Saito Yosuke, Suzuki Shuhei, Sanomachi Tomomi, Kato Kaho, Otake Hiroya, Nishise Yuko, Yamada Yuta, Saito Koki, Takahashi Koshi, Kumanishi Ryosuke, Fukui Tadahisa, Yoshioka Takashi
Department of Clinical Oncology, Yamagata University Hospital, Yamagata, Japan.
Department of Clinical Oncology, Yamagata University Hospital, Yamagata, Japan;
In Vivo. 2025 Mar-Apr;39(2):1173-1181. doi: 10.21873/invivo.13921.
BACKGROUND/AIM: Cowden syndrome (CS)/PTEN hamartoma tumor syndrome (PHTS) is a hereditary disorder caused by germline variants. While patients with CS/PHTS have increased risk of various cancers, pancreatic cancer is not typically associated with this syndrome. We report a rare case of pancreatic mixed acinar-neuroendocrine carcinoma in a patient with a germline variant, aiming to understand its molecular characteristics and clinical implications.
A male in his late 40s presented with pancreatic cancer and hepatic metastases. His medical history included thyroid cancer and familial gastrointestinal malignancies. Liver biopsy revealed mixed acinar-endocrine carcinoma. Cancer genome profiling identified pathogenic variants in and , along with a germline variant (V201fs*1), leading to a diagnosis of CS. Notably, mutations, commonly found in pancreatic cancer, were absent. The patient showed extreme resistance to multiple chemotherapy regimens, including FOLFIRINOX, gemcitabine plus nab-paclitaxel, and cisplatin plus etoposide, resulting in rapid clinical decline.
This case highlights a rare presentation of pancreatic cancer in CS/PHTS with distinct molecular and histological features. The absence of mutation and presence of germline variant may have contributed to the aggressive clinical course and treatment resistance. These findings underscore the need for further research into the molecular mechanisms of PTEN-associated pancreatic cancers and the development of targeted therapeutic strategies.
背景/目的：考登综合征（CS）/PTEN错构瘤肿瘤综合征（PHTS）是一种由种系变异引起的遗传性疾病。虽然CS/PHTS患者患各种癌症的风险增加，但胰腺癌通常与该综合征无关。我们报告了一例患有种系变异的胰腺混合性腺泡-神经内分泌癌罕见病例，旨在了解其分子特征和临床意义。
一名40多岁的男性因胰腺癌和肝转移就诊。他的病史包括甲状腺癌和家族性胃肠道恶性肿瘤。肝脏活检显示为混合性腺泡-内分泌癌。癌症基因组分析确定了 和 中的致病变异，以及一种种系变异（V|201fs*|），从而诊断为CS。值得注意的是，胰腺癌中常见的 突变并不存在。该患者对多种化疗方案，包括FOLFIRINOX、吉西他滨加纳米白蛋白结合型紫杉醇和顺铂加依托泊苷，均表现出极强的耐药性，导致临床状况迅速恶化。
本病例突出了CS/PHTS中胰腺癌的罕见表现，具有独特的分子和组织学特征。 突变的缺失和种系变异的存在可能导致了侵袭性的临床病程和治疗耐药性。这些发现强调了进一步研究PTEN相关胰腺癌的分子机制和开发靶向治疗策略的必要性。
