# Primary pancreatic signet ring cell carcinoma: molecular mechanisms and advances in clinical diagnosis and treatment

## TL;DR

This paper reviews the rare and aggressive pancreatic cancer subtype PPSRCC, focusing on its molecular features, diagnostic challenges, and treatment strategies to improve clinical outcomes.

## Contribution

The paper provides a comprehensive synthesis of clinicopathologic data and proposes a diagnostic workflow and management recommendations for PPSRCC.

## Key findings

- PPSRCC involves molecular pathways like ErbB2/ErbB3-MUC4 and PI3K/MAPK, with frequent KRAS mutations.
- Current treatment relies on PDAC strategies, but targeted therapies against KRAS and PD-L1 immunotherapy are promising.
- Standardized diagnostic workflows and multidisciplinary care are critical for improving PPSRCC outcomes.

## Abstract

To comprehensively integrate current evidence on the molecular mechanisms, diagnostic approaches, and treatment options for primary pancreatic signet ring cell carcinoma (PPSRCC), guiding clinical decision-making and improving prognosis.

In addition to the narrative synthesis, we performed a targeted extraction and comparative synthesis of published patient-level cases, case series, and registry studies to generate pooled clinicopathologic summaries, propose an operational diagnostic workflow (imaging–EUS-FNA–IHC–molecular testing), and formulate PPSRCC-specific management recommendations.

Primary pancreatic signet ring cell carcinoma (PPSRCC) is a rare pancreatic cancer subtype with extremely high malignancy and very poor prognosis. Current research on this disease is limited with weak evidence, leading to insufficient clinical awareness. PPSRCC exhibits unique epidemiological characteristics, molecular mechanisms, and clinical diagnostic and therapeutic features. Molecular studies suggest that its carcinogenic pathways involve abnormal activation of the ErbB2/ErbB3-MUC4 axis, activation of the PI3K and MAPK pathways, and frequent mutations in classical pancreatic cancer driver genes such as KRAS; however, the lack of specific molecular biomarkers and typical imaging findings makes clinical diagnosis challenging. In terms of treatment, clinical practice mostly refers to the therapeutic strategies for pancreatic ductal adenocarcinoma (PDAC), primarily surgery combined with radiochemotherapy. Targeted therapies against KRAS mutations and immunotherapy targeting PD-L1 may provide new directions for future management. In-depth elucidation of the molecular features of PPSRCC, clarification of diagnostic and therapeutic strategies, and development of novel targeted agents are key to improving clinical outcomes.

Deeper mechanistic interrogation and standardized diagnostic workflows are needed to enable earlier detection and tailored therapy in PPSRCC. Multidisciplinary care and emerging precision strategies may improve outcomes.

The online version contains supplementary material available at 10.1186/s12957-025-04106-4.