Background: The reliance on LI-RADS 5 imaging criteria for the non-invasive diagnosis of hepatocellular carcinoma (HCC) can be precarious in the setting of advanced liver fibrosis, where benign inflammatory mimics may exhibit deceptive vascular kinetics. Hepatic xanthogranulomatous inflammation (XGI) represents a rare but significant diagnostic pitfall, as it can strictly simulate the arterial phase hyperenhancement and subsequent washout characteristic of malignancy. This diagnostic ambiguity is exacerbated in diabetic patients by“diabetic immunoparesis”which masks localized infection through a deceptive absence of systemic leukocytosis. This study highlights a novel diagnostic signature, termed “WBC-HBP Dissociation”utilizing Heparin-Binding Protein (HBP) to unveil occult neutrophil activation otherwise obscured by normocytosis. Case Presentation: A 50-year-old male with chronic hepatitis B and biopsy-confirmed advanced fibrosis (LSM: 11. 6 kPa) presented with a solitary, hypervascular liver mass. Despite uncontrolled Type 2 Diabetes (HbA1c: 12. 00%) and a broad panel of negative tumor markers (AFP, PIVKA-II, CEA, CA19-9), both CEUS and MRI yielded a definitive LI-RADS 5 classification with suspected local invasion. Notably, while the white blood cell (WBC) count remained within the normal range (5. 83× 10⁹/L), a marked elevation in HBP (16. 7ng/mL; Ref: < 11. 4ng/mL) suggested a localized inflammatory response. Guided by the radiological mandate for malignancy, the patient underwent an anatomical hepatectomy. Postoperative histopathology revealed XGI characterized by dense infiltration of lipid-laden foamy histiocytes, with immunohistochemistry (CD68+, SMA+, ALK-, IgG4-) effectively excluding neoplasia and IgG4-related disease. Conclusion: XGI can authentically mimic the hemodynamic signature of HCC, a challenge compounded by the “relative washout” effect of background fibrosis. The “WBC-HBP Dissociation” identified here serves as a critical serological red flag for occult inflammation in patients with metabolic comorbidities. Integrating HBP assessment into the diagnostic algorithm for LI-RADS 5 masses—especially when tumor markers are negative—may justify advanced metabolic imaging or biopsy, potentially sparing high-risk patients from unnecessary and morbid major hepatic resections. Plain Language Summary: Diagnosing Hepatocellular Carcinoma usually relies on specific patterns seen on CT or MRI scans. Yet, this method has a flaw. In patients with liver fibrosis, benign inflammatory lumps can mimic the exact appearance of a tumor. Such mimicry creates a dangerous trap, often leading to unnecessary major surgeries. The risk is even higher for diabetic patients. Diabetes causes “diabetic immunoparesis” a condition where the immune system reacts slowly. Consequently, standard blood tests may show normal white blood cell counts despite an active, hidden infection. We report a case where a diabetic patient’s liver mass mimicked cancer on all imaging modalities. His normal blood counts initially masked the infection. However, we detected a sharp rise in Heparin-Binding Protein (HBP). Unlike routine markers, HBP is released early and remains elevated even in diabetic patients. We term this mismatch “WBC-HBP Dissociation”. It was the critical clue identifying the mass as Xanthogranulomatous Inflammation, not cancer. Testing for HBP offers a safety net, helping surgeons avoid operating on inflammatory mimics. Keywords: xanthogranulomatous inflammation, heparin-binding protein, hepatocellular carcinoma, diagnostic biomarkers, neutrophil activation, hemodynamic illusion
Zhu et al. (Sun,) studied this question.