Multiple Primary Malignancy-Related Gallbladder Cancer: An Important Recommendation for the Early Detection of Gallbladder Cancer

<b>Background</b>: Gallbladder cancer (GBC) is a highly lethal malignancy that is often asymptomatic in its early stages and difficult to treat once clinical symptoms appear. Although established risk factors include female sex, gallstones, and chronic biliary inflammation, other clinical contexts associated with GBC remain insufficiently characterized. Multiple primary malignancies (MPMs), in which more than one primary cancer develops in the same individual, have recently attracted attention; however, their relationship with GBC has only rarely been examined. In this study, we aimed to clarify the clinical features of MPM-related GBC and explore its implications for early detection. <b>Methods</b>: We retrospectively compared 22 patients with GBC associated with other malignancies (MPM-positive GBC) and 16 patients with GBC alone (MPM-negative GBC). Clinical characteristics, major risk factors, tumor presentation, and imaging findings were evaluated. Special attention was paid to the sequence of cancer development and the diagnostic utility of contrast-enhanced ultrasonography (CEUS). <b>Results</b>: In all MPM-positive cases, GBC occurred as a second primary malignancy, most commonly following gastrointestinal cancers (12/22). Gallstones were significantly less frequent in the MPM-positive group than in the MPM-negative group (2/22 vs. 6/16). The MPM-positive group showed a slight male predominance (12 males and 10 females). Neither pancreaticobiliary maljunction nor porcelain gallbladder was identified in either group. CEUS was useful for both the detection and qualitative diagnosis of GBC in all patients. <b>Conclusions</b>: MPM-related GBC frequently develops as a second primary malignancy in patients with prior gastrointestinal cancer and may arise in the absence of classical risk factors. Careful long-term surveillance after cancer treatment is therefore essential for identifying second primary GBC at a potentially resectable stage. The combined use of ultrasonography and CEUS may facilitate earlier and more accurate diagnosis in this clinical setting.