A Rational Approach to the Diagnosis of Liver Metastases

The diagnosis of liver metastases encompasses a broad spectrum of entities and relies on clinicopathological correlation, with some cases being diagnosable using hematoxylin and eosin staining alone. For more challenging cases, ancillary testing is often required, with a focus on maximizing diagnostic yield while preserving tissue. This review draws on years of experience at a high-volume, tertiary referral center and incorporates an in-depth analysis of the existing literature in the field. When evaluating a liver lesion, the first step is to determine whether it represents a primary hepatic tumor or a metastasis. This review discusses a practical panel of immunohistochemical stains valuable in making this distinction. Next, it outlines a morphologic pattern-based approach to metastatic liver tumors, categorized by epithelioid, spindle, undifferentiated, and small round blue cell morphology. For each category, readers will find a proposed list of differentials based on the morphologic pattern, a suggested screening immunohistochemical panel, a focused discussion of potential pitfalls and practical tips for ancillary testing ("important aspects of ancillary testing"), and additional insights on specific entities within each group ("special diagnostic considerations"). This review provides a comprehensive overview of the diagnosis of liver metastases, along with a current guide to immunohistochemical and molecular testing for the classification of these tumors. It underscores the importance of careful consideration and prioritizing site-agnostic biomarkers and tumor lineage classification (eg, carcinoma, sarcoma, lymphoma, or melanoma) when choosing ancillary stains in challenging cases with limited material.