DICER1 screening in 15 paediatric paratesticular sarcomas unveils an unusual DICER1-associated sarcoma
DICER1 screening in 15 paediatric paratesticular sarcomas unveils an unusual DICER1-associated sarcoma
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DOI：
10.1002/cjp2.164
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发表时间：
2020-03-28
影响因子：
4.1
通讯作者：
Foulkes, William D.
中科院分区：
文献类型：
--
作者：
Apellaniz-Ruiz, Maria;Cullinan, Noelle;Foulkes, William D.
DICER 1综合征是一种由DICER 1中的致病性生殖系变异引起的遗传性疾病，患有DICER 1综合征的个体患上一系列主要为儿童期发病的疾病的风险增加，包括泌尿生殖系统肉瘤。然而，关于DICER 1参与睾丸旁肉瘤的数据尚未发表。在此，我们分析了一系列的15个小儿睾丸旁肉瘤和详细描述的情况下，一个男婴睾丸旁粘液样肿瘤，被认为是一个低级别的肉瘤，谁也表现出囊性肾瘤，一个经典的DICER 1综合征表型。他在每个肿瘤中都携带了致病性生殖系DICER 1变体和不同的体细胞热点突变。睾丸旁肿瘤表现出强烈的和弥漫性的表达WT 1和CD 10，一个不寻常的免疫表型在儿科肉瘤，但典型的肿瘤苗勒起源。肿瘤被假定来自睾丸附件，位于睾丸旁的苗勒管残端。这种起源类似于其他DICER 1相关的非上皮性妇科肿瘤，被认为是由苗勒管衍生物引起的。这些发现指向DICER 1在Mullerian衍生结构中的关键作用。支持这一假设的事实是，该系列的其他睾丸旁肉瘤WT1和CD10阴性或局灶性阳性，并且没有任何DICER 1突变。总之，我们提出了第一例睾丸旁肉瘤与DICER 1综合征，强调睾丸旁肿瘤与一个不寻常的组织学外观可能表明潜在的DICER 1突变，特别是在存在的个人或家族病史的DICER 1相关的疾病。在这种情况下，DICER1突变检测可能会导致临床护理的变化，包括实施癌症护理监测策略。
Individuals with DICER1 syndrome, a genetic disorder caused by pathogenic germline variants in DICER1, are at increased risk of developing a wide array of predominantly childhood onset conditions, including genitourinary sarcomas. However, data on DICER1 involvement in paratesticular sarcomas have not been published. Herein, we analyse a series of 15 paediatric paratesticular sarcomas and describe in detail the case of a male infant with a paratesticular myxoid tumour, considered to be a low-grade sarcoma, who also manifested a cystic nephroma, a classic DICER1 syndrome phenotype. He harboured a pathogenic germline DICER1 variant and different somatic hot-spot mutations in each tumour. The paratesticular tumour showed strong and diffuse expression for WT1 and CD10, an unusual immunophenotype in paediatric sarcomas, but typical of tumours of Mullerian origin. The tumour was postulated to arise from the appendix testis, a Mullerian remnant located in the paratestis. Such an origin would be analogous to other DICER1-associated non-epithelial gynaecological tumours, thought to arise from Mullerian derivatives. These findings point towards a key role of DICER1 in Mullerian-derived structures. Supporting this hypothesis is the fact that the other paratesticular sarcomas from the series were either negative or focally positive for WT1 and for CD10, and none had any DICER1 mutations. In summary, we present the first case of a paratesticular sarcoma associated with DICER1 syndrome, emphasising that paratesticular tumours with an unusual histological appearance may suggest an underlying DICER1 mutation, especially in the presence of a personal or family history of DICER1-associated disease. In this context, DICER1 mutation testing could lead to changes in clinical care including implementation of cancer care surveillance strategies.