Legras Antoine, Tallet Anne, Didelot Audrey, Cazes Aurélie, Danel Claire, Hin Angela, Borie Raphaël, Crestani Bruno, Castier Yves, Bagan Patrick, Le Pimpec-Barthes Françoise, Riquet Marc, Blons Hélène, Mordant Pierre
Division of Thoracic Surgery and Lung Transplantation, Georges Pompidou European Hospital, Paris-Descartes University, Sorbonne Paris Cité University, Paris, France.
INSERM UMR-S1147, CNRS SNC 5014, Paris-Descartes University, Sorbonne Paris Cité University, Paris, France.
J Thorac Dis. 2018 Apr;10(4):2079-2088. doi: 10.21037/jtd.2018.03.159.
Unicentric mediastinal Castleman disease (CD) is a rare condition, poorly characterized due to the small number of cases and the absence of genomic study. We analyzed clinical, radiological, histological and genomic patterns associated with mediastinal CD in a substantial case series. We retrospectively reviewed cases of unicentric mediastinal CD managed in 2 French thoracic surgery departments between 1988 and 2012. Clinical, radiological, surgical and pathological data were recorded. On available FFPE blocks we performed mutation screening by next-generation-sequencing, using AmpliSeq™ Cancer Hotspot v2 (Life Technologies) and immunohistochemistry (IHC) (AKT-mTOR pathway).
Eleven patients were identified (mean age 41±15 years, sex-ratio 0.8, median follow-up 78 months). Surgical approach was thoracotomy (n=6), sternotomy (n=4), and VATS (n=1). Additional procedures included thymectomy in three cases, mediastinal lymphadenectomy in two cases, and bilobectomy in one case. One patient presented local relapse as a follicular dendritic cell sarcoma, leading to death 48 months after the first resection. Within 9 patients whose FFPE blocks were available, 2 mutations were found: VHL (p.F119L, 35%, n=1) and JAK3 (p.V718L, 53%, n=1). Phospho-AKT and phospho-mTOR stainings were negative in all cases, whereas phospho-S6RP staining was positive in eight cases, mainly in interfollicular cell cytoplasm.
From this series of patients with unicentric mediastinal CD, we observed 2 cases of potential driver mutations and 8 cases of phospho-S6RP activation not related to AKT-mTOR. Larger studies are required to decipher more precisely the molecular abnormalities and potential therapeutic targets underlying this uncommon condition.
单中心纵隔型Castleman病（CD）是一种罕见疾病，由于病例数量少且缺乏基因组研究，其特征尚不明确。我们在一个大量病例系列中分析了与纵隔型CD相关的临床、放射学、组织学和基因组模式。我们回顾性分析了1988年至2012年期间在法国两个胸外科接受治疗的单中心纵隔型CD病例。记录了临床、放射学、手术和病理数据。在可用的福尔马林固定石蜡包埋（FFPE）组织块上，我们使用AmpliSeq™癌症热点v2（Life Technologies）通过下一代测序进行突变筛查，并进行免疫组织化学（IHC）检测（AKT-mTOR通路）。
共识别出11例患者（平均年龄41±15岁，性别比0.8，中位随访78个月）。手术方式包括开胸手术（n = 6）、胸骨切开术（n = 4）和电视辅助胸腔镜手术（VATS，n = 1）。额外的手术包括3例胸腺切除术、2例纵隔淋巴结清扫术和1例双叶切除术。1例患者出现局部复发，表现为滤泡树突状细胞肉瘤，在首次切除后48个月死亡。在9例有可用FFPE组织块的患者中，发现了2个突变：VHL（p.F119L，35%，n = 1）和JAK3（p.V718L，53%，n = 1）。所有病例中磷酸化AKT和磷酸化mTOR染色均为阴性，而磷酸化S6RP染色在8例中为阳性，主要在滤泡间细胞质中。
在这一系列单中心纵隔型CD患者中，我们观察到2例潜在的驱动基因突变和8例与AKT-mTOR无关的磷酸化S6RP激活。需要更大规模的研究来更精确地解读这种罕见疾病潜在的分子异常和治疗靶点。
