Suemitsu Yamato, Ono Yusuke, Mizukami Yusuke, Ye Juanjuan, Yamakawa Keiko, Takamoto Takeshi, Nakano-Narusawa Yuko, Mukai Yuri, Takamatsu Manabu, Nakazawa Atsuko, Mino-Kenudson Mari, Kumasaka Toshio, Matsuda Yoko
Department of Pathology, Japanese Red Cross Medical Center, Shibuya, Japan.
Cancer Genetics, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
Front Oncol. 2021 Aug 27;11:725290. doi: 10.3389/fonc.2021.725290. eCollection 2021.
Pancreatoblastoma is a rare malignant epithelial neoplasm of the pancreas that mainly occurs in children and involves abnormalities in the WNT/β-catenin pathway, such as mutation. However, the molecular abnormalities in adult pancreatoblastoma are not well known.
An elderly man, who underwent elective distal pancreatectomy and splenectomy, was referred to our hospital with a mass in the tail of the pancreas. Histologically, the lesion revealed proliferation of clear, basophilic, and cartilaginous tumor cells with lymphatic metastasis. Each of the morphologically distinct tumor components showed different immunohistochemical patterns, indicating heterogeneous differentiation, including epithelial (both acinar and ductal), mesenchymal, and neuroendocrine differentiation. All tumor components showed nuclear expression of β-catenin and cyclin D1. Per next-generation sequencing (NGS), the clear and basophilic tumor cells shared mutations in , , and . Among the mutations, , c.1816_1817insA showed the highest frequency in both cell types, indicating that mutation was a driver mutation of the tumor. A diagnosis of PB was rendered.
In conclusion, the clear and basophilic cells of the tumor were supposedly derived from the same clone and subsequently acquired additional mutations. This is the first report of clonal evolution in pancreatoblastoma.
胰腺母细胞瘤是一种罕见的胰腺恶性上皮性肿瘤，主要发生于儿童，涉及WNT/β-连环蛋白通路异常，如突变。然而，成人胰腺母细胞瘤的分子异常尚不清楚。
一名接受择期远端胰腺切除术和脾切除术的老年男性因胰腺尾部肿块被转诊至我院。组织学上，病变显示透明、嗜碱性和软骨样肿瘤细胞增殖并伴有淋巴转移。形态学上不同的肿瘤成分各自显示出不同的免疫组化模式，表明存在异质性分化，包括上皮（腺泡和导管）、间充质和神经内分泌分化。所有肿瘤成分均显示β-连环蛋白和细胞周期蛋白D1的核表达。通过下一代测序（NGS），透明和嗜碱性肿瘤细胞在 、 和 存在共同突变。在这些突变中，c.1816_1817insA在两种细胞类型中出现频率最高，表明 突变是肿瘤的驱动突变。作出了胰腺母细胞瘤的诊断。
总之，肿瘤的透明和嗜碱性细胞推测来自同一克隆，随后获得了额外的突变。这是胰腺母细胞瘤克隆进化的首例报道。
