胰腺腺鳞癌临床病理特征与分子机制研究进展

doi:10.19723/j.issn.1671-167X.2026.02.032

摘要/Abstract

摘要：

胰腺腺鳞癌(pancreatic adenosquamous carcinoma, PASC)是一种罕见的胰腺外分泌恶性肿瘤，兼具腺癌与鳞癌双重特征。相较于胰腺导管腺癌(pancreatic ductal adenocarcinoma，PDAC)，PASC表现出更强的侵袭性与异质性，且患者预后更差。PASC的生物学行为特殊，目前临床缺乏特异性的术前诊断方法和针对性的治疗策略，临床治疗多沿用PDAC方案，患者生存获益有限。此外，PASC的细胞起源与演化路径、分子分型图谱也有待阐明。本文系统综述了PASC的流行病学与临床病理特征，并探讨含铂化疗方案、放疗及免疫治疗在改善患者预后方面的潜在价值，同时，总结了PASC在克隆起源模式、独特的基因组和转录组改变以及肿瘤微环境异质性等方面的最新研究进展。

关键词: 胰腺腺鳞癌, 流行病学, 免疫疗法, 多组学技术, 分子分型

Abstract:

Pancreatic adenosquamous carcinoma (PASC) is a rare exocrine malignancy of the pancreas with an increasing incidence, histologically defined by the coexistence of adenocarcinoma and squamous carcinoma components. Current pathological diagnosis typically requires the squamous component to comprise at least 30% of the tumor. However, this threshold remains controversial given the unconfirmed independent prognostic value of the extent of squamous differentiation. Compared with pancreatic ductal adenocarcinoma (PDAC), PASC exhibits greater aggressiveness and heterogeneity, contributing to a poorer prognosis with a median survival of approximately 9 months. Despite its distinct biological behavior, specific preoperative diagnostic methods and targeted therapeutic strategies remain elusive. Diagnostically, while PASC lacks specific molecular markers, the ring-enhancement sign observed in the arterial phase of contrast-enhanced CT may aid distinction from PDAC. Owing to the lack of standardized therapeutic strategies, treatment largely follows guidelines established for PDAC, offering limited survival benefits, though platinum-based chemotherapy and radiotherapy show potential efficacy. Notably, the rationale for immunotherapy lies in the high programmed death-ligand 1 (PD-L1) expression in the squamous component and an immunosuppressive microenvironment characterized by specific checkpoint interactions, such as the TIGIT-CD155 axis. Furthermore, the cellular origin and evolutionary trajectory of PASC remain debated. While monoclonal origin is the prevailing theory, it remains unclear whether the squamous component arises from adenocarcinoma transdifferentiation or from pancreatic pluripotent stem cells. At the molecular level, PASC shares genomic and transcriptomic features with PDAC yet maintains a distinct identity. Concurrently, its tumor microenvironment (TME) displays unique landscapes, differing significantly from PDAC in immune and stromal components like T cells, macrophages, and fibroblasts. Moreover, marked intratumoral heterogeneity is observed between the adenocarcinoma and squamous carcinoma regions within the same tumor. Future efforts should prioritize multi-omics and laser microdissection technologies to establish a refined molecular classification system, alongside the integration of liquid biopsy and artificial intelligence (AI)-assisted radiomics for accurate preoperative diagnosis. This comprehensive strategy is essential to shift clinical practice from empirical treatment to personalized precision medicine, ultimately improving outcomes for this refractory disease. This article systematically reviews the epidemiology and clinicopathological features of PASC, and specifically explores the therapeutic potential of platinum-based chemotherapy, radiotherapy, and immunotherapy. Furthermore, special attention is given to recent advances in monoclonal origin patterns, unique genomic and transcriptomic alterations, and TME heterogeneity.

Key words: Pancreatic adenosquamous carcinoma, Epidemiology, Immunotherapy, Multi-omics, Molecular typing

中图分类号:

R735.9

潘子晨, 陈凯, 侯钰坤, 杨博涵, 张继新, 马永蔌, 田孝东, 杨尹默. 胰腺腺鳞癌临床病理特征与分子机制研究进展[J]. 北京大学学报（医学版）, 2026, 58(2): 431-435.

Zichen PAN, Kai CHEN, Yukun HOU, Bohan YANG, Jixin ZHANG, Yongsu MA, Xiaodong TIAN, Yinmo YANG. Research progress in clinical pathology and molecular mechanisms of pancreatic adenosquamous carcinoma[J]. Journal of Peking University (Health Sciences), 2026, 58(2): 431-435.

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