High-grade transformation of pancreatic neuroendocrine tumor associated with TP53 mutations: A diagnostic pitfall mimicking neuroendocrine carcinoma.
High-grade transformation of pancreatic neuroendocrine tumor associated with TP53 mutations: A diagnostic pitfall mimicking neuroendocrine carcinoma.
复制标题
与 TP53 突变相关的胰腺神经内分泌肿瘤的高级别转化：模仿神经内分泌癌的诊断陷阱。
DOI：
10.1111/pin.13252
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Ushiku T.
中科院分区：
文献类型：
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作者：
Tanaka M;Shinozaki-Ushiku A;Kunita A;Yasunaga Y;Akamatsu N;Hasegawa K;Ushiku T.
在胰腺神经内分泌肿瘤中，ATRX、DAXX和MEN 1突变是神经内分泌肿瘤（NETs）的特异性突变，而TP 53和RB 1突变是神经内分泌癌（NECs）的特征性突变。我们报告了一例胰腺NET，其发生了与获得TP 53突变相关的高度转化。原发性胰腺肿瘤包括传统的2级NET，伴有α地中海贫血/智力低下缺失、X连锁表达和野生型TP 53，小病灶表现出显著的多形性，肿瘤细胞有丝分裂活性增加，伴有两个致病性TP 53突变。两年后，多发性肝转移发展，并手术切除。转移性肿瘤表现出明显的多形性，核分裂活性增加（17/2 mm 2），TP 53突变与原发性肿瘤中具有TP 53突变的小区域相同。还发现了具有单个TP 53突变的肝转移。值得注意的是，激素表型在进展过程中发生了变化，转移灶中胰高血糖素表达降低，胰岛素表达增加。我们的观察结果表明，TP 53突变可以发生在胰腺NETs的进展，并可能与表型转化。重要的是，多形性增加、有丝分裂活性增加以及TP 53突变可能是导致NEC过度诊断的诊断陷阱。
Among pancreatic neuroendocrine neoplasms, mutations inATRX,DAXX, andMEN1are specific to neuroendocrine tumors (NETs), whereasTP53andRB1mutations are characteristic of neuroendocrine carcinomas (NECs). We report a case of pancreatic NET that underwent high‐grade transformation associated with acquisition ofTP53mutations. The primary pancreatic tumor consisted of conventional grade 2 NET with loss of alpha‐thalassemia/mental retardation, X‐linked expression and wild‐typeTP53, with a small focus exhibiting significant pleomorphism and increased mitotic activity of the neoplastic cells with two pathogenicTP53mutations. Two years later, multiple liver metastases developed and were surgically resected. The metastatic tumors showed marked pleomorphism with increased mitotic activity (17/2 mm2) andTP53mutations identical to the small area withTP53mutations in the primary tumor. Liver metastases with a singleTP53mutation were also noted. Notably, hormonal phenotype has changed during progression with decreased glucagon and increased insulin expression in the metastases. Our observations suggest thatTP53mutation can occur in pancreatic NETs during progression and can be associated with phenotypic transformation. Importantly, increased pleomorphism, mitotic activity, as well asTP53mutations could be diagnostic pitfalls leading to an overdiagnosis of NEC.