and aggressive NK-cell leukemia after a median of 12 years.	大多数患者的临床病程延长，中位12年后发生噬血细胞淋巴组织细胞增多症和侵袭性NK细胞白血病的风险增加。
EBV潜伏模式：
Latency II.	II型潜伏模式
EBV原位杂交染色模式（EBER）：
A fraction of the NK cells are usually positive for Epstein-Barr encoding region (EBER) and a much higher density of EBV-positive cells should raise suspicion of NK-cell lymphoma/leukemia.	一部分NK细胞通常EBER呈阳性，而EBV阳性细胞的密度更高应高度怀疑是NK细胞淋巴瘤/白血病可能。

（4）EBV阳性皮肤黏膜溃疡  EBV–Positive Mucocutaneous Ulcer
定义和临床特征：
EBV-positive mucocutaneous ulcer (MCU) is an entity described in immunosuppressed patients who present with painful, well-circumscribed ulcer arising at mucosal or cutaneous sites, with the oropharyngeal mucosa as the most common site of presentation.	EBV阳性皮肤黏膜溃疡（MCU）是一发生于免疫抑制患者的疾病，表现为黏膜或皮肤部位的疼痛性、境界清楚溃疡，口咽黏膜为最常见部位。
No mass lesion or lymphadenopathies are detected clinically or by imaging. The cause of immunosuppression is variable and includes elderly individuals, after therapeutic immunosuppression for immune-mediated disorders, and after solid and allogeneic stem cell transplant.	临床或影像学检查均未发现肿块或淋巴结病变。免疫抑制的原因不一，包括老年人、免疫介导疾病治疗后免疫抑制、实体器官和异基因干细胞移植后。
形态学特点：
A well-circumscribed ulcer is noted with a mixed inflammatory background and a variable number of CD30-positive, EBV-positive large immunoblasts.	界限清楚的溃疡伴有混合性炎症背景和数量不等的CD30阳性、EBV阳性的大免疫母细胞。
Some of the immunoblasts can look atypical or Reed-Sternberg–like. The base of the lesion is usually sharply demarcated by a rim of CD3-positive small lymphocytes.	一些免疫母细胞可以看起来非典型或Reed-Sternberg样。病变的底部通常有一条CD3阳性的小淋巴细胞带。
发病机制（Pathogenesis）：
The cause of the disorder is not fully known but it is hypothesized that the immune surveillance of T cells is diminished, either because of age-related immune senescence or iatrogenic immunosuppression, to a level that is only just enough to maintain the virus dormant systemically but additional exposure to a site-restricted immune-modulating factor leads to a localized EBV-driven proliferation.	病因尚不完全清楚，但假设T细胞的免疫监视功能减弱，可能是由于年龄相关的免疫衰老或医源性免疫抑制，达到一个仅仅足以维持病毒系统休眠的水平，但额外暴露于一个受位点限制的免疫调节因子会导致局部EBV驱动的增殖。
临床病程与预后：
Spontaneous regression in elderly immunocompetent individuals or following reduction in immunosuppression usually occurs.	老年人免疫功能正常或免疫抑制减少后常出现自发性消退。
EBV潜伏模式：
The EBV latency pattern has not been fully studied but the transformed cells are commonly positive for LMP1 and EBER, which may be suggestive of latency II or latency III pattern.	EBV潜伏期模式尚未得到充分研究，但转化细胞通常为LMP1和EBER阳性，这可能提示潜伏模式为II型或III型。
EBV原位杂交染色模式（EBER）：
EBV is variably expressed, with most cases showing scattered EBV-positive cells that range in size from small to large, tend to be concentrated near the surface of the ulcer and away from the base, and are composed predominantly of B cells.	EBV表达不一，多数病例可见散在分布的EBV阳性细胞，大小不等，往往集中在溃疡表面附近，远离基底部，主要由B细胞组成。

 

Fig. 1. The classification scheme for EBV-associated lymphoproliferative disorders. DLBCL, diffuse large B-cell lymphoma; HHV8, human virus herpes 8; HIV, human immunodeficiency virus; NOS, not otherwise specified; PTLDs, posttransplant lymphoproliferative disorders.

图1 EBV相关淋巴增生性疾病的分类方案：DLBCL，弥漫性大B细胞淋巴瘤；HHV8，人类疱疹病毒8型；HIV，人类免疫缺陷病毒；NOS，非特指型；PTLDs，移植后淋巴增生性疾病；

第一部分《EBV相关的淋巴组织反应性增生》疾病内容已讲述完，对于EBV相关淋巴瘤在“穿越疫情”医之本公益直播讲座中有涉及，且在翟琼莉老师的公众号《轻松诊断086》中有详细的讲解，本文就不一一叙述了。

参考文献:

[1] EBV-Associated Lymphoproliferative Disorders:Update in Classification.2019.

～～～End～～～

作者简介

慧海拾穗，主治医师。

从事儿童病理诊断，对淋巴造血、软组织和泌尿生殖系统肿瘤有着浓厚的兴趣