Metachronous Liver Lesions in Patients with Known Solid Tumors: Benign, Related to the Known Tumor, or Entirely New Malignant Etiology?

Purpose: To investigate the etiology of metachronous focal liver lesions (FLL) detected in patients with solid primary tumors (PT) and to evaluate the factors influencing the nature of these lesions. Materials and Methods: This retrospective study analyzed 202 patients with a history of solid PT who developed metachronous FLL, defined as lesions detected at least 3 months after the initial PT diagnosis. Latency period (LP) was defined as the time interval, in months, between the initial diagnosis of PT and the detection of the FLL. All patients underwent hepatic ultrasound (US) at our tertiary university hospital between June 2016 and December 2023. Data were retrieved from a prospectively maintained registry. Diagnosis of malignant FLL (mFLL) was histologically confirmed and subclassified as metastases from the known primary tumor (M-PT) or de novo primary tumors (DNPT), which were further divided into metastases from a de novo primary tumor (M-DNPT) and hepatobiliary de novo primary tumors (HB-DNPT). Benign FLL (bFLL) were diagnosed either histologically or based on characteristic features on contrast-enhanced imaging and clinical follow-up, following current diagnostic guidelines. The prevalence, clinical parameters, and sonographic characteristics of the different lesion groups were analyzed and compared. Multinominal and binary regression analyses were used to examine the association between different variables and FLL types. The PT-FLL concordance rate (PT-FLLCR) for each PT was defined as the proportion of FLLs identified as metastases from the corresponding PT. Results: The study cohort included 202 patients, including 98 males and 104 females, with a mean age of 64 ± 13 years. The average LP was 62.4 ± 72.6 months. Of all detected FLLs, 144 (71.3%) were malignant (mFLL) and 58 (28.7%) were benign (bFLL). M-PT was the most frequent etiology, accounting for 117 lesions (57.9%). Among DNPT, 19 (9.4%) were M-DNPT, and 8 (4.0%) were HB-DNPT. The most common benign lesions were hemangiomas (23; 11.4%), followed by fat deposition/sparing (10; 5.0%) and simple hepatic cysts (9; 4.5%). The final etiology of FLLs varied according to lesion’s echogenicity (p = 0.01), size (p = 0.009), multiple FLL (p = 0.002), and presence of extrahepatic metastases (p = 0.004). The highest PT-FLL-CRs were noted in pancreatobiliary (76.2%) and breast tumors (72.1%), while the lowest rates were seen in prostate carcinoma (20%) and malignant melanoma (6/16; 37.5%). However, there was no statistically significant association between PT-FLL-CR and either the anatomical site or histological subtype of the primary tumor (p > 0.05). Among the 144 mFLL cases, the likelihood of an FLL being a DNPT rather than an M-PT increased with longer LP; specifically, for each additional month of latency, the odds of the lesion being an M-DNPT (vs. M-PT) rose by 0.6% (OR 1.006, p = 0.036). Conclusion: M-PT represents the most common etiology of metachronous FLL in patients with solid tumors. While lesion characteristics—such as size, echogenicity, multiplicity, and presence of extrahepatic metastases—differed significantly between FLL groups, neither PT origin nor PT histology independently predicted lesion type. Both benign lesions and de novo malignant FLLs can occur. Notably, among mFLLs, a longer LP was associated with a higher probability of DNPT. These findings underscore the importance of histological confirmation of FLLs in patients with a history of solid tumors.